Timothy Durazzo

All Publications

• Frontal Brain N-Acetylaspartate at Treatment Entry is Related to Future WHO Risk Drinking Levels in Individuals with Alcohol Use Disorder. Journal of studies on alcohol and drugs May, A. C., Stephens, L. H., Kraybill, E. P., Meyerhoff, D. J., Durazzo, T. C. 2024

  Abstract

  To assess the viability of regional brain metabolite levels of individuals with alcohol use disorder (AUD) at treatment entry as a biomarker of post-treatment levels of alcohol use, categorized according to the World Health Organization risk drinking levels (WHO-RDL).Eighty-five individuals initiating treatment for AUD (16 ± 13 days after last alcohol consumption), and 45 light/non-drinking controls (LN) completed a 1.5T proton multislice magnetic resonance spectroscopic imaging study. N-acetylaspartate (NAA), a marker of neuronal viability, and other metabolites were quantitated for cortical gray matter (GM), white matter (WM) and select subcortical regions. Individuals with AUD were classified according to their post-treatment alcohol consumption, as abstainers (AB, n=42), low risk (RL, n=20), or higher risk (RH, n=23), based on the WHO-RDL taxonomy.Within frontal GM, RH exhibited significantly lower NAA levels than LN and AB but did not differ from RL. RH had significantly lower NAA concentration in frontal WM than all groups who did not significantly differ from one another. RH showed significantly lower parietal WM NAA than LN and AB; RL and RH did not differ from one another. Across RH and RL, lower frontal GM and WM NAA was related to shorter period of abstinence before first post-treatment alcohol consumption and longer post-treatment duration of alcohol resumption. There were no significant group differences in myo-inositol or choline- or creatine-containing compound concentrations.Frontal and parietal lobar NAA concentrations, near treatment entry, are associated with WHO-RDL categorized post-treatment alcohol consumption levels and may serve as predictive biomarkers of clinical outcomes following treatment for AUD.

  View details for DOI 10.15288/jsad.24-00168

  View details for PubMedID 39126661

• Greater ventral striatal functional connectivity in cigarette smokers relative to non-smokers across a spectrum of alcohol consumption. Brain imaging and behavior Halcomb, M. E., Dzemidzic, M., Avena-Koenigsberger, A., Hile, K. L., Durazzo, T. C., Yoder, K. K. 2024

  Abstract

  Cigarette smoking is associated with elevated risk of disease and mortality and contributes to heavy healthcare-related economic burdens. The nucleus accumbens is implicated in numerous reward-related behaviors, including reinforcement learning and incentive salience. The established functional connectivity of the accumbens includes regions associated with motivation, valuation, and affective processing. Although the high comorbidity of cigarette smoking with drinking behaviors may collectively affect brain activity, there could be independent effects of smoking in alcohol use disorder that impact brain function and behavior. We hypothesized that smoking status, independent of alcohol use, would be associated with aberrations of nucleus accumbens functional connectivity to brain regions that facilitate reward processing, salience attribution, and inhibitory control. Resting state functional magnetic resonance imaging data from thirty-one nonsmokers and nineteen smoking individuals were analyzed using seed-based correlations of the bilateral accumbens with all other brain voxels. Statistical models accounted for drinks consumed per week. The smoking group demonstrated significantly higher functional connectivity between the left accumbens and the bilateral insula and anterior cingulate cortex, as well as hyperconnectivity between the right accumbens and the insula. Confirmatory analyses using the insula and cingulate clusters generated from the original analysis as seed regions reproduced the hyperconnectivity in smokers between the bilateral insular regions and the accumbens. In conclusion, smoking status had distinct effects on neural activity; hyperconnectivity between the accumbens and insula in smokers may reflect enhanced encoding of the reinforcing effects of smoking and greater orientation toward smoking-associated stimuli.

  View details for DOI 10.1007/s11682-024-00903-9

  View details for PubMedID 39106000

• Pro-atherogenic medical conditions are associated with widespread regional brain metabolite abnormalities in those with alcohol use disorder. Alcohol and alcoholism (Oxford, Oxfordshire) Durazzo, T. C., Kraybill, E. P., Stephens, L. H., May, A. C., Meyerhoff, D. J. 2024; 59 (5)

  Abstract

  Widespread brain metabolite abnormalities in those with alcohol use disorder (AUD) were reported in numerous studies, but the effects of the pro-atherogenic conditions of hypertension, type 2 diabetes mellitus, hepatitis C seropositivity, and hyperlipidemia on metabolite levels were not considered. These conditions were associated with brain metabolite abnormalities in those without AUD. We predicted treatment-seeking individuals with AUD and pro-atherogenic conditions (Atherogenic+) demonstrate lower regional metabolite markers of neuronal viability [N-acetylaspartate (NAA)] and cell membrane turnover/synthesis [choline-containing compounds (Cho)], compared with those with AUD without pro-atherogenic conditions (Atherogenic-) and healthy controls (CON).Atherogenic+ (n = 59) and Atherogenic- (n = 51) and CON (n = 49) completed a 1.5 T proton magnetic resonance spectroscopic imaging study. Groups were compared on NAA, Cho, total creatine, and myoinositol in cortical gray matter (GM), white matter (WM), and select subcortical regions.Atherogenic+ had lower frontal GM and temporal WM NAA than CON. Atherogenic+ showed lower parietal GM, frontal, parietal and occipital WM and lenticular nuclei NAA level than Atherogenic- and CON. Atherogenic- showed lower frontal GM and WM NAA than CON. Atherogenic+ had lower Cho level than CON in the frontal GM, parietal WM, and thalamus. Atherogenic+ showed lower frontal WM and cerebellar vermis Cho than Atherogenic- and CON.Findings suggest proatherogenic conditions in those with AUD were associated with increased compromise of neuronal integrity and cell membrane turnover/synthesis. The greater metabolite abnormalities observed in Atherogenic+ may relate to increased oxidative stress-related compromise of neuronal and glial cell structure and/or impaired arterial vasoreactivity/lumen viability.

  View details for DOI 10.1093/alcalc/agae055

  View details for PubMedID 39127890

  View details for PubMedCentralID PMC11316785

• Regional cortical brain volumes at treatment entry relates to post treatment WHO risk drinking levels in those with alcohol use disorder. Drug and alcohol dependence Durazzo, T. C., Stephens, L. H., Kraybill, E. P., May, A. C., Meyerhoff, D. J. 2024; 255: 111082

  Abstract

  Abstinence following treatment for alcohol use disorder (AUD) is associated with significant improvements in psychiatric and physical health, however, recent studies suggest resumption of low risk levels of alcohol use can also be beneficial. The present study assessed whether post-treatment levels of alcohol use were associated with cortical brain volumedifferences at treatment entry.Individuals seeking treatment for AUD (n=75) and light/non-drinking controls (LN, n=51) underwent 1.5T magnetic resonance imaging. The volumes of 34 bilateral cortical regions of interest (ROIs) were quantitated via FreeSurfer. Individuals with AUD were classified according to post-treatment alcohol consumption using the WHO risk drinking levels (abstainers: AB; low risk: RL; or higher risk: RH). Regional volumes for AB, RL and RH, at treatment entry, were compared to LN.Relative to LN, AB demonstrated smaller volumes in 18/68 (26%), RL in 24/68 (35%) and RH in 34/68 (50%) ROIs with the largest magnitude volume differences observed between RH and LN. RH and RL reported a higher frequency of depressive disorders than AB. Among RH and RL, level of depressive and anxiety symptomatology were associated with daily number of drinks consumed after treatment.Volumetric differences, at treatment entry, in brain regions implicated in executive function and salience networks corresponded with post-treatment alcohol consumption levels suggesting that pre-existing differences in neural integrity may contribute to treatment outcomes. Depressive and anxiety symptomatology was also associated with brain morphometrics and alcohol use patterns, highlighting the importance of effectively targeting these conditions during AUD treatment.

  View details for DOI 10.1016/j.drugalcdep.2024.111082

  View details for PubMedID 38219355

• A pilot, randomized clinical trial: Left dorsolateral prefrontal cortex intermittent theta burst stimulation improves treatment outcomes in veterans with alcohol use disorder. Alcohol, clinical & experimental research Padula, C. B., McCalley, D. M., Tenekedjieva, L., MacNiven, K., Rauch, A., Morales, J. M., Knutson, B., Humphreys, K., Williams, L. M., Durazzo, T. C. 2024; 48 (1): 164-177

  Abstract

  BACKGROUND: Transcranial magnetic stimulation (TMS) offers a promising treatment avenue to modulate brain function in alcohol use disorder (AUD). To the best of our knowledge, this pilot study is the first randomized, double-blind, sham-controlled trial to deliver intermittent theta burst stimulation to the left dorsolateral prefrontal cortex (DLPFC) among US veterans with AUD. We hypothesized that 20 sessions of real TMS are tolerable and feasible. As a secondary line of inquiry, we hypothesized that, relative to sham TMS, individuals receiving real TMS would experience greater reductions in 6-month relapse rates, anhedonia, and alcohol cue-reactivity.METHODS: Veterans (n=17, one woman) were enrolled in a double-blind, sham-controlled trial (2-3 sessions/day; 7-10days; 600 pulses/session; 20 sessions). Pre- and posttreatment assessments included responses to self-report questionnaires and functional magnetic resonance imaging measures of alcohol cue-reactivity. Alcohol consumption was assessed for 6months. Linear mixed-effects models were constructed to predict posttreatment craving, mood, and cue-reactivity.RESULTS: Individuals who received active iTBS (n=8) were less likely to relapse within 3months after treatment than the sham-treated group (n=9) (OR=12.0). Greater reductions in anhedonia were observed following active iTBS (Cohen's d=-0.59), relative to sham (d=-0.25). Alcohol cue-reactivity was reduced following active iTBS and increased following sham within the left insula (d=-0.19 vs. 0.51), left thalamus (d=-0.28 vs. 0.77), right insula (d=0.18 vs. 0.52), and right thalamus (d=-0.06 vs. 0.62).CONCLUSIONS: Relative to sham, we demonstrate that 20 sessions of real left DLPFC iTBS reduced the likelihood of relapse for at least 3months. The potential utility of this approach is underscored by observed decreases in anhedonia and alcohol cue-reactivity-strong predictors of relapse among veterans. These initial data offer a valuable set of effect sizes to inform future clinical trials in this patient population.

  View details for DOI 10.1111/acer.15224

  View details for PubMedID 38197808

• Leadership Styles Experienced During Military Service Predict Later Anhedonic Depressive Symptoms and Self-Efficacy in Veterans With Alcohol Use Disorder. Military medicine Durazzo, T. C., Humphreys, K., LaRocca, M. A. 2023

  Abstract

  Lifetime and past-year alcohol use disorder (AUD) prevalence is significantly higher in US Armed Services Veterans than in non-veterans across adulthood. This study examined the associations of perceived transformational leadership styles (TLS) experienced during military service and anhedonic depression and self-efficacy related to confidence to abstain or reduce alcohol consumption in Veterans seeking treatment for AUD. The ramifications of perceived leadership styles on multiple aspects of follower psychiatric functioning, including depressive and PTSD symptomatology, during and after military service, may be substantial and enduring. Higher anhedonic depression and lower abstinence self-efficacy are related to increased risk of relapse after treatment. We predicted Veterans, in treatment for AUD, who reported higher perceived levels of transformational leadership during military service, demonstrate lower anhedonic depressive symptoms and higher alcohol abstinence self-efficacy.Veterans with AUD (n = 60; 50 ± 14 years of age) were recruited from residential treatment at the VA Palo Alto Health Care System. All procedures were approved by the VA Palo Alto Health Care System and Stanford University institutional review boards. A series of mediation analyses were completed with The Multifactor Leadership Questionnaire measures of TLS (average across leadership measures [transformational leadership average; TLS average]) as predictor and the Alcohol Abstinence Self-Efficacy Scale, Mood and Anxiety Symptom Questionnaire, anhedonic depression subscale, as dependent measures. PTSD Checklist for DSM-5 score was tested as a mediator variable.Higher reported perceived TLS average during military service was significantly related to lower anhedonic depressive symptoms. Higher TLS average was related to higher self-efficacy to resist alcohol use in contexts involving experience of physical issues and withdrawal/cravings and urges. These relationships were not mediated by PTSD symptomatology or duration of military service, age, education, time since military service, military branch, combat exposure, or current psychiatric diagnosis.The significant associations of perceived TLS during military service with anhedonic depression and alcohol use self-efficacy are clinically relevant because these measures are associated with relapse risk after AUD treatment. Further study of the implications of perceived TLS during military service for AUD and other substance use disorder treatment outcome is warranted in Veterans.

  View details for DOI 10.1093/milmed/usad405

  View details for PubMedID 37897693

• Non-abstinent recovery in alcohol use disorder is associated with greater regional cortical volumes than heavy drinking ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH May, A. C., Meyerhoff, D. J., Durazzo, T. C. 2023: 1850-1858

  Abstract

  Harm-reduction (i.e., non-abstinent recovery) approaches to substance use treatment have garnered increasing attention. Reduced levels of alcohol consumption post-treatment have been associated with better psychosocial functioning and physical health, yet less is known regarding differences in brain structures associated with varying levels of alcohol consumption. This study investigated regional cortical volumes after alcohol use disorder (AUD) treatment among individuals who achieved complete abstinence and those who returned to lower and higher levels of consumption.Data were collected from individuals with AUD (n = 68) approximately 8 months after the initiation of treatment. Using risk drinking levels defined by the World Health Organization, participants were classified as abstaining (AB) or relapsing with low (RL) or higher (RH) levels. Data were also obtained from 34 age-matched light/non-drinking controls (LN). All participants completed a 1.5 T magnetic resonance imaging session and volumes for 34 bilateral cortical regions of interest were quantitated with FreeSurfer. Generalized linear models were used to examine group differences in cortical volume. All group findings are significant at an FDR-corrected value of 0.018.Adjusting for age and intracranial volume, significant group differences were found in 13/34 cortical regions. AB showed greater volumes than RL in 2/13 regions and RH in 6/13 regions. RH demonstrated significantly smaller volumes than LN in 12/13 ROIs, whereas RL differed from LN in 9/13 regions. RH and RL differed in only two cortical regions.Individuals who consumed low-risk levels of alcohol post-treatment exhibited regional cortical volumes more similar to abstainers than individuals who returned to higher-risk levels. This suggests that low-risk levels of alcohol consumption are associated with brain integrity that is comparable to that seen with complete abstinence. Given the previously demonstrated improvement in psychosocial and physical health with reduced levels of alcohol consumption post-treatment, harm reduction may be a beneficial and more attainable goal for some individuals with AUD who are seeking treatment.

  View details for DOI 10.1111/acer.15169

  View details for Web of Science ID 001084751300001

  View details for PubMedID 37864525

• Regional cortical thickness recovery with extended abstinence after treatment in those with alcohol use disorder. Alcohol (Fayetteville, N.Y.) Durazzo, T. C., Stephens, L. H., Meyerhoff, D. J. 2023

  Abstract

  Several cross-sectional investigations reported widespread cortical thinning in those with alcohol use disorder (AUD). The few longitudinal studies investigating cortical thickness changes during abstinence are limited to the first month of sobriety. Consequently, cortical thickness changes during extended abstinence in those with AUD is unclear. In this study, AUD participants were studied at approximately 1 week (n=68), 1 month (n=88) and 7.3 months (n=40) of abstinence. Forty-five never-smoking controls (CON) completed a baseline study, and 15 were reassessed after approximately 9.6 months. Participants completed magnetic resonance imaging studies at 1.5T and cortical thickness for 34 bilateral regions of interest (ROI) was quantitated with FreeSurfer. AUD demonstrated significant linear thickness increases in 25/34 ROI over 7.3 months of abstinence. The rate of change from 1 week to 1 month was greater than 1 month to 7.3 months in 19/34 ROIs. Proatherogenic conditions were associated with lower thickness recovery in anterior frontal, inferior parietal and lateral/mesial temporal regions. After 7.3 months of abstinence, AUD were statistically equivalent to CON on cortical thickness in 24/34 ROIs; the cortical thickness differences between AUD and CON in the banks superior temporal gyrus, post central, posterior cingulate, superior parietal, supramarginal and superior frontal cortices were driven by thinner cortices in AUD with proatherogenic conditions relative to CON. In actively smoking AUD, increasing pack-years was associated with decreasing thickness recovery primarily in the anterior frontal ROIs. Widespread bilateral linear cortical thickness recovery over 7.3 months of abstinence was the central finding for this AUD cohort. Proatherogenic conditions were associated with decreased thickness recovery and thinner cortex after 7.3 months of abstinence in several ROIs; this suggests alterations in perfusion or vascular integrity may relate to structural recovery in AUD. These results support the adaptive and beneficial effects of sustained sobriety on brain structural recovery in those with AUD.

  View details for DOI 10.1016/j.alcohol.2023.08.011

  View details for PubMedID 37657667

• BDNF rs6265 Met carriers with alcohol use disorder show greater age-related decline of N-acetylaspartate in left dorsolateral prefrontal cortex. Drug and alcohol dependence Durazzo, T. C., McNerney, M. W., Hansen, A. M., Gu, M., Sacchet, M. D., Padula, C. B. 2023; 248: 109901

  Abstract

  BACKGROUND: Brain-derived neurotrophic factor (BDNF) is implicated in neuronal and glial cell growth and differentiation, synaptic plasticity, and apoptotic mechanisms. A single-nucleotide polymorphism of the BDNF rs6265 gene may contribute to the pattern and magnitude of brain metabolite abnormalities apparent in those with an Alcohol Use Disorder (AUD). We predicted that Methionine (Met) carriers would demonstrate lower magnetic resonance spectroscopy (MRS) measures of N-acetylaspartate level (NAA) and greater age-related decline in NAA than Valine (Val) homozygotes.METHODS: Veterans with AUD (n=95; 46±12 years of age, min = 25, max = 71) were recruited from VA Palo Alto residential treatment centers. Single voxel MRS, at 3 Tesla, was used to obtain NAA, choline (Cho) and creatine (Cr) containing compounds from the left dorsolateral prefrontal cortex (DLPFC). Metabolite spectra were fit with LC Model and NAA and Cho were standardized to total Cr level and NAA was also standardized to Cho.RESULTS: Val/Met (n=35) showed markedly greater age-related decline in left DLPFC NAA/Cr level than Val/Val (n=60); no differences in mean metabolite levels were observed between Val/Met and Val/Val. Val/Met demonstrated greater frequency of history of MDD and higher frequency of cannabis use disorder over 12 months prior to study.CONCLUSIONS: The greater age-related decline in left DLPFC NAA/Cr and the higher frequency of MDD history and Cannabis Use disorder in BDNF rs6265 Met carriers with AUD are novel and may have implications for non-invasive brain stimulation targeting the left DLFPC and other psychosocial interventions typically utilized in the treatment of AUD.

  View details for DOI 10.1016/j.drugalcdep.2023.109901

  View details for PubMedID 37146499

• Active Cigarette Smoking Is Associated With Increased Age-Related Decline on Measures of Visuospatial Learning and Memory and Executive Function in Alcohol Use Disorder. Alcohol and alcoholism (Oxford, Oxfordshire) Padula, C. B., Durazzo, T. C. 2022

  Abstract

  AIMS: The goal of this study was to determine if active cigarette smoking in Veterans with alcohol use disorder (AUD) was associated with greater age-related neurocognitive decline.METHODS: Veterans with AUD, in residential treatment (n=125; 47±14years of age, min=24, max=76, 29±26days of abstinence), completed measures of executive functions, learning and memory, processing speed and working memory. Actively smoking AUD (AsAUD, n=47) were active daily cigarette smokers; former smoking AUD (FsAUD, n=45) were predominately daily smokers prior to study but did not smoke at the time of study; non-smoking AUD (NsAUD, n=33) never used cigarettes or smoked 'only a few times' during lifetime.RESULTS: AsAUD demonstrated greater age-related decline on measures of visuospatial learning and memory, and response inhibition/cognitive flexibility, primarily relative to NsAUD; there were no age-related differences between FsAUD and NsAUD on any measure. There were few significant mean differences between groups across the 15 neurocognitive measures. In AsAUD, higher scores on indices of smoking severity were associated with poorer performance on measures of auditory-verbal learning and memory, response inhibition, set-shifting and working memory. In FsAUD, longer smoking cessation duration was related to lower PTSD, anxiety and depressive symptomatology.CONCLUSIONS: Active smoking was associated with accelerated age-related decline on cognitive functions implicated in response to common evidence-based AUD interventions. Results suggest that smoking history contributes to the considerable heterogeneity observed in neurocognitive function in early AUD recovery, and reinforce the clinical movement to offer smoking cessation resources concurrent with treatment for AUD.

  View details for DOI 10.1093/alcalc/agac022

  View details for PubMedID 35552594

• Targeting the Salience Network: A Mini-Review on a Novel Neuromodulation Approach for Treating Alcohol Use Disorder. Frontiers in psychiatry Padula, C. B., Tenekedjieva, L., McCalley, D. M., Al-Dasouqi, H., Hanlon, C. A., Williams, L. M., Kozel, F. A., Knutson, B., Durazzo, T. C., Yesavage, J. A., Madore, M. R. 2022; 13: 893833

  Abstract

  Alcohol use disorder (AUD) continues to be challenging to treat despite the best available interventions, with two-thirds of individuals going on to relapse by 1 year after treatment. Recent advances in the brain-based conceptual framework of addiction have allowed the field to pivot into a neuromodulation approach to intervention for these devastative disorders. Small trials of repetitive transcranial magnetic stimulation (rTMS) have used protocols developed for other psychiatric conditions and applied them to those with addiction with modest efficacy. Recent evidence suggests that a TMS approach focused on modulating the salience network (SN), a circuit at the crossroads of large-scale networks associated with AUD, may be a fruitful therapeutic strategy. The anterior insula or dorsal anterior cingulate cortex may be particularly effective stimulation sites given emerging evidence of their roles in processes associated with relapse.

  View details for DOI 10.3389/fpsyt.2022.893833

  View details for PubMedID 35656355

• Repetitive Transcranial Magnetic Stimulation as a Treatment for Veterans with Cognitive Impairment and Multiple Comorbidities. Journal of Alzheimer's disease : JAD Cheng, J., Fairchild, J. K., McNerney, M. W., Noda, A., Ashford, J. W., Suppes, P., Chao, S. Z., Taylor, J., Rosen, A., Durazzo, T., Lazzeroni, L. C., Yesavage, J. 1800

  Abstract

  BACKGROUND: Despite decades of research efforts, current treatments for Alzheimer's disease (AD) are of limited effectiveness and do not halt the progression of the disease and associated cognitive decline. Studies have shown that repetitive transcranial magnetic stimulation (rTMS) may improve cognition.OBJECTIVE: We conducted a pilot study to investigate the effect of rTMS on cognitive function in Veterans with numerous medical comorbidities.METHODS: Participants underwent 20 sessions, over the course of approximately 4 weeks, of 10 Hz rTMS at the left dorsolateral prefrontal cortex with intensity of 120% resting motor threshold. Outcome measures including memory, language, verbal fluency, and executive functions were acquired at baseline, end of treatment, and 4 months after the last rTMS session. Twenty-six Veterans completed the study (13 in the active rTMS group, 13 in the sham rTMS group).RESULTS: The study protocol was well-tolerated. Active, compared to sham, rTMS showed improved auditory-verbal memory at the end of treatment and at 4-month follow-up. However, the active rTMS group demonstrated a trend in decreased semantic verbal fluency at the end of treatment and at 4-month follow up.CONCLUSION: These preliminary results show rTMS is safe in general in this elderly Veteran population with multiple co-morbidities. Patients in the sham group showed an expected, slight decline in the California Verbal Learning Test scores over the course of the study, whereas the active treatment group showed a slight improvement at the 4-month post-treatment follow up. These effects need to be confirmed by studies of larger sample sizes.

  View details for DOI 10.3233/JAD-210349

  View details for PubMedID 34958013

• The Role of Neural Reward Expectancy and Valuation in Readiness to Change Among Treatment Seeking Veterans With Alcohol Use Disorder (AUD) Hagerty, S. L., Durazzo, T. C., Williams, L. M., Padula, C. B. ELSEVIER SCIENCE INC. 2021: S342

  View details for Web of Science ID 000645683800822

• GABA concentrations in the anterior cingulate and dorsolateral prefrontal cortices: Associations with chronic cigarette smoking, neurocognition, and decision making. Addiction biology Durazzo, T. C., Meyerhoff, D. J. 2021; 26 (3): e12948

  Abstract

  Chronic cigarette smoking is associated with regional metabolite abnormalities in choline-containing compounds, creatine-containing compounds, glutamate, and N-acetylaspartate. The effects of cigarette smoking on anterior frontal cortical gamma-aminobutyric acid (GABA) concentration are unknown. This study compared chronic smokers (n = 33) and nonsmokers (n = 31) on anterior cingulate cortex (ACC) and right dorsolateral prefrontal cortex (DLPFC) GABA+ (the sum of GABA and coedited macromolecules) concentrations and associations of GABA+ levels in these regions with seven neurocognitive domains of functioning, decision making, and impulsivity measures. Smokers had significantly lower right DLPFC GABA+ concentration than nonsmokers, but groups were equivalent on ACC GABA+ level. Across groups, greater number of days since end of menstrual cycle was related to higher GABA+ level in the ACC but not right DLPFC GABA+ concentration. In exploratory correlation analyses, higher ACC and right DLPFC GABA+ levels were associated with faster processing speed and better auditory-verbal memory, respectively, in the combined group of smokers and nonsmokers; in smokers only, higher ACC GABA+ was related to better decision making and auditory-verbal learning. This study contributes additional novel data on the adverse effects of chronic cigarette smoking on the adult human brain and demonstrated ACC and DLPFC GABA+ concentrations were associated with neurocognition and decision making/impulsivity in active cigarette smokers. Longitudinal studies on the effects of smoking cessation on regional brain GABA levels, with a greater number of female participants, are required to determine if the observed metabolite abnormalities are persistent or normalize with smoking cessation.

  View details for DOI 10.1111/adb.12948

  View details for PubMedID 33860602

• Not All Is Lost for Relapsers: Relapsers With Low WHO Risk Drinking Levels and Complete Abstainers Have Comparable Regional Gray Matter Volumes ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Meyerhoff, D. J., Durazzo, T. C. 2020

  View details for DOI 10.1111/acer.14377

  View details for Web of Science ID 000540628100001

• Evaluation of adding the CANTAB computerized neuropsychological assessment battery to a traditional battery in a tertiary care center for veterans APPLIED NEUROPSYCHOLOGY-ADULT Schulz-Heik, R., Fahimi, A., Durazzo, T. C., Friedman, M., Bayley, P. J. 2020; 27 (3): 256–66

  View details for DOI 10.1080/23279095.2018.1534735

  View details for Web of Science ID 000523570900005

• Predicting relapse after alcohol use disorder treatment in a high-risk cohort: The roles of anhedonia and smoking. Journal of psychiatric research Nguyen, L., Durazzo, T. C., Dwyer, C. L., Rauch, A. A., Humphreys, K., Williams, L. M., Padula, C. B. 2020; 126: 1–7

  Abstract

  On average, two-thirds of individuals treated for alcohol use disorder (AUD) relapse within six months. There is a critical need to identify modifiable risk factors associated with relapse that can be addressed during AUD treatment. Candidate factors include mood disorders and cigarette smoking, which frequently co-occur with AUD. We predicted that co-occurrence of mood disorders, cigarette smoking, and other modifiable conditions will predict relapse within six months of AUD treatment. Ninety-five Veterans, 23-91 years old, completed assessments of multiple characteristics including demographic information, co-occurring psychiatric disorders, and medical conditions during residential treatment for AUD. Participants' alcohol consumption was monitored over six months after participation. Logistic regression was used to determine if, mood disorders, cigarette smoking status, alcohol consumption, educational level, and comorbid general medical conditions are associated with relapse after AUD treatment. Sixty-nine percent of Veterans (n=66) relapsed within six months of study while 31% remained abstinent (n=29). While education, comorbid general medical conditions, and mood disorder diagnoses were not predictors of relapse, Veterans with greater symptoms of anhedonia, active smokers, and fewer days of abstinence prior to treatment showed significantly greater odds for relapse within six months. Anhedonia and cigarette smoking are modifiable risk factors, and effective treatment of underlying anhedonic symptoms and implementation of smoking cessation concurrent with AUD-focused interventions may decrease risk of relapse.

  View details for DOI 10.1016/j.jpsychires.2020.04.003

  View details for PubMedID 32403028

• Cigarette Smoking History is associated with Poorer Recovery in Multiple Neurocognitive Domains Following Treatment for an Alcohol Use Disorder. Alcohol (Fayetteville, N.Y.) Durazzo, T. C., Meyerhoff, D. J. 2020

  Abstract

  Cigarette smoking is associated with neurocognitive dysfunction in various populations, including those seeking treatment for an alcohol use disorder (AUD). This study compared the rate and extent of recovery on measures of processing speed, executive functions, general intelligence, visuospatial skills and working memory in treatment-seeking alcohol dependent individuals (ALC) who were never-smokers (nvsALC), former-smoker (fsALC), and active smokers (asALC), over approximately 8 months of abstinence from alcohol. Methods: ALC participants were evaluated at approximately 1 month of abstinence (AP1; n=132) and reassessed after 8 months of sobriety (AP2; n=54). Never-smoking controls (CON; n=33) completed a baseline and follow-up (n=19) assessment approximately 9 months later. Domains evaluated were executive functions, general intelligence, processing speed, visuospatial skills and working memory; a domain composite was formed from the arithmetic average of the foregoing domains. nvsALC showed greater improvement than fsALC, asALC and CON on most domains over the AP1-AP2 interval. fsALC demonstrated greater recovery than asALC on all domains except visuospatial skills; fsALC also showed greater improvements than CON on general intelligence, working memory and domain composite. asALC did not show significant improvement on any domain over the AP1-AP2 interval. At 8 months of abstinence, asALC were inferior to CON and nvsALC on multiple domains, fsALC performed worse than nvsALC on several domains, but nvsALC were not different from CON on any domain. Our results provide robust evidence that smoking status influenced the rate and extent of neurocognitive recovery between 1 and 8 months of abstinence in this ALC cohort. Chronic smoking in AUD likely contributes to the considerable heterogeneity observed in neurocognitive recovery during extended abstinence. The findings provide additional strong support for the benefits of smoking cessation and the increasing clinical movement to offer smoking cessation resources concurrent with treatment for AUD.

  View details for DOI 10.1016/j.alcohol.2019.12.003

  View details for PubMedID 31923562

• Medical Conditions Linked to Atherosclerosis Are Associated With Magnified Cortical Thinning in Individuals With Alcohol Use Disorders. Alcohol and alcoholism (Oxford, Oxfordshire) Durazzo, T. C., Nguyen, L. C., Meyerhoff, D. J. 2020

  Abstract

  Magnetic resonance imaging (MRI) studies report widespread cortical thinning in individuals with alcohol use disorder (AUD), but did not consider potential effects of pro-atherogenic conditions such as hypertension, type 2 diabetes mellitus, hepatitis C seropositivity and hyperlipidemia on cortical thickness. The conditions are associated with regional cortical thinning in those without AUD. We predicted that individuals with concurrent AUD and pro-atherogenic conditions demonstrate the greatest regional cortical thinning in areas most vulnerable to decreased perfusion.Treatment-seeking individuals with AUD (n = 126) and healthy controls (CON; n = 49) completed a 1.5 T MRI study. Regional cortical thickness was quantitated via FreeSurfer. Individuals with AUD and pro-atherogenic conditions (Atherogenic+), AUD without pro-atherogenic conditions (Atherogenic-) and CON were compared on regional cortical thickness.Individuals with AUD showed significant bilateral cortical thinning compared to CON, but Atherogenic+ demonstrated the most widespread and greatest magnitude of regional thinning, while Atherogenic- had reduced thickness primarily in anterior frontal and posterior parietal lobes. Atherogenic+ also showed a thinner cortex than Atherogenic- in lateral orbitofrontal and dorso/dorsolateral frontal cortex, mesial and lateral temporal and inferior parietal regions.Our results demonstrate significant bilateral cortical thinning in individuals with AUD relative to CON, but the distribution and magnitude were influenced by comorbid pro-atherogenic conditions. The magnitude of cortical thinning in Atherogenic+ strongly corresponded to cortical watershed areas susceptible to decreased perfusion, which may result in morphometric abnormalities. The findings indicate that pro-atherogenic conditions may contribute to cortical thinning in those seeking treatment for AUD.

  View details for DOI 10.1093/alcalc/agaa034

  View details for PubMedID 32445335

• Modeling neurocognitive and neurobiological recovery in addiction COGNITION AND ADDICTION: A RESEARCHER'S GUIDE FROM MECHANISMS TOWARDS INTERVENTIONS Meyerhoff, D. J., Durazzo, T. C., VerdejoGarcia, A. 2020: 379–92

  View details for DOI 10.1016/B978-0-12-815298-0.00028-9

  View details for Web of Science ID 000514572900030

• Evaluation of adding the CANTAB computerized neuropsychological assessment battery to a traditional battery in a tertiary care center for veterans. Applied neuropsychology. Adult Schulz-Heik, R. J., Fahimi, A., Durazzo, T. C., Friedman, M., Bayley, P. J. 2019: 1–11

  Abstract

  Numerous advantages of and concerns about computerized neuropsychological assessment systems have been noted. Here we report a program evaluation of incorporating a computerized system, the Cambridge Neuropsychological Test Automated Battery (CANTAB), in our tertiary assessment center for Veterans. Patients were 23 consecutive referrals to the Western War Related Illness and Injury Study Center, an interdisciplinary assessment center within the Veterans Affairs Healthcare System for Veterans with complex medical presentations. Patients were administered both the CANTAB and a brief traditional neuropsychological battery. The correlation between global composite scores from each method was .71 (p<.05), indicating "good" concordance. Concordance was "fair" to "good" for scores on specific cognitive domains. However, concordance was lower when classifying patients' cognition as "impaired" or "not-impaired" based on a cutoff score. Despite the CANTAB's primarily visuospatial interface, discrepancy between the two methods' scores was not associated with patients' visuospatial abilities. The two methods were similarly sensitive to deficits associated with posttraumatic stress disorder, which is prevalent among the Center's patients. The CANTAB was judged to be a valid and useful complement to, but not an acceptable alternative to a traditional neuropsychologist-administered cognitive assessment battery for the Center's specific patients and needs.

  View details for PubMedID 30633552

• Changes of frontal cortical subregion volumes in alcohol dependent individuals during early abstinence: associations with treatment outcome. Brain imaging and behavior Durazzo, T. C., Meyerhoff, D. J. 2019

  Abstract

  We previously reported that at 1-and-4 weeks of sobriety, those who relapsed after treatment demonstrated significantly smaller total frontal cortical volume than individuals who maintained abstinence for at least 12 months post treatment. The segmentation method employed did not permit examination of frontal subregions that serve as nodes of the executive, salience and emotional regulation networks; structural abnormalities in these circuits are associated with relapse in those seeking treatment for alcohol use disorders (AUD). The primary goal of this study was to determine if frontal cortical subregion volume recovery during early abstinence is associated with long-term abstinence from alcohol. We compared bilateral components of the dorsal prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex and insula volumes, at 1 and 4 weeks of abstinence, between individuals who resumed drinking within 12 months of treatment (Relapsers) those who showed sustained abstinence over 12 months following treatment (Abstainers) and healthy Controls. At 1 and 4 weeks of sobriety, Relapsers demonstrated significantly smaller volumes than Controls in 15 of 20 regions of interest, while Abstainers only had smaller volumes than Controls in 5 of 20 regions. In Relapsers, increasing volumes over 1 month in multiple frontal subregions and the insula were associated with longer duration of abstinence after treatment. The persistent bilateral frontal and insula volume deficits in Relapsers over 4 weeks from last alcohol use may have implications for neurostimulation methods targeting anterior frontal/insula regions, and represent an endophenotype that differentiates those who respond more favorably to available psychosocial and pharmacological interventions.

  View details for DOI 10.1007/s11682-019-00089-5

  View details for PubMedID 31197582

• Cerebellar Morphometry and Cognition in the Context of Chronic Alcohol Consumption and Cigarette Smoking. Alcoholism, clinical and experimental research Cardenas, V. A., Hough, C. M., Durazzo, T. C., Meyerhoff, D. J. 2019

  Abstract

  Cerebellar atrophy (especially involving the superior-anterior cerebellar vermis) is among the most salient and clinically significant effects of chronic hazardous alcohol consumption on brain structure. Smaller cerebellar volumes are also associated with chronic cigarette smoking. The present study investigated effects of both chronic alcohol consumption and cigarette smoking on cerebellar structure and its relation to performance on select cognitive/behavioral tasks.Using T1-weighted Magnetic Resonance Images (MRIs), the Cerebellar Analysis Tool Kit segmented the cerebellum into bilateral hemispheres and 3 vermis parcels from 4 participant groups: smoking (s) and nonsmoking (ns) abstinent alcohol-dependent treatment seekers (ALC) and controls (CON) (i.e., sALC, nsALC, sCON, and nsCON). Cognitive and behavioral data were also obtained.We found detrimental effects of chronic drinking on all cerebellar structural measures in ALC participants, with largest reductions seen in vermis areas. Furthermore, both smoking groups had smaller volumes of cerebellar hemispheres but not vermis areas compared to their nonsmoking counterparts. In exploratory analyses, smaller cerebellar volumes were related to lower measures of intelligence. In sCON, but not sALC, greater smoking severity was related to smaller cerebellar volume and smaller superior-anterior vermis area. In sALC, greater abstinence duration was associated with larger cerebellar and superior-anterior vermis areas, suggesting some recovery with abstinence.Our results show that both smoking and alcohol status are associated with smaller cerebellar structural measurements, with vermal areas more vulnerable to chronic alcohol consumption and less affected by chronic smoking. These morphometric cerebellar deficits were also associated with lower intelligence and related to duration of abstinence in sALC only.

  View details for DOI 10.1111/acer.14222

  View details for PubMedID 31730240

• White matter microstructural correlates of relapse in alcohol dependence PSYCHIATRY RESEARCH-NEUROIMAGING Zou, Y., Murray, D. E., Durazzo, T. C., Schmidt, T. P., Murray, T. A., Meyerhoff, D. J. 2018; 281: 92-100

  View details for DOI 10.1016/j.pscychresns.2018.09.004

  View details for Web of Science ID 000448020100013

• Cigarette smoking is associated with cortical thinning in anterior frontal regions, insula and regions showing atrophy in early Alzheimer's Disease DRUG AND ALCOHOL DEPENDENCE Durazzo, T. C., Meyerhoff, D. J., Yoder, K. K. 2018; 192: 277-284

  View details for DOI 10.1016/j.drugalcdep.2018.08.009

  View details for Web of Science ID 000449447400041

• Cigarette smoking is associated with cortical thinning in anterior frontal regions, insula and regions showing atrophy in early Alzheimer's Disease. Drug and alcohol dependence Durazzo, T. C., Meyerhoff, D. J., Yoder, K. K. 2018; 192: 277–84

  Abstract

  BACKGROUND: Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure primarily focused on cortical volumes. Much less is known about the effects of smoking on cortical thickness. Smokers and Non-smokers were compared on regional cortical thickness. We predicted smokers would demonstrate greater age-related thinning localized to anterior frontal regions that serve as nodes for the executive, salience, and emotional regulation networks (ESER regions) and those demonstrating significant atrophy in early Alzheimer's Disease (AD regions).METHODS: Non-smokers (n=41) and smokers (n=41), 22-70 years of age, completed a 4T MRI study. Regional cortical thickness was quantitated via FreeSurfer. In smokers, associations between smoking severity, decision-making, impulsivity, and regional cortical thickness were examined.RESULTS: Smokers demonstrated cortical thinning in the medial and lateral OFC, insula, entorhinal, fusiform, middle temporal, and Composite AD regions. In Smokers, greater pack-years were associated with thinner lateral OFC, middle temporal, inferior parietal, fusiform, precuneus, and Composite AD regions. In Smokers, poorer decision-making/greater risk taking was related to thinner cortices in caudal ACC, rostral middle frontal and superior frontal gyri, and Composite ESER. Higher self-reported impulsivity was associated with thinner rostral and caudal ACC.CONCLUSIONS: This study provides additional evidence that cigarette smoking is associated with thinner cortices in regions implicated in the development and maintenance of substance use disorders and in regions demonstrating significant atrophy in early AD. The novel structure-function relationships in Smokers further our understanding of the neurobiological substrates potentially underlying the neuropsychological abnormalities documented in smokers.

  View details for PubMedID 30300802

• White matter microstructural correlates of relapse in alcohol dependence. Psychiatry research. Neuroimaging Zou, Y., Murray, D. E., Durazzo, T. C., Schmidt, T. P., Murray, T. A., Meyerhoff, D. J. 2018; 281: 92–100

  Abstract

  Identification of neural correlates of relapse to alcohol after treatment is clinically important as it may inform better substance abuse treatment. Few studies have specifically analyzed the white matter microstructure in treatment seekers as it might relate to relapse risk versus long-term abstinence. Using 4 Tesla diffusion tensor imaging, we compared two groups of one-month-abstinent treatment-seekers, who were classified based on their drinking status between six and nine months after treatment initiation. We hypothesized that subsequent relapsers had greater white matter microstructural deficits in specific brain regions than long-term abstainers. At one month of abstinence, 37 future relapsers versus 25 future abstainers had lower fractional anisotropy (a measure of axonal organization and membrane integrity) in the corpus callosum and right stria terminalis/fornix, higher diffusivity in the genu of the corpus callosum, left and right stria terminalis/fornix, and lower diffusivity in left anterior corona radiata. These differences existed despite similar lifetime and recent drinking and smoking histories in the groups. Longer smoking duration in relapsers was associated with lower fractional anisotropy in right stria terminalis/fornix. The study identified specific microstructural biomarkers of alcohol relapse risk in adults, contributing to the definition of a neurobiological relapse risk profile in alcohol use disorder.

  View details for PubMedID 30273793

• Regional Brain Volume Changes in Alcohol-Dependent Individuals During Short-Term and Long-Term Abstinence ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Zou, X., Durazzo, T. C., Meyerhoff, D. J. 2018; 42 (6): 1062–72

  Abstract

  Widespread brain atrophy in alcohol-dependent individuals (ALC) has been consistently documented in pathological and magnetic resonance imaging (MRI) studies. Longitudinal MRI studies have shown that the regional brain volume losses in ALC are partially reversible during abstinence from alcohol. The goal of this study was to determine volume reductions in cortical and subcortical regions functionally important to substance use behavior and their changes during short-term (1 week to 1 month) and long-term abstinence (1 to 7 months) from alcohol. The regions of interest (ROIs) were as follows: anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), insula, amygdala, and hippocampus.A total of 85 unique ALC were assessed at 1 week (n = 65), 1 month (n = 82), and 7 months (n = 36) of abstinence. In addition, 17 light/nondrinking healthy controls (CON) were assessed at baseline and follow-up over a 10-month interval. Regional brain volumes were derived from FreeSurfer. Cross-sectional statistical analyses using 1-way analysis of variance or Fisher's exact test were applied to identify group differences. Longitudinal statistical analyses using linear mixed models were applied to identify regional volume increases and nonlinear volume recovery trajectories.We demonstrated significant regional volume reductions in ACC, DLPFC, and hippocampus. Older age was associated with smaller DLPFC and OFC, and higher average monthly drinking over 1 year prior to study was associated with smaller OFC. We also demonstrated significant volume increases of all ROIs except amygdala in ALC and significant nonlinear volume recovery trajectories of DLPFC, OFC, and insula.Results showed significant volume reductions in key regions of the executive control, salience, and emotion networks in ALC at entry into treatment and significant volume increases during short-term and long-term abstinence that were nonlinear over the entire abstinence period for the DLPFC, OFC, and insula. This gray matter plasticity during alcohol abstinence may have important neurobiological and neurocognitive implications in ALC, and it may contribute to an individual's ability to maintain abstinence from alcohol at different phases.

  View details for PubMedID 29672876

• Differences in White Matter Microstructure and Connectivity in Nontreatment-Seeking Individuals with Alcohol Use Disorder ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Chumin, E. J., Goni, J., Halcomb, M. E., Durazzo, T. C., Dzemidzic, M., Yoder, K. K. 2018; 42 (5): 889–96

  Abstract

  Diffusion-weighted imaging (DWI) has been widely used to investigate the integrity of white matter (WM; indexed by fractional anisotropy [FA]) in alcohol dependence and cigarette smoking. These disorders are highly comorbid, yet cigarette use has often not been adequately controlled in neuroimaging studies of alcohol-dependent populations. In addition, information on WM deficits in currently drinking, nontreatment-seeking (NTS) individuals with alcohol dependence is limited. Therefore, the aim of this work was to investigate WM microstructural integrity in alcohol use disorder by comparing matched samples of cigarette smoking NTS and social drinkers (SD).Thirty-eight smoking NTS and 19 smoking SD subjects underwent DWI as well as structural magnetic resonance imaging. After an in-house preprocessing of the DWI data, FA images were analyzed with tract-based spatial statistics (TBSS). FA obtained from the TBSS skeleton was tested for correlation with recent alcohol consumption.Smoking NTS had lower FA relative to smoking SD, predominantly in the left hemisphere (p < 0.05, family-wise error rate corrected across FA skeleton). Across the full sample, FA and number of drinks per week were negatively related (ρ = -0.348, p = 0.008). Qualitative analyses of the structural connections through compromised WM as identified by TBSS showed differential connectivity of gray matter in NTS compared to SD subjects of left frontal, temporal, and parietal regions.NTS subjects had lower WM FA than SD, indicating compromised WM integrity in the NTS population. The inverse relationship of entire WM skeleton FA with self-reported alcohol consumption supports previous evidence of a continuum of detrimental effects of alcohol consumption on WM. These results provide additional evidence that alcohol dependence is associated with reduced WM integrity in currently drinking NTS alcohol-dependent individuals, after controlling for the key variable of cigarette smoking.

  View details for PubMedID 29543332

  View details for PubMedCentralID PMC5919256

• Brain GABA and Glutamate Concentrations Following Chronic Gabapentin Administration: A Convenience Sample Studied During Early Abstinence From Alcohol FRONTIERS IN PSYCHIATRY Meyerhoff, D. J., Murray, D. E., Durazzo, T. C., Pennington, D. L. 2018; 9: 78

  Abstract

  Gabapentin (GBP), a GABA analog that may also affect glutamate (Glu) production, can normalize GABA and Glu tone during early abstinence from alcohol, effectively treating withdrawal symptoms and facilitating recovery. Using in vivo magnetic resonance spectroscopy, we tested the degree to which daily GBP alters regional brain GABA and Glu levels in short-term abstinent alcohol-dependent individuals. Regional metabolite levels were compared between 13 recently abstinent alcohol-dependent individuals who had received daily GBP for at least 1 week (GBP+) and 25 matched alcohol-dependent individuals who had not received GBP (GBP-). Magnetic resonance spectra from up to five different brain regions were analyzed to yield absolute GABA and Glu concentrations. GABA and Glu concentrations in the parieto-occipital cortex were not different between GBP- and GBP+. Glu levels in anterior cingulate cortex, dorsolateral prefrontal cortex, and basal ganglia did not differ between GBP- and GBP+. However, in a subgroup of individuals matched on age, sex, and abstinence duration, GBP+ had markedly lower Glu in the frontal white matter (WM) than GBP-, comparable to concentrations found in light/non-drinking controls. Furthermore, lower frontal WM Glu in GBP+ correlated with a higher daily GBP dose. Daily GBP treatment at an average of 1,600 mg/day for at least 1 week was not associated with altered cortical GABA and Glu concentrations during short-term abstinence from alcohol, but with lower Glu in frontal WM. GBP for the treatment of alcohol dependence may work through reducing Glu in WM rather than increasing cortical GABA.

  View details for PubMedID 29599727

• Regional cerebral blood flow in opiate dependence relates to substance use and neuropsychological performance ADDICTION BIOLOGY Murray, D. E., Durazzo, T. C., Schmidt, T. P., Murray, T. A., Abe, C., Guydish, J., Meyerhoff, D. J. 2018; 23 (2): 781–95

  Abstract

  Neuroimaging of opiate-dependent individuals indicates both altered brain structure and function. Magnetic resonance-based arterial spin labeling has been used to measure noninvasively cerebral blood flow (i.e. perfusion) in alcohol, tobacco and stimulant dependence; only one arterial spin labeling paper in opiate-dependent individuals demonstrated frontal and parietal perfusion deficits. Additional research on regional brain perfusion in opiate dependence and its relationship to cognition and self-regulation (impulsivity, risk taking and decision making) may inform treatment approaches for opiate-dependent individuals. Continuous arterial spin labeling magnetic resonance imaging at 4 T and neuropsychological measures assessed absolute brain perfusion levels, cognition and self-regulation in 18 cigarette smoking opiate-dependent individuals (sODI) stable on buprenorphine maintenance therapy. The sODI were compared with 20 abstinent smoking alcohol-dependent individuals (a substance-dependent control group), 35 smoking controls and 29 nonsmoking controls. sODI had lower perfusion in several cortical and subcortical regions including regions within the brain reward/executive oversight system compared with smoking alcohol-dependent individuals and nonsmoking controls. Perfusion was increased in anterior cingulate cortex and globus pallidus of sODI. Compared with all other groups, sODI had greater age-related declines in perfusion in most brain reward/executive oversight system and some other regions. In sODI, lower regional perfusion related to greater substance use, higher impulsivity and weaker visuospatial skills. Overall, sODI showed cortical and subcortical hypoperfusion and hyperperfusion. Relating to neuropsychological performance and substance use quantities, the frontal perfusion alterations are clinically relevant and constitute potential targets for pharmacological and cognitive-based therapeutic interventions to improve treatment outcome in opiate dependence.

  View details for PubMedID 28627790

  View details for PubMedCentralID PMC5736471

• Cigarette smoking is associated with amplified age-related volume loss in subcortical brain regions. Drug and alcohol dependence Durazzo, T. C., Meyerhoff, D. J., Yoder, K. K., Murray, D. E. 2017; 177: 228-236

  Abstract

  Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure have primarily employed voxel-based morphometry, and the most consistently reported finding was smaller volumes or lower density in anterior frontal regions and the insula. Much less is known about the effects of smoking on subcortical regions. We compared smokers and non-smokers on regional subcortical volumes, and predicted that smokers demonstrate greater age-related volume loss across subcortical regions than non-smokers.Non-smokers (n=43) and smokers (n=40), 22-70 years of age, completed a 4T MRI study. Bilateral total subcortical lobar white matter (WM) and subcortical nuclei volumes were quantitated via FreeSurfer. In smokers, associations between smoking severity measures and subcortical volumes were examined.Smokers demonstrated greater age-related volume loss than non-smokers in the bilateral subcortical lobar WM, thalamus, and cerebellar cortex, as well as in the corpus callosum and subdivisions. In smokers, higher pack-years were associated with smaller volumes of the bilateral amygdala, nucleus accumbens, total corpus callosum and subcortical WM.Results provide novel evidence that chronic smoking in adults is associated with accelerated age-related volume loss in subcortical WM and GM nuclei. Greater cigarette quantity/exposure was related to smaller volumes in regions that also showed greater age-related volume loss in smokers. Findings suggest smoking adversely affected the structural integrity of subcortical brain regions with increasing age and exposure. The greater age-related volume loss in smokers may have implications for cortical-subcortical structural and/or functional connectivity, and response to available smoking cessation interventions.

  View details for DOI 10.1016/j.drugalcdep.2017.04.012

  View details for PubMedID 28622625

• Effects of abstinence and chronic cigarette smoking on white matter microstructure in alcohol dependence: Diffusion tensor imaging at 4T. Drug and alcohol dependence Zou, Y., Murray, D. E., Durazzo, T. C., Schmidt, T. P., Murray, T. A., Meyerhoff, D. J. 2017; 175: 42-50

  Abstract

  We previously reported widespread microstructural deficits of brain white matter in alcohol-dependent individuals (ALC) compared to light drinkers in a small 1.5T diffusion tensor imaging study employing tract-based spatial statistics. Using a larger dataset acquired at 4T, the present study is an extension that investigated the effects of alcohol consumption, abstinence from alcohol, and comorbid cigarette smoking on white matter microstructure.Tract-based spatial statistics were performed on 20 1-week-abstinent ALC, 52 1-month-abstinent ALC, and 30 controls. Regional measures of fractional anisotropy (FA) and mean diffusivity (MD) in the significant clusters were compared by Analysis of Covariance. The metrics were correlated with substance use history and behavioral measures.1-week-abstinent ALC showed lower FA than controls in the corpus callosum, right cingulum, external capsule, and hippocampus. At 1 month of abstinence, only the FA in the body of the corpus callosum of ALC remained significantly different from controls. Some regional FA deficits correlated with more severe measures of drinking and smoking histories but only weakly with mood and impulsivity measures.White matter microstructure is abnormal during early abstinence in alcohol dependent treatment seekers and recovers into the normal range within about four weeks. The compromised white matter was related to substance use severity, mood, and impulsivity. Our findings suggest that ALC may benefit from interventions that facilitate normalization of DTI metrics to maintain abstinence, via smoking cessation, cognitive-based therapy, and perhaps pharmacology to support remyelination.

  View details for DOI 10.1016/j.drugalcdep.2017.01.032

  View details for PubMedID 28384535

• Neurocognition and inhibitory control in polysubstance use disorders: Comparison with alcohol use disorders and changes with abstinence JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY Schmidt, T. P., Pennington, D. L., Cardoos, S. L., Durazzo, T. C., Meyerhoff, D. J. 2017; 39 (1): 22-34

  Abstract

  Intact neurocognition and early cognitive recovery during abstinence are important for substance use treatment outcome. Yet, little is known about them in the largest group of treatment seekers today, individuals with polysubstance use disorders (PSU). This study primarily contrasted PSU and individuals with an alcohol use disorder (AUD) on neurocognitive and inhibitory control measures and, secondarily, measured changes during abstinence in PSU.At one month of abstinence from all substances except tobacco, 36 PSU and 69 AUD completed neurocognitive assessments of executive function, general intelligence, auditory-verbal learning/memory, visuospatial learning/memory/skills, processing speed, working memory, fine motor skills, and cognitive efficiency. The groups were also assessed on inhibitory control measures of self-reported impulsivity, risk-taking, and decision-making. Seventeen PSU repeated the assessments after approximately four months of abstinence. All cross-sectional and longitudinal analyses included smoking status as a possible confound.At baseline, PSU performed significantly worse than AUD on auditory-verbal memory and on an inhibitory control measure of impulsivity. Polysubstance users showed trends to worse performance than AUD on general intelligence, auditory-verbal learning, and a decision-making task. Between one and four months of abstinence, PSU showed significant improvements on several neurocognitive and inhibitory control measures.Polysubstance users exhibit distinct differences in neurocognition and inhibitory control compared to AUD. Between one and four months of abstinence, neurocognition and inhibitory control improve in PSU. This neurocognitive recovery in some domains of abstinent PSU is influenced by smoking status. These results underscore the clinical value of select methods to augment neurocognitive recovery in PSU through appropriate interventions.

  View details for DOI 10.1080/13803395.2016.1196165

  View details for Web of Science ID 000389499700003

• Regional brain volume changes in alcohol-dependent individuals during early abstinence: associations with relapse following treatment. Addiction Biology Durazzo, T. C., Mon, A., Gazdzinski, S., Meyerhoff, D. J. 2017; 22 (5): 1416-1425
• Psychiatric, Demographic, and Brain Morphological Predictors of Relapse After Treatment for an Alcohol Use Disorder. Alcoholism, clinical and experimental research Durazzo, T. C., Meyerhoff, D. J. 2017; 41 (1): 107-116

  Abstract

  Relapse in alcohol use disorders (AUD) is related to a complex interplay among multiple biological, psychiatric, psychological, and psychosocial factors, which may change dynamically during and after treatment. At treatment entry for AUD, morphological abnormalities in anterior frontal regions and the insula have been observed in those who ultimately relapse following treatment. The goal of this study was to determine whether anterior frontal and insula measures of brain thickness, surface area, and volume predict posttreatment drinking status (i.e., relapser or abstainer) over an extended period after outpatient treatment for AUD, while concurrently considering common psychiatric, psychological, and psychosocial factors previously associated with relapse.Alcohol-dependent individuals (n = 129) were followed for 18 months after treatment to determine posttreatment drinking status (abstainers [n = 47] or relapsers [n = 82]). Brain morphometrics were derived from FreeSurfer. Receiver operating characteristic (ROC) curve analysis was used to identify the regional brain thickness, surface area, and volume (all scaled to intracranial volume), demographic, psychiatric, other substance use (e.g., cigarette smoking), and alcohol consumption variables, obtained at entry into treatment, that best predicted posttreatment drinking status. Survival analyses determined variables that were related to duration of abstinence after treatment.ROC analyses indicated that mood disorders, education, and volumes of the right caudal anterior cingulate cortex (ACC), right rostral ACC, and total right frontal gray matter were significant predictors of posttreatment drinking status. Among relapsers, survival analyses showed smokers and individuals with a comorbid medical condition relapsed earlier after treatment. Additionally, a greater frequency of smokers relapsed within 6 months of AUD treatment.Results reinforce that relapse in AUD is a function of multiple biological, psychiatric, psychological, and psychosocial factors. Effective treatment of depressive disorders and cigarette smoking concurrent with AUD-focused interventions may promote better treatment outcomes.

  View details for DOI 10.1111/acer.13267

  View details for PubMedID 27883214

• Neurocognition and inhibitory control in polysubstance use disorders: Comparison with alcohol use disorders and changes with abstinence. Journal of clinical and experimental neuropsychology Schmidt, T. P., Pennington, D. L., Cardoos, S. L., Durazzo, T. C., Meyerhoff, D. J. 2016: 1-13

  Abstract

  Intact neurocognition and early cognitive recovery during abstinence are important for substance use treatment outcome. Yet, little is known about them in the largest group of treatment seekers today, individuals with polysubstance use disorders (PSU). This study primarily contrasted PSU and individuals with an alcohol use disorder (AUD) on neurocognitive and inhibitory control measures and, secondarily, measured changes during abstinence in PSU.At one month of abstinence from all substances except tobacco, 36 PSU and 69 AUD completed neurocognitive assessments of executive function, general intelligence, auditory-verbal learning/memory, visuospatial learning/memory/skills, processing speed, working memory, fine motor skills, and cognitive efficiency. The groups were also assessed on inhibitory control measures of self-reported impulsivity, risk-taking, and decision-making. Seventeen PSU repeated the assessments after approximately four months of abstinence. All cross-sectional and longitudinal analyses included smoking status as a possible confound.At baseline, PSU performed significantly worse than AUD on auditory-verbal memory and on an inhibitory control measure of impulsivity. Polysubstance users showed trends to worse performance than AUD on general intelligence, auditory-verbal learning, and a decision-making task. Between one and four months of abstinence, PSU showed significant improvements on several neurocognitive and inhibitory control measures.Polysubstance users exhibit distinct differences in neurocognition and inhibitory control compared to AUD. Between one and four months of abstinence, neurocognition and inhibitory control improve in PSU. This neurocognitive recovery in some domains of abstinent PSU is influenced by smoking status. These results underscore the clinical value of select methods to augment neurocognitive recovery in PSU through appropriate interventions.

  View details for PubMedID 27690739

• Fat may affect magnetic resonance signal intensity and brain tissue volumes. Obesity research & clinical practice Mon, A., Abé, C., Durazzo, T. C., Meyerhoff, D. J. 2016; 10 (2): 211-5

  Abstract

  Obesity/overweight is reported to affect MR-measured brain tissue volume and white matter (WM) signal intensity. This study investigated possible effects of fat on these measures, using pig fat on three participants at a 4T magnet. Grey matter volumes in the presence of fat were lower than baseline measures. Total WM volumes in the presence of fat were higher than baseline measures. WM hypo-intensities on T1-weighted images were higher in the presence of fat than baseline measures. Therefore physical effects of head fat of obese/overweight individual may at least, partly contribute to the association of obesity/overweight with MR structural measures.

  View details for DOI 10.1016/j.orcp.2015.07.009

  View details for PubMedID 26259685

  View details for PubMedCentralID PMC4876040

• Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to Substance Use, Cognition, and Self-Regulation. Journal of addiction research & therapy Murray, D. E., Durazzo, T. C., Schmidt, T. P., Abé, C., Guydish, J., Meyerhoff, D. J. 2016; 7 (4)

  Abstract

  Proton magnetic resonance spectroscopy (1H MRS) in opiate dependence showed abnormalities in neuronal viability and glutamate concentration in the anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological correlates have not been investigated in opiate dependence.Single-volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21 opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC), commonly investigated treatment-seekers providing context for OD evaluation. Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto-occipital cortical (POC) regions.Compared to CON, OD had lower concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and choline-containing metabolites were elevated and lower Cr concentration related to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had significant DLPFC metabolite deficits.The anterior frontal metabolite profile of OD differed significantly from that of CON and ALC. The frontal lobe metabolite abnormalities in OD and their neuropsychological correlates may play a role in treatment outcome and could be explored as specific targets for improved OD treatment.

  View details for PubMedID 27695638

• Active Cigarette Smoking in Cognitively-Normal Elders and Probable Alzheimer's Disease is Associated with Elevated Cerebrospinal Fluid Oxidative Stress Biomarkers. Journal of Alzheimer's disease : JAD Durazzo, T. C., Korecka, M., Trojanowski, J. Q., Weiner, M. W., O' Hara, R., Ashford, J. W., Shaw, L. M. 2016; 54 (1): 99-107

  Abstract

  Neurodegenerative diseases and chronic cigarette smoking are associated with increased cerebral oxidative stress (OxS). Elevated F2-isoprostane levels in biological fluid is a recognized marker of OxS. This study assessed the association of active cigarette smoking with F2-isoprostane in concentrations in cognitively-normal elders (CN), and those with mild cognitive impairment (MCI) and probable Alzheimer's disease (AD). Smoking and non-smoking CN (n = 83), MCI (n = 164), and probable AD (n = 101) were compared on cerebrospinal fluid (CSF) iPF2α-III and 8,12, iso-iPF2α-VI F2-isoprostane concentrations. Associations between F2-isoprostane levels and hippocampal volumes were also evaluated. In CN and AD, smokers had higher iPF2α-III concentration; overall, smoking AD showed the highest iPF2α-III concentration across groups. Smoking and non-smoking MCI did not differ on iPF2α-III concentration. No group differences were apparent on 8,12, iso-iPF2α-VI concentration, but across AD, higher 8,12, iso-iPF2α-VI level was related to smaller left and total hippocampal volumes. Results indicate that active cigarette smoking in CN and probable AD is associated with increased central nervous system OxS. Further investigation of factors mediating/moderating the absence of smoking effects on CSF F2-isoprostane levels in MCI is warranted. In AD, increasing magnitude of OxS appeared to be related to smaller hippocampal volume. This study contributes additional novel information to the mounting body of evidence that cigarette smoking is associated with adverse effects on the human central nervous system across the lifespan.

  View details for DOI 10.3233/JAD-160413

  View details for PubMedID 27472882

• Chronic Cigarette Smoking in Healthy Middle-Aged Individuals Is Associated With Decreased Regional Brain N-acetylaspartate and Glutamate Levels. Biological psychiatry Durazzo, T. C., Meyerhoff, D. J., Mon, A., Abé, C., Gazdzinski, S., Murray, D. E. 2016; 79 (6): 481-8

  Abstract

  Cigarette smoking is associated with metabolite abnormalities in anterior brain regions, but it is unclear if these abnormalities are apparent in other regions. Additionally, relationships between regional brain metabolite levels and measures of decision making, risk taking, and impulsivity in smokers and nonsmokers have not been investigated.In young to middle-aged (predominately male) nonsmokers (n = 30) and smokers (n = 35), N-acetylaspartate (NAA), choline-containing compounds, creatine-containing compounds (Cr), myo-inositol (mI), and glutamate (Glu) levels in the anterior cingulate cortex and right dorsolateral prefrontal cortex (DLPFC) were compared via 4-tesla proton single volume magnetic resonance spectroscopy. Groups also were compared on NAA, choline-containing compounds, Cr, and mI concentrations in the gray matter and white matter of the four cerebral lobes and subcortical nuclei/regions with 1.5-tesla proton magnetic resonance spectroscopy. Associations of regional metabolite levels with neurocognitive, decision-making, risk-taking, and self-reported impulsivity measures were examined.Smokers showed lower DLPFC NAA, Cr, mI and Glu concentrations and lower lenticular nuclei NAA level; smokers also demonstrated greater age-related decreases of DLPFC NAA and anterior cingulate cortex and DLPFC Glu levels. Smokers exhibited poorer decision making and greater impulsivity. Across the sample, higher NAA and Glu in the DLPFC and NAA concentrations in multiple lobar gray matter and white matter regions and subcortical nuclei were associated with better neurocognition and lower impulsivity.This study provides additional novel evidence that chronic smoking in young and middle-aged individuals is associated with significant age-related neurobiological abnormalities in anterior frontal regions implicated in the development and maintenance of addictive disorders.

  View details for DOI 10.1016/j.biopsych.2015.03.029

  View details for PubMedID 25979621

  View details for PubMedCentralID PMC4600002

• Interaction of Cigarette Smoking History With APOE Genotype and Age on Amyloid Level, Glucose Metabolism, and Neurocognition in Cognitively Normal Elders. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco Durazzo, T. C., Mattsson, N., Weiner, M. W. 2016; 18 (2): 204-11

  Abstract

  Chronic cigarette smoking is associated with increased risk for Alzheimer's disease (AD). The goal of this study was to determine if smoking history moderated the associations of age and APOE genotype (the most robust risk factors for AD) on brain amyloid deposition, glucose metabolism, and neurocognition in cognitively-normal elders.Participants (n = 264) were grouped according to their APOE ε4 carrier status (ε4 carrier: APOE4+; non-ε4 carrier: APOE4-) and smoking status (smokers: at least 1 year of smoking during lifetime; never-smokers: no history of smoking). Approximately 89% of the smoking sample was former-smokers. We specifically tested for interactions of smoking status with APOE ε4 carrier status and age on measures of cortical amyloid deposition, glucose metabolism, and neurocognition.(1) smoking status interacted with APOE ε4 carrier status, where smoker APOE4+ showed lower glucose metabolism and poorer auditory-verbal learning and memory than never-smoking APOE4-, never-smoking APOE4+, and smoking APOE4-; (2) smoking status interacted with age on measures of semantic fluency, processing speed/set-shifting and global neurocognition; smokers, irrespective of APOE ε4 carrier status, demonstrated poorer performance with increasing age than never-smokers; and (3) smoking APOE4+ and never-smoking APOE4+ showed greater cortical amyloid deposition than never-smoking APOE4- and smoking APOE4-.The findings indicate consideration of smoking history is essential to both better understand the factors associated with neurobiological and neurocognitive abnormalities in elders, and the risk for development of AD-related neuropathology.

  View details for DOI 10.1093/ntr/ntv075

  View details for PubMedID 25847292

  View details for PubMedCentralID PMC5967295

• Serial longitudinal magnetic resonance imaging data indicate non-linear regional gray matter volume recovery in abstinent alcohol-dependent individuals. Addiction biology Durazzo, T. C., Mon, A., Gazdzinski, S., Yeh, P. H., Meyerhoff, D. J. 2015; 20 (5): 956-67

  Abstract

  The trajectory of regional volume changes during the first year of sustained abstinence in those recovering from an alcohol use disorder is unclear because previous research typically employed only two assessment points. To better understand the trajectory of regional brain volume recovery in treatment-seeking alcohol-dependent individuals (ALC), regional brain volumes were measured after 1 week, 1 month and 7.5 months of sustained abstinence via magnetic resonance imaging at 1.5 T. ALC showed significant volume increases in frontal, parietal and occipital gray matter (GM) and white matter (WM), total cortical GM and total lobar WM, thalamus and cerebellum, and decreased ventricular volume over 7.5 months of abstinence. Volume increases in regional GM were significantly greater over 1 week to 1 month than from 1 month to 7.5 months of abstinence, indicating a non-linear rate of change in regional GM over 7.5 months. Overall, regional lobar WM showed linear volume increases over 7.5 months. With increasing age, smoking ALC showed lower frontal and total cortical GM volume recovery than non-smoking ALC. Despite significant volume increases, ALC showed smaller GM volumes in all regions, except the frontal cortex, than controls after 7.5 months of abstinence. ALC and controls showed no regional WM volume differences at any assessment point. In non-smoking ALC only, increasing regional GM and WM volumes were related to improving processing speed. Findings may indicate a differential rate of recovery of cell types/cellular components contributing to GM and WM volume during early abstinence, and that GM volume deficits persist after 7.5 months of sustained sobriety in this ALC cohort.

  View details for DOI 10.1111/adb.12180

  View details for PubMedID 25170881

  View details for PubMedCentralID PMC4345147

• Comparison of Regional Brain Perfusion Levels in Chronically Smoking and Non-Smoking Adults. International journal of environmental research and public health Durazzo, T. C., Meyerhoff, D. J., Murray, D. E. 2015; 12 (7): 8198-213

  Abstract

  Chronic cigarette smoking is associated with numerous abnormalities in brain neurobiology, but few studies specifically investigated the chronic effects of smoking (compared to the acute effects of smoking, nicotine administration, or nicotine withdrawal) on cerebral perfusion (i.e., blood flow). Predominately middle-aged male (47 ± 11 years of age) smokers (n = 34) and non-smokers (n = 27) were compared on regional cortical perfusion measured by continuous arterial spin labeling magnetic resonance studies at 4 Tesla. Smokers showed significantly lower perfusion than non-smokers in the bilateral medial and lateral orbitofrontal cortices, bilateral inferior parietal lobules, bilateral superior temporal gyri, left posterior cingulate, right isthmus of cingulate, and right supramarginal gyrus. Greater lifetime duration of smoking (adjusted for age) was related to lower perfusion in multiple brain regions. The results indicated smokers showed significant perfusion deficits in anterior cortical regions implicated in the development, progression, and maintenance of all addictive disorders. Smokers concurrently demonstrated reduced blood flow in posterior brain regions that show morphological and metabolic aberrations as well as elevated beta amyloid deposition demonstrated by those with early stage Alzheimer disease. The findings provide additional novel evidence of the adverse effects of cigarette smoking on the human brain.

  View details for DOI 10.3390/ijerph120708198

  View details for PubMedID 26193290

  View details for PubMedCentralID PMC4515717

• Brain perfusion in polysubstance users: relationship to substance and tobacco use, cognition, and self-regulation. Drug and alcohol dependence Murray, D. E., Durazzo, T. C., Mon, A., Schmidt, T. P., Meyerhoff, D. J. 2015; 150: 120-8

  Abstract

  Brain perfusion is altered in both alcohol dependence and stimulant dependence. Although most substance users also abuse/depend on alcohol concurrently (polysubstance users; PSU), rigorous perfusion research in PSU is limited. Also, the relationships of perfusion abnormalities with cognition, impulsivity, or decision making are not well known.Arterial spin labeling MRI and neuropsychological measures assessed perfusion levels and neurocognition in 20 alcohol-dependent individuals with comorbid-stimulant dependence (PSU), 26 individuals dependent on alcohol only (ALC), and 31 light/non-drinking controls (LD). The patient groups included smokers and non-smokers.ALC had lower perfusion than LD in subcortical and cortical brain regions including the brain reward/executive oversight system (BREOS). Contrary to our hypothesis, regional perfusion was generally not lower in PSU than ALC. However, smoking PSU had lower perfusion than smoking ALC in several regions, including BREOS. Lower BREOS perfusion related to greater drinking severity in smoking substance users and to greater smoking severity in smoking ALC. Lower regional perfusion in ALC and PSU correlated with worse performance in different cognitive domains; smoking status affected perfusion-cognition relationships in ALC only. Lower BREOS perfusion in both substance using groups related to higher impulsivity.Although regional perfusion was not decreased in PSU as a group, the combination of cigarette smoking and polysubstance use is strongly related to hypoperfusion in important cortical and subcortical regions. As lower perfusion relates to greater smoking severity, worse cognition and higher impulsivity, smoking cessation is warranted for treatment-seeking PSU and ALC.

  View details for DOI 10.1016/j.drugalcdep.2015.02.022

  View details for PubMedID 25772434

  View details for PubMedCentralID PMC4387082

• Alcohol use disorder with and without stimulant use: brain morphometry and its associations with cigarette smoking, cognition, and inhibitory control. PloS one Pennington, D. L., Durazzo, T. C., Schmidt, T. P., Abé, C., Mon, A., Meyerhoff, D. J. 2015; 10 (3): e0122505

  Abstract

  Little is known about the effects of polysubstance use and cigarette smoking on brain morphometry. This study examined neocortical brain morphometric differences between abstinent polysubstance dependent and alcohol-only dependent treatment seekers (ALC) as well as light drinking controls (CON), the associations of cigarette smoking in these polysubstance users (PSU), and morphometric relationships to cognition and inhibitory control.All participants completed extensive neuropsychological assessments and 4 Tesla brain magnetic resonance imaging. PSU and ALC were abstinent for one month at the time of study. Parcellated morphological data (volume, surface area, thickness) were obtained with FreeSurfer methodology for the following bilateral components: dorso-prefrontal cortex (DPFC), anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and insula. Regional group differences were examined and structural data correlated with domains of cognition and inhibitory control.PSU had significantly smaller left OFC volume and surface area and trends to smaller right DPFC volume and surface area compared to CON; PSU did not differ significantly from ALC on these measures. PSU, however, had significantly thinner right ACC than ALC. Smoking PSU had significantly larger right OFC surface area than non-smoking PSU. No significant relationships between morphometry and quantity/frequency of substance use, alcohol use, or age of onset of heavy drinking were observed. PSU exhibited distinct relationships between brain structure and processing speed, cognitive efficiency, working memory and inhibitory control that were not observed in ALC or CON.Polysubstance users have unique morphometric abnormalities and structure-function relationships when compared to individuals dependent only on alcohol and light drinking controls. Chronic cigarette smoking is associated with structural brain irregularities in polysubstance users. Further elucidation of these distinctive characteristics could help inform the development of targeted and thus potentially more effective treatments in this large but understudied population.

  View details for DOI 10.1371/journal.pone.0122505

  View details for PubMedID 25803861

  View details for PubMedCentralID PMC4372577

• Effects of cigarette smoking history on neurocognitive recovery over 8 months of abstinence in alcohol-dependent individuals. Alcoholism, clinical and experimental research Durazzo, T. C., Pennington, D. L., Schmidt, T. P., Meyerhoff, D. J. 2014; 38 (11): 2816-25

  Abstract

  This study compared the rate and extent of recovery on measures of learning and memory, processing speed, and working memory in treatment-seeking alcohol-dependent individuals (ALC) who were never smokers (nvsALC), former smokers (fsALC), and active smokers (asALC) over the first 8 months of sustained abstinence from alcohol. Assessments after 1 week, 1 month, and 8 months of abstinence in ALC enabled a comparison of the rates of neurocognitive changes from 1 week to 1 month versus 1 to 8 months of abstinence.ALC and never-smoking controls were administered standardized measures of auditory-verbal and visuospatial learning and memory, processing speed, and working memory. Controls completed a baseline assessment and a follow-up approximately 9 months later.Over 8 months of abstinence, asALC showed poorer recovery than nvsALC on visuospatial learning, and both fsALC and asALC recovered less than nvsALC on processing speed measures. The corresponding recovery rates for the ALC group, as a whole, were greater from 1 week to 1 month than from 1 to 8 months of abstinence; these findings were largely driven by improvements in nvsALC. The recovery levels for fsALC on most measures were similar to those in asALC. Additionally, over 8 months, asALC showed significantly less improvement with increasing age than nvsALC on measures of processing speed and learning and memory. At 8 months of abstinence, asALC were inferior to controls and nvsALC on multiple measures, fsALC performed worse than nvsALC on several tests, but nvsALC were not different from controls on any measure.Overall, ALC showed rapid improvement on measures of visuospatial learning and processing speed during the first month of abstinence from alcohol. Results also provide robust evidence that smoking status influenced the rate and level of neurocognitive recovery over 8 months of abstinence in this ALC cohort.

  View details for DOI 10.1111/acer.12552

  View details for PubMedID 25336410

  View details for PubMedCentralID PMC4245379

• Genetic and behavioral determinants of hippocampal volume recovery during abstinence from alcohol. Alcohol (Fayetteville, N.Y.) Hoefer, M. E., Pennington, D. L., Durazzo, T. C., Mon, A., Abé, C., Truran, D., Hutchison, K. E., Meyerhoff, D. J. 2014; 48 (7): 631-8

  Abstract

  Alcohol-dependent individuals (ALC) have smaller hippocampi and poorer neurocognition than healthy controls. Results from studies on the association between alcohol consumption and hippocampal volume have been mixed, suggesting that comorbid or premorbid factors (i.e., those present prior to the initiation of alcohol dependence) determine hippocampal volume in ALC. We aimed to characterize the effects of select comorbid (i.e., cigarette smoking) and premorbid factors (brain-derived neurotrophic factor [BDNF] genotype [Val66Met rs6265]) on hippocampal volume in an ALC cohort followed longitudinally into extended abstinence. One hundred twenty-one adult ALC in treatment (76 smokers, 45 non-smokers) and 35 non-smoking light-drinking controls underwent quantitative magnetic resonance imaging, BDNF genotyping, and neurocognitive assessments. Representative subgroups were studied at 1 week, 1 month, and at an average of 7 months of abstinence. ALC had smaller hippocampi than healthy controls at all time points. Hippocampal volume at 1 month of abstinence correlated with lower visuospatial function. Smoking status did not influence hippocampal volume or hippocampal volume recovery during abstinence. However, only BDNF Val homozygotes tended to have hippocampal volume increases over 7 months of abstinence, and Val homozygotes had significantly larger hippocampi than Met carriers at 7 months of abstinence. These findings suggest that BDNF genotype, but not smoking status or measures of drinking severity, regulate functionally relevant hippocampal volume recovery in abstinent ALC. Future studies aimed at exploring genetic determinants of brain morphometry in ALC may need to evaluate individuals during extended abstinence after the acute environmental effects of chronic alcohol consumption have waned.

  View details for DOI 10.1016/j.alcohol.2014.08.007

  View details for PubMedID 25262572

  View details for PubMedCentralID PMC4266697

• Structural brain differences in alcohol-dependent individuals with and without comorbid substance dependence. Drug and alcohol dependence Mon, A., Durazzo, T. C., Abe, C., Gazdzinski, S., Pennington, D., Schmidt, T., Meyerhoff, D. J. 2014; 144: 170-7

  Abstract

  Over 50% of individuals with alcohol use disorders (AUD) also use other substances; brain structural abnormalities observed in alcohol dependent individuals may not be entirely related to alcohol consumption. This MRI study assessed differences in brain regional tissue volumes between short-term abstinent alcohol dependent individuals without (ALC) and with current substance use dependence (polysubstance users, PSU).Nineteen, one-month-abstinent PSU and 40 ALC as well as 27 light-drinkers (LD) were studied on a 1.5 T MR system. Whole brain T1-weighted images were segmented automatically into regional gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volumes. MANOVA assessed group differences of intracranial volume-normalized tissue volumes of the frontal, parietal, occipital, and temporal lobes and regional subcortical GM volumes. The volumetric measures were correlated with neurocognitive measures to assess their functional relevance.Despite similar lifetime drinking and smoking histories, PSU had significantly larger normalized WM volumes than ALC in all lobes. PSU also had larger frontal and parietal WM volumes than LD, but smaller temporal GM volumes and smaller lenticular and thalamic nuclei than LD. ALC had smaller frontal, parietal, and temporal GM, thalamic GM and cerebellar volumes than LD. ALC had more sulcal CSF volumes than both PSU and LD.One-month-abstinent ALC and PSU exhibited different patterns of gross brain structural abnormalities. The larger lobar WM volumes in PSU in the absence of widespread GM volume loss contrast with widespread GM atrophy in ALC. These structural differences may demand different treatment approaches to mitigate specific functionally relevant brain abnormalities.

  View details for DOI 10.1016/j.drugalcdep.2014.09.010

  View details for PubMedID 25263262

  View details for PubMedCentralID PMC4280666

• History of cigarette smoking in cognitively-normal elders is associated with elevated cerebrospinal fluid biomarkers of oxidative stress. Drug and alcohol dependence Durazzo, T. C., Mattsson, N., Weiner, M. W., Korecka, M., Trojanowski, J. Q., Shaw, L. M. 2014; 142: 262-8

  Abstract

  Cigarette smoking in adults is associated with abnormalities in brain neurobiology. Smoking-induced central nervous system oxidative stress (OxS) is a potential mechanism associated with these abnormalities. The goal of this study was to compare cognitively-normal elders on cerebrospinal fluid (CSF) levels of F2-isoprostane biomarkers of OxS.Elders with a lifetime history of smoking (smokers; n=50; 75±5 years of age; 34±28 pack-years; approximately 12% were actively smoking at the time of study) were compared to never-smokers (n=61; 76±6 years of age) on CSF iPF2α-III and 8,12, iso-iPF2α-VI F2-isoprostanes levels. F2-isoprostanes levels were quantitated with HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry. Associations between F2-isoprostanes levels, hippocampal volumes, and cigarette exposure measures were also evaluated.Smokers showed higher iPF2α-III level than never-smokers. An age×smoking status interaction was observed for 8,12, iso-iPF2α-VI, where smokers demonstrate a significantly greater concentration with increasing age than never-smokers. In smokers only, higher 8,12, iso-iPF2α-VI concentration was associated with smaller hippocampal volume, and greater iPF2α-III level was related to greater pack years.This is the first study to demonstrate that a history of cigarette smoking in cognitively-normal elders was associated with significantly elevated CSF F2-isoprostane levels and greater age-related increases in F2-isoprostanes, and that higher F2-isoprostane levels in smokers were related to smaller hippocampal volume. These findings provide additional novel evidence that a history of chronic smoking during adulthood is associated with adverse effects on the human brain that are potentially enduring even with extended smoking cessation.

  View details for DOI 10.1016/j.drugalcdep.2014.06.030

  View details for PubMedID 25037769

  View details for PubMedCentralID PMC4144023

• Postural stability in cigarette smokers and during abstinence from alcohol. Alcoholism, clinical and experimental research Schmidt, T. P., Pennington, D. L., Durazzo, T. C., Meyerhoff, D. J. 2014; 38 (6): 1753-60

  Abstract

  Static postural instability is common in alcohol-dependent individuals (ALC). Chronic alcohol consumption has deleterious effects on the neural and perceptual systems subserving postural stability. However, little is known about the effects of chronic cigarette smoking on postural stability and its changes during abstinence from alcohol.A modified Fregly ataxia battery was administered to a total of 115 smoking (sALC) and nonsmoking ALC (nsALC) and to 71 smoking (sCON) and nonsmoking light/nondrinking controls (nsCON). Subgroups of abstinent ALC were assessed at 3 time points (TPs; approximately 1, 5, 34 weeks of abstinence from alcohol); a subset of nsCON was retested at 40 weeks. We tested whether cigarette smoking affects postural stability in CON and in ALC during extended abstinence from alcohol, and we used linear mixed effects modeling to measure change across TPs within ALC.Chronic smoking was associated with reduced performance on the Sharpened Romberg eyes-closed task in abstinent ALC at all 3 TPs and in CON. The test performance of nsALC increased significantly between 1 and 32 weeks of abstinence, whereas the corresponding increases for sALC between 1 and 35 weeks were nonsignificant. With long-term abstinence from alcohol, nsALC recovered into the range of nsCON and sALC recovered into the range of sCON. Static postural stability decreased with age and correlated with smoking variables but not with drinking measures.Chronic smoking was associated with reduced static postural stability with eyes closed and with lower increases of postural stability during abstinence from alcohol. Smoking cessation in alcohol dependence treatment may facilitate recovery from static postural instability during abstinence.

  View details for DOI 10.1111/acer.12409

  View details for PubMedID 24721012

  View details for PubMedCentralID PMC4063446

• Smoking and increased Alzheimer's disease risk: a review of potential mechanisms. Alzheimer's & dementia : the journal of the Alzheimer's Association Durazzo, T. C., Mattsson, N., Weiner, M. W. 2014; 10 (3 Suppl): S122-45

  Abstract

  Cigarette smoking has been linked with both increased and decreased risk for Alzheimer's disease (AD). This is relevant for the US military because the prevalence of smoking in the military is approximately 11% higher than in civilians.A systematic review of published studies on the association between smoking and increased risk for AD and preclinical and human literature on the relationships between smoking, nicotine exposure, and AD-related neuropathology was conducted. Original data from comparisons of smoking and never-smoking cognitively normal elders on in vivo amyloid imaging are also presented.Overall, literature indicates that former/active smoking is related to a significantly increased risk for AD. Cigarette smoke/smoking is associated with AD neuropathology in preclinical models and humans. Smoking-related cerebral oxidative stress is a potential mechanism promoting AD pathology and increased risk for AD.A reduction in the incidence of smoking will likely reduce the future prevalence of AD.

  View details for DOI 10.1016/j.jalz.2014.04.009

  View details for PubMedID 24924665

  View details for PubMedCentralID PMC4098701

• Interactive effects of chronic cigarette smoking and age on brain volumes in controls and alcohol-dependent individuals in early abstinence. Addiction biology Durazzo, T. C., Mon, A., Pennington, D., Abé, C., Gazdzinski, S., Meyerhoff, D. J. 2014; 19 (1): 132-43

  Abstract

  Chronic alcohol-use disorders (AUDs) have been shown to interact with normal age-related volume loss to exacerbate brain atrophy with increasing age. However, chronic cigarette smoking, a highly co-morbid condition in AUD and its influence on age-related brain atrophy have not been evaluated. We performed 1.5 T quantitative magnetic resonance imaging in non-smoking controls [non-smoking light drinking controls (nsCONs); n = 54], smoking light drinking controls (sCONs, n = 34), and one-week abstinent, treatment-seeking alcohol-dependent (ALC) non-smokers (nsALCs, n = 35) and smokers (sALCs, n = 43), to evaluate the independent and interactive effects of alcohol dependence and chronic smoking on regional cortical and subcortical brain volumes, emphasizing the brain reward/executive oversight system (BREOS). The nsCONs and sALCs showed greater age-related volume losses than the nsALCs in the dorsal prefrontal cortex (DPFC), total cortical BREOS, superior parietal lobule and putamen. The nsALCs and sALCs demonstrated smaller volumes than the nsCONs in most cortical region of interests (ROIs). The sCONs had smaller volumes than the nsCONs in the DPFC, insula, inferior parietal lobule, temporal pole/parahippocampal region and all global cortical measures. The nsALCs and sALCs had smaller volumes than the sCONs in the DPFC, superior temporal gyrus, inferior and superior parietal lobules, precuneus and all global cortical measures. Volume differences between the nsALCs and sALCs were observed only in the putamen. Alcohol consumption measures were not related to volumes in any ROI for ALC; smoking severity measures were related to corpus callosum volume in the sCONs and sALCs. The findings indicate that consideration of smoking status is necessary for a better understanding of the factors contributing to regional brain atrophy in AUD.

  View details for DOI 10.1111/j.1369-1600.2012.00492.x

  View details for PubMedID 22943795

  View details for PubMedCentralID PMC3528793

• Effects of fat on MR-measured metabolite signal strengths: implications for in vivo MRS studies of the human brain. NMR in biomedicine Mon, A., Abé, C., Durazzo, T. C., Meyerhoff, D. J. 2013; 26 (12): 1768-74

  Abstract

  Recent MRS studies have indicated that a higher body mass index (BMI) is associated with lower brain metabolite levels. Generally, individuals with higher BMIs have more body fat deposits than individuals with normal BMIs. This single-voxel spectroscopy (SVS) study investigated possible effects of fat on MR-measured metabolite signal areas, which may at least partly explain the observed associations of BMI with MR-measured brain metabolite levels in vivo. SVS data were acquired at 4 T from a phantom containing N-acetylaspartate, glutamate and creatine, as well as from three healthy male adults. Back fat obtained from pig was used to assess the effects of fat on metabolite signals. With the same voxel size and placement, the phantom was first scanned without fat (baseline), and then with 0.7-cm- and 1.4-cm-thick fat layers placed on it. Each participant was also scanned first without fat and then with two 0.7-cm fat layers, one placed beneath the occiput and the other on the forehead. Two spectra were acquired per participant from the anterior cingulate and the parieto-occipital cortices. The metabolite resonance and corresponding water peak areas were then fitted and metabolite to water signal ratios were used for analyses. In both phantom and in vivo experiments, the metabolite-to-water ratios decreased in the presence of fat relative to baseline metabolite-to-water ratios. The reduced metabolite signals in the presence of fat reported here are reminiscent of the negative correlations observed between BMI and MR-measured metabolite levels. These apparent physical effects of fat have potentially far-reaching consequences for the accuracy of MR measurements of brain metabolite levels and their interpretation, particularly when large fat stores exist around the skull, such as in individuals with higher BMI.

  View details for DOI 10.1002/nbm.3016

  View details for PubMedID 24115006

  View details for PubMedCentralID PMC4103156

• Loss in connectivity among regions of the brain reward system in alcohol dependence. Human brain mapping Kuceyeski, A., Meyerhoff, D. J., Durazzo, T. C., Raj, A. 2013; 34 (12): 3129-42

  Abstract

  A recently developed measure of structural brain connectivity disruption, the loss in connectivity (LoCo), is adapted for studies in alcohol dependence. LoCo uses independent tractography information from young healthy controls to project the location of white matter (WM) microstructure abnormalities in alcohol-dependent versus nondependent individuals onto connected gray matter (GM) regions. LoCo scores are computed from WM abnormality masks derived at two levels: (1) groupwise differences of alcohol-dependent individuals (ALC) versus light-drinking (LD) controls and (2) differences of each ALC individual versus the LD control group. LoCo scores based on groupwise WM differences show that GM regions belonging to the extended brain reward system (BRS) network have significantly higher LoCo (i.e., disconnectivity) than those not in this network (t = 2.18, P = 0.016). LoCo scores based on individuals' WM differences are also higher in BRS versus non-BRS (t = 5.26, P = 3.92 × 10(-6) ) of ALC. These results suggest that WM alterations in alcohol dependence, although subtle and spatially heterogeneous across the population, are nonetheless preferentially localized to the BRS. LoCo is shown to provide a more sensitive estimate of GM involvement than conventional volumetric GM measures by better differentiating between brains of ALC and LD controls (rates of 89.3% vs. 69.6%). However, just as volumetric measures, LoCo is not significantly correlated with standard metrics of drinking severity. LoCo is a sensitive WM measure of regional cortical disconnectivity that uniquely characterizes anatomical network disruptions in alcohol dependence.

  View details for DOI 10.1002/hbm.22132

  View details for PubMedID 22815206

  View details for PubMedCentralID PMC3931305

• Interactive effects of chronic cigarette smoking and age on hippocampal volumes. Drug and alcohol dependence Durazzo, T. C., Meyerhoff, D. J., Nixon, S. J. 2013; 133 (2): 704-11

  Abstract

  Previous cross-sectional MRI studies with healthy, young-to-middle-aged adults reported no significant differences between smokers and non-smokers on total hippocampal volume. However, these studies did not specifically test for greater age-related volume loss in the total hippocampus or hippocampal subregions in smokers, and did they did not examine relationships between hippocampal and subfield volumes and episodic learning and memory performance.Healthy, young-to-middle-aged (45 ± 12 years of age) smokers (n=39) and non-smokers (n=43) were compared on total hippocampal and subfield volumes derived from high-resolution 4 Tesla MRI, emphasizing testing for greater age-related volume losses in smokers. Associations between hippocampal volumes and measures of episodic learning and memory were examined.Smokers showed significantly smaller volumes, as well as greater volume loss with increasing age than non-smokers in the bilateral total hippocampus and multiple subfields. In smokers, greater pack-years were associated with smaller volumes of the total hippocampus, presubiculum, and subiculum. In the entire cohort, performance on measures of learning and memory was related to larger total hippocampal and several subfield volumes, predominately in the left hemisphere.Chronic cigarette smoking in this young-to-middle aged cohort was associated with smaller total hippocampal and subfield volumes, which were exacerbated by advancing age. Findings also indicated an adverse smoking dose/duration response (i.e., pack-years) with total hippocampal and select subfield volumes. These hippocampal volume abnormalities in smokers may be related to the deficiencies in episodic learning and memory in young-to-middle-aged smokers reported in previous studies.

  View details for DOI 10.1016/j.drugalcdep.2013.08.020

  View details for PubMedID 24051060

  View details for PubMedCentralID PMC3870586

• Neurocognition in 1-month-abstinent treatment-seeking alcohol-dependent individuals: interactive effects of age and chronic cigarette smoking. Alcoholism, clinical and experimental research Durazzo, T. C., Pennington, D. L., Schmidt, T. P., Mon, A., Abé, C., Meyerhoff, D. J. 2013; 37 (10): 1794-803

  Abstract

  Increasing age and chronic cigarette smoking are independently associated with adverse effects on multiple aspects of neurocognition in those seeking treatment for alcohol use disorders. However, the potential interactive effects of age and cigarette smoking on neurocognition in early abstinent alcohol-dependent individuals (ALC) have not investigated.Cross-sectional performances of never-smoking healthy comparison participants (nvsCOM; n = 39) and 1-month-abstinent, treatment-seeking, never-smoking (nvsALC; n = 30), former-smoking (fsALC; n = 21), and actively smoking (asALC; n = 68) ALC were compared on a comprehensive neurocognitive battery. Domains of functioning evaluated were cognitive efficiency, executive functions, fine motor skills, general intelligence, learning and memory, processing speed, visuospatial functions and working memory. Participants were between 26 and 71 years of age at the time of assessment.asALC showed steeper age-related effects than nvsCOM on the domains of visuospatial learning, auditory-verbal memory, cognitive efficiency, executive functions, processing speed, and fine motor skills. In pairwise comparisons, fsALC and asALC performed more poorly than both nvsCOM and nvsALC on multiple domains; nvsCOM and nvsALC showed no significant differences. Domain scores for the ALC groups generally fell in the low-to-high-average range of functioning. A clinically significant level of impairment was apparent in only 25% of ALC participants on visuospatial learning, visuospatial memory, and fine motor skills domains. Measures of alcohol use or consumption were not significantly related to neurocognition in the ALC cohorts.The age-related findings suggest that the combination of active chronic smoking and alcohol dependence in this 1-month-abstinent ALC cohort was associated with greater than normal age-related effects in multiple domains. In general, a low level of clinically significant impairment was observed in the alcohol-dependent participants. The findings from this study, in conjunction with previous research, strongly support smoking cessation interventions for those seeking treatment for alcohol and substance use disorders.

  View details for DOI 10.1111/acer.12140

  View details for PubMedID 23682867

  View details for PubMedCentralID PMC3749254

• The effects of chronic cigarette smoking on cognitive recovery during early abstinence from alcohol. Alcoholism, clinical and experimental research Pennington, D. L., Durazzo, T. C., Schmidt, T. P., Mon, A., Abé, C., Meyerhoff, D. J. 2013; 37 (7): 1220-7

  Abstract

  Alcohol use disorders are related to neurocognitive abnormalities during early abstinence in those seeking treatment for alcohol dependence (ALC). Considerable evidence indicates that chronic cigarette smoking is associated with multiple neurocognitive deficiencies. However, very little is known about the effects of chronic smoking on neurocognitive recovery during early abstinence from alcohol. We evaluated whether cigarette smoking interferes with cognitive improvement during early abstinence from alcohol, a period thought important for maintaining long-term sobriety.Neurocognitive functions previously shown to be adversely affected by both alcohol use disorders and chronic cigarette smoking were evaluated. We assessed 35 smoking ALC (sALC) and 34 nonsmoking ALC (nsALC) at approximately 1 and 5 weeks of monitored abstinence.Although neither group was clinically impaired, both cross-sectional and longitudinal deficiencies were observed in sALC versus nsALC in processing speed, working memory, and auditory-verbal learning and memory. Lifetime alcohol consumption, medical, and psychiatric comorbidities did not predict neurocognitive performance or improvement across assessments. Within sALC, greater drinking and smoking severities were synergistically (more than additively) related to less improvement on visuospatial learning and memory. Former smoking status in the nsALC-mediated group differences in auditory-verbal delayed recall.Chronic cigarette smoking appears to negatively impact neurocognition during early abstinence from alcohol. Although the cognitive deficiencies observed in this cohort were not in a clinical range of impairment, they should be considered to enhance treatment efficacy. Our findings lend support to integrating smoking cessation as well as the individual assessment of cognition into early ALC treatment. Additionally, there is a need to elucidate the effects of current and former smoking status in future reports of neurocognition.

  View details for DOI 10.1111/acer.12089

  View details for PubMedID 23432133

  View details for PubMedCentralID PMC3664254

• Metabolic abnormalities in lobar and subcortical brain regions of abstinent polysubstance users: magnetic resonance spectroscopic imaging. Alcohol and alcoholism (Oxford, Oxfordshire) Abé, C., Mon, A., Hoefer, M. E., Durazzo, T. C., Pennington, D. L., Schmidt, T. P., Meyerhoff, D. J. 2013; 48 (5): 543-51

  Abstract

  The aim of the study was to explore neurometabolic and associated cognitive characteristics of patients with polysubstance use (PSU) in comparison with patients with predominant alcohol use using proton magnetic resonance spectroscopy.Brain metabolite concentrations were examined in lobar and subcortical brain regions of three age-matched groups: 1-month-abstinent alcohol-dependent PSU, 1-month-abstinent individuals dependent on alcohol alone (ALC) and light drinking controls (CON). Neuropsychological testing assessed cognitive function.While CON and ALC had similar metabolite levels, persistent metabolic abnormalities (primarily higher myo-inositol) were present in temporal gray matter, cerebellar vermis and lenticular nuclei of PSU. Moreover, lower cortical gray matter concentration of the neuronal marker N-acetylaspartate within PSU correlated with higher cocaine (but not alcohol) use quantities and with a reduced cognitive processing speed.These metabolite group differences reflect cellular/astroglial injury and/or dysfunction in alcohol-dependent PSU. Associations of other metabolite concentrations with neurocognitive performance suggest their functional relevance. The metabolic alterations in PSU may represent polydrug abuse biomarkers and/or potential targets for pharmacological and behavioral PSU-specific treatment.

  View details for DOI 10.1093/alcalc/agt056

  View details for PubMedID 23797281

  View details for PubMedCentralID PMC3746806

• Chronic alcohol consumption, abstinence and relapse: brain proton magnetic resonance spectroscopy studies in animals and humans. Current topics in behavioral neurosciences Meyerhoff, D. J., Durazzo, T. C., Ende, G. 2013; 13: 511-40

  Abstract

  This chapter summarizes the peer-reviewed literature of proton magnetic resonance spectroscopy ((1)H MRS) studies on the effects of chronic and excessive alcohol consumption in both the animal and human brain. After a brief summary of the neuropathology of alcohol use disorders (AUD), we describe the primary brain metabolites measured by in vivo (1)H MRS. We then focus on published MRS studies of animal models of alcohol dependence and of treatment-seeking humans with AUD. We also summarize the scant MRS research on the much larger fraction of treatment-naïve individuals with AUD and the similarities and discrepancies relative to treatment-seekers. It is exceedingly apparent that premorbid and/or comorbid disorders/conditions, especially chronic smoking, among individuals with AUD contribute to the considerable variability in the pattern and magnitude of neurobiological and neurocognitive abnormalities in AUD. Therefore, we also review studies on the neurobiological consequences of the combined effects of chronic drinking and smoking in AUD. Finally, as AUD is characterized by a chronically relapsing/remitting course over lifetime and identification of those at greatest risk for relapse is important, we review (1)H MRS studies on brain spectroscopic measures that contribute to the prediction of relapse in AUD. We conclude with an overall assessment of the MRS research literature on brain alcohol effects, the role of animal and human studies in understanding the disease, and discuss the need of widely integrative MRS studies of cohorts that include individuals with comorbidies that are reflective of the general population with AUD.

  View details for DOI 10.1007/7854_2011_131

  View details for PubMedID 21688208

• The influence of chronic cigarette smoking on neurocognitive recovery after mild traumatic brain injury. Journal of neurotrauma Durazzo, T. C., Abadjian, L., Kincaid, A., Bilovsky-Muniz, T., Boreta, L., Gauger, G. E. 2013; 30 (11): 1013-22

  Abstract

  The majority of the approximately 1.7 million civilians in the United States who seek emergency care for traumatic brain injury (TBI) are classified as mild (MTBI). Premorbid and comorbid conditions that commonly accompany MTBI may influence neurocognitive and functional recovery. This study assessed the influence of chronic smoking and hazardous alcohol consumption on neurocognitive recovery after MTBI. A comprehensive neurocognitive battery was administered to 25 non-smoking MTBI participants (nsMTBI), 19 smoking MTBI (sMTBI) 38 ± 22 days (assessment point 1: AP1) and 230 ± 36 (assessment point 2: AP2) days after injury. Twenty non-smoking light drinkers served as controls (CON). At AP1, nsMTBI and sMTBI were inferior to CON on measures of auditory-verbal learning and memory; nsMTBI performed more poorly than CON on processing speed and global neurocognition, and sMTBI performed worse than CON on working memory measures; nsMTBI were inferior to sMTBI on visuospatial memory. Over the AP1-AP2 interval, nsMTBI showed significantly greater improvement than sMTBI on measures of processing speed, visuospatial learning and memory, visuospatial skills, and global neurocognition, whereas sMTBI only showed significant improvement on executive skills. At AP2, sMTBI remained inferior to CON on auditory-verbal learning and auditory-verbal memory; there were no significant differences between nsMTBI and CON or among nsMTBI and sMTBI on any domain at AP2. Hazardous alcohol consumption was not significantly associated with change in any neurocognitive domain. For sMTBI, over the AP1-AP2 interval, greater lifetime duration of smoking and pack-years were related to significantly less improvement on multiple domains. Results suggest consideration of the effects of chronic cigarette smoking is necessary to understand the potential factors influencing neurocognitive recovery after MTBI.

  View details for DOI 10.1089/neu.2012.2676

  View details for PubMedID 23421788

  View details for PubMedCentralID PMC3748416

• Polysubstance and alcohol dependence: unique abnormalities of magnetic resonance-derived brain metabolite levels. Drug and alcohol dependence Abé, C., Mon, A., Durazzo, T. C., Pennington, D. L., Schmidt, T. P., Meyerhoff, D. J. 2013; 130 (1-3): 30-7

  Abstract

  Although comorbid substance misuse is common in alcohol dependence, and polysubstance abusers (PSU) represent the largest group of individuals seeking treatment for drug abuse today, we know little about potential brain abnormalities in this population. Brain magnetic resonance spectroscopy studies of mono-substance use disorders (e.g., alcohol or cocaine) reveal abnormal levels of cortical metabolites (reflecting neuronal integrity, cell membrane turnover/synthesis, cellular bioenergetics, gliosis) and altered concentrations of glutamate and γ-aminobutyric acid (GABA). The concurrent misuse of several substances may have unique and different effects on brain biology and function compared to any mono-substance misuse.High field brain magnetic resonance spectroscopy at 4 T and neurocognitive testing were performed at one month of abstinence in 40 alcohol dependent individuals (ALC), 28 alcohol dependent PSU and 16 drug-free controls. Absolute metabolite concentrations were calculated in anterior cingulate (ACC), parieto-occipital (POC) and dorso-lateral prefrontal cortices (DLPFC).Compared to ALC, PSU demonstrated significant metabolic abnormalities in the DLPFC and strong trends to lower GABA in the ACC. Metabolite levels in ALC and light drinking controls were statistically equivalent. Within PSU, lower DLPFC GABA levels are related to greater cocaine consumption. Several cortical metabolite concentrations were associated with cognitive performance.While metabolite concentrations in ALC at one month of abstinence were largely normal, PSU showed persistent and functionally significant metabolic abnormalities, primarily in the DLPFC. Our results point to specific metabolic deficits as biomarkers in polysubstance misuse and as targets for pharmacological and behavioral PSU-specific treatment.

  View details for DOI 10.1016/j.drugalcdep.2012.10.004

  View details for PubMedID 23122599

  View details for PubMedCentralID PMC3624044

• Chronic cigarette smoking in alcohol dependence: associations with cortical thickness and N-acetylaspartate levels in the extended brain reward system. Addiction biology Durazzo, T. C., Mon, A., Gazdzinski, S., Meyerhoff, D. J. 2013; 18 (2): 379-91

  Abstract

  Chronic smoking in alcohol dependence is associated with abnormalities in brain morphology and metabolite levels in large lobar regions (e.g. frontal lobe). Here, we evaluated if these abnormalities are specifically apparent in several cortical and select subcortical components of the extended brain reward system (BRS), a network that is critically involved in the development and maintenance of all forms of addictive disorders. We studied 33 non-smoking and 43 smoking alcohol-dependent individuals (ALC) with 1 week of abstinence and 42 non-smoking Controls. At 1.5 Tesla, we obtained regional measures of cortical thickness and N-acetylaspartate (NAA; a surrogate marker of neuronal integrity) concentration in major components of the BRS as well as the corresponding measures throughout the cortex. Smoking ALC and non-smoking ALC demonstrated decreased thickness compared with Controls in the dorsolateral prefrontal cortex (DLPFC), insula, orbitofrontal cortex (OFC), the total BRS, total frontal cortex and global cortex. Smoking ALC had significantly decreased thickness compared to non-smoking ALC in the ACC, insula, the total BRS and total frontal cortex. Smoking ALC had also lower NAA concentrations than both non-smoking ALC and Controls in the DLPFC, insula, superior corona radiata and the total BRS. Alcohol consumption and common medical and psychiatric co-morbidities did not mediate differences between smoking and non-smoking ALC. This dual modality magnetic resonance (MR) study indicated that chronic smoking in ALC was associated with significant cortical thinning and NAA abnormalities in anterior brain regions that are implicated in the development and maintenance of addictive disorders.

  View details for DOI 10.1111/j.1369-1600.2011.00407.x

  View details for PubMedID 22070867

  View details for PubMedCentralID PMC4157587

• Neurometabolite concentration and clinical features of chronic alcohol use: a proton magnetic resonance spectroscopy study. Psychiatry research Yeo, R. A., Thoma, R. J., Gasparovic, C., Monnig, M., Harlaar, N., Calhoun, V. D., Kalyanam, R., Mayer, A. R., Durazzo, T. C., Hutchison, K. E. 2013; 211 (2): 141-7

  Abstract

  Chronic, heavy alcohol consumption may affect the concentration of neurometabolites assessed with proton magnetic resonance spectroscopy ((1)H-MRS). We investigated the largest sample reported to date (N=213) with the primary goal of determining how specific clinical features impact neurometabolite concentrations in an anterior cingulate gray matter voxel. This community-dwelling sample included both treatment-seeking and non-treatment-seeking individuals. A healthy control group (N=66) was matched for age and education. In multivariate analyses predicting neurometabolite concentrations, the heavy drinking group had greater concentrations overall. An age by group interaction was noted, as group difference across neurometabolites increased with age. More years drinking, but not more drinks per drinking day (DPDD), predicted greater concentrations of choline-containing compounds (Cho), creatine-phosphocreatine (Cre), glutamate-glutamine (Glx), and N-acetyl-aspartate (NAA). The effects of other clinical variables (depression, cigarette smoking, marijuana use) were negligible. After controlling for DPDD and years drinking, treatment-seeking status had no impact on neurometabolites. In the very oldest portion of the sample (mean age=50), however, a negative relationship was seen between NAA and years drinking. These results suggest that the nature of neurometabolite abnormalities in chronic heavy drinkers may vary as a function of duration of abuse.

  View details for DOI 10.1016/j.pscychresns.2012.05.005

  View details for PubMedID 23154093

  View details for PubMedCentralID PMC3570754

• Brain-derived neurotrophic factor genotype is associated with brain gray and white matter tissue volumes recovery in abstinent alcohol-dependent individuals. Genes, brain, and behavior Mon, A., Durazzo, T. C., Gazdzinski, S., Hutchison, K. E., Pennington, D., Meyerhoff, D. J. 2013; 12 (1): 98-107

  Abstract

  Neuroimaging studies have linked the methionine (Met) allele of the brain-derived neurotrophic factor (BDNF) gene to abnormal regional brain volumes in several psychiatric and neurodegenerative diseases. However, no neuroimaging studies assessed the effects of this allele on brain morphology in alcohol use disorders and its demonstrated change during abstinence from alcohol. Here we assessed the effects of the BDNF Val66Met (rs6265) polymorphism on regional brain tissue volumes and their recovery during short-term abstinence in treatment-seeking alcohol-dependent individuals. 3D T1 weighted magnetic resonance images from 62 individuals were acquired at 1.5 T at one week of abstinence from alcohol; 41 of the participants were rescanned at 5 weeks of abstinence. The images were segmented into gray matter (GM), white matter (WM) and cerebrospinal fluid and parcellated into regional volumes. The BDNF genotype was determined from blood samples using the TaqMan technique. Alcohol-dependent Val (Valine)/Met heterozygotes and Val homozygotes had similar regional brain volumes at either time point. However, Val homozygotes had significant GM volume increases, while Val/Met heterozygotes increased predominantly in WM volumes over the scan interval. Longitudinal increases in GM but not WM volumes were related to improvements in neurocognitive measures during abstinence. The findings suggest that functionally significant brain tissue volume recovery during abstinence from alcohol is influenced by BDNF genotype.

  View details for DOI 10.1111/j.1601-183X.2012.00854.x

  View details for PubMedID 22989210

  View details for PubMedCentralID PMC4140861

• Greater regional brain atrophy rate in healthy elderly subjects with a history of cigarette smoking. Alzheimer's & dementia : the journal of the Alzheimer's Association Durazzo, T. C., Insel, P. S., Weiner, M. W. 2012; 8 (6): 513-9

  Abstract

  Little is known about the effects of cigarette smoking on longitudinal brain morphological changes in the elderly. This study investigated the effects of a history of cigarette smoking on changes in regional brain volumes over 2 years in healthy, cognitively intact elderly individuals. We predicted that individuals with a history of cigarette smoking, compared with never smokers, demonstrate greater rate of atrophy over 2 years in regions that manifest morphological abnormalities in the early stages of Alzheimer's disease (AD), as well as in the extended brain reward/executive oversight system (BREOS), which is implicated in the development and maintenance of substance use disorders.Participants were healthy, cognitively normal elderly control subjects (75.9 ± 4.8 years of age) with any lifetime history of cigarette smoking (n = 68) or no history of smoking (n = 118). Data were obtained through the Alzheimer Disease Neuroimaging Initiative from 2005 to 2010. Participants completed four magnetic resonance scans over 2 years. A standardized protocol using high-resolution three-dimensional T1-weighted sequences at 1.5 T was used for structural imaging and regional brain volumetric analyses.Smokers demonstrated a significantly greater atrophy rate over 2 years than nonsmokers in multiple brain regions associated with the early stages of AD, as well as in the BREOS system. Groups did not differ on the rate of global cortical atrophy.A history of cigarette smoking in this healthy elderly cohort was associated with decreased structural integrity of multiple brain regions, which manifested as a greater rate of atrophy over 2 years in regions specifically affected by incipient AD as well as chronic substance abuse.

  View details for DOI 10.1016/j.jalz.2011.10.006

  View details for PubMedID 23102121

  View details for PubMedCentralID PMC3484322

• Associations of Cigarette Smoking and Polymorphisms in Brain-Derived Neurotrophic Factor and Catechol-O-Methyltransferase with Neurocognition in Alcohol Dependent Individuals during Early Abstinence. Frontiers in pharmacology Durazzo, T. C., Hutchison, K. E., Fryer, S. L., Mon, A., Meyerhoff, D. J. 2012; 3: 178

  Abstract

  Chronic cigarette smoking and polymorphisms in brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) are associated with neurocognition in normal controls and those with various neuropsychiatric conditions. The influence of BDNF and COMT on neurocognition in alcohol dependence is unclear. The primary goal of this report was to investigate the associations of single nucleotide polymorphisms (SNPs) in BDNF Val66Met (rs6265) and COMT Val158Met (rs4680) with neurocognition in a treatment-seeking alcohol dependent cohort and determine if neurocognitive differences between non-smokers and smokers previously observed in this cohort persist when controlled for these functional SNPs. Genotyping was conducted on 70 primarily male treatment-seeking alcohol dependent participants (ALC) who completed a comprehensive neuropsychological battery after 33 ± 9 days of monitored abstinence. After controlling for COMT and BDNF genotypes, smoking ALC performed significantly worse than non-smoking ALC on the domains of auditory-verbal and visuospatial learning and memory, cognitive efficiency, general intelligence, processing speed, and global neurocognition. In smoking ALC, greater number of years of smoking over lifetime was related to poorer performance on multiple domains after controlling for genotypes and alcohol consumption. In addition, COMT Met homozygotes were superior to Val homozygotes on measures of executive skills and showed trends for higher general intelligence and visuospatial skills, while COMT Val/Met heterozygotes showed significantly better general intelligence than Val homozygotes. COMT Val homozygotes performed better than heterozygotes on auditory-verbal memory. BDNF genotype was not related to any neurocognitive domain. The findings are consistent with studies in normal controls and neuropsychiatric cohorts that reported COMT Met carriers demonstrated better performance on measures of executive skills and general intelligence. Results also indicated that the poorer performance of smoking compared to non-smoking ALC across multiple neurocognitive domains was not mediated by COMT or BDNF genotype. Overall, the findings lend support to the expanding clinical movement to make smoking cessation programs available to smokers at the inception of treatment for alcohol/substance use disorders.

  View details for DOI 10.3389/fphar.2012.00178

  View details for PubMedID 23087644

  View details for PubMedCentralID PMC3469037

• Glutamate, GABA, and other cortical metabolite concentrations during early abstinence from alcohol and their associations with neurocognitive changes. Drug and alcohol dependence Mon, A., Durazzo, T. C., Meyerhoff, D. J. 2012; 125 (1-2): 27-36

  Abstract

  Little is known about the effects of alcohol dependence on cortical concentrations of glutamate (Glu) or gamma aminobutyric acid (GABA). We used proton magnetic resonance spectroscopy (MRS) to study cross-sectionally and longitudinally the concentrations of these in alcohol dependent individuals (ALC) during early abstinence from alcohol.Twenty ALC were studied at about one week of abstinence from alcohol (baseline) and 36 ALC at five weeks of abstinence and compared to 16 light/non-drinking controls (LD). Eleven ALC were studied twice during abstinence. Participants underwent clinical interviewing, blood work, neuropsychological testing, structural imaging and single-volume proton MRS at 4Tesla. Absolute concentrations of Glu, GABA and those of other (1)H MRS-detectable metabolites were measured in the anterior cingulate (ACC), parieto-occipital cortex (POC) and dorso-lateral prefrontal cortex (DLPFC). Relationships of metabolite levels to drinking severity and neurocognition were also assessed.ALC at baseline had lower concentrations of Glu, N-acetylaspartate (NAA), choline- (Cho) and creatine-containing metabolites (Cr) than LD in the ACC, but had normal GABA and myo-inositol (mI) levels. At five weeks of abstinence, metabolite concentrations were not significantly different between groups. Between one and five weeks of abstinence, Glu, NAA and Cho levels in the ACC increased significantly. Higher cortical mI concentrations in ALC related to worse neurocognitive outcome.These MRS data suggest compromised and regionally specific bioenergetics/metabolism in one-week-abstinent ALC that largely normalizes over four weeks of sustained abstinence. The correlation between mI levels and neurocognition affirms the functional relevance of this putative astrocyte marker.

  View details for DOI 10.1016/j.drugalcdep.2012.03.012

  View details for PubMedID 22503310

  View details for PubMedCentralID PMC3419314

• A comprehensive assessment of neurocognition in middle-aged chronic cigarette smokers. Drug and alcohol dependence Durazzo, T. C., Meyerhoff, D. J., Nixon, S. J. 2012; 122 (1-2): 105-11

  Abstract

  The majority of studies investigating the neurocognitive consequences of chronic smoking have been conducted with adults 60 years and older. Therefore, the scope of neurocognitive dysfunction associated with chronic cigarette smoking in middle age (i.e., 30-60 age range) has not been fully delineated.Twenty-seven (44±9 years of age; 4 females) non-smoking and 30 smoking (49±8 years of age; 4 females) participants completed a comprehensive neurocognitive battery and measures of fine motor dexterity and postural stability. All participants were free of biomedical or psychiatric conditions that may have influenced neurocognitive and motor function.Smokers performed significantly worse than non-smokers on the following domains: auditory-verbal and visuospatial learning, visuospatial memory, cognitive efficiency, executive skills, general intelligence, processing speed, fine motor dexterity and postural stability. The differences between smokers and non-smokers evidenced moderate to strong effect sizes and were not mediated by age, education, vocational level, estimated verbal intelligence or alcohol consumption. In smokers, a greater number of lifetime years of smoking was related to poorer performance on measures of cognitive efficiency, processing speed and visuospatial skills.Results from this middle-aged cohort replicated previous research and provides novel findings indicating that chronic smoking was associated with inferior performance on measures of general intelligence, visuospatial learning and memory and fine motor dexterity. Research that relates measures of neurobiological function/integrity to neurocognition is needed to better understand the mechanisms contributing to the poorer performance across multiple domains demonstrated by smokers.

  View details for DOI 10.1016/j.drugalcdep.2011.09.019

  View details for PubMedID 21992872

  View details for PubMedCentralID PMC3258460

• A mathematical formula for prediction of gray and white matter volume recovery in abstinent alcohol dependent individuals. Psychiatry research Mon, A., Delucchi, K., Durazzo, T. C., Gazdzinski, S., Meyerhoff, D. J. 2011; 194 (2): 198-204

  Abstract

  We propose a mathematical formula that predicts the trajectory of the recovery from lobar gray and white matter volume deficits in individuals with sustained abstinence from alcohol. The formula was validated by using MRI-measured volumetric data from 16 alcohol dependent individuals who had brain scans at three time points during abstinence from alcohol. Using the measured volumetric data of each individual from the first two time points, we estimated the individual's gray and white matter volume of the frontal, parietal and temporal lobes for the third time point using the formula. Similarly, using the measured data for the second and third time points, we estimated the first time point data for each individual. The data predicted from the formula were very similar to the experimentally measured data for all lobes and for both gray and white matter. The intra-class correlation coefficients between the measured data and the data estimated from the formula were >0.95 for almost all the tissues. The formula may also be applicable in other neuroimaging studies of tissue volume changes such as white matter myelination during brain development and white matter demyelination or brain volume loss in neurodegenerative diseases, such as Alzheimer's disease.

  View details for DOI 10.1016/j.pscychresns.2011.05.003

  View details for PubMedID 21903361

  View details for PubMedCentralID PMC3196029

• Brain morphology at entry into treatment for alcohol dependence is related to relapse propensity. Biological psychiatry Cardenas, V. A., Durazzo, T. C., Gazdzinski, S., Mon, A., Studholme, C., Meyerhoff, D. J. 2011; 70 (6): 561-7

  Abstract

  We examined whether any differences in brain volumes at entry into alcohol dependence treatment differentiate subsequent Abstainers from Relapsers.Individuals in alcohol dependence treatment (n = 75) underwent magnetic resonance imaging approximately 6 ± 4 days after their last alcoholic drink, and 40 age-matched nonsmoking light drinkers (LD) were studied as control subjects. At follow-up 7.8 ± 2.6 months later, 23 alcoholics (31%) had abstained from drinking and 52 (69%) had relapsed. Deformation morphometry compared Relapsers, Abstainers, and LD.Compared with LD, future Abstainers had smaller brain tissue volumes in the left amygdala, hippocampal head, and entorhinal cortex and bilaterally in the thalamus and adjacent subcortical white matter (WM) and had larger volume in the left lateral orbitofrontal region. Compared with LD, future Relapsers had smaller brain tissue volumes in the right middle temporal, occipital, and superior frontal WM. Compared with future Abstainers, future Relapsers had smaller tissue volumes primarily in bilateral orbitofrontal cortex and surrounding WM. Results were virtually unaffected after controlling for common comorbidities.At entry into alcohol dependence treatment, the brain structure of future Relapsers differs from that of future Abstainers. Future Relapsers have smaller brain volumes in regions of the mesocorticolimbic reward system that are critically involved in impulse control, emotional regulation, craving, and evaluation and anticipation of stimulus salience and hedonics. Structural abnormalities of this circuitry might confer greater risk for resumption of hazardous drinking after treatment and might contribute to the definition of a neurobiological relapse risk profile in alcohol dependence.

  View details for DOI 10.1016/j.biopsych.2011.04.003

  View details for PubMedID 21601177

  View details for PubMedCentralID PMC3162109

• Cortical thickness, surface area, and volume of the brain reward system in alcohol dependence: relationships to relapse and extended abstinence. Alcoholism, clinical and experimental research Durazzo, T. C., Tosun, D., Buckley, S., Gazdzinski, S., Mon, A., Fryer, S. L., Meyerhoff, D. J. 2011; 35 (6): 1187-200

  Abstract

  At least 60% of those treated for an alcohol use disorder will relapse. Empirical study of the integrity of the brain reward system (BRS) is critical to understanding the mechanisms of relapse as this collection of circuits is implicated in the development and maintenance of all forms of addictive disorders. This study compared thickness, surface area, and volume in neocortical components of the BRS among nonsmoking light-drinking controls (controls), individuals who remained abstinent and those who relapsed after treatment.Seventy-five treatment-seeking alcohol-dependent individuals (abstinent for 7±3 days) and 43 controls completed 1.5T proton magnetic resonance imaging studies. Parcellated morphological data were obtained for following bilateral components of the BRS: rostral and caudal anterior cingulate cortex, insula, medial and lateral orbitofrontal cortex (OFC), rostral and caudal middle and superior frontal gyri, amygdala and hippocampus as well as for 26 other bilateral neocortical regions. Alcohol-dependent participants were followed over 12-months after baseline study and were classified as abstainers (no alcohol consumption; n=24) and relapsers (any alcohol consumption; n=51) at follow-up.Relapsers and abstainers demonstrated lower cortical thickness in the vast majority of BRS regions as well as lower global thickness compared to controls. Relapsers had lower total BRS surface area than both controls and abstainers, but abstainers were not significantly different from controls on any surface area measure. Relapsers demonstrated lower volumes than controls in the majority of regions, while abstainers showed lower volumes than controls in the superior frontal gyrus, insula, amygdala, and hippocampus, bilaterally. Relapsers exhibited smaller volumes than abstainers in the right rostral middle and caudal middle frontal gyri and the lateral OFC, bilaterally. In relapsers, lower baseline volumes and surface areas in multiple regions were associated with a greater magnitude of post-treatment alcohol consumption.Results suggest relapsers demonstrated morphological abnormalities in regions involved in the "top down" regulation/modulation of internal drive states, emotions, reward processing, and behavior, which may impart increased risk for the relapse/remit cycle that afflicts many with an alcohol use disorder. Results also highlight the importance of examining both cortical thickness and surface area to better understand the nature of regional volume loss frequently observed in alcohol use disorders. Results from this report are consistent with previous research implicating plastic neurobiological changes in the BRS in the maintenance of addictive disorders.

  View details for DOI 10.1111/j.1530-0277.2011.01452.x

  View details for PubMedID 21410483

  View details for PubMedCentralID PMC3097308

• Body mass index is associated with brain metabolite levels in alcohol dependence--a multimodal magnetic resonance study. Alcoholism, clinical and experimental research Gazdzinski, S., Durazzo, T. C., Mon, A., Meyerhoff, D. J. 2010; 34 (12): 2089-96

  Abstract

  Recent studies demonstrated that alcohol dependence and excessive alcohol consumption are associated with increased rates of obesity. In healthy light-drinkers, we and others have observed associations between elevated body mass index (BMI) and reductions in brain volumes, lower concentrations of N-acetyl-aspartate (NAA, marker of neuronal viability) and choline-containing compounds (Cho, involved in membrane turnover), and lower glucose utilization, particularly in frontal lobe-a brain region that is particularly vulnerable to the effects of alcohol dependence. Here, we evaluated whether BMI in alcohol-dependent individuals was independently associated with regional measures of brain structure, metabolite concentrations, and neocortical blood flow.As part of a study on the effects of alcohol dependence on neurobiology, we analyzed retrospectively data from 54 alcohol-dependent males, abstinent from alcohol for about 1 month and with BMI between 20 and 37 kg/m(2) by structural MRI, perfusion MRI (blood flow), and proton magnetic resonance spectroscopic imaging.After correction for age, smoking status, and various measures of alcohol consumption, higher BMI was associated with lower concentrations of NAA, Cho, creatine and phosphocreatine (Cr, involved in high energy metabolism), and myo-inositol (m-Ino, a putative marker of astrocytes) primarily in the frontal lobe, in subcortical nuclei, and cerebellar vermis (p < 0.004). Regional brain volumes and perfusion were not significantly related to BMI. Furthermore, comorbid conditions, clinical laboratory measures, and nutritional assessments were not significant predictors of these MR-based measures.The results suggest that BMI, independent of age, alcohol consumption, and common comorbidities, is related to regional NAA, Cho, Cr, and m-Ino concentrations in this cohort of alcohol-dependent individuals. Additionally, as some common comorbid conditions in alcohol dependence such as cigarette smoking are associated with BMI, their associations with regional brain metabolite levels in alcohol-dependent individuals may also be influenced by BMI.

  View details for DOI 10.1111/j.1530-0277.2010.01305.x

  View details for PubMedID 21087290

  View details for PubMedCentralID PMC3058677

• Measures of learning, memory and processing speed accurately predict smoking status in short-term abstinent treatment-seeking alcohol-dependent individuals. Alcohol and alcoholism (Oxford, Oxfordshire) Durazzo, T. C., Fryer, S. L., Rothlind, J. C., Vertinski, M., Gazdzinski, S., Mon, A., Meyerhoff, D. J. 2010; 45 (6): 507-13

  Abstract

  Chronic cigarette smoking appears to adversely affect several domains of neurocognition in those with alcohol use disorders (AUDs). The primary goal of this study was to identify which measures commonly used to assess neurocognition in AUDs accurately predict smoking status of individuals seeking treatment of alcohol dependence.Treatment-seeking alcohol-dependent participants (ALC; n = 92) completed a comprehensive neuropsychological battery after 33 ± 9 days of abstinence. Measures significantly different between smoking and non-smoking ALC were entered as predictors in binary logistic regression and discriminant analysis models, with smoking status as the dependent variable.Smoking ALC performed significantly worse than non-smoking ALC on measures assessing processing speed, auditory-verbal and visuospatial learning and memory. Using these measures as predictors, a logistic regression model accurately classified 91% of smokers and non-smokers into their respective groups overall and accounted for 68% of the variance in smoking status. The discriminant analysis confirmed the findings from the logistic regression. In smoking ALC, smoking chronicity was inversely related to performance on multiple measures after controlling for lifetime alcohol consumption.Measures of processing speed, learning and memory robustly predicted the smoking status of ALC with high sensitivity and specificity during early abstinence. The results identified specific measures within a comprehensive neurocognitive battery that discriminated smoking and non-smoking alcohol-dependent individuals with a high sensitivity and specificity. The association of greater smoking chronicity and poorer performance on multiple measures after control for alcohol consumption suggests that chronic smoking adds an additional burden to neurocognitive function in those with alcohol dependence.

  View details for DOI 10.1093/alcalc/agq057

  View details for PubMedID 20923865

  View details for PubMedCentralID PMC2981519

• Chronic cigarette smoking: implications for neurocognition and brain neurobiology. International journal of environmental research and public health Durazzo, T. C., Meyerhoff, D. J., Nixon, S. J. 2010; 7 (10): 3760-91

  Abstract

  Compared to the substantial volume of research on the general health consequences associated with chronic smoking, little research has been specifically devoted to the investigation of its effects on human neurobiology and neurocognition. This review summarizes the peer-reviewed literature on the neurocognitive and neurobiological implications of chronic cigarette smoking in cohorts that were not seeking treatment for substance use or psychiatric disorders. Studies that specifically assessed the neurocognitive or neurobiological (with emphasis on computed tomography and magnetic resonance-based neuroimaging studies) consequences of chronic smoking are highlighted. Chronic cigarette smoking appears to be associated with deficiencies in executive functions, cognitive flexibility, general intellectual abilities, learning and/or memory processing speed, and working memory. Chronic smoking is related to global brain atrophy and to structural and biochemical abnormalities in anterior frontal regions, subcortical nuclei and commissural white matter. Chronic smoking may also be associated with an increased risk for various forms of neurodegenerative diseases. The existing literature is limited by inconsistent accounting for potentially confounding biomedical and psychiatric conditions, focus on cross-sectional studies with middle aged and older adults and the absence of studies concurrently assessing neurocognitive, neurobiological and genetic factors in the same cohort. Consequently, the mechanisms promoting the neurocognitive and neurobiological abnormalities reported in chronic smokers are unclear. Longitudinal studies are needed to determine if the smoking-related neurobiological and neurocognitive abnormalities increase over time and/or show recovery with sustained smoking cessation.

  View details for DOI 10.3390/ijerph7103760

  View details for PubMedID 21139859

  View details for PubMedCentralID PMC2996190

• Cortical perfusion in alcohol-dependent individuals during short-term abstinence: relationships to resumption of hazardous drinking after treatment. Alcohol (Fayetteville, N.Y.) Durazzo, T. C., Gazdzinski, S., Mon, A., Meyerhoff, D. J. 2010; 44 (3): 201-10

  Abstract

  Relapse to hazardous levels of alcohol consumption after treatment for alcohol use disorders is common. Investigation of the neurobiological correlates of resumption of hazardous drinking is necessary to clarify the mechanisms contributing to relapse. Fifty-seven treatment-seeking alcohol-dependent participants (ALC) completed arterial spin labeling perfusion MRI of the frontal and parietal gray matter (GM) at 7+/-3 days of abstinence (baseline). ALC participants were restudied after 35+/-11 days of abstinence (assessment point 2: AP2). Twenty-eight nonsmoking, light-drinking control participants (nsLD) from the community were studied with perfusion MRI. ALC participants were followed over 12 months after baseline study and were classified as abstainers (no alcohol consumption; n=19) and resumers (any alcohol consumption; n=38) at follow-up. Cross-sectional and longitudinal perfusion was compared in abstainers, resumers, and nsLD. At baseline, resumers demonstrated significantly lower frontal and parietal GM perfusion than nsLD and abstainers. Abstainers and nsLD were not different on frontal or parietal GM perfusion. No significant longitudinal perfusion changes were observed in abstainers and resumers. At AP2, resumers showed significantly lower frontal GM perfusion than nsLD and abstainers, whereas no group differences were observed for parietal GM. Abstainers and nsLD were not different on frontal GM perfusion. The significantly decreased frontal GM perfusion in resumers compared with both abstainers and nsLD across the assessment interval suggests premorbid and/or acquired neurobiological abnormalities of the frontal GM in resumers.

  View details for DOI 10.1016/j.alcohol.2010.03.003

  View details for PubMedID 20682188

  View details for PubMedCentralID PMC3038637

• Cerebral white matter recovery in abstinent alcoholics--a multimodality magnetic resonance study. Brain : a journal of neurology Gazdzinski, S., Durazzo, T. C., Mon, A., Yeh, P. H., Meyerhoff, D. J. 2010; 133 (Pt 4): 1043-53

  Abstract

  Most previous neuroimaging studies of alcohol-induced brain injury and recovery thereof during abstinence from alcohol used a single imaging modality. They have demonstrated widespread microstructural, macrostructural or metabolite abnormalities that were partially reversible with abstinence, with the cigarette smoking potentially modulating these processes. The goals of this study were to evaluate white matter injury and recovery thereof, simultaneously with diffusion tensor imaging, magnetic resonance imaging and spectroscopy in the same cohort; and to evaluate the relationships between outcome measures of similar regions. We scanned 16 non-smoking and 20 smoking alcohol-dependent individuals at 1 week of abstinence from alcohol and 22 non-smoking light drinkers using a 1.5 T magnetic resonance scanner. Ten non-smoking alcohol-dependent individuals and 11 smoking alcohol-dependent individuals were re-scanned at 1 month of abstinence. All regional diffusion tensor imaging, magnetic resonance imaging and spectroscopic outcome measures were calculated over comparable volumes of frontal, temporal, parietal and occipital white matter. At 1 week of abstinence and relative to non-smoking light drinkers, non-smoking alcohol-dependent individuals had higher mean diffusivity in frontal, temporal and parietal white matter (all P<0.008), whereas smoking alcohol-dependent individuals had elevated mean diffusivity only in frontal white matter (P=0.03). Smoking alcohol-dependent individuals demonstrated lower concentrations of N-acetyl-aspartate (a marker of neuronal viability) in frontal white matter (P=0.03), whereas non-smoking alcohol-dependent individuals had lower N-acetyl-aspartate in parietal white matter (P=0.05). These abnormalities were not accompanied by detectable white matter atrophy. However, the patterns of white matter recovery were different between non-smoking alcohol-dependent individuals and smoking alcohol-dependent individuals. In non-smoking alcohol-dependent individuals, the increase in fractional anisotropy of temporal white matter (P=0.003) was accompanied by a pattern of decreases mean diffusivity in all regions over 1 month of abstinence; no corresponding changes were observed in smoking alcohol-dependent individuals. In contrast, a pattern of white matter volume increase in frontal and temporal lobes was apparent in smoking alcohol-dependent individuals but not in non-smoking alcohol-dependent individuals. These results were not accompanied by significant changes in metabolite concentrations. Finally, there were no consistent patterns of association between measures obtained with different imaging modalities, either cross-sectionally or longitudinally. These data demonstrate significant white matter improvements with abstinence from alcohol, reflected either as microstructural recovery or volumetric increases that depend on the smoking status of the participants. We believe our results to be important, as they demonstrate that use of a single imaging modality provides an incomplete picture of neurobiological processes associated with alcohol-induced brain injury and recovery thereof that may even lead to improper interpretation of results.

  View details for DOI 10.1093/brain/awp343

  View details for PubMedID 20133395

  View details for PubMedCentralID PMC2850577

• BMI and neuronal integrity in healthy, cognitively normal elderly: a proton magnetic resonance spectroscopy study. Obesity (Silver Spring, Md.) Gazdzinski, S., Millin, R., Kaiser, L. G., Durazzo, T. C., Mueller, S. G., Weiner, M. W., Meyerhoff, D. J. 2010; 18 (4): 743-8

  Abstract

  Recent studies associated excess body weight with brain structural alterations, poorer cognitive function, and lower prefrontal glucose metabolism. We found that higher BMI was related to lower concentrations of N-acetyl-aspartate (NAA, a marker of neuronal integrity) in a healthy middle-aged cohort, especially in frontal lobe. Here, we evaluated whether NAA was also associated with BMI in a healthy elderly cohort. We used 4 Tesla proton magnetic resonance spectroscopy ((1)H MRS) data from 23 healthy, cognitively normal elderly participants (69.4 +/- 6.9 years; 12 females) and measured concentrations of NAA, glutamate (Glu, involved in cellular metabolism), choline-containing compounds (Cho, involved in membrane metabolism), and creatine (Cr, involved in high-energy metabolism) in anterior (ACC) and posterior cingulate cortices (PCC). After adjustment for age, greater BMI was related to lower NAA/Cr and NAA/Cho ratios (beta < -0.56, P < 0.008) and lower Glu/Cr and Glu/Cho ratios (beta < -0.46, P < 0.02) in ACC. These associations were not significant in PCC (beta > -0.36, P > 0.09). The existence of an association between NAA and BMI in ACC but not in PCC is consistent with our previous study in healthy middle-aged individuals and with reports of lower frontal glucose metabolism in young healthy individuals with elevated BMI. Taken together, these results provide evidence that elevated BMI is associated with neuronal abnormalities mostly in frontal brain regions that subserve higher cognitive functions and impulse control. Future studies need to evaluate whether these metabolite abnormalities are involved in the development and maintenance of weight problems.

  View details for DOI 10.1038/oby.2009.325

  View details for PubMedID 19816410

  View details for PubMedCentralID PMC2847061

• Metabolite levels in the brain reward pathway discriminate those who remain abstinent from those who resume hazardous alcohol consumption after treatment for alcohol dependence. Journal of studies on alcohol and drugs Durazzo, T. C., Pathak, V., Gazdzinski, S., Mon, A., Meyerhoff, D. J. 2010; 71 (2): 278-89

  Abstract

  This study compared baseline metabolite levels in components of the brain reward system among individuals who remained abstinent and those who resumed hazardous alcohol consumption after treatment for alcohol dependence.Fifty-one treatment-seeking alcohol-dependent individuals (abstinent for approximately 7 days [SD = 3]) and 26 light-drinking nonsmoking controls completed 1.5-T proton magnetic resonance spectroscopic imaging, yielding regional concentrations of N-acetylaspartate, choline-containing compounds, creatine-containing compounds, and myoinositol. Metabolite levels were obtained in the following component of the brain reward system: dorsolateral prefrontal cortex, anterior cingulate cortex, insula, superior corona radiata, and cerebellar vermis. Alcohol-dependent participants were followed over a 12-month period after baseline study (i.e., at 7 days of abstinence [SD = 3]) and were classified as abstainers (no alcohol consumption; n = 18) and resumers (any alcohol consumption; n = 33) at follow-up. Baseline metabolite levels in abstainers and resumers and light-drinking nonsmoking controls were compared in the above regions of interest.Resumers demonstrated significantly lower baseline N-acetylaspartate concentrations than light-drinking nonsmoking controls and abstainers in all regions of interest. Resumers also exhibited lower creatine-containing-compound concentrations than abstainers in the dorsolateral prefrontal cortex, superior corona radiata, and cerebellar vermis. Abstainers did not differ from light-drinking nonsmoking controls on baseline metabolite concentrations in any region of interest.The significantly decreased N-acetylaspartate and creatine-containing-compound concentrations in resumers suggest compromised neuronal integrity and abnormalities in cellular bioenergetics in major neocortical components and white-matter interconnectivity of the brain reward pathway. The lack of metabolite differences between abstainers and light-drinking nonsmoking controls suggests premorbid factors potentially contributed to the baseline brain metabolite abnormalities observed in resumers.

  View details for DOI 10.15288/jsad.2010.71.278

  View details for PubMedID 20230726

  View details for PubMedCentralID PMC2841738

• The impact of chronic cigarette smoking on recovery from cortical gray matter perfusion deficits in alcohol dependence: longitudinal arterial spin labeling MRI. Alcoholism, clinical and experimental research Mon, A., Durazzo, T. C., Gazdzinski, S., Meyerhoff, D. J. 2009; 33 (8): 1314-21

  Abstract

  Neuroimaging studies reported cerebral perfusion abnormalities in individuals with alcohol use disorders. However, no longitudinal magnetic resonance imaging (MRI) studies of cerebral perfusion changes during abstinence from alcohol have been reported.Arterial spin labeling MRI was used to evaluate cortical gray matter perfusion changes in short-term abstinent alcohol dependent individuals in treatment and to assess the impact of chronic cigarette smoking on perfusion changes during abstinence. Seventy-six patients were scanned at least once. Data from 19 non-smoking (17 males, 2 females) and 22 smoking (21 males, 1 female) patients scanned at 1 and 5 weeks of abstinence were used to assess perfusion changes over time. Twenty-eight age-equated healthy controls (25 males, 3 females) were scanned for cross-sectional comparison, 13 of them were scanned twice. Given the age range of the cohort (28 to 68 years), age was used as a covariate in the analyses. Mean perfusion was measured in voxels of at least 80% gray matter in the frontal and parietal lobes and related to neurocognitive and substance use measures.At 1 week of abstinence, frontal and parietal gray matter perfusion in smoking alcoholics was not significantly different from that in non-smoking alcoholics, but each group's perfusion values were significantly lower than in controls. After 5 weeks of abstinence, perfusion of frontal and parietal gray matter in non-smoking alcoholics was significantly higher than that at baseline. However, in smoking alcoholics, perfusion was not significantly different between the time-points in either region. The total number of cigarettes smoked per day was negatively correlated with frontal gray matter perfusion measured at 5 weeks of abstinence. Lobar perfusion measures did not correlate significantly with drinking severity or cognitive domain measures at either time-point.Although cerebral perfusion in alcohol dependent individuals shows improvement with abstinence from alcohol, cigarette smoking appears to hinder perfusion improvement.

  View details for DOI 10.1111/j.1530-0277.2009.00960.x

  View details for PubMedID 19413652

  View details for PubMedCentralID PMC2975051

• Tract-Based Spatial Statistics (TBSS) of diffusion tensor imaging data in alcohol dependence: abnormalities of the motivational neurocircuitry. Psychiatry research Yeh, P. H., Simpson, K., Durazzo, T. C., Gazdzinski, S., Meyerhoff, D. J. 2009; 173 (1): 22-30

  Abstract

  Previous diffusion tensor imaging (DTI) studies indicated microstructural disruption of white matter in alcohol dependence. To investigate the microstructure of primary neurocircuitry involved in alcohol use disorders, the present study used Tract-Based Spatial Statistics (TBSS) of DTI measures as well as probabilistic tractography. Eleven recovering alcoholics in their first week of abstinence from alcohol were compared with 10 light-drinking controls; diffusion measures were correlated with measures of neurocognition and drinking severity. Regions characterized by low fractional anisotropy and high mean diffusivity included cortico-striatal fibers and those in frontal white matter and limbic pathways. Greater diffusion abnormalities in sections of commissural fibers (inter-hemispheric connections) were associated with greater drinking severity, and lower fractional anisotropy measures in frontal and limbic fiber tracts correlated with lower visuospatial memory performance. These study findings provide direct evidence of compromised integrity of the motivational brain circuitry in alcohol use disorders. These abnormalities in fiber connections could be partially responsible for deficiencies in executive functions, behavioral regulation, and impulse control commonly described in alcohol dependence.

  View details for DOI 10.1016/j.pscychresns.2008.07.012

  View details for PubMedID 19442492

  View details for PubMedCentralID PMC2774502

• MRSI and DTI: a multimodal approach for improved detection of white matter abnormalities in alcohol and nicotine dependence. NMR in biomedicine Wang, J. J., Durazzo, T. C., Gazdzinski, S., Yeh, P. H., Mon, A., Meyerhoff, D. J. 2009; 22 (5): 516-22

  Abstract

  Our previous proton magnetic resonance spectroscopic imaging ((1)H MRSI) studies showed that the frontal lobe white matter (WM) in smoking recovering alcoholics (sRA) had lower concentrations of N-acetylaspartate (NAA), a marker for neuron viability, compared to both nonsmoking recovering alcoholics (nsRA) and a control group of nonsmoking light drinkers (nsLD). Using diffusion tensor imaging (DTI) in a similar population, we found lower fractional anistropy (FA), a microstructural measure of WM fiber integrity, in regions of specific fiber bundles within frontal WM of recovering alcoholics compared to light drinkers. In this study, we hypothesized that in these regions of lower FA, NAA concentrations in the alcoholic groups are lower than in non-alcoholic controls. We hypothesized further that sRA have lower regional NAA concentrations than nsRA. We retrospectively analyzed existing (1)H MRSI data by quantitating metabolite concentrations from voxels that corresponded to previously identified WM regions of lower FA, and from a control region of normal FA in alcoholics. We found significant NAA concentration differences between groups in regions of abnormal FA. In particular, sRA had significantly lower NAA concentration than nsLD, but in no region was NAA significantly lower in nsRA than nsLD. Furthermore, no NAA group differences were detected in a frontal WM region of normal FA. These results indicate regionally localized NAA loss within the frontal WM, and specifically NAA loss in regions of low FA. Compared to our previous lobar analyses, DTI-guided MRSI analysis allows the selective evaluation of small WM regions with microstructural injury, thereby increasing statistical power to detect relevant pathology and group differences. DTI-guided MRSI analyses promise to contribute to a better understanding of brain injury in alcohol and nicotine dependence and, by extension, perhaps in other neurodegenerative diseases as well.

  View details for DOI 10.1002/nbm.1363

  View details for PubMedID 19156697

  View details for PubMedCentralID PMC4156512

• Combined neuroimaging, neurocognitive and psychiatric factors to predict alcohol consumption following treatment for alcohol dependence. Alcohol and alcoholism (Oxford, Oxfordshire) Durazzo, T. C., Gazdzinski, S., Yeh, P. H., Meyerhoff, D. J. 2008; 43 (6): 683-91

  Abstract

  Resumption of hazardous drinking after treatment is common in alcohol use disorders (AUD). This study examined the ability of multimodality magnetic resonance, neurocognitive, psychiatric and demographic, to predict alcohol consumption after treatment for AUD.Seventy treatment-seeking participants completed 1.5T magnetic resonance studies, yielding regional gray matter (GM) and white matter (WM) surrogate markers of neuronal integrity (N-acetylaspartate: NAA) and cell membrane turnover/synthesis (choline: Cho), assessment of major psychiatric disorders and comprehensive neurocognitive assessment after approximately 1 month of abstinence. Participants were followed up 6-12 months after treatment and classified as Abstainers (no alcohol consumption; n=26) and Resumers (any alcohol consumption; n=44). Abstainers and Resumers were contrasted on various outcome measures, and those that significantly differed between groups were entered as factors in a logistical regression model to predict drinking status at follow-up.The following variables were independent predictors of resumption of drinking: temporal GM NAA, frontal WM NAA, frontal GM Cho, processing speed and comorbid unipolar mood disorder. With each standard deviation unit decrease in temporal GM NAA, frontal WM NAA, frontal GM Cho and processing speed, the odds of resumption of drinking were increased 3.1, 3.3, 6.4 and 14.2 times, respectively. Diagnosis of a unipolar mood disorder was associated with 14.5-fold increased odds of resumed drinking.The findings suggest that Resumers, relative to Abstainers, demonstrated greater abnormalities in anterior frontal-subcortical circuits involved in mood and behavioral regulation, and development and maintenance of alcohol use disorders, The magnetic resonance-derived variables used in this study may provide additional information regarding the prediction and neurobiological correlates of resumption of hazardous drinking.

  View details for DOI 10.1093/alcalc/agn078

  View details for PubMedID 18818189

  View details for PubMedCentralID PMC2720770

• The relationships of sociodemographic factors, medical, psychiatric, and substance-misuse co-morbidities to neurocognition in short-term abstinent alcohol-dependent individuals. Alcohol (Fayetteville, N.Y.) Durazzo, T. C., Rothlind, J. C., Gazdzinski, S., Meyerhoff, D. J. 2008; 42 (6): 439-49

  Abstract

  Co-morbidities that commonly accompany those afflicted with an alcohol use disorder (AUD) may promote variability in the pattern and magnitude of neurocognitive abnormalities demonstrated. The goal of this study was to investigate the influence of several common co-morbid medical conditions (primarily hypertension and hepatitis C), psychiatric (primarily unipolar mood and anxiety disorders), and substance use (primarily psychostimulant and cannabis) disorders, and chronic cigarette smoking on the neurocognitive functioning in short-term abstinent, treatment-seeking individuals with AUD. Seventy-five alcohol-dependent participants (ALC; 51+/-9 years of age; three females) completed comprehensive neurocognitive testing after approximately 1 month of abstinence. Multivariate multiple linear regression evaluated the relationships among neurocognitive variables and medical conditions, psychiatric, and substance-use disorders, controlling for sociodemographic factors. Sixty-four percent of ALC had at least one medical, psychiatric, or substance-abuse co-morbidity (excluding smoking). Smoking status (smoker or nonsmoker) and age were significant independent predictors of cognitive efficiency, general intelligence, postural stability, processing speed, and visuospatial memory after age-normed adjustment and control for estimated pre-morbid verbal intelligence, education, alcohol consumption, and medical, psychiatric, and substance-misuse co-morbidities. Results indicated that chronic smoking accounted for a significant portion of the variance in the neurocognitive performance of this middle-aged AUD cohort. The age-related findings for ALC suggest that alcohol dependence, per se, was associated with diminished neurocognitive functioning with increasing age. The study of participants who demonstrate common co-morbidities observed in AUD is necessary to fully understand how AUD, as a clinical syndrome, affects neurocognition, brain neurobiology, and their changes with extended abstinence.

  View details for DOI 10.1016/j.alcohol.2008.06.001

  View details for PubMedID 18760713

  View details for PubMedCentralID PMC2597590

• Proton magnetic resonance spectroscopy in alcohol use disorders: a potential new endophenotype? Alcoholism, clinical and experimental research Meyerhoff, D. J., Durazzo, T. C. 2008; 32 (7): 1146-58

  Abstract

  Current effort is directed at defining new classification schemes for alcohol use disorders (AUD) based on genetic/biological, physiological, and behavioral endophenotypes.We describe briefly findings of in vivo brain proton magnetic resonance spectroscopy ((1)H MRS) studies in AUD and propose that they be further explored and expanded regarding their value as a potential endophenotype for AUD.In vivo (1)H MRS, as part of the emerging field of "imaging genomics," may provide readily accessible, objective, functionally significant and region-specific neurobiological measures that successfully link genotypes to neurocognition and to psychiatric symptomatology in relatively small patient cohorts. We discuss several functional gene variants that may affect specific (1)H MRS-detectable metabolites and provide recent data from our own work that supports the view of genetic effects on metabolite measures.MRS-genetics research will not only offer clues to the functional significance and downstream effects of genetic differences in AUD, but, via monitoring and/or predicting the efficacy of pharmacological and behavioral interventions as a function of genotype, has the potential to influence future clinical management of AUD.

  View details for DOI 10.1111/j.1530-0277.2008.00695.x

  View details for PubMedID 18540913

  View details for PubMedCentralID PMC2547131

• Are treated alcoholics representative of the entire population with alcohol use disorders? A magnetic resonance study of brain injury. Alcohol (Fayetteville, N.Y.) Gazdzinski, S., Durazzo, T. C., Weiner, M. W., Meyerhoff, D. J. 2008; 42 (2): 67-76

  Abstract

  Almost all we know about neurobiological brain injury in alcohol use disorders has been derived from convenience samples of treated alcoholics. Recent research has demonstrated more comorbid conditions, poorer psychosocial functioning, and higher dependence levels in treated alcoholics than in their treatment-naive counterparts. Thus, it is not clear whether neuroimaging results from convenience samples of treated alcoholics can be generalized to the entire population with alcohol use disorders. We compared 35 treated alcoholics at 1 week of abstinence (ALC) and 32 treatment-naive heavy drinkers (HD) on regional brain volumes and metabolite concentrations obtained by in vivo magnetic resonance at 1.5 Tesla to evaluate for potential group differences. Then, we evaluated whether comorbid cigarette smoking and common demographic and clinical variables mediated any existing neurobiological group differences. ALC demonstrated smaller lobar gray matter volumes and thalami than HD, exacerbated by chronic smoking. Furthermore, concentrations of N-acetyl-aspartate (an accepted marker of neuronal viability), choline-containing metabolites (involved in membrane turnover), and myo-inositol (a putative marker of glial cells and osmolyte) were lower in multiple brain regions of ALC compared to HD. The lower N-acetyl-aspartate concentrations in white matter of ALC versus HD were explained by average number of drinks per month over the year preceding study. However, the other group differences were not explained by common drinking, demographic, and clinical variables (used as covariates at the same time) or by excluding participants with comorbid mood disorders. Taken together, this suggests that the degree of brain atrophy, as well as neuronal and membrane injury in clinical samples of alcoholics cannot be generalized to the much larger population with alcohol use disorders that does not seek treatment.

  View details for DOI 10.1016/j.alcohol.2008.01.002

  View details for PubMedID 18358984

  View details for PubMedCentralID PMC2426953

• Chronic cigarette smoking modulates injury and short-term recovery of the medial temporal lobe in alcoholics. Psychiatry research Gazdzinski, S., Durazzo, T. C., Yeh, P. H., Hardin, D., Banys, P., Meyerhoff, D. J. 2008; 162 (2): 133-45

  Abstract

  Memory function is largely mediated by the medial temporal lobe (MTL), and its compromise has been observed in alcohol dependence and chronic cigarette smoking. The effects of heavy alcohol consumption and chronic smoking on hippocampal volumes and MTL metabolites and their recovery during abstinence from alcohol have not been assessed. Male alcoholics in treatment (ALC) [13 smokers (sALC) and 11 non-smokers (nsALC)] underwent quantitative magnetic resonance imaging and short-echo proton magnetic resonance spectroscopic imaging at 1 week and 1 month of sobriety. Outcome measures were compared with 14 age-matched, non-smoking light-drinkers and were related to visuospatial learning and memory. Over 1 month of abstinence, N-acetyl-aspartate, a neuronal marker, and membrane-associated choline-containing metabolites normalized in the MTL of nsALC subjects, but remained low in the MTL of sALC subjects. Metabolite concentration changes in both groups were associated with improvements in visuospatial memory. Hippocampal volumes increased in both groups during abstinence, but increasing volumes correlated with visuospatial memory improvements only in nsALC subjects. In summary, chronic cigarette smoking in alcohol-dependent men appears to have adverse effects on MTL metabolite recovery during short-term sobriety. These data may also have implications for other conditions with established MTL involvement and significant smoking co-morbidity, such as schizophrenia-spectrum and mood disorders.

  View details for DOI 10.1016/j.pscychresns.2007.04.003

  View details for PubMedID 18178068

  View details for PubMedCentralID PMC2270338

• Hierarchical linear modeling (HLM) of longitudinal brain structural and cognitive changes in alcohol-dependent individuals during sobriety. Drug and alcohol dependence Yeh, P. H., Gazdzinski, S., Durazzo, T. C., Sjöstrand, K., Meyerhoff, D. J. 2007; 91 (2-3): 195-204

  Abstract

  Hierarchical linear modeling (HLM) can reveal complex relationships between longitudinal outcome measures and their covariates under proper consideration of potentially unequal error variances. We demonstrate the application of HLM to the study of magnetic resonance imaging (MRI)-derived brain volume changes and cognitive changes in abstinent alcohol-dependent individuals as a function of smoking status, smoking severity, and drinking quantities.Twenty non-smoking recovering alcoholics (nsALC) and 30 age-matched smoking recovering alcoholics (sALC) underwent quantitative MRI and cognitive assessments at 1 week, 1 month, and 7 months of sobriety. Eight non-smoking light drinking controls were studied at baseline and 7 months later. Brain and ventricle volumes at each time point were quantified using MRI masks, while the boundary shift integral method measured volume changes between time points. Using HLM, we modeled volumetric and cognitive outcome measures as a function of cigarette and alcohol use variables.Different hierarchical linear models with unique model structures are presented and discussed. The results show that smaller brain volumes at baseline predict faster brain volume gains, which were also related to greater smoking and drinking severities. Over 7 months of abstinence from alcohol, sALC compared to nsALC showed less improvements in visuospatial learning and memory despite larger brain volume gains and ventricular shrinkage.Different and unique hierarchical linear models allow assessments of the complex relationships among outcome measures of longitudinal data sets. These HLM applications suggest that chronic cigarette smoking modulates the temporal dynamics of brain structural and cognitive changes in alcoholics during prolonged sobriety.

  View details for DOI 10.1016/j.drugalcdep.2007.05.027

  View details for PubMedID 17644276

• Chronic cigarette smoking and heavy drinking in human immunodeficiency virus: consequences for neurocognition and brain morphology. Alcohol (Fayetteville, N.Y.) Durazzo, T. C., Rothlind, J. C., Cardenas, V. A., Studholme, C., Weiner, M. W., Meyerhoff, D. J. 2007; 41 (7): 489-501

  Abstract

  Alcohol use disorders (AUD) and chronic cigarette smoking are common among individuals with human immunodeficiency virus infection (HIV). Concurrent AUD in HIV is related to greater abnormalities in brain morphology and neurocognition than either condition alone. However, the potential influence of chronic smoking on brain morphology and neurocognition in those concurrently afflicted with AUD and HIV has not been examined. The goal of this retrospective analysis was to determine if chronic smoking affected neurocognition and brain morphology in a subsample of HIV-positive non-treatment-seeking heavy drinking participants (HD+) from our earlier work. Regional volumetric and neurocognitive comparisons were made among age-equivalent smoking HD+(n=17), nonsmoking HD+ (n=27), and nonsmoking HIV-negative light drinking controls (n=27) obtained from our original larger sample. Comprehensive neuropsychological assessment evaluated multiple neurocognitive domains of functioning and for potential psychiatric comorbidities. Quantitative volumetric measures of neocortical gray matter (GM), white matter (WM), subcortical structures, and sulcal and ventricular cerebral spinal fluid (CSF) were derived from high-resolution magnetic resonance images. The main findings were (1) smoking HD+ performed significantly worse than nonsmoking HD+ on measures of auditory-verbal (AV) learning, AV memory, and cognitive efficiency; (2) relative to controls, smoking HD+ demonstrated significantly lower neocortical GM volumes in all lobes except the occipital lobe, while nonsmoking HD+ showed only lower frontal GM volume compared with controls; (3) in the HD+ group, regional brain volumes and neurocognition were not influenced by viremia, highly active antiretroviral treatment, or Center for Disease Control symptom status, and no interactions were apparent with these variables or smoking status. Overall, the findings suggested that the direct and/or indirect effects of chronic cigarette smoking created an additional burden on the integrity of brain neurobiology and neurocognition in this cohort of HIV-positive heavy drinkers.

  View details for DOI 10.1016/j.alcohol.2007.07.007

  View details for PubMedID 17923369

  View details for PubMedCentralID PMC2443733

• Chronic smoking is associated with differential neurocognitive recovery in abstinent alcoholic patients: a preliminary investigation. Alcoholism, clinical and experimental research Durazzo, T. C., Rothlind, J. C., Gazdzinski, S., Banys, P., Meyerhoff, D. J. 2007; 31 (7): 1114-27

  Abstract

  Approximately 50 to 90% of individuals in North America seeking treatment for alcoholism are chronic smokers. A growing body of evidence suggests that chronic cigarette smokers show a pattern of neurocognitive dysfunction similar to that observed in alcoholic patients. However, previous studies investigating neurocognitive recovery in abstinent alcoholic patients did not specifically consider the potential effects of chronic cigarette smoking.This study comprehensively compared longitudinal neurocognitive changes over 6 to 9 months of abstinence among 13 nonsmoking recovering alcoholic patients (ALC) and 12 actively smoking ALC. The neurocognitive performance of the alcoholic groups was compared with nonsmoking light-drinking controls (nonsmoking LD).Nonsmoking ALC exhibited a significantly greater magnitude of longitudinal improvement than smoking ALC on measures of cognitive efficiency, executive skills, visuospatial skills, and working memory. Both nonsmoking ALC and smoking ALC demonstrated equivalent improvement on auditory-verbal learning, auditory-verbal memory, and processing speed. Nonsmoking LD showed no significant changes in neurocognition over time. In cross-sectional comparisons at 6 to 9 months of abstinence, nonsmoking ALC were superior to smoking ALC on measures of auditory-verbal learning, auditory-verbal memory, cognitive efficiency, executive skills, processing speed, and working memory. The longitudinal and cross-sectional neurocognitive differences observed between nonsmoking and smoking ALC remained significant after covarying for group differences in education, estimated premorbid intelligence alcohol consumption, and other potentially confounding variables. In smoking ALC, greater smoking severity was inversely related to longitudinal improvement on multiple neurocognitive measures.These preliminary results suggest that chronic smoking may modulate neurocognitive recovery in abstinent alcoholic patients. More generally, chronic smoking may impact neurocognition in other conditions where is it a prevalent behavior.

  View details for DOI 10.1111/j.1530-0277.2007.00398.x

  View details for PubMedID 17451399

• The neurobiological and neurocognitive consequences of chronic cigarette smoking in alcohol use disorders. Alcohol and alcoholism (Oxford, Oxfordshire) Durazzo, T. C., Gazdzinski, S., Meyerhoff, D. J. 2007; 42 (3): 174-85

  Abstract

  A vast body of research attests to the adverse effects of chronic smoking on cardiac, pulmonary, and vascular function as well as the increased risk for various forms of cancer. However, comparatively little is known about the effects of chronic smoking on human brain function. Although smoking rates have decreased in the developed world, they remain high in individuals with alcohol use disorders. Despite the high prevalence of comorbid chronic smoking in alcohol use disorders, very few studies have addressed the potential neurobiological or neurocognitive effects of chronic smoking in alcohol use disorders. Here, we briefly review the existing literature on the neurobiological and neurocognitive consequences of chronic cigarette smoking and summarize our neuroimaging and neurocognitive studies on the effects of comorbid chronic excessive alcohol consumption and cigarette smoking in treatment-seeking and treatment-naïve populations. Our research suggests comorbid chronic cigarette smoking modulates magnetic resonance-detectable brain injury and neurocognition in alcohol use disorders and that neurobiological recovery in our abstinent alcoholics is adversely affected by chronic smoking. Consideration of the potential separate effects and interactions of chronic smoking and alcohol consumption may foster a better understanding of specific mechanisms and neurocognitive consequences of brain injury in alcoholism and of brain recovery during sustained abstinence from alcohol. The material presented also contributes to ongoing discussions about treatment strategies for comorbid alcoholism and cigarette smoking and will hopefully stimulate further research into the neurobiological and neurocognitive consequences of chronic smoking in alcoholism and other substance use disorders.

  View details for DOI 10.1093/alcalc/agm020

  View details for PubMedID 17526627

• Neurobiological and neurocognitive effects of chronic cigarette smoking and alcoholism. Frontiers in bioscience : a journal and virtual library Durazzo, T. C., Meyerhoff, D. J. 2007; 12: 4079-100

  Abstract

  Chronic cigarette smoking is associated with adverse effects on cardiac, pulmonary, and vascular function as well as the increased risk for various forms of cancer. However, little is known about the effects of chronic smoking on human brain function. Although smoking rates have decreased in the developed world, they remain high in individuals with alcohol use disorders (AUD) and other neuropsychiatric conditions. Despite the high prevalence of chronic smoking in AUD, few studies have addressed the potential neurobiological or neurocognitive consequences of chronic smoking in alcohol use disorders. Here, we review the the neurobiological and neurocognitive findings in both AUD and chronic cigarette smoking, followed by a review of the effects of comorbid cigarette smoking on neurobiology and neurocognition in AUD. Recent research suggests that comorbid chronic cigarette smoking modulates magnetic resonance-detectable brain injury and neurocognition in alcohol use disorders and adversely affects neurobiological and neurocognitive recovery in abstinent alcoholics.. Consideration of the potential separate and interactive effects of chronic smoking and alcohol use disorders may have significant implications for pharmacological and behavioral treatment interventions.

  View details for DOI 10.2741/2373

  View details for PubMedID 17485360

• Non-treatment-seeking heavy drinkers: effects of chronic cigarette smoking on brain structure. Drug and alcohol dependence Durazzo, T. C., Cardenas, V. A., Studholme, C., Weiner, M. W., Meyerhoff, D. J. 2007; 87 (1): 76-82

  Abstract

  We previously reported [Cardenas, V.A., Studholme, C., Meyerhoff, D.J., Song, E., Weiner, M.W., 2005. Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes. Psychiatry Res. 138, 115-130] that non-treatment-seeking, active heavy drinkers (HD) demonstrated smaller regional neocortical gray matter volumes compared to light drinking controls; however, the potential effects of chronic cigarette smoking on regional brain volumes were not addressed. The goal of this retrospective analysis was to determine if chronic smoking affected brain structure in the non-treatment-seeking heavy drinking sample from our earlier report (i.e., Cardenas et al., 2005). Regional volumetric comparisons were made among age-matched smoking HD (n=17), non-smoking HD (n=16), and non-smoking light drinkers (nsLD; n=20) from our original sample. Quantitative volumetric measures of neocortical gray matter (GM), white matter (WM), subcortical structures, and cerebral spinal fluid (CSF) were derived from high-resolution magnetic resonance imaging. Smoking HD demonstrated smaller volumes than nsLD in the frontal, parietal, temporal GM, and for total neocortical GM. Smoking HD also demonstrated smaller temporal and total GM volumes than non-smoking HD. Non-smoking HD and nsLD did not differ significantly on GM volumes. Further, the three groups did not differ on lobar WM, subcortical structures or regional CSF volumes. These retrospective analyses indicate neocortical GM volume reductions in non-treatment-seeking smoking HD, but not in non-smoking HD, which are consistent with our studies in recently detoxified treatment-seeking alcohol-dependent samples.

  View details for DOI 10.1016/j.drugalcdep.2006.08.003

  View details for PubMedID 16950573

  View details for PubMedCentralID PMC2443734

• Deformation-based morphometry of brain changes in alcohol dependence and abstinence. NeuroImage Cardenas, V. A., Studholme, C., Gazdzinski, S., Durazzo, T. C., Meyerhoff, D. J. 2007; 34 (3): 879-87

  Abstract

  Brain atrophy associated with chronic alcohol consumption is partially reversible after cessation of drinking. Recovering alcoholics (RA, 45+/-8 years) were studied with MRI within 1 week of entering treatment, with follow-up at 8 months. Light drinkers (LD) were studied with MRI twice 1 year apart. For each participant, deformation maps of baseline structure and longitudinal size changes between baseline and follow-up scans were created using nonlinear registration techniques. ANCOVA assessed group differences and regression methods examined relationships between deformation maps and measures of drinking severity or baseline atrophy. At baseline, RA showed significant atrophy in the frontal and temporal lobes. Longitudinally, abstainers recovered tissue volumes significantly faster than LD in parietal and frontal lobes. When comparing abstainers to relapsers, additional regions with significantly greater recovery in abstainers were temporal lobes, thalamus, brainstem, cerebellum, corpus callosum, anterior cingulate, insula, and subcortical white matter. Gray matter volume at baseline predicted volume recovery during abstinence better than white matter. Drinking severity was not significantly related to brain structural changes assessed with this method. Longitudinally, deformation-based morphometry confirmed tissue recovery in RAs who maintain long-term sobriety. Abstinence-associated tissue volume gains are significant in focal parts of the fronto-ponto-cerebellar circuit that is adversely affected by heavy drinking.

  View details for DOI 10.1016/j.neuroimage.2006.10.015

  View details for PubMedID 17127079

  View details for PubMedCentralID PMC1865510

• A comparison of neurocognitive function in nonsmoking and chronically smoking short-term abstinent alcoholics. Alcohol (Fayetteville, N.Y.) Durazzo, T. C., Rothlind, J. C., Gazdzinski, S., Banys, P., Meyerhoff, D. J. 2006; 39 (1): 1-11

  Abstract

  Approximately 70-90% of individuals in North America seeking treatment for alcoholism are chronic smokers. A growing body of evidence suggests chronic cigarette smoking alone adversely affects neurocognition in adults. However, few studies on the neurocognitive function of short-term abstinent alcoholics have specifically considered the potential effects of chronic cigarette smoking. In this study, 20 nonsmoking recovering alcoholics (nsRA) and 22 actively smoking recovering alcoholics (sRA) participants, matched on age and education, were contrasted on a comprehensive neurocognitive battery after 34+/-9 days of abstinence. nsRA were superior to sRA on measures of auditory-verbal learning and memory, processing speed, cognitive efficiency, and static postural stability. These group differences were not a function of group disparities in age, education, estimated premorbid verbal intelligence, lifetime alcohol consumption, or other measured comorbid psychiatric or medical factors. In sRA, longer smoking duration was negatively correlated with executive skills, visuospatial learning, general cognitive efficiency, and static postural stability. These results indicate that greater consideration of the potential neurobiological effects of current chronic smoking on neurocognitive functioning is warranted in studies of alcoholism and other conditions where smoking is a common comorbid factor.

  View details for DOI 10.1016/j.alcohol.2006.06.006

  View details for PubMedID 16938624

• Smoking comorbidity in alcoholism: neurobiological and neurocognitive consequences. Alcoholism, clinical and experimental research Meyerhoff, D. J., Tizabi, Y., Staley, J. K., Durazzo, T. C., Glass, J. M., Nixon, S. J. 2006; 30 (2): 253-64

  Abstract

  Considerable research attests to the adverse effects of chronic smoking on cardiac, pulmonary, and vascular function as well as on increased risk for various cancers. However, comparatively little is known about the effects of chronic smoking on brain function. Although smoking rates have decreased in the developed world (they have increased in the developing world), smoking rates have been at a persistently high level in individuals with alcohol use disorders. Despite the high prevalence of comorbid chronic smoking and alcohol dependence, very few studies have addressed the separate and interactive effects that smoking and alcoholic drinking may have on neurobiology and brain function. This symposium, which took place at the annual meeting of the Research Society on Alcoholism in Santa Barbara, California, on June 29, 2005, postulates that the neurobiologic and neurocognitive abnormalities commonly described in studies of alcohol-dependent individuals are modulated by concurrent abuse of tobacco products and that brain recovery in abstinent alcoholic individuals is affected by chronic smoking. Four expert speakers and a discussant from different research disciplines focus in this symposium on the description of neurobiological and neurobehavioral effects because of concomitant drinking and smoking. Understanding the potential separate effects and interactions of chronic nicotine/smoking and alcohol consumption promotes a better understanding of specific mechanisms and neurocognitive consequences of brain injury and brain recovery with abstinence. The material presented contributes useful information to ongoing discussions about treatment strategies for these comorbid disorders and valuable educational material that can be used to affect public perception about smoking and perhaps health policy.

  View details for DOI 10.1111/j.1530-0277.2006.00034.x

  View details for PubMedID 16441274

• Quantitative brain MRI in alcohol dependence: preliminary evidence for effects of concurrent chronic cigarette smoking on regional brain volumes. Alcoholism, clinical and experimental research Gazdzinski, S., Durazzo, T. C., Studholme, C., Song, E., Banys, P., Meyerhoff, D. J. 2005; 29 (8): 1484-95

  Abstract

  Recent in vivo research using magnetic resonance spectroscopy demonstrated that chronic cigarette smoking exacerbates regional chronic alcohol-induced brain injury. Other studies associated cigarette smoking with gray matter volume reductions in healthy adults, with greater brain atrophy in aging, and with poorer neurocognition. Although cigarette smoking is common among alcohol-dependent individuals, previous research did not account for the potential effects of chronic smoking on regional brain volumes in alcoholism.High-resolution T1-weighted magnetic resonance images from one-week-abstinent, alcohol-dependent individuals and light drinkers were automatically segmented into gray matter, white matter, and cerebral spinal fluid of lobes and subcortical structures. A brief neuropsychological test battery was used to assess cognition in alcohol-dependent individuals. The alcoholic and nondrinking groups were retrospectively divided into chronic smokers and nonsmokers, and the volumetric data were analyzed as a function of alcohol and smoking status.Chronic alcohol dependence was associated with smaller volumes of frontal and parietal white matter, parietal and temporal gray matter, and thalami, accompanied by widespread sulcal but not ventricular enlargements. Chronic cigarette smoking was associated with less parietal and temporal gray matter and with more temporal white matter. Among alcoholics, better visuospatial learning and memory and greater visuomotor scanning speed were correlated with larger lobar white matter volumes in the nonsmoking alcohol-dependent group only.These data provide preliminary evidence that comorbid chronic cigarette smoking accounts for some of the variance associated with cortical gray matter loss and appears to alter relationships between brain structure and cognitive functions in alcohol-dependent individuals.

  View details for DOI 10.1097/01.alc.0000175018.72488.61

  View details for PubMedID 16131857

• Temporal dynamics and determinants of whole brain tissue volume changes during recovery from alcohol dependence. Drug and alcohol dependence Gazdzinski, S., Durazzo, T. C., Meyerhoff, D. J. 2005; 78 (3): 263-73

  Abstract

  Brain shrinkage and its partial reversibility with abstinence is a common neuroimaging finding in alcohol dependent individuals. We used an automated three-dimensional whole brain magnetic resonance imaging method (boundary shift integral) in 23 alcohol dependent individuals to measure the temporal dynamics of cerebral tissue and spinal fluid volume changes over a 12-month interval and to examine the major determinants of brain tissue change rates during abstinence and non-abstinence. We found more rapid brain tissue gain during the first month of sobriety than in the following months. The most rapid volume recovery was observed in abstinent individuals with the greatest baseline brain shrinkage and drinking severity. The rapid reversal of brain volume gains in non-abstinent individuals and tissue volume changes are modulated by duration of abstinence and non-abstinence periods, as well as recency of non-abstinence. Age, family history density of alcoholism, relapse severity, and duration or age of onset of heavy drinking were not major determinants of brain shrinkage and brain volume recovery rates. Treatment providers may use this tangible information to reinforce the biomedical benefits of sobriety. Previous quantitative measurements of brain volumes in alcohol dependent individuals performed after several weeks of abstinence likely underestimated the full extent of chronic alcohol-associated brain shrinkage.

  View details for DOI 10.1016/j.drugalcdep.2004.11.004

  View details for PubMedID 15893157

• Cigarette smoking exacerbates chronic alcohol-induced brain damage: a preliminary metabolite imaging study. Alcoholism, clinical and experimental research Durazzo, T. C., Gazdzinski, S., Banys, P., Meyerhoff, D. J. 2004; 28 (12): 1849-60

  Abstract

  Cigarette smoking is common among alcohol-dependent individuals. Nevertheless, previous research has typically not accounted for the potential independent or compounding effects of cigarette smoking on alcohol-induced brain injury and neurocognition.Twenty-four 1-week-abstinent recovering alcoholics (RAs; 14 smokers and 10 nonsmokers) in treatment and 26 light-drinking controls (7 smokers and 19 nonsmokers) were compared on measures of common brain metabolites in gray matter and white matter of the major lobes, basal ganglia, midbrain, and cerebellar vermis, obtained via multislice short-echo time proton magnetic resonance spectroscopic imaging. Smoking and nonsmoking RAs were also contrasted on measures of neurocognitive functioning, as well as laboratory markers of drinking severity and nutritional status.Chronic alcohol dependence, independent of smoking, was associated with lower concentrations of frontal N-acetylaspartate (NAA) and frontal choline-containing compounds, as well as lower parietal and thalamic choline. Smoking RAs had lower NAA concentrations in frontal white matter and midbrain and lower midbrain choline than nonsmoking RAs. A four-group analysis of covariance also demonstrated that chronic cigarette smoking was associated with lower midbrain NAA and choline and with lower vermian choline. In smoking RAs, heavier drinking was associated with heavier smoking, which correlated with numerous subcortical metabolite abnormalities. The 1-week-abstinent smoking and nonsmoking RAs did not differ significantly on a brief neurocognitive battery. In smoking RAs, lower cerebellar vermis NAA was associated with poorer visuomotor scanning speed and incidental learning, and in nonsmoking RAs lower vermis NAA was related to poorer visuospatial learning and memory.These human in vivo proton magnetic resonance spectroscopic imaging findings indicate that chronic cigarette smoking exacerbates chronic alcohol-induced neuronal injury and cell membrane damage in the frontal lobes of RAs and has independent adverse effects on neuronal viability and cell membranes in the midbrain and on cell membranes of the cerebellar vermis. Higher smoking levels are associated with metabolite concentrations in select subcortical structures. Greater consideration of the potential effects of comorbid cigarette smoking on alcohol-induced brain damage and other diseases affecting the central nervous system is warranted.

  View details for DOI 10.1097/01.alc.0000148112.92525.ac

  View details for PubMedID 15608601

• Technical report: the subcutaneous administration of cocaine in the rat. Pharmacology, biochemistry, and behavior Durazzo, T. C., Gauvin, D. V., Goulden, K. L., Briscoe, R. J., Holloway, F. A. 1994; 49 (4): 1007-10

  Abstract

  Eight male Sprague-Dawley rats were treated with 32 mg/kg cocaine, twice daily, for 2 weeks using a SC route of administration. Using a cocaine stock solution of 1.2-1.6 mg of cocaine hydrochloride per ml of sterile saline, we demonstrate, for the first time, the relative safety of subcutaneously administered cocaine in the rat. There was absolutely no evidence for focal dermal necrosis, in any rat, after the 2-week chronic period.

  View details for DOI 10.1016/0091-3057(94)90256-9

  View details for PubMedID 7886068

• Cocaine-induced conditioned place approach in rats: the role of dose and route of administration. Pharmacology, biochemistry, and behavior Durazzo, T. C., Gauvin, D. V., Goulden, K. L., Briscoe, R. J., Holloway, F. A. 1994; 49 (4): 1001-5

  Abstract

  The hedonic valence of the interoceptive stimuli associated with a wide range of cocaine doses administered by either SC or intraperitoneal injections was assessed in rats. Ninety-six male Sprague-Dawley rats were randomly assigned to different dose- and route-of-administration dependent groups (n = 8/group) and conditioned in a place learning task. During half of the conditioning trials, rats received either SC or intraperitoneal injections of saline or an individual dose of cocaine from 0.32 to 32 mg/kg (10 groups, 0.5 log common log unit increments), and were immediately placed in the initially nonpreferred compartment of a straight alley-way place-conditioning chamber. Prior to the other conditioning trials, rats received equivalent volumes of saline injections via the same routes of administration and were immediately placed in the initially preferred compartment. Two additional control groups received saline injections on both sides. Each rat received eight conditioning trials (four on each side). Significant conditioned place approach was produced by both SC- and IP-injected cocaine. However, the IP route of cocaine administration required a dose of 10 mg/kg cocaine to elicit a conditioned place approach, whereas a 0.32 mg/kg SC cocaine injection produced a CPP. Saline injections alone did not change the initial preference scores, and conditioned place aversions were not produced by any cocaine dose. The results of the present study demonstrate the relative safety of SC cocaine administration in the rat and a behavioral potency difference between these two routes of administration relative to the hedonic valence of the associated subjective states.

  View details for DOI 10.1016/0091-3057(94)90255-0

  View details for PubMedID 7886067