Christine Blasey
Clinical Professor, Psychiatry and Behavioral Sciences
Academic Appointments
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Clinical Professor, Psychiatry and Behavioral Sciences
Professional Education
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MS, Stanford School of Medicine, Epidemiology (2009)
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PhD, U of Southern California, Psychology (1996)
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Intern, University of Hawai'i at Manoa (1995)
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MA, Pepperdine University, Clinical Psycholgy (1991)
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BA, U of North Carolina Chapel Hill, Psychology (1988)
All Publications
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Self-Reported Depressive Symptoms in Active and Retired Professional Hockey Players
CANADIAN JOURNAL OF BEHAVIOURAL SCIENCE-REVUE CANADIENNE DES SCIENCES DU COMPORTEMENT
2020; 52 (2): 97–106
View details for DOI 10.1037/cbs0000169
View details for Web of Science ID 000522152100002
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Attenuation of Anti-Suicidal Effects of Ketamine by Opioid Receptor Antagonism
ELSEVIER SCIENCE INC. 2019: S113
View details for DOI 10.1016/j.biopsych.2019.03.284
View details for Web of Science ID 000472661000271
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Rigorous Translational Models Are Key to Studying Ketamine's Antidepressant Mechanism: Response to Wang and Kaplin
AMERICAN JOURNAL OF PSYCHIATRY
2019; 176 (5): 412
View details for DOI 10.1176/appi.ajp.2019.19010044r
View details for Web of Science ID 000466364500015
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Interpreting Ketamine's Opioid Receptor Dependent Effect: Response to Sanacora
AMERICAN JOURNAL OF PSYCHIATRY
2019; 176 (3): 249–50
View details for DOI 10.1176/appi.ajp.2018.18091061r
View details for Web of Science ID 000462846900011
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Target Population, Dose, and Timing Considerations for Understanding Naltrexone's Subjective Effect: Response to Amiaz
AMERICAN JOURNAL OF PSYCHIATRY
2019; 176 (3): 251–52
View details for DOI 10.1176/appi.ajp.2018.18111231r
View details for Web of Science ID 000462846900013
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Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism.
Molecular psychiatry
2019
Abstract
We recently reported that naltrexone blocks antidepressant effects of ketamine in humans, indicating that antidepressant effects of ketamine require opioid receptor activation. However, it is unknown if opioid receptors are also involved in ketamine's antisuicidality effects. Here, in a secondary analysis of our recent clinical trial, we test whether naltrexone attenuates antisuicidality effects of ketamine. Participants were pretreated with naltrexone or placebo prior to intravenous ketamine in a double-blinded crossover design. Suicidality was measured with the Hamilton Depression Rating Scale item 3, Montgomery-Åsberg Depression Rating Scale item 10, and Columbia Suicide Severity Rating Scale. In the 12 participants who completed naltrexone and placebo conditions, naltrexone attenuated the antisuicidality effects of ketamine on all three suicidality scales/subscales (linear mixed model, fixed pretreatment effect, p < 0.01). Results indicate that opioid receptor activation plays a significant role in the antisuicidality effects of ketamine.
View details for DOI 10.1038/s41380-019-0503-4
View details for PubMedID 31467392
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Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism.
The American journal of psychiatry
2018: appiajp201818020138
Abstract
OBJECTIVE: In addition to N-methyl-d-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of this study was to determine whether opioid receptor antagonism prior to administration of intravenous ketamine attenuates its acute antidepressant or dissociative effects.METHOD: In a proposed double-blind crossover study of 30 adults with treatment-resistant depression, the authors performed a planned interim analysis after studying 14 participants, 12 of whom completed both conditions in randomized order: placebo or 50 mg of naltrexone preceding intravenous infusion of 0.5 mg/kg of ketamine. Response was defined as a reduction ≥50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D) score on postinfusion day 1.RESULTS: In the interim analysis, seven of 12 adults with treatment-resistant depression met the response criterion during the ketamine plus placebo condition. Reductions in 6-item and 17-item HAM-D scores among participants in the ketamine plus naltrexone condition were significantly lower than those of participants in the ketamine plus placebo condition on postinfusion days 1 and 3. Secondary analysis of all participants who completed the placebo and naltrexone conditions, regardless of the robustness of response to ketamine, showed similar results. There were no differences in ketamine-induced dissociation between conditions. Because naltrexone dramatically blocked the antidepressant but not the dissociative effects of ketamine, the trial was halted at the interim analysis.CONCLUSIONS: The findings suggest that ketamine's acute antidepressant effect requires opioid system activation. The dissociative effects of ketamine are not mediated by the opioid system, and they do not appear sufficient without the opioid effect to produce the acute antidepressant effects of ketamine in adults with treatment-resistant depression.
View details for PubMedID 30153752
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Psychological Flexibility and Set-Shifting Among Veterans Participating in a Yoga Program: A Pilot Study.
Military medicine
2018
Abstract
Trauma-focused psychotherapies do not meet the needs of all veterans. Yoga shows some potential in reducing stress and perhaps even PTSD in veterans, although little is understood about the mechanisms of action. This study identifies preliminary correlates of change in PTSD and perceived stress for veterans participating in yoga.Nine veterans (seven males and two females) were recruited from an existing clinical yoga program and observed over 16 wk. Severity of PTSD symptoms (PCL-5) and perceived stress (PSS-10) were collected at baseline and weeks 4, 6, 8, and 16. Psychological flexibility (AAQ-II) and set-shifting (ratio of trail making test A to B) were collected at baseline and at week 6. Subjects attended yoga sessions freely, ranging from 1 to 23 classes over the 16 weeks. The Stanford University Institutional Review Board approved this research protocol.Self-reported PTSD symptoms significantly reduced while perceived stress did not. Lower baseline set-shifting predicted greater improvements in PTSD between baseline and 4 weeks; early improvements in set-shifting predicted overall reduction in PTSD. Greater psychological flexibility was associated with lower PTSD and perceived stress; more yoga practice, before and during the study, was associated with greater psychological flexibility. Other predictors were not supported.In a small uncontrolled sample, psychological flexibility and set-shifting predicted changes in PTSD symptoms in veterans participating in a clinical yoga program, which supports findings from prior research. Future research should include an active comparison group and record frequency of yoga practiced outside formal sessions.
View details for PubMedID 29590487
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Anxiety and Related Disorders and Concealment in Sexual Minority Young Adults
BEHAVIOR THERAPY
2016; 47 (1): 91-101
View details for Web of Science ID 000368315200008
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Anxiety and Related Disorders and Concealment in Sexual Minority Young Adults.
Behavior therapy
2016; 47 (1): 91-101
Abstract
Sexual minorities face greater exposure to discrimination and rejection than heterosexuals. Given these threats, sexual minorities may engage in sexual orientation concealment in order to avoid danger. This social stigma and minority stress places sexual minorities at risk for anxiety and related disorders. Given that three fourths of anxiety disorder onset occurs before the age of 24, the current study investigated the symptoms of generalized anxiety disorder, social phobia, panic disorder, posttraumatic stress disorder, and depression in sexual minority young adults relative to their heterosexual peers. Secondarily, the study investigated sexual orientation concealment as a predictor of anxiety and related disorders. A sample of 157 sexual minority and 157 heterosexual young adults matched on age and gender completed self-report measures of the aforementioned disorders, and indicated their level of sexual orientation concealment. Results revealed that sexual minority young adults reported greater symptoms relative to heterosexuals across all outcome measures. There were no interactions between sexual minority status and gender, however, women had higher symptoms across all disorders. Sexual minority young women appeared to be at the most risk for clinical levels of anxiety and related disorders. In addition, concealment of sexual orientation significantly predicted symptoms of social phobia. Implications are offered for the cognitive and behavioral treatment of anxiety and related disorders in this population.
View details for DOI 10.1016/j.beth.2015.09.006
View details for PubMedID 26763500
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Depression Subtypes in Predicting Antidepressant Response: A Report From the iSPOT-D Trial
AMERICAN JOURNAL OF PSYCHIATRY
2015; 172 (8): 743-750
Abstract
The study aims were 1) to describe the proportions of individuals who met criteria for melancholic, atypical, and anxious depressive subtypes, as well as subtype combinations, in a large sample of depressed outpatients, and 2) to compare subtype profiles on remission and change in depressive symptoms after acute treatment with one of three antidepressant medications.Participants 18-65 years of age (N=1,008) who met criteria for major depressive disorder were randomly assigned to 8 weeks of treatment with escitalopram, sertraline, or extended-release venlafaxine. Participants were classified by subtype. Those who met criteria for no subtype or multiple subtypes were classified separately, resulting in eight mutually exclusive groups. A mixed-effects model using the intent-to-treat sample compared the groups' symptom score trajectories, and logistic regression compared likelihood of remission (defined as a score ≤5 on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report).Thirty-nine percent of participants exhibited a pure-form subtype, 36% met criteria for more than one subtype, and 25% did not meet criteria for any subtype. All subtype groups exhibited a similar significant trajectory of symptom reduction across the trial. Likelihood of remission did not differ significantly between subtype groups, and depression subtype was not a moderator of treatment effect.There was substantial overlap of the three depressive subtypes, and individuals in all subtype groups responded similarly to the three antidepressants. The consistency of these findings with those of the Sequenced Treatment Alternatives to Relieve Depression trial suggests that subtypes may be of minimal value in antidepressant selection.
View details for DOI 10.1176/appi.ajp.2015.14020181
View details for Web of Science ID 000359274700014
View details for PubMedID 25815419
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Low Circulating 25-Hydroxyvitamin D Concentrations Are Associated with Defects in Insulin Action and Insulin Secretion in Persons with Prediabetes
JOURNAL OF NUTRITION
2015; 145 (4): 714-719
Abstract
Individuals with prediabetes mellitus (PreDM) and low circulating 25-hydroxyvitamin D [25(OH)D] are at increased risk of type 2 diabetes mellitus (T2DM).We aimed to determine whether low 25(OH)D concentrations are associated with defects in insulin action and insulin secretion in persons with PreDM.In this cross-sectional study, we stratified 488 nondiabetic subjects as having PreDM or normal fasting glucose (NFG) and a 25(OH)D concentration ≤20 ng/mL (deficient) or >20 ng/mL (sufficient). We determined insulin resistance by steady state plasma glucose (SSPG) concentration and homeostasis model assessment of insulin resistance (HOMA-IR) and insulin secretion by homeostasis model assessment of β-cell function (HOMA-β). We compared insulin resistance and secretion measures in PreDM and NFG groups; 25(OH)D-deficient and 25(OH)D-sufficient groups; and PreDM-deficient, PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups, adjusting for age, sex, race, body mass index, multivitamin use, and season.In the PreDM group, mean SSPG concentration and HOMA-IR were higher and mean HOMA-β was lower than in the NFG group (P < 0.001 for all comparisons). In the 25(OH)D-deficient group, mean SSPG concentration was higher (P < 0.001), but neither mean HOMA-IR nor HOMA-β was significantly different from that in the 25(OH)D-sufficient group. In the PreDM-deficient subgroup, mean (95% CI) SSPG concentration was higher (P < 0.01) than in the PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups [192 (177-207) mg/dL vs. 166 (155-177) mg/dL, 148 (138-159) mg/dL, and 136 (127-144) mg/dL, respectively]. Despite greater insulin resistance, mean HOMA-β was not significantly higher in the PreDM-deficient subgroup than in the PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups [98 (85-112) vs. 91 (82-101), 123 (112-136), and 115 (106-124), respectively].Subjects with PreDM and low circulating 25(OH)D concentrations are the subgroup of nondiabetic individuals who are the most insulin resistant and have impaired β-cell function, attributes that put them at enhanced risk of T2DM.
View details for DOI 10.3945/jn.114.209171
View details for Web of Science ID 000352180500007
View details for PubMedID 25740907
View details for PubMedCentralID PMC4381771
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Magnetic Resonance Imaging Measures of Brain Structure to Predict Antidepressant Treatment Outcome in Major Depressive Disorder.
EBioMedicine
2015; 2 (1): 37-45
Abstract
Less than 50% of patients with Major Depressive Disorder (MDD) reach symptomatic remission with their initial antidepressant medication (ADM). There are currently no objective measures with which to reliably predict which individuals will achieve remission to ADMs.157 participants with MDD from the International Study to Predict Optimized Treatment in Depression (iSPOT-D) underwent baseline MRIs and completed eight weeks of treatment with escitalopram, sertraline or venlafaxine-ER. A score at week 8 of 7 or less on the 17 item Hamilton Rating Scale for Depression defined remission. Receiver Operator Characteristics (ROC) analysis using the first 50% participants was performed to define decision trees of baseline MRI volumetric and connectivity (fractional anisotropy) measures that differentiated non-remitters from remitters with maximal sensitivity and specificity. These decision trees were tested for replication in the remaining participants.Overall, 35% of all participants achieved remission. ROC analyses identified two decision trees that predicted a high probability of non-remission and that were replicated: 1. Left middle frontal volume < 14 · 8 mL & right angular gyrus volume > 6 · 3 mL identified 55% of non-remitters with 85% accuracy; and 2. Fractional anisotropy values in the left cingulum bundle < 0 · 63, right superior fronto-occipital fasciculus < 0 · 54 and right superior longitudinal fasciculus < 0 · 50 identified 15% of the non-remitters with 84% accuracy. All participants who met criteria for both decision trees were correctly identified as non-remitters.Pretreatment MRI measures seem to reliably identify a subset of patients who do not remit with a first step medication that includes one of these commonly used medications. Findings are consistent with a neuroanatomical basis for non-remission in depressed patients.Brain Resource Ltd is the sponsor for the iSPOT-D study (NCT00693849).
View details for DOI 10.1016/j.ebiom.2014.12.002
View details for PubMedID 26137532
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Cognitive Testing to Identify Children With ADHD Who Do and Do Not Respond to Methylphenidate.
Journal of attention disorders
2014
Abstract
To explore the utility of cognitive measures for predicting response of children and adolescents to methylphenidate (MPH).Participants from the International Study to Predict Optimized Treatment-in ADHD (iSPOT-A) completed a cognitive test battery prior to receiving 6 weeks of MPH. The responder criterion was a 25% reduction in ADHD-Rating Scale-IV scores. Receiver Operator Characteristics (ROC) classified non-responders from responders with maximal sensitivity and specificity.Overall, 62% of participants responded to MPH. Response rates for ROC-identified groups ranged from 18% to 85%. Non-responders showed compromised cognition related to switching of attention, sustained attention, planning, and impulsivity. One group of responders were 10 years of age or older and had impaired switching of attention and impulsivity; a second group had enhanced switching of attention, normal or higher Continuous Performance Task (CPT) scores, and above average scores on digit span.Cognitive tests may provide a simple, low-cost tool for treatment planning for children and adolescents with ADHD.
View details for PubMedID 25122732
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Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone
ADDICTION
2013; 108 (12): 2141-2149
Abstract
To evaluate the safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX).Randomized, double-blind, placebo-controlled trial. Subjects received either four buprenorphine implants (80 mg/implant) (n = 114), four placebo implants (n = 54) or open-label BNX (12-16 mg/day) (n = 119).Twenty addiction treatment centers.Adult out-patients (ages 18-65) with DSM-IV-TR opioid dependence.The primary efficacy end-point was the percentage of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF).The BI CDF was significantly different from placebo (P < 0.0001). Mean [95% confidence interval (CI)] proportions of urines negative for opioids were: BI = 31.2% (25.3, 37.1) and PI = 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64 versus 26%, P < 0.0001), lower clinician-rated (P < 0.0001) and patient-rated (P < 0.0001) withdrawal, lower patient-ratings of craving (P < 0.0001) and better subjects' (P = 0.031) and clinicians' (P = 0.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P = 0.0016). Minor implant-site reactions were comparable in the buprenorphine [27.2% (31 of 114)] and placebo groups [25.9% (14 of 54)]. BI were non-inferior to BNX on percentage of urines negative for opioids [mean (95% CI) = 33.5 (27.3, 39.6); 95% CI for the difference of proportions = (-10.7, 6.2)].Compared with placebo, buprenorphine implants result in significantly less frequent opioid use and are non-inferior to sublingual buprenorphine/naloxone tablets.
View details for DOI 10.1111/add.12315
View details for Web of Science ID 000327954000018
View details for PubMedID 23919595
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Detecting critical decision points in psychotherapy and psychotherapy + medication for chronic depression.
Journal of consulting and clinical psychology
2013; 81 (5): 783-792
Abstract
Objective: We sought to quantify clinical decision points for identifying depression treatment nonremitters prior to end-of-treatment. Method: Data came from the psychotherapy arms of a randomized clinical trial for chronic depression. Participants (n = 352; 65.6% female; 92.3% White; mean age = 44.3 years) received 12 weeks of cognitive behavioral analysis system of psychotherapy (CBASP) or CBASP plus an antidepressant medication. In half of the sample, receiver operating curve analyses were used to identify efficient percentage of symptom reduction cut points on the Inventory of Depressive Symptoms-Self-Report (IDS-SR) for predicting end-of-treatment nonremission based on the Hamilton Rating Scale for Depression (HRSD). Sensitivity, specificity, predictive values, and Cohen's kappa for identified cut points were calculated using the remaining half of the sample. Results: Percentage of IDS-SR symptom reduction at Weeks 6 and 8 predicted end-of-treatment HRSD remission status in both the combined treatment (Week 6 cut point = 50.0%, Cohen's κ = .42; Week 8 cut point = 54.3%, Cohen's κ = .45) and psychotherapy only (Week 6 cut point = 60.7%, Cohen's κ = .41; Week 8 cut point = 48.7%, Cohen's κ = .49). Status at Week 8 was more reliable for identifying nonremitters in psychotherapy-only treatment. Conclusions: Those with chronic depression who will not remit in structured, time-limited psychotherapy for depression, either with therapy alone or in combination with antidepressant medication, are identifiable prior to end of treatment. Findings provide an operationalized strategy for designing adaptive psychotherapy interventions. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
View details for DOI 10.1037/a0033250
View details for PubMedID 23750462
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Beyond fasting plasma glucose: The association between coronary heart disease risk and postprandial glucose, postprandial insulin and insulin resistance in healthy, nondiabetic adults.
Metabolism: clinical and experimental
2013; 62 (9): 1223-1226
Abstract
Prediabetes is defined by elevations of plasma glucose concentration, and is aimed at identifying individuals at increased risk of type 2 diabetes and coronary heart disease (CHD). However, since these individuals are also insulin resistant and hyperinsulinemic, we evaluated the association between several facets of carbohydrate metabolism and CHD risk profile in apparently healthy, nondiabetic individuals.Plasma glucose and insulin concentrations were measured before and at hourly intervals for eight hours after two test meals in 281 nondiabetic individuals. Insulin action was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. CHD risk was assessed by measurements of blood pressure and fasting lipoprotein profile.For purposes of analysis, the population was divided into tertiles, and the results demonstrated that the greater the 1) fasting plasma glucose (FPG) concentration, 2) incremental plasma insulin response to meals, and 3) SSPG concentration, the more adverse the CHD risk profile (p<0.05). In contrast, the CHD risk profile did not significantly worsen with increases in the incremental plasma glucose response to meals.In nondiabetic individuals, higher FPG concentrations, accentuated daylong incremental insulin responses to meals, and greater degrees of insulin resistance are each associated with worse CHD risk profile (higher blood pressures, higher triglycerides, and lower high density lipoprotein cholesterol concentrations). Interventional efforts aimed at decreasing CHD in such individuals should take these abnormalities into consideration.
View details for DOI 10.1016/j.metabol.2013.04.012
View details for PubMedID 23809477
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Cardiometabolic risk factors and obesity: does it matter whether BMI or waist circumference is the index of obesity?
American journal of clinical nutrition
2013; 98 (3): 637-640
Abstract
It has been suggested that the cardiometabolic risk associated with excess adiposity is particularly related to central obesity.The objective was to compare the associations between cardiometabolic risk of apparently healthy individuals and measures of central obesity [waist circumference (WC)] and overall obesity [body mass index (BMI)].In this cross-sectional, observational study, 492 subjects (306 women and 303 non-Hispanic whites) were classified by BMI (in kg/m(2)) as normal weight (BMI <25) or overweight/obese (BMI = 25.0-34.9) and as having an abnormal WC (≥80 cm in women and ≥94 cm in men) or a normal WC (<80 cm in women and <94 cm in men). Measurements were also made of the cardiometabolic risk factors: age, systolic blood pressure (SBP), and fasting plasma glucose (FPG), triglyceride, and high-density lipoprotein (HDL)-cholesterol concentrations. Associations among cardiometabolic risk factors and BMI and WC were evaluated with Pearson correlations.There was a considerable overlap in the normal and abnormal categories of BMI and WC, and ∼81% of the subjects had both an abnormal BMI and WC. In women, BMI and WC correlated with SBP (r = 0.30 and 0.19, respectively), FPG (r = 0.25 and 0.22, respectively), triglycerides (r = 0.17 and 0.20, respectively), and HDL cholesterol (r = -0.23 and -0.20, respectively) (P < 0.01 for all). In men, BMI and WC also correlated with SBP (r = 0.22 and 0.22, respectively), FPG (r = 0.22 and 0.25, respectively), triglycerides (r = 0.21 and 0.18, respectively), and HDL cholesterol (r = -0.20 and -0.13, respectively) [P < 0.05 for all, except for the association of WC with HDL cholesterol (P = 0.08)].Most individuals with an abnormal BMI also have an abnormal WC. Both indexes of excess adiposity are positively associated with SBP, FPG, and triglycerides and inversely associated with HDL cholesterol.
View details for DOI 10.3945/ajcn.112.047506
View details for PubMedID 23885045
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The relationship between the therapeutic alliance and treatment outcome in two distinct psychotherapies for chronic depression.
Journal of consulting and clinical psychology
2013; 81 (4): 627-638
Abstract
Objective: This study tested whether the quality of the patient-rated working alliance, measured early in treatment, predicted subsequent symptom reduction in chronically depressed patients. Secondarily, the study assessed whether the relationship between early alliance and response to treatment differed between patients receiving cognitive behavioral analysis system of psychotherapy (CBASP) vs. brief supportive psychotherapy (BSP). Method: 395 adults (57% female; Mage = 46; 91% Caucasian) who met criteria for chronic depression and did not fully remit during a 12-week algorithm-based, open-label pharmacotherapy trial were randomized to receive either 16-20 sessions of CBASP or BSP in addition to continued, algorithm-based antidepressant medication. Of these, 224 patients completed the Working Alliance Inventory-Short Form at Weeks 2 or 4 of treatment. Blind raters assessed depressive symptoms at 2-week intervals across treatment using the Hamilton Rating Scale for Depression. Linear mixed models tested the association between early alliance and subsequent symptom ratings while accounting for early symptom change. Results: A more positive early working alliance was associated with lower subsequent symptom ratings in both the CBASP and BSP, F(1, 1236) = 62.48, p < .001. In addition, the interaction between alliance and psychotherapy type was significant, such that alliance quality was more strongly associated with symptom ratings among those in the CBASP treatment group, F(1, 1234) = 8.31, p = .004. Conclusions: The results support the role of the therapeutic alliance as a predictor of outcome across dissimilar treatments for chronic depression. Contrary to expectations, the therapeutic alliance was more strongly related to outcome in CBASP, the more directive of the 2 therapies. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
View details for DOI 10.1037/a0031530
View details for PubMedID 23339536
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The relationship between the therapeutic alliance and treatment outcome in two distinct psychotherapies for chronic depression.
Journal of consulting and clinical psychology
2013; 81 (4): 627-638
Abstract
Objective: This study tested whether the quality of the patient-rated working alliance, measured early in treatment, predicted subsequent symptom reduction in chronically depressed patients. Secondarily, the study assessed whether the relationship between early alliance and response to treatment differed between patients receiving cognitive behavioral analysis system of psychotherapy (CBASP) vs. brief supportive psychotherapy (BSP). Method: 395 adults (57% female; Mage = 46; 91% Caucasian) who met criteria for chronic depression and did not fully remit during a 12-week algorithm-based, open-label pharmacotherapy trial were randomized to receive either 16-20 sessions of CBASP or BSP in addition to continued, algorithm-based antidepressant medication. Of these, 224 patients completed the Working Alliance Inventory-Short Form at Weeks 2 or 4 of treatment. Blind raters assessed depressive symptoms at 2-week intervals across treatment using the Hamilton Rating Scale for Depression. Linear mixed models tested the association between early alliance and subsequent symptom ratings while accounting for early symptom change. Results: A more positive early working alliance was associated with lower subsequent symptom ratings in both the CBASP and BSP, F(1, 1236) = 62.48, p < .001. In addition, the interaction between alliance and psychotherapy type was significant, such that alliance quality was more strongly associated with symptom ratings among those in the CBASP treatment group, F(1, 1234) = 8.31, p = .004. Conclusions: The results support the role of the therapeutic alliance as a predictor of outcome across dissimilar treatments for chronic depression. Contrary to expectations, the therapeutic alliance was more strongly related to outcome in CBASP, the more directive of the 2 therapies. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
View details for DOI 10.1037/a0031530
View details for PubMedID 23339536
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Discovery of a novel non-steroidal GR antagonist with in vivo efficacy in the olanzapine-induced weight gain model in the rat
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
2012; 22 (24): 7376-7380
Abstract
We report the optimization of a series of non-steroidal GR antagonists that led to the identification of compound 7. This compound is efficacious when dosed orally in an olanzapine-induced weight gain model in rats.
View details for DOI 10.1016/j.bmcl.2012.10.074
View details for Web of Science ID 000311425500017
View details for PubMedID 23131342
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Administration of a selective glucocorticoid antagonist attenuates electroconvulsive shock-induced retrograde amnesia
JOURNAL OF NEURAL TRANSMISSION
2012; 119 (3): 337-344
Abstract
Mifepristone, a glucocorticoid and progesterone receptor antagonist, has been shown to attenuate retrograde amnesia induced by repeated electroconvulsive shocks (ECS). We examined the efficacy of CORT 108297, a selective glucocorticoid antagonist, in this regard. Adult, male, Wistar rats (n = 69) received either vehicle or CORT 108297 (1 mg/kg) 2 h before each of 5 once-daily true or sham 30 mC ECS. Recall of previous exposure to a noxious stimulus in a passive avoidance (step-through) paradigm was tested 1 day after the 5-ECS course. Analyses were conducted using recall operationalized in different ways: using the absolute final latency scores; defining adequate recall as a final latency of 30 s or greater; defining perfect recall as a final latency of 180 s; and using visual, subjective assessments of animal behavior. ECS was associated with significant impairment of recall, and this impairment was significantly attenuated by CORT 108297 on all outcome measures (with the exception of the perfect recall analyses, where outcomes narrowly missed statistical significance). In conclusion, these findings strengthen previous data from our laboratory implicating glucocorticoid mechanisms in ECS-induced retrograde amnesia. We suggest that the administration of a selective glucocorticoid receptor antagonist shortly before electroconvulsive therapy (ECT) treatments may attenuate the deleterious effect of ECT-induced acute hypercortisolemia on neural mechanisms involved in learning and memory.
View details for DOI 10.1007/s00702-011-0712-8
View details for Web of Science ID 000300587900005
View details for PubMedID 21922193
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Plasma glucose and insulin responses to mixed meals: Impaired fasting glucose re-visited
DIABETES & VASCULAR DISEASE RESEARCH
2011; 8 (4): 271-275
Abstract
In individuals with varying glucose tolerance, glucose and insulin comparisons are usually made based on response to oral glucose challenge. However, an oral glucose tolerance test may not reflect daylong glucose and insulin excursions in response to meals. To better understand individuals with impaired fasting glucose (IFG), we compared insulin action as well as plasma glucose and insulin responses to mixed meals in individuals with normal fasting glucose (NFG; n = 141) and IFG (n = 148) concentrations.Insulin action was quantified by determining steady-state plasma glucose (SSPG) concentrations during the insulin suppression test. Plasma glucose and insulin concentrations were measured before and hourly after two mixed meals.SSPG concentrations were significantly higher in the IFG group (11.8 ± 3.6 vs. 9.1 ± 3.8 mmol/l). Mean hourly daylong glucose (6.4 ± 0.07 vs. 5.5 ± 0.04 mmol/l) and insulin (390 ± 20 vs. 279 ± 15 pmol/l) concentrations were also higher in those with IFG (p < 0.001). Daylong incremental meal-stimulated glucose response, however, was comparable (p = 0.77) in the two groups, whereas the incremental insulin response was 44% higher in the IFG group.Although individuals are currently defined as having IFG based on fasting plasma glucose concentration, our data show that these individuals with IFG also are insulin resistant and have higher daylong insulin concentrations.
View details for DOI 10.1177/1479164111421036
View details for Web of Science ID 000296976700004
View details for PubMedID 21933842
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Does Gender Moderate the Relationship Between Childhood Maltreatment and Adult Depression?
CHILD MALTREATMENT
2011; 16 (3): 175-183
Abstract
Although considerable evidence demonstrates that adults who report childhood maltreatment are at increased risk of depression in adulthood, little is known about whether gender moderates risk. In a sample of 5,673 adult Health Maintenance Organization (HMO) patients, the authors employed the Patient Health Questionnaire-8 (PHQ-8) to assess major depressive disorder (MDD) and the Childhood Trauma Questionnaire (CTQ) to assess five different types of childhood maltreatment: emotional, physical, and sexual abuse, as well as emotional and physical neglect. Logistic regression models tested the main and interactive effects of gender and childhood maltreatment. Consistent with previous studies, men and women with histories of each type of childhood adversity were significantly more likely to meet criteria for MDD. However, the authors found no evidence that gender moderates the risk of depression. These findings suggest that men and women reporting history of childhood maltreatment are equally likely to suffer major depression in adulthood.
View details for DOI 10.1177/1077559511412067
View details for PubMedID 21727161
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Efficacy and Safety of Mifepristone for the Treatment of Psychotic Depression
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
2011; 31 (4): 436-440
Abstract
Open-label studies and randomized clinical trials have suggested that mifepristone may be effective for the treatment of major depression with psychotic features (psychotic depression). A recent study reported a correlation between mifepristone plasma concentration and clinical response. The current study aimed to evaluate the safety and efficacy of mifepristone and, secondarily, to test whether response was significantly greater among patients with mifepristone plasma concentrations above an a priori hypothesized threshold. A total of 433 patients who met criteria for psychotic depression were randomly assigned to receive 7 days of either mifepristone (300, 600, or 1200 mg) or placebo. Response was defined as a 50% reduction in psychotic symptoms on both days 7 and 56. Cochran-Mantel-Haenszel tests compared (1) the proportion of responders among patients assigned mifepristone versus placebo and (2) the proportion of responders among the subset of patients with plasma concentrations greater than 1660 ng/mL versus placebo. Mifepristone was well tolerated at all 3 doses. The proportion of responders randomized to mifepristone did not statistically differ from placebo. Patients with trough mifepristone plasma concentrations greater than 1660 ng/mL were significantly more likely to have a rapid and sustained reduction in psychotic symptoms than those who received placebo. The study failed to demonstrate efficacy on its primary end point. However, the replication of a statistically significant linear association between mifepristone plasma concentration and clinical response indicates that mifepristone at sufficient plasma levels may potentially be effective in rapidly and durably reducing the psychotic symptoms of patients with psychotic depression.
View details for DOI 10.1097/JCP.0b013e3182239191
View details for Web of Science ID 000292284600006
View details for PubMedID 21694614
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Selective glucocorticoid receptor (type II) antagonists prevent weight gain caused by olanzapine in rats
EUROPEAN JOURNAL OF PHARMACOLOGY
2011; 655 (1-3): 117-120
Abstract
The use of antipsychotic medication has consistently been associated with serious side effects including weight gain and metabolic abnormalities. Strategies for mitigating these side effects have been tested, yet effective interventions have not been identified. The current study tested whether two recently identified selective glucocorticoid receptor antagonists would prevent weight gain induced by the antipsychotic olanzapine. Female Sprague-Dawley rats fed a normal chow diet were randomized (n=10 per group) to receive one of the following for 18days: vehicle, olanzapine plus vehicle (2.4mg/kg), olanzapine plus CORT 112716 (20mg/kg), olanzapine plus CORT 112716 (60mg/kg), olanzapine plus CORT 113083 (20mg/kg), or olanzapine plus CORT 113083 (60mg/kg). Rats receiving olanzapine plus CORT 112716 (60mg/kg) or olanzapine plus CORT 113083 (60mg/kg) gained significantly less weight than rats receiving only olanzapine. Both glucocorticoid receptor antagonists significantly attenuated the weight gain induced by olanzapine in a dose dependent manner. Differences in weight gain were not attributable to decreased food intake.
View details for DOI 10.1016/j.ejphar.2011.01.019
View details for Web of Science ID 000288841000016
View details for PubMedID 21269600
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Catastrophizing, depression and pain-related disability
GENERAL HOSPITAL PSYCHIATRY
2011; 33 (2): 150-156
Abstract
The objective of the study was to examine catastrophizing, depression and their interactive effects in predicting disability in patients with chronic pain.A battery of questionnaires was mailed to primary care patients in a large integrated health care delivery system. The Patient Health Questionnaire was used to assess major depression, the Coping Strategies Questionnaire assessed catastrophizing and the Graded Chronic Pain Scale was used to assess pain intensity and two measures of disability, including self-report of pain interference and days missed from usual activities. Patient medical records were used to assess severe medical illness. Of the 5808 respondents, 2618 met criteria for chronic pain. Multiple regression analyses, covarying for age, gender, severe medical illness and pain intensity, estimated the main and interactive effects of catastrophic thinking and depression on two measures of pain-related disability.Both catastrophic thinking and depression were statistically significant predictors of both measures of pain-related disability, with larger effect sizes observed for catastrophic thinking.Routine assessment of both catastrophic thinking and depression is important in the treatment of chronic pain patients, and modification of these factors may reduce disability and increase the ability of chronic pain patients to participate in daily life activity.
View details for DOI 10.1016/j.genhosppsych.2010.12.008
View details for PubMedID 21596208
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Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice.
Journal of nutrition and metabolism
2011; 2011: 235389-?
Abstract
Previous research has shown that mifepristone can prevent and reverse weight gain in animals and human subjects taking antipsychotic medications. This proof-of-concept study tested whether a more potent and selective glucocorticoid receptor antagonist could block dietary-induced weight gain and increase insulin sensitivity in mice. Ten-week-old, male, C57BL/6J mice were fed a diet containing 60% fat calories and water supplemented with 11% sucrose for 4 weeks. Groups (n = 8) received one of the following: CORT 108297 (80 mg/kg QD), CORT 108297 (40 mg/kg BID), mifepristone (30 mg/kg BID), rosiglitazone (10 mg/kg QD), or vehicle. Compared to mice receiving a high-fat, high-sugar diet plus vehicle, mice receiving a high-fat, high-sugar diet plus either mifepristone or CORT 108297 gained significantly less weight. At the end of the four week treatment period, mice receiving CORT 108297 40 mg/kg BID or CORT 108297 80 mg/kg QD also had significantly lower steady plasma glucose than mice receiving vehicle. However, steady state plasma glucose after treatment was not highly correlated with reduced weight gain, suggesting that the effect of the glucocorticoid receptor antagonist on insulin sensitivity may be independent of its mitigating effect on weight gain.
View details for DOI 10.1155/2011/235389
View details for PubMedID 21811679
View details for PubMedCentralID PMC3146995
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Mifepristone Reduces Weight Gain and Improves Metabolic Abnormalities Associated With Risperidone Treatment in Normal Men
OBESITY
2010; 18 (12): 2295-2300
Abstract
Antipsychotic medications are associated with significant weight gain, type 2 diabetes mellitus, dyslipidemia, and increased cardiovascular risk. The objective of this study was to determine whether mifepristone, a glucocorticoid receptor antagonist, could prevent risperidone-induced weight gain. Using a 2:2:1 randomization scheme, 76 lean, healthy men (BMI 18-23 kg/m(2)) age 18-40 years were randomized to risperidone (n = 30), risperidone plus mifepristone (n = 30) or mifepristone (n = 16) daily for 28 days in an institutional setting. Subjects were provided food ad libitum. Body weight was measured daily. Metabolic measures were taken at study onset, midpoint, and end. Analyses of covariance indicated that the group receiving risperidone plus placebo gained significantly more weight (P < 0.001) and exhibited a significantly greater increase in waist circumference (P < 0.05) than the group receiving risperidone plus mifepristone. Significant differences were also observed for metabolic measures including fasting insulin (P < 0.001) and triglyceride levels (P < 0.05). Mifepristone attenuated increases in weight and reduced the metabolic changes induced by risperidone use, replicating results from a prior study of olanzapine-induced weight gain. These findings suggest mechanistic involvement of the hypothalamic-pituitary-adrenal axis in the weight and cardiometabolic side effects of antipsychotic medications. Future research should continue to test the potential of glucocorticoid antagonists to alleviate the deleterious side effects associated with use of antipsychotic medications.
View details for DOI 10.1038/oby.2010.51
View details for Web of Science ID 000284524700009
View details for PubMedID 20339369
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Preliminary evidence that plasma oxytocin levels are elevated in major depression
PSYCHIATRY RESEARCH
2010; 178 (2): 359-362
Abstract
It is well established that the neuropeptide oxytocin (OT) is involved in regulating social behavior, anxiety, and hypothalamic-pituitary-adrenal (HPA) axis physiology in mammals. Because individuals with major depression often exhibit functional irregularities in these measures, we test in this pilot study whether depressed subjects (n=11) exhibit dysregulated OT biology compared to healthy control subjects (n=19). Subjects were hospitalized overnight and blood samples were collected hourly between 1800 and 0900h. Plasma levels of OT, the closely related neuropeptide argine-vasopressin (AVP), and cortisol were quantified. Results indicated that depressed subjects exhibit increased OT levels compared to healthy control subjects, and this difference is most apparent during the nocturnal peak. No depression-related differences in AVP or cortisol levels were discerned. This depression-related elevation in plasma OT levels is consistent with reports of increased hypothalamic OT-expressing neurons and OT mRNA in depressed patients. This present finding is likewise consistent with the hypothesis that dysregulated OT biology may be a biomarker of the emotional distress and impaired social relationships which characterize major depression. Additional research is required to elucidate the role of OT in the pathophysiology of this psychiatric disorder.
View details for DOI 10.1016/j.psychres.2009.09.017
View details for Web of Science ID 000279988900025
View details for PubMedID 20494448
View details for PubMedCentralID PMC2902664
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Selective glucocorticoid receptor (type II) antagonist prevents and reverses olanzapine-induced weight gain
DIABETES OBESITY & METABOLISM
2010; 12 (6): 545-547
Abstract
Use of antipsychotic medications has been associated consistently with weight gain and metabolic disturbances, and a subsequent increased risk for diabetes and cardiovascular disease. Two experiments tested whether CORT 108297, a newly identified selective glucocorticoid antagonist could (i) reduce and (ii) prevent olanzapine-induced weight gain in rats. In the first experiment, rats dosed only with olanzapine gained a statistically significant amount of weight. When vehicle was added to their olanzapine dose, they continued to gain weight; when CORT 108297 was added to their regimen, they lost a significant amount of weight. Rats administered CORT 108297 plus olanzapine had significantly less abdominal fat than those who received olanzapine alone. In the second experiment, rats receiving olanzapine plus CORT 108297 gained significantly less weight than rats receiving only olanzapine. Increasing doses of CORT 108297 were associated with less weight gain.
View details for DOI 10.1111/j.1463-1326.2009.01185.x
View details for Web of Science ID 000276948400009
View details for PubMedID 20518810
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Mifepristone treatment of olanzapine-induced weight gain in healthy men
ADVANCES IN THERAPY
2009; 26 (10): 959-969
Abstract
Antipsychotic medications are associated with significant weight gain, type 2 diabetes mellitus, dyslipidemia, and increased cardiovascular risk. Suggested mechanisms of weight gain from antipsychotic medication include antagonism of histamine and serotonin receptors, and effects on the hypothalamic-pituitary-adrenal axis. The objective of this study was to determine if mifepristone, a glucocorticoid receptor antagonist, could prevent olanzapine-induced weight gain.This was a randomized, double-blind trial. Fifty-seven lean, healthy men (body mass index 18-25 kg/m(2)) aged 19-38 years were randomized to olanzapine (7.5 mg) (n=22), olanzapine (7.5 mg) plus mifepristone (600 mg) (n=24), or mifepristone (600 mg) (n=11) daily for 2 weeks in an institutional setting. Subjects were provided food ad libitum to accentuate weight gain. Body weight was measured daily.The mean change in baseline weight was +3.2+/-0.9 kg in subjects receiving olanzapine versus +2.0+/-1.2 kg in those receiving olanzapine plus mifepristone (P<0.0001). Subjects receiving mifepristone alone had a similar degree of weight gain compared to those receiving olanzapine plus mifepristone. The olanzapine group had significant increases in waist circumference when compared with the olanzapine plus mifepristone group (3.7+/-1.3 cm vs. 2.2+/-1.9 cm, respectively; P=0.006). Fasting insulin and triglycerides increased more in the olanzapine group, although differences were not statistically significant.Mifepristone was effective in attenuating the increase in weight associated with olanzapine treatment over a 2-week period. Longer-term studies are required to examine the durability and full magnitude of this response.
View details for DOI 10.1007/s12325-009-0070-1
View details for Web of Science ID 000272459100006
View details for PubMedID 19888560
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A multisite trial of mifepristone for the treatment of psychotic depression: A site-by-treatment interaction
CONTEMPORARY CLINICAL TRIALS
2009; 30 (4): 284-288
Abstract
Major Depression with Psychotic Features (psychotic depression) is a common, debilitating psychiatric disease. We hypothesized that mifepristone, a cortisol receptor (GRII) antagonist, would significantly reduce psychotic symptoms in psychotic depression. Two hundred fifty-eight patients with psychotic depression enrolled at 29 sites were randomized to mifepristone or placebo for 7 days. The primary outcome was rapid and sustained response, defined as a 50% or greater decrease in Brief Psychiatric Rating Scale - Positive Symptom Subscale scores at the end of treatment (day7) and 49 days later (day 56). Cochran-Mantel-Haenszel compared proportions of responders to mifepristone versus placebo adjusting for site. Exploratory analyses compared response of patients with mifepristone plasma concentrations of > or =1800 ng/ml to placebo. The primary endpoint was not statistically significant. However, the Breslow-Day test indicated a statistically significant site-by-treatment interaction. Mifepristone produced significantly higher response among the twenty sites who participated from the trial onset (p<.05), whereas no difference was observed at the nine sites added late in the trial. Patients with mifepristone plasma levels > or =1800 ng/ml were significantly more likely to respond than placebo patients (Intent-to-Treat: OR=2.4, p=.03; Initial 20 sites: OR=4.1, p=.002). The results of this trial are instructive in two respects. First, while statistical adjustments for [corrected] site are common in multisite clinical trials, this study reminds trialists to formally evaluate the interaction of site by treatment.Second, the association between increased mifepristone plasma concentration levels and greater clinical response, detected despite the site-by-treatment interaction, suggests that higher plasma levels may be needed for maximizing the probability of a positive response.
View details for DOI 10.1016/j.cct.2009.03.001
View details for Web of Science ID 000266853900002
View details for PubMedID 19318138
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In search of moderators and mediators of hyperglycemia with atypical antipsychotic treatment
JOURNAL OF PSYCHIATRIC RESEARCH
2009; 43 (11): 997-1002
Abstract
Signal detection methods were used to identify values of metabolic variables that predict development of prediabetes or diabetes before (moderators) or associated with treatment (mediators), utilizing data from two multi-center clinical trials of patients with schizophrenia, treated for 6 months with olanzapine (OLZ) or ziprasidone (ZIP). At baseline, participants were often overweight/obese (63% with a body mass index >or=25.0kg/m(2)), dyslipidemic [more than one-third had elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations], and prediabetic (20%). Weight gain was significantly greater in OLZ-treated patients, as was accentuation of dyslipidemia. However, there were no significant correlations between weight gain and lipid changes from baseline to weeks 2, 4, 8 or to last observation. Type 2 diabetes developed in 4% and prediabetes in 18% of the population. Significant baseline predictors of diabetes were a HDL-C concentration <28mg/dL, or being >or=58-years-old if HDL-C concentration was >or=28mg/dL. Baseline plasma glucose concentration >or=92mg/dL was the only significant predictor of developing prediabetes, accounting for 60% of cases. Post-treatment increments in plasma TG concentrations >or=145mg/dL or >or=59mg/dL were significant predictors of diabetes (23%) or prediabetes (27%), respectively. If the increase in TG was <145mg/dL, rapid weight gain >or=6.1kg in 2 weeks predicted development of diabetes (18%). These findings provide a quantitative approach to identify those at greatest treatment-associated risk to develop glucose intolerance, and emphasize the need to address co-morbid medical disorders in these patients.
View details for DOI 10.1016/j.jpsychires.2009.01.010
View details for Web of Science ID 000268287100006
View details for PubMedID 19268968
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Psychosocial Predictors of Resilience After the September 11, 2001 Terrorist Attacks
JOURNAL OF NERVOUS AND MENTAL DISEASE
2009; 197 (4): 266-273
Abstract
The terrorist attacks of September 11, 2001 inflicted distress beyond those directly exposed, thereby providing an opportunity to examine the contributions of a range of factors (cognitive, emotional, social support, coping) to psychological resilience for those indirectly exposed. In an Internet convenience sample of 1281, indices of resilience (higher well-being, lower distress) at baseline (2.5-12 weeks post-attack) were each associated with less emotional suppression, denial and self-blame, and fewer negative worldview changes. After controlling for initial outcomes, baseline negative worldview changes and aspects of social support and coping all remained significant predictors of 6-month outcomes, with worldview changes bearing the strongest relationship to each. These findings highlight the role of emotional, coping, social support, and particularly, cognitive variables in adjustment after terrorism.
View details for DOI 10.1097/NMD.0b013e31819d9334
View details for Web of Science ID 000265249600008
View details for PubMedID 19363383
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Relationships Among Depression, Chronic Pain, Chronic Disabling Pain, and Medical Costs
PSYCHIATRIC SERVICES
2009; 60 (3): 344-350
Abstract
Although evidence suggests that patients with depression use more medical services than those without depression, few studies have examined whether specific subgroups of patients with depression have higher utilization than others. The study compared costs for general medical care with and without psychiatric care for patients with major depression and disabling chronic pain (reference group) with costs for five other groups: those with depression and nondisabling chronic pain, those with major depressive disorder alone, those with no depression who had disabling chronic pain, those with depression who had chronic pain that was not disabling, and those who had neither pain nor depression. Costs for the group with major depressive disorder alone were compared to costs for the three groups without depression.A questionnaire assessing major depressive disorder, chronic pain, and pain-related disability was mailed to a random sample of Kaiser Permanente patients who visited a primary care clinic. A total of 5,808 patients responded (54% participation rate). Costs for a two-year period were obtained from Kaiser Permanente's Cost Management Information System. Analyses were adjusted for presence of any of four major chronic medical illnesses.Total costs for patients in the reference group were significantly higher than costs for the other five subgroups. Regression analyses indicated that continuous measures of severity of pain and severity of depression were associated with increased costs, but no statistically significant interaction of depression and pain on total cost was observed.Patients with major depressive disorder and comorbid disabling chronic pain had higher medical service costs than other groups of patients with and without depression. However, findings suggest that the increases in cost from having both pain and depression are additive and not multiplicative.
View details for Web of Science ID 000263723600010
View details for PubMedID 19252047
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Meditation with yoga, group therapy with hypnosis, and psychoeducation for long-term depressed mood: A randomized pilot trial
JOURNAL OF CLINICAL PSYCHOLOGY
2008; 64 (7): 806-820
Abstract
This randomized pilot study investigated the effects of meditation with yoga (and psychoeducation) versus group therapy with hypnosis (and psychoeducation) versus psychoeducation alone on diagnostic status and symptom levels among 46 individuals with long-term depressive disorders. Results indicate that significantly more meditation group participants experienced a remission than did controls at 9-month follow-up. Eight hypnosis group participants also experienced a remission, but the difference from controls was not statistically significant. Three control participants, but no meditation or hypnosis participants, developed a new depressive episode during the study, though this difference did not reach statistical significance in any case. Although all groups reported some reduction in symptom levels, they did not differ significantly in that outcome. Overall, these results suggest that these two interventions show promise for treating low- to moderate-level depression.
View details for DOI 10.1002/jclp.20496
View details for Web of Science ID 000256994900002
View details for PubMedID 18459121
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Supportive-expressive group therapy for primary breast cancer patients: a randomized prospective multicenter trial
PSYCHO-ONCOLOGY
2008; 17 (5): 438-447
Abstract
The aim is to evaluate the effectiveness of a manualized 12-week supportive-expressive group therapy program among primary breast cancer patients treated in community settings, to determine whether highly distressed patients were most likely to benefit and whether therapist's training or experience was related to outcome.Three hundred and fifty-three women within one year of diagnosis with primary breast cancer were randomly assigned to receive supportive-expressive group therapy or to an education control condition. Participants were recruited from two academic centers and nine oncology practices, which were members of NCI's Community Clinical Oncology Program (CCOP) and were followed over 2 years.A 2x2x19 analysis of variance was conducted with main effects of treatment condition, cohort, and baseline distress and their interactions. There was no main effect for treatment condition after removing one subject with an extreme score. Highly distressed women did not derive a greater benefit from treatment. Therapist training and psychotherapy experience were not associated with a treatment effect.This study provides no evidence of reduction in distress as the result of a brief supportive-expressive intervention for women with primary breast cancer. Future studies might productively focus on women with higher initial levels of distress.
View details for DOI 10.1002/pon.1280
View details for Web of Science ID 000256463200003
View details for PubMedID 17935144
View details for PubMedCentralID PMC3037799
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Depression symptoms during pregnancy
ARCHIVES OF WOMENS MENTAL HEALTH
2008; 11 (1): 43-48
Abstract
Pregnancy impacts common symptoms of major depressive disorder (MDD), such as energy, appetite, weight change, and sleep and somatic complaints. However, it is not known whether the presentation of depression during pregnancy is different from that at other times in women's lives. This study compares the severity of symptoms of depression in 61 pregnant women with MDD (PD), 50 nonpregnant women with MDD (D), and 41 pregnant women without MDD (P). Despite equivalent overall depression severity, PD women had lower scores on suicidality, guilt, and early insomnia and higher scores on psychomotor retardation than D women. The severity of other depressive symptoms was similar in the two depressed groups. As expected on the basis of the selection criteria, overall depression severity and the severity of individual symptoms were significantly higher in the PD group than in the P group but effect sizes for somatic symptoms were smaller than for psychological symptoms. The results suggest that the profile of depression symptoms of women with MDD who are pregnant does not differ much from that of depressed nonpregnant women. Depressive symptoms, particularly psychological symptoms of depression, during pregnancy should be taken seriously and not be dismissed as a normal part of the pregnancy experience.
View details for DOI 10.1007/s00737-008-0216-1
View details for Web of Science ID 000253695000006
View details for PubMedID 18270654
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Dropouts versus completers among chronically depressed outpatients
JOURNAL OF AFFECTIVE DISORDERS
2007; 97 (1-3): 197-202
Abstract
Premature termination is common among patients treated for depression with either pharmacotherapy or psychotherapy. Yet little is known about factors associated with premature treatment termination among depressed patients.This study examines predictors of, time to, and reasons for dropout from the 12-week acute phase treatment of nonpsychotic adult outpatients, age 18-75, with chronic major depression who were randomly assigned to nefazadone alone (MED), cognitive behavioral analysis system of psychotherapy alone (CBASP) or both treatments (COMB).Of 681 randomized study participants, 156 were defined as dropouts. Dropout rates were equivalent across the three treatments. Among dropouts, those in COMB remained in treatment (Mean=40 days) significantly longer than those in either MED (Mean=27 days) or CBASP (Mean=28 days). Dropouts attributed to medication side-effects were significantly lower in COMB than in MED, suggesting that the relationship with the psychotherapist may increase patient willingness to tolerate side-effects associated with antidepressant medications. Ethnic or racial minority status, younger age, lower income, and co-morbid anxiety disorders significantly predicted dropout in the full sample. Within treatments, differences between completers and dropouts in minority status and the prevalence of anxiety disorders were most pronounced in MED. Among those receiving CBASP, dropouts had significantly lower therapeutic alliance scores than completers.The sample included only individuals with chronic depression.Predictors of dropout included baseline patient characteristics, but not early response to treatment. Ethnic and racial minorities and those with comorbid anxiety are at higher risk of premature termination, particularly in pharmacotherapy, and may require modified treatment strategies.
View details for DOI 10.1016/j.jad.2006.06.017
View details for Web of Science ID 000243734600023
View details for PubMedID 16857266
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Mifepristone versus placebo in the treatment of psychosis in patients with psychotic major depression
43rd Annual Meeting of the American-College-of-Neuropsychopharmacology
ELSEVIER SCIENCE INC. 2006: 1343–49
Abstract
Abnormalities in the hypothalamic pituitary adrenal axis have been implicated in the pathophysiology of psychotic major depression (PMD). Recent studies have suggested that the antiglucocorticoid, mifepristone might have a role in the treatment of PMD. The current study tested the efficacy of mifepristone treatment of the psychotic symptoms of PMD.221 patients, aged 19 to 75 years, who met DSM-IV and SCID criteria for PMD and were not receiving antidepressants or antipsychotics, participated in a double blind, randomized, placebo controlled study. Patients were randomly assigned to either 7 days of mifepristone (n = 105) or placebo (n = 116) followed by 21 days of usual treatment.Patients treated with mifepristone were significantly more likely to achieve response, defined as a 30% reduction in the Brief Psychiatric Rating Scale (BPRS). In addition, mifepristone treated patients were significantly more likely to achieve a 50% reduction in the BPRS Positive Symptom Scale (PSS). No significant differences were observed on measures of depression.A seven day course of mifepristone followed by usual treatment appears to be effective and well tolerated in the treatment of psychosis in PMD. This study suggests that the antiglucocorticoid, mifepristone, might represent an alternative to traditional treatments of psychosis in psychotic depression.
View details for DOI 10.1016/j.biopsych.2006.05.034
View details for Web of Science ID 000242735700011
View details for PubMedID 16889757
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The efficacy of mifepristone in the reduction and prevention of olanzapine-induced weight gain in rats
BEHAVIOURAL BRAIN RESEARCH
2006; 171 (2): 225-229
Abstract
Atypical antipsychotics, such as olanzapine, have been associated with clinically significant weight gain. Changes to the hypothalamic pituitary adrenal axis may partially mediate this weight increase. Two experiments were conducted to test the effects of mifepristone on both mitigating and preventing olanzapine-induced weight gain. In the first experiment, adult female Sprague-Dawley rats gained significantly more weight on average when administered olanzapine for 35 days compared to vehicle controls. Subsequently, the olanzapine-treated rats were randomized to three dose levels of mifepristone (20, 60, and 200 mg/kg) in conjunction with olanzapine. Weight measurements were taken for 21 additional days. Rats receiving olanzapine plus mifepristone rapidly lost a significant portion of the weight gained during the olanzapine only phase (p = 0.0001). Rats in the 200 mg/kg dose group had significantly less abdominal fat compared to controls (p < 0.001) at study end. In the second experiment, daily mifepristone (20, 60, 200 mg/kg) initiated concomitantly with olanzapine was compared with olanzapine alone to determine if mifepristone prevented olanzapine-induced weight gain. After 21 days of treatment, mifepristone treated rats gained significantly less weight and had significantly less abdominal fat than rats administered olanzapine alone (p = 0.0002). Results suggest that mifepristone, a potent glucocorticoid antagonist, may both reduce and prevent olanzapine-induced weight gain in rats.
View details for DOI 10.1016/j.bbr.2006.03.039
View details for Web of Science ID 000239197500006
View details for PubMedID 16782211
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Comorbid depression, chronic pain, and disability in primary care
PSYCHOSOMATIC MEDICINE
2006; 68 (2): 262-268
Abstract
The objectives of this study were to provide estimates of the prevalence and strength of association between major depression and chronic pain in a primary care population and to examine the clinical burden associated with the two conditions, singly and together.A random sample of Kaiser Permanente patients who visited a primary care clinic was mailed a questionnaire assessing major depressive disorder (MDD), chronic pain, pain-related disability, somatic symptom severity, panic disorder, other anxiety, probable alcohol abuse, and health-related quality of life (HRQL). Instruments included the Patient Health Questionnaire, SF-8, and Graded Chronic Pain Questionnaire. A total of 5808 patients responded (54% of those eligible to participate).Among those with MDD, a significantly higher proportion reported chronic (i.e., nondisabling or disabling) pain than those without MDD (66% versus 43%, respectively). Disabling chronic pain was present in 41% of those with MDD versus 10% of those without MDD. Respondents with comorbid depression and disabling chronic pain had significantly poorer HRQL, greater somatic symptom severity, and higher prevalence of panic disorder than other respondents. The prevalence of probable alcohol abuse/dependence was significantly higher among persons with MDD compared with individuals without MDD regardless of pain or disability level. Compared with participants without MDD, the prevalence of other anxiety among those with MDD was more than sixfold greater regardless of pain or disability level.Chronic pain is common among those with MDD. Comorbid MDD and disabling chronic pain are associated with greater clinical burden than MDD alone.
View details for DOI 10.1097/01.psy.0000204851.15499.fc
View details for Web of Science ID 000236591400013
View details for PubMedID 16554392
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Assessing insomnia severity in depression: comparison of depression rating scales and sleep diaries
JOURNAL OF PSYCHIATRIC RESEARCH
2005; 39 (5): 481-488
Abstract
Depression and sleep researchers typically assess insomnia severity differently. Whereas depression researchers usually assess insomnia with items on depression symptom inventories, sleep researchers usually assess the subjective experience of insomnia with sleep diaries. The present manuscript utilizes baseline data from 397 participants in a large multi-site chronic depression study to assess agreement between these two methodologies. The results indicate that the early, middle, and late insomnia items of the Hamilton Rating Scale for Depression (HRSD(24)) and the Inventory of Depression Symptoms - Self Report (IDS-SR(30)) are highly correlated with the weekly mean values of time to sleep onset, time awake after sleep onset, and time awake prior to the planned wake-up obtained from prospective sleep diaries. Results also reveal significant correspondence between the weekly-mean of daily sleep efficiency, an accepted measure of sleep continuity (the ratio between reported time asleep and time in bed), and the insomnia scale scores of the HRSD(24) and the IDS-SR(30) (the mean score on the three insomnia items of each depression measure). Unit increments in HRSD(24) scores for early, middle and late insomnia were associated with significant increases in unwanted minutes awake for corresponding periods on sleep diaries. Similar relationships were found for early insomnia on the IDS-SR(30) but not for middle and late insomnia. Overall, with few exceptions, findings revealed substantial agreement between the HRSD(24), IDS-SR(30) and prospective sleep diary data. The study supports the validity of the sleep items and sleep subscales of the HRSD(24) and the IDS-SR(30) as global measures of insomnia severity in depression. Conventional sleep assessment procedures can complement depression scales by providing additional information about specific aspects of sleep in depression.
View details for DOI 10.1016/j.jpsychires.2004.12.003
View details for Web of Science ID 000231579300005
View details for PubMedID 15992557
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The association between patient characteristics and the therapeutic alliance in cognitive-behavioral and interpersonal therapy for bulimia nervosa
JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
2005; 73 (2): 203-211
Abstract
The therapeutic alliance is an established predictor of psychotherapy outcome. However, alliance research in the treatment of eating disorders has been scant, with even less attention paid to correlates of alliance development. The goal of this study was to examine the relation between specific patient characteristics and the development of the alliance in 2 different treatments for bulimia nervosa (BN). Data derive from a large, randomized clinical trial comparing cognitive- behavioral therapy (CBT) and interpersonal therapy (IPT) for BN. Across both treatments, patient expectation of improvement was positively associated with early- and middle-treatment alliance quality. In CBT, baseline symptom severity was negatively related to middle alliance. In IPT, more baseline interpersonal problems were associated with poorer alliance quality at midtreatment.
View details for DOI 10.1037/0022-006X.73.2.203
View details for Web of Science ID 000227924100002
View details for PubMedID 15796627
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From research to practice: Teacher and pediatrician awareness of phenotypic traits in neurogenetic syndromes
AMERICAN JOURNAL ON MENTAL RETARDATION
2005; 110 (2): 100-106
Abstract
Pediatricians' and teachers' knowledge of physical, cognitive, and behavioral features associated with three genetic syndromes were assessed and the effectiveness of information sources about these syndromes evaluated. The surveyed sample included 53 pediatricians and 69 teachers from Northern and Central California. Respondents demonstrated limited knowledge regarding the physical phenotype of fragile X syndrome and significantly less knowledge of velo-cardio-facial syndrome (VCFS). In the cognitive and behavioral domains, significantly more was known about Down and fragile X syndromes than VCFS. Pediatricians and teachers make critical treatment and education decisions for children with these syndromes and would benefit from continued professional development about these syndromes through conferences, professional/association publications, in-service teacher training, and journals.
View details for Web of Science ID 000227920600003
View details for PubMedID 15762820
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A randomized trial of the efficacy of group therapy in changing viral load and CD4 counts in individuals living with HIV infection
INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE
2005; 35 (4): 349-362
Abstract
This randomized pilot study evaluates whether seropositive patients who are randomly assigned to receive a supportive-expressive group therapy plus education intervention show greater improvements in increased immune function and decreased viral load compared to those randomly assigned to an education-only intervention.Fifty-nine individuals who had been HIV-seropositive for at least 6 months prior to inclusion in the study and had been receiving standard pharmacologic treatment were entered in a prospective randomized trial of the effects of weekly supportive-expressive group therapy on changes in immune status. Participants were matched for AIDS status and sex and randomized to receive weekly sessions of group psychotherapy plus educational materials on HIV/AIDS, or to receive the educational materials alone. Participants were assessed before treatment and then 12 weeks later.Individuals who were randomized to group therapy showed a statistically significant increase in CD4 count and decrease in HIV viral load. Among individuals randomized to the education only condition, no significant change occurred in CD4 count or viral load.These results provide preliminary data suggesting that HIV-seropositive individuals who receive supportive-expressive group psychotherapy may experience concomitant improvements in CD4 cell count and viral load. Further research with a larger sample should examine the possible underlying mechanisms of such benefits.
View details for Web of Science ID 000236681800004
View details for PubMedID 16673835
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Acupuncture: a promising treatment for depression during
JOURNAL OF AFFECTIVE DISORDERS
2004; 83 (1): 89-95
Abstract
Few medically acceptable treatments for depression during pregnancy are available. The aim of this randomized controlled pilot study was to determine whether acupuncture holds promise as a treatment for depression during pregnancy.Sixty-one pregnant women with major depressive disorder and a 17-item Hamilton Rating Scale for Depression (HRSD17) score >or=14 were randomly assigned to one of three treatments, delivered over 8 weeks: an active acupuncture (SPEC, N=20), an active control acupuncture (NSPEC, N=21), and massage (MSSG, N=20). Acupuncture treatments were standardized, but individually tailored, and were provided in a double-blind fashion. Responders to acute phase treatment (HRSD17 score<14 and >or=50% reduction from baseline) continued the treatment they were initially randomized to until 10 weeks postpartum.Response rates at the end of the acute phase were statistically significantly higher for SPEC (69%) than for MSSG (32%), with an intermediate NSPEC response rate (47%). The SPEC group also exhibited a significantly higher average rate of reduction in BDI scores from baseline to the end of the first month of treatment than the MSSG group. Responders to the acute phase of all treatments combined had significantly lower depression scores at 10 weeks postpartum than nonresponders.Generalizability is limited by the small sample and its relative homogeneity.Acupuncture holds promise for the treatment of depression during pregnancy.
View details for DOI 10.1016/j.jad.2004.05.009
View details for Web of Science ID 000225913900012
View details for PubMedID 15546651
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Emotional attribution in high-functioning individuals with autistic spectrum disorder: A functional imaging study
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
2004; 43 (4): 473-480
Abstract
To determine whether expertise in the attribution of emotion from basic facial expressions in high-functioning individuals with autistic spectrum disorder (ASD) is supported by the amygdala, fusiform, and prefrontal regions of interest (ROI) and is comparable to that of typically developing individuals.Functional magnetic resonance imaging scans were acquired from 14 males with ASD and 10 matched adolescent controls while performing emotion match (EM) (perceptual), emotion label (EL) (linguistic), and control tasks. Accuracy, response time, and average activation were measured for each ROI.There was no significant difference in accuracy, response time, or ROI activation between groups performing the EL task. The ASD group was as accurate as the control group performing the EM task but had a significantly longer response time and lower average fusiform activation.Expertise in the attribution of emotion from basic facial expressions was task-dependent in the high-functioning ASD group. The hypothesis that the high-functioning ASD group would be less expert and would have reduced fusiform activation was supported in the perceptual task but not the linguistic task. The reduced fusiform activation in the perceptual task was not explained by reduced expertise; it is therefore concluded that reduced fusiform activation is associated with the diagnosis of ASD.
View details for DOI 10.1097/01.chi.0000111363.94169.37
View details for Web of Science ID 000220384300014
View details for PubMedID 15187808
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Centring in regression analyses: a strategy to prevent errors in statistical inference
INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH
2004; 13 (3): 141-151
Abstract
Regression analyses are perhaps the most widely used statistical tools in medical research. Centring in regression analyses seldom appears to be covered in training and is not commonly reported in research papers. Centring is the process of selecting a reference value for each predictor and coding the data based on that reference value so that each regression coefficient that is estimated and tested is relevant to the research question. Using non-centred data in regression analysis, which refers to the common practice of entering predictors in their original score format, often leads to inconsistent and misleading results. There is very little cost to unnecessary centring, but the costs of not centring when it is necessary can be major. Thus, it would be better always to centre in regression analyses. We propose a simple default centring strategy: (1) code all binary independent variables +1/2; (2) code all ordinal independent variables as deviations from their median; (3) code all 'dummy variables' for categorical independent variables having m possible responses as 1 - 1/m and -1/m instead of 1 and 0; (4) compute interaction terms from centred predictors. Using this default strategy when there is no compelling evidence to centre protects against most errors in statistical inference and its routine use sensitizes users to centring issues.
View details for Web of Science ID 000223930100001
View details for PubMedID 15297898
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Neuropsychological correlates of psychotic features in major depressive disorders: a review and meta-analysis
Conference on Non Schizophrenic Psychoses
PERGAMON-ELSEVIER SCIENCE LTD. 2004: 27–35
Abstract
Neuropsychological functioning has been a focus of study in psychotic disorders for many decades. These studies have focused primarily on schizophrenia, and less so on the affective psychoses, including psychotic major depression PMD. Several studies have provided evidence of cognitive dysfunction in PMD. However, these studies have utilized different assessment methods and instruments. Consequently, a clear picture of the nature and severity of cognitive impairment in PMD has yet to emerge in the literature. The current review seeks to provide a summary of the literature by composing a quantitative and qualitative review of the research to date on the cognitive impairment in psychotic major depression, specifically as it contrasts to those deficits observed in nonpsychotic depression. This review also provides a summary model of the pathophysiology of PMD to provide the necessary context to understanding the biological mechanisms of these impairments.
View details for DOI 10.1016/S0022-3956(03)00100-6
View details for Web of Science ID 000220190700004
View details for PubMedID 14690768
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A typology of non-adherence in pediatric renal transplant recipients
PEDIATRIC TRANSPLANTATION
2003; 7 (6): 489-493
Abstract
We reviewed 112 pediatric renal transplant recipients to document the rate of medication non-adherence (NA) and to examine the relationships between NA, comorbid psychiatric illness, and the outcome variables of acute and chronic rejection and graft loss. A total of 32.5% of subjects had clinically significant NA with treatment based on review of serum immunosuppressant levels. NA was found to be significantly related to acute and chronic rejection, and graft loss (p < 0.001). NA was also related to the presence of comorbid psychiatric illness (p < 0.001). Logistic regression indicated that NA was a significant predictor for acute and chronic rejection, while psychiatric illness predicted graft loss. Adolescents had significantly higher rates of NA as well as shorter intervals between transplant date and onset of NA when compared with child patients (p < 0.001). Physician ratings of the primary reasons for NA suggested that lack of parental supervision and parent-child conflict were the major factors related to NA.
View details for Web of Science ID 000186500400014
View details for PubMedID 14870900
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Therapeutic reactance as a predictor of outcome in the treatment of chronic depression
JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
2003; 71 (6): 1025-1035
Abstract
This study examined whether reactance would negatively influence treatment outcome in 347 patients diagnosed with chronic forms of depression and treated at 9 sites with either Nefazodone, cognitive-behavioral analysis system of psychotherapy (CBASP), or combination therapy. Contrary to our hypotheses, reactance positively predicted treatment outcome in CBASP on 2 of 4 scales. These effects were independent of the therapeutic alliance, which also positively predicted outcome. Reactance did not predict outcome in the groups receiving medication alone or in combination with CBASP. The findings suggest that reactance may be an asset in psychotherapy among chronically depressed individuals and that reactant patients can benefit from directive psychotherapy when therapists flexibly respond to perturbations in the therapeutic relationship. Results support the importance of Aptitude * Treatment interactions in psychotherapy outcome. The direction and significance of such interactions may vary with different forms of psychopathology.
View details for DOI 10.1037/0022-006X.71.6.1025
View details for Web of Science ID 000186693600008
View details for PubMedID 14622078
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Temperament characteristics of child and adolescent bipolar offspring
JOURNAL OF AFFECTIVE DISORDERS
2003; 77 (1): 11-19
Abstract
We wished to characterize temperament of children at high risk for bipolar disorder (BD).We collected data from the Dimensions of Temperament-Revised (DOTS-R) from 53 biological offspring of at least one parent with BD.Overall, our cohort differed from population means for the DOTS-R, having decreased Activity Level-General scores, and increased Approach, and Rhythmicity-Sleep scores. Offspring with psychiatric disorders differed from those without in having decreased Flexibility, Mood, and Task Orientation scores. Temperament profiles for diagnostic categories of BD and attention-deficit/hyperactivity disorder were performed in a descriptive manner.Self- or parent-report of temperament was used rather than clinical observation. Temperament characterization was cross-sectional and retrospective rather than prospective and may overlap with clinical diagnoses.Assessment of temperament may be useful in characterizing bipolar offspring. Decreased flexibility and task orientation, and presence of negative moods may be correlated with development of psychopathology.
View details for DOI 10.1016/S0165-0327(02)00105-2
View details for PubMedID 14550931
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Effects of X-monosomy and X-linked imprinting on superior temporal gyrus morphology in Turner syndrome
BIOLOGICAL PSYCHIATRY
2003; 54 (6): 636-646
Abstract
Turner syndrome (TS) results from complete or partial monosomy X. The cognitive phenotype of TS involves preservation of verbal skills with visuospatial functioning deficits. The superior temporal gyrus (STG), which is involved in language capacities, has not been investigated in TS.The STG was measured in 30 female subjects (mean age = 14.73 +/- 6.41; range = 7.56-33.30) with TS and 30 age-matched control subjects (mean age = 14.63 +/- 5.90; range = 6.35-32.65) using volumetric magnetic resonance imaging analyses.-Right STG, including both gray and white matter volumes, was significantly larger in TS compared with control subjects. Overall left STG volume was not significantly different between groups, although left white matter volume was increased in the TS subjects. The TS subgroup with a maternally derived X chromosome (Xm) demonstrated more aberrant STG volumes compared with subjects with a paternally (Xp) derived X and control subjects. The difference in STG volumes between Xm and control subjects involved both white and gray matter. The Xm subjects differed from Xp subjects only in terms of gray matter.These findings suggest that X-monosomy and X-linked imprinting negatively affect STG development, possibly by disrupting neural pruning mechanisms.
View details for DOI 10.1016/S0006-3223(03)00289-0
View details for Web of Science ID 000185264700007
View details for PubMedID 13129659
View details for PubMedCentralID PMC3061621
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Divalproex monotherapy in the treatment of bipolar offspring with mood and behavioral disorders and at least mild affective symptoms
41st Annual Meeting of the New-Clinical-Drug-Evaluation-Unit
PHYSICIANS POSTGRADUATE PRESS. 2003: 936–42
Abstract
Offspring of parents with bipolar disorder, by virtue of their high-risk status for developing bipolar disorder, merit an investigation of the efficacy of treatment with mood stabilizers. Behavioral and mood difficulties in this population may represent prodromal forms of bipolar disorder. We studied the efficacy of divalproex in treating child and adolescent bipolar offspring with mood or behavioral disorders who did not yet meet criteria for bipolar I or II disorder.We studied 24 children aged 6-18 years (mean = 11.3 years; 17 boys/7 girls) with at least 1 biological parent with bipolar disorder. Participants were diagnosed by the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia with at least 1 of the following DSM-IV disorders: major depressive disorder, dysthymic disorder, cyclothymic disorder, or attention-deficit/hyperactivity disorder. Subjects all had at least moderate affective symptoms (28-item Hamilton Rating Scale for Depression or Young Mania Rating Scale score > 12). After a 2-week washout period, subjects were treated with divalproex for 12 weeks, titrated to achieve serum levels of 50-120 micro g/mL (mean final dose = 821 mg/day; mean final serum level = 79.0 micro g/mL).One subject discontinued after 2 weeks due to continuation of symptoms. Of the remaining 23 subjects, 18 (78%) were considered responders by primary outcome criteria ("very much improved" or "much improved" on the Clinical Global Impressions-Improvement scale). Divalproex was well tolerated with no discontinuations due to adverse effects.Bipolar offspring with mood or behavioral disorders and at least mild affective symptoms may respond to divalproex treatment. Our study was limited by the open treatment, lack of a placebo group, and the heterogeneous nature of the sample. Controlled studies are warranted in the use of divalproex in symptomatic bipolar offspring.
View details for Web of Science ID 000184920400012
View details for PubMedID 12927009
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Factors associated with parenting stress in mothers of children with fragile X syndrome
JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
2003; 24 (4): 267-275
Abstract
Whereas previous research has demonstrated elevated levels of parenting stress in parents of children with general developmental disability, there has been little investigation of stress in parents of children specifically affected by the common neurogenetic disorder fragile X syndrome (FraX). This study elucidates stress profiles in mothers of children with FraX and delineates the contribution of child characteristics, home environment, and maternal psychological functioning to specific dimensions of parental stress. Data on child, home, and family characteristics were collected from 75 families with a child affected by FraX. These characteristics were entered into multiple regression analyses with a domain or subscale of the Parenting Stress Index as the dependent variable in each analysis. The results demonstrated that aspects of child behavior, family cohesion, household income, and maternal psychopathology differentially correlate with specific dimensions of parenting stress. Determining the relative contribution of factors associated with stress will assist in the development of interventions to improve parental well-being in mothers of children with FraX.
View details for Web of Science ID 000184777800007
View details for PubMedID 12915799
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Patient's therapeutic skill acquisition and response to psychotherapy, alone or in combination with medication
PSYCHOLOGICAL MEDICINE
2003; 33 (4): 693-702
Abstract
We tested the hypotheses that the addition of medication to psychotherapy enhances participation in the latter by: (1) speeding the acquisition of the psychotherapy's targeted skill; and (2) facilitating higher skill level acquisition.Participants were 431 chronically depressed patients who received Cognitive Behavioral Analysis System of Psychotherapy (CBASP), alone (N=214) or in combination with nefazodone (N=217), as part of a randomized chronic depression study (Keller et al. 2000). CBASP, developed specifically to treat chronic depression, uses a specific procedure, 'situational analysis' to help patients engage in more effective goal-oriented interpersonal behaviours. At the end of each session, therapists rated patients on their performance of situational analysis. Outcome on depressive symptoms was assessed with the 24-item Hamilton Rating Scale for Depression.Although reductions in depression were significantly greater in combined treatment compared to CBASP alone, there were no between-group differences in either the rate of skill acquisition or overall skill level at the end of treatment. Proficiency in the use of the main skill taught in psychotherapy at treatment midpoint predicted outcome independently of medication status and of baseline depressive severity.Effective participation in CBASP, as reflected by proficiency in the compensatory skill taught in psychotherapy, is not enhanced by the addition of medication and does not mediate the between-group difference in depression outcome.
View details for DOI 10.1017/S0033291703007608
View details for Web of Science ID 000183495600013
View details for PubMedID 12785471
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Premorbid intellectual functioning, education, and brain size in traumatic brain injury: An investigation of the cognitive reserve hypothesis
APPLIED NEUROPSYCHOLOGY
2003; 10 (3): 153-162
Abstract
Cognitive reserve theories have been postulated in an attempt to explain individual differences in functional outcome following cerebral insult or disease. These theories suggest that higher education and psychometric intelligence may preserve functional capacity regardless of injury or disease severity. This study investigated cognitive reserve in 25 participants with traumatic brain injury (TBI) using high-resolution magnetic resonance imaging (MRI) analyses. We examined the relationships between total intracranial volume (TICV), ventricle-tobrain ratio (VBR), education level, and standardized testing obtained prior to injury with post-injury cognitive outcome. Participants with lower post-injury IQ scores had significantly lower TICV values, irrespective of injury severity, and experienced significantly greater change in IQ from pre- to post-injury. TICV and education correctly predicted participants' post-injury IQ category ( Y 90 or < 90). However, premorbid standardized testing (PST) scores did not predict cognitive outcome. The results of this study suggest that larger premorbid brain volume and higher education level may decrease vulnerability to cognitive deficits following TBI, consistent with the notion of a cognitive reserve.
View details for Web of Science ID 000189387500004
View details for PubMedID 12890641
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Amygdalar activation associated with positive and negative facial expressions
NEUROREPORT
2002; 13 (14): 1737-1741
Abstract
Most theories of amygdalar function have underscored its role in fear. One broader theory suggests that neuronal activation of the amygdala in response to fear-related stimuli represents only a portion of its more widespread role in modulating an organism's vigilance level. To further explore this theory, the amygdalar response to happy, sad, angry, fearful, and neutral faces in 17 subjects was characterized using 3 T fMRI. Utilizing a random effects model and hypothesis-driven analytic strategy, it was observed that each of the four emotional faces was associated with reliable bilateral activation of the amygdala compared with neutral. These findings suggest a broader role for the amygdala in modulating the vigilance level during the perception of several negative and positive facial emotions.
View details for Web of Science ID 000179156600009
View details for PubMedID 12395114
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Cortisol and behavior in fragile X syndrome
PSYCHONEUROENDOCRINOLOGY
2002; 27 (7): 855-872
Abstract
The purpose of this study was to determine if children with fragile X syndrome, who typically demonstrate a neurobehavioral phenotype that includes social anxiety, withdrawal, and hyper-arousal, have increased levels of cortisol, a hormone associated with stress. The relevance of adrenocortical activity to the fragile X phenotype also was examined.One hundred and nine children with the fragile X full mutation (70 males and 39 females) and their unaffected siblings (51 males and 58 females) completed an in-home evaluation including a cognitive assessment and a structured social challenge task. Multiple samples of salivary cortisol were collected throughout the evaluation day and on two typical non-school days. Measures of the fragile X mental retardation (FMR1) gene, child intelligence, the quality of the home environment, parental psychopathology, and the effectiveness of educational and therapeutic services also were collected. Linear mixed-effects analyses were used to examine differences in cortisol associated with the fragile X diagnosis and gender (fixed effects) and to estimate individual subject and familial variation (random effects) in cortisol hormone levels. Hierarchical multiple regression analyses were conducted to determine whether adrenocortical activity is associated with behavior problems after controlling for significant genetic and environmental factors.Results showed that children with fragile X, especially males, had higher levels of salivary cortisol on typical days and during the evaluation. Highly significant family effects on salivary cortisol were detected, consistent with previous work documenting genetic and environmental influences on adrenocortical activity. Increased cortisol was significantly associated with behavior problems in boys and girls with fragile X but not in their unaffected siblings.These results provide evidence that the function of the hypothalamic-pituitary-adrenal axis may have an independent association with behavioral problems in children with fragile X syndrome.
View details for Web of Science ID 000178462800008
View details for PubMedID 12183220
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Characterization of children of bipolar parents by parent report CBCL
JOURNAL OF PSYCHIATRIC RESEARCH
2002; 36 (5): 337-345
Abstract
In past research the Child Behavior Checklist (CBCL) has differentiated among various diagnostic categories for children and adolescents. However, research has not been conducted on whether the CBCL differentiates among diagnostic categories for children at high risk for development of psychopathology. This study compares four diagnostic groups [bipolar disorder (BD), attention/deficit-hyperactivity disorder (ADHD), Depressed/Anxious and No Diagnosis] within a cohort of 58 children of bipolar parents to determine whether their CBCL scores will replicate the scores of children not at high risk for bipolar disorder. The cohort of children of bipolar parents received elevated scores on the CBCL scales in comparison with non-clinical populations. In addition, the CBCL distinguished between children of bipolar parents with and without clinical disorders. Finally the BD group differed from the ADHD group only on the Aggressive Behaviors, Withdrawn and Anxious/Depressed subscales of the CBCL. Therefore the CBCL did not discriminate between the BD and ADHD groups as it had in previous studies of children with BD and unspecified family history. It is possible that this discrepancy is due to a group of children of bipolar parents with ADHD who are currently prodromal for bipolar disorder and therefore received higher scores on the CBCL based on prodromal symptomatology. A longitudinal follow-up of this cohort is necessary to ascertain whether this is the case.
View details for Web of Science ID 000178254700009
View details for PubMedID 12127602
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Language skills in children with velocardiofacial syndrome (deletion 22q11.2)
JOURNAL OF PEDIATRICS
2002; 140 (6): 753-758
Abstract
To further define the language profile of children with velocardiofacial syndrome (VCFS) and explore the influence of parental origin of the deletion on language.Children and adolescents with VCFS (n = 27) were group-matched for sex, age, and IQ with 27 children and adolescents with idiopathic developmental delay. Fifty-four typically developing control subjects were also included in the analyses investigating word association abilities.Children with VCFS had significantly lower receptive than expressive language skills, a unique finding when compared with IQ-matched control subjects. However, no significant differences in word association were detected. Children with a deletion of paternal origin score significantly higher on receptive language when compared with children with a deletion of maternal origin.The Clinical Evaluation of Language Fundamentals-III results suggest that children with VCFS show more severe deficits in receptive than expressive language abilities. Language skills of children with VCFS could be influenced by parental origin of the deletion and thus related to neuroanatomic alterations at the deletion site.
View details for DOI 10.1067/mpd.2002.124774
View details for Web of Science ID 000176520300021
View details for PubMedID 12072882
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A developmental fMRI study of the stroop color-word task
NEUROIMAGE
2002; 16 (1): 61-75
Abstract
We used fMRI to investigate developmental changes in brain activation during a Stroop color-word interference task. A positive correlation was observed between age and Stroop-related activation (n = 30) in the left lateral prefrontal cortex, the left anterior cingulate, and the left parietal and parieto-occipital cortices. No regions showed a negative correlation between activation and age. We further investigated age-related differences by stratifying the sample into three age groups: children (ages 7-11), adolescents (ages 12-16), and young adults (ages 18-22). Young adult subjects (n = 11) displayed significant activation in the inferior and middle frontal gyri bilaterally, the left anterior cingulate, and bilateral inferior and superior parietal lobules. Between-group comparisons revealed that young adults had significantly greater activation than adolescent subjects (n = 11) in the left middle frontal gyrus and that young adults showed significantly greater activation than children (n = 8) in the anterior cingulate and left parietal and parieto-occipital regions, as well as in the left middle frontal gyrus. Compared to children, both adult and adolescent subjects exhibited significantly greater activation in the parietal cortex. Adult and adolescent groups, however, did not differ in activation for this region. Together, these data suggest that Stroop task-related functional development of the parietal lobe occurs by adolescence. In contrast, prefrontal cortex function contributing to the Stroop interference task continues to develop into adulthood. This neuromaturational process may depend on increased ability to recruit focal neural resources with age. Findings from this study, the first developmental fMRI investigation of the Stroop interference task, provide a template with which normal development and neurodevelopmental disorders of prefrontal cortex function can be assessed.
View details for DOI 10.1006/nimg.2001.1046
View details for Web of Science ID 000176624700007
View details for PubMedID 11969318
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Psychiatric disorders and behavioral problems in children with velocardiofacial syndrome: Usefulness as phenotypic indicators of schizophrenia risk
BIOLOGICAL PSYCHIATRY
2002; 51 (4): 312-318
Abstract
Velocardiofacial syndrome (VCFS), a genetic deletion condition with numerous cognitive sequelae, is associated with a high rate of psychiatric disorders in childhood. More recently, VCFS has been identified as a high-risk factor for developing adult onset schizophrenia. However, it has never been demonstrated that the childhood psychiatric disorders found in children with VCFS differ from those found in children with a similar degree of cognitive impairment. Identification of a specific behavioral (psychiatric) phenotype in childhood VCFS offers the potential for elucidating the symptomatic precursors of adult onset schizophrenia.Twenty-eight children with VCFS and 29 age- and cognitively matched control subjects received a standardized assessment of childhood psychiatric disorders and behaviors measured by the Child Behavior Checklist (CBCL). Findings from the two groups were compared.The rates and types of psychiatric disorder and behavior problems in VCFS and cognitively matched control subjects were very high, but showed no significant differences.Psychopathology in children with VCFS may not differ from that found in cognitively matched control subjects. Another explanation is that subtle phenotypic differences in behavior found in VCFS can not be observed using standard symptom inventories. The high rate of psychopathology in children with VCFS is not a useful phenotypic indicator of high risk for adult onset schizophrenia.
View details for Web of Science ID 000174281200006
View details for PubMedID 11958782
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Neurobehavioral phenotype in carriers of the fragile X premutation
AMERICAN JOURNAL OF MEDICAL GENETICS
2001; 103 (4): 314-319
Abstract
There have been contradictory findings in the fragile X (fraX) literature about possible neurocognitive and psychological symptoms due to the fraX premutation (pM). The purpose of the present study was to investigate the relationship between CGG repeat length and neurobehavioral functioning in carriers of the fraX pM. Eighty-five female carriers of the pM with allele sizes ranging from 59-166 were administered a comprehensive IQ test (WAIS-III) and completed a questionnaire designed to measure psychopathology (Symptom Checklist (SCL)-90-R). No relationship between allele size and cognition was identified. A significant negative relationship between allele size and age was found, as well as a positive relationship between allele size and depression. Follow-up analyses separating small and large allele sizes (below and above 100 CGG repeats) indicated that individuals with larger allele sizes scored significantly higher on the Interpersonal Sensitivity and Depression subscales of the SCL-90-R. Despite the limitation of few individuals with high CGG repeat lengths, our findings suggest that females with larger premutated alleles (> or = 100 repeats) display some clinical manifestations of fraX syndrome.
View details for Web of Science ID 000171752600009
View details for PubMedID 11746012
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Brain anatomy, gender and IQ in children and adolescents with fragile X syndrome
BRAIN
2001; 124: 1610-1618
Abstract
This study utilized MRI data to describe neuroanatomical morphology in children and adolescents with fragile X syndrome, the most common inherited cause of developmental disability. The syndrome provides a model for understanding how specific genetic factors can influence both neuroanatomy and cognitive capacity. Thirty-seven children and adolescents with fragile X syndrome received an MRI scan and cognitive testing. Scanning procedures and analytical strategies were identical to those reported in an earlier study of 85 typically developing children, permitting a comparison with a previously published template of normal brain development. Regression analyses indicated that there was a normative age-related decrease in grey matter and an increase in white matter. However, caudate and ventricular CSF volumes were significantly enlarged, and caudate volumes decreased with age. Rates of reduction of cortical grey matter were different for males and females. IQ scores were not significantly correlated with volumes of cortical and subcortical grey matter, and these relationships were statistically different from the correlational patterns observed in typically developing children. Children with fragile X syndrome exhibited several typical neurodevelopmental patterns. Aberrations in volumes of subcortical nuclei, gender differences in rates of cortical grey matter reduction and an absence of correlation between grey matter and cognitive performance provided indices of the deleterious effects of the fragile X mutation on the brain's structural organization.
View details for Web of Science ID 000170453400013
View details for PubMedID 11459752
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Family environment of children and adolescents with bipolar parents
BIPOLAR DISORDERS
2001; 3 (2): 73-78
Abstract
The effect of family environment on the development of bipolar disorder (BD) in children is not known. We sought to characterize families with children at high risk for developing BD in order to better understand the contributions of family environment to the development of childhood BD.We collected demographic data and parental ratings on the Family Environment Scale (FES) for 56 children (aged 6-18 years) from 36 families with at least one biological parent with BD. The cohort had previously been psychiatrically diagnosed according to semistructured interviews.Statistical comparisons with normative data indicated that parents' ratings were significantly lower on the FES Cohesion and Organization scales and were significantly higher on the FES Conflict scale. Multivariate analyses of variance indicated that families with both parents having a mood disorder had no significantly different FES scores than families with only one parent with a mood disorder (BD). Diagnostic data indicated that while 54% of the children in the sample had an Axis I disorder and 14% had BD, FES scores did not differ significantly for subjects with or without an Axis I disorder, or with or without BD.Families with a bipolar parent differ from the average family in having less cohesion and organization, and more conflict. Despite this difference, it does not appear that the environment alone of families with a bipolar parent determines the outcome of psychopathology in the children, or that the psychopathology of the children determines the family environment.
View details for PubMedID 11333066
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Velocardiofacial syndrome: Are structural changes in the temporal and mesial temporal regions related to schizophrenia?
AMERICAN JOURNAL OF PSYCHIATRY
2001; 158 (3): 447-453
Abstract
Velocardiofacial syndrome results from a microdeletion on chromosome 22 (22q11.2). Clinical studies indicate that more than 30% of children with the syndrome will develop schizophrenia. The authors sought to determine whether neuroanatomical features in velocardiofacial syndrome are similar to those reported in the literature on schizophrenia by measuring the volumes of the temporal lobe, superior temporal gyrus, and mesial temporal structures in children and adolescents with velocardiofacial syndrome.Twenty-three children and adolescents with velocardiofacial syndrome and 23 comparison subjects, individually matched for age and gender, received brain magnetic resonance imaging (MRI) scans. Analysis of covariance models were used to compare regional brain volumes. Correlations between residualized brain volumes and age were standardized and compared with the Fisher r-to-z transformation.Children with velocardiofacial syndrome had significantly smaller average temporal lobe, superior temporal gyrus, and hippocampal volumes than normal comparison children, although these differences were commensurate with a lower overall brain size in the affected children. In a cross-sectional analysis, children with velocardiofacial syndrome exhibited aberrant volumetric reductions with age that were localized to the temporal lobe and left hippocampal regions.Abnormal temporal lobe and hippocampal development in velocardiofacial syndrome is potentially concordant with MRI findings in the schizophrenia literature. Temporal lobe and mesial temporal structures may represent a shared substrate for the effects of the 22q11.2 deletion and for the complex etiological pathways that lead to schizophrenia. Longitudinal research may help determine which children with velocardiofacial syndrome are at risk for serious psychiatric illness in adulthood.
View details for Web of Science ID 000167323000017
View details for PubMedID 11229987
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Functional brain imaging study of mathematical reasoning abilities in velocardiofacial syndrome (del22q11.2)
GENETICS IN MEDICINE
2001; 3 (1): 49-55
Abstract
Children with velocardiofacial syndrome (VCFS) often have deficits in mathematical reasoning. Previous research has suggested that structural abnormalities in the parietal lobe region might underlie these deficits. The present study utilized functional magnetic resonance imaging (fMRI) to explore the relationship between brain function and mathematical performance in VCFS.Eight children with VCFS and eight comparison subjects underwent fMRI scanning and completed an arithmetic computation task.In the VCFS group, increased activation was observed in the left supramarginal gyrus (LSMG) as the task difficulty increased.Aberrant LSMG activation, possibly due to structural deficits of the left parietal lobe, may explain decrements in arithmetic performance observed in VCFS.
View details for Web of Science ID 000167393400011
View details for PubMedID 11339378