Academic Appointments

  • Professor - University Medical Line, Psychiatry and Behavioral Sciences

Current Research and Scholarly Interests

The mission of the Durazzo BRASS lab is to better understand how the interplay between biomedical, psychological and social factors influences treatment outcome in Veterans and civilians seeking treatment for alcohol and substance use disorders. To accomplish this mission, our multidisciplinary team integrates information from advanced neuroimaging, neurocognitive assessment, psychodiagnostic and genotyping methods to identify the biopsychosocial factors associated with relapse and sustained sobriety. Veteran's Administration and Stanford funded Clinical trials are currently being conducted by the BRASS lab that evaluate repetitive transcranial magnetic stimulation techniques as novel complementary treatments to reduce the high rate of relapse experienced by individuals with alcohol and substance abuse disorders. The ultimate goal of our multidisciplinary research program is to promote the development of more effective biomedical and behavioral treatments for alcohol and substance use disorders through consideration of the brain biology, psychology and social circumstances of each individual.

2022-23 Courses

Stanford Advisees

All Publications

  • 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


    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


    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


    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


    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

  • 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


    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

  • 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
  • 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. 2020

    View details for DOI 10.1111/adb.12948

    View details for Web of Science ID 000557408800001

  • 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
  • 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


    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


    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


    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
  • 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


    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


    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


    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

  • 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


    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


    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


    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


    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


    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


    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


    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


    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
  • Reply to: On the Correction of Effects of Flip Angle in 1H Magnetic Resonance Spectroscopy Signal Acquired Using Stimulated Echo Acquisition Mode Sequence. Biological psychiatry Durazzo, T. C., Murray, D. E., Meyerhoff, D. J. 2017; 81 (2): e17

    View details for DOI 10.1016/j.biopsych.2016.02.025

    View details for PubMedID 27063070

    View details for PubMedCentralID PMC5010527

  • 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


    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

  • 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
  • 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


    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

  • 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)


    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


    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