Showing papers in "Archives of General Psychiatry in 2010"

Overweight, Obesity, and Depression A Systematic Review and Meta-analysis of Longitudinal Studies

Abstract: Context: Association between obesity and depression has repeatedly been established. For treatment and prevention purposes, it is important to acquire more insight into their longitudinal interaction. Objective: To conduct a systematic review and meta-analysis on the longitudinal relationship between depression, overweight, and obesity and to identify possible influencing factors. Data Sources: Studies were found using PubMed, PsycINFO, and EMBASE databases and selected on several criteria. Study Selection: Studies examining the longitudinal bidirectional relation between depression and overweight (body mass index 25-29.99) or obesity (body mass index >= 30) were selected. Data Extraction: Unadjusted and adjusted odds ratios (ORs) were extracted or provided by the authors. Data Synthesis: Overall, unadjusted ORs were calculated and subgroup analyses were performed for the 15 included studies (N = 58 745) to estimate the effect of possible moderators (sex, age, depression severity). Obesity at baseline increased the risk of onset of depression at follow-up (unadjusted OR, 1.55; 95% confidence interval [CI], 1.22-1.98; P = 60 years) but not among younger persons (aged < 20 years). Baseline depression (symptoms and disorder) was not predictive of overweight over time. However, depression increased the odds for developing obesity (OR, 1.58; 95% CI, 1.33-1.87; P < .001). Subgroup analyses did not reveal specific moderators of the association. Conclusions: This meta-analysis confirms a reciprocal link between depression and obesity. Obesity was found to increase the risk of depression, most pronounced among Americans and for clinically diagnosed depression. In addition, depression was found to be predictive of developing obesity.

Childhood Adversities and Adult Psychiatric Disorders in the National Comorbidity Survey Replication I: Associations With First Onset of DSM-IV Disorders

Abstract: Context Although significant associations of childhood adversities (CAs) with adult mental disorders have been documented consistently in epidemiological surveys, these studies generally have examined only 1 CA per study. Because CAs are highly clustered, this approach results in overestimating the importance of individual CAs. Multivariate CA studies have been based on insufficiently complex models. Objective To examine the joint associations of 12 retrospectively reported CAs with the first onset of DSM-IV disorders in the National Comorbidity Survey Replication using substantively complex multivariate models. Design Cross-sectional community survey with retrospective reports of CAs and lifetime DSM-IV disorders. Setting Household population in the United States. Participants Nationally representative sample of 9282 adults. Main Outcome Measures Lifetime prevalences of 20 DSM-IV anxiety, mood, disruptive behavior, and substance use disorders assessed using the Composite International Diagnostic Interview. Results The CAs studied were highly prevalent and intercorrelated. The CAs in a maladaptive family functioning (MFF) cluster (parental mental illness, substance abuse disorder, and criminality; family violence; physical abuse; sexual abuse; and neglect) were the strongest correlates of disorder onset. The best-fitting model included terms for each type of CA, number of MFF CAs, and number of other CAs. Multiple MFF CAs had significant subadditive associations with disorder onset. Little specificity was found for particular CAs with particular disorders. Associations declined in magnitude with life course stage and number of previous lifetime disorders but increased with length of recall. Simulations suggest that CAs are associated with 44.6% of all childhood-onset disorders and with 25.9% to 32.0% of later-onset disorders. Conclusions The fact that associations increased with length of recall raises the possibility of recall bias inflating estimates. Even considering this, the results suggest that CAs have powerful and often subadditive associations with the onset of many types of largely primary mental disorders throughout the life course.

A Meta-analysis of Depression During Pregnancy and the Risk of Preterm Birth, Low Birth Weight, and Intrauterine Growth Restriction

Abstract: Context Maternal depressive symptoms during pregnancy have been reported in some, but not all, studies to be associated with an increased risk of preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IUGR). Objective To estimate the risk of PTB, LBW, and IUGR associated with antenatal depression. Data Sources and Study Selection We searched for English-language and non–English-language articles via the MEDLINE, PsycINFO, CINAHL, Social Work Abstracts, Social Services Abstracts, and Dissertation Abstracts International databases (January 1980 through December 2009). We aimed to include prospective studies reporting data on antenatal depression and at least 1 adverse birth outcome: PTB ( Data Extraction Information was extracted on study characteristics, antenatal depression measurement, and other biopsychosocial risk factors and was reviewed twice to minimize error. Data Synthesis Pooled relative risks (RRs) for the effect of antenatal depression on each birth outcome were calculated using random-effects methods. In studies of PTB, LBW, and IUGR that used a categorical depression measure, pooled effect sizes were significantly larger (pooled RR [95% confidence interval] = 1.39 [1.19-1.61], 1.49 [1.25-1.77], and 1.45 [1.05-2.02], respectively) compared with studies that used a continuous depression measure (1.03 [1.00-1.06], 1.04 [0.99-1.09], and 1.02 [1.00-1.04], respectively). The estimates of risk for categorically defined antenatal depression and PTB and LBW remained significant when the trim-and-fill procedure was used to correct for publication bias. The risk of LBW associated with antenatal depression was significantly larger in developing countries (RR = 2.05; 95% confidence interval, 1.43-2.93) compared with the United States (RR = 1.10; 95% confidence interval, 1.01-1.21) or European social democracies (RR = 1.16; 95% confidence interval, 0.92-1.47). Categorically defined antenatal depression tended to be associated with an increased risk of PTB among women of lower socioeconomic status in the United States. Conclusions Women with depression during pregnancy are at increased risk for PTB and LBW, although the magnitude of the effect varies as a function of depression measurement, country location, and US socioeconomic status. An important implication of these findings is that antenatal depression should be identified through universal screening and treated.

Prevalence of mental health problems and functional impairment among active component and National Guard soldiers 3 and 12 months following combat in Iraq.

Abstract: Context A growing body of literature has demonstrated the association of combat in Iraq and Afghanistan with postdeployment mental health problems, particularly posttraumatic stress disorder (PTSD) and depression. However, studies have shown varying prevalence rates of these disorders based on different case definitions and have not assessed functional impairment, alcohol misuse, or aggressive behavior as comorbid factors occurring with PTSD and depression. Objectives To (1) examine the prevalence rates of depression and PTSD using several case definitions including functional impairment, (2) determine the comorbidity of alcohol misuse or aggressive behaviors with depression or PTSD, and (3) compare rates between Active Component and National Guard soldiers at the 3- and 12-month time points following their deployment to Iraq. Design Population-based, cross-sectional study. Setting United States Army posts and National Guard armories. Participants A total of 18 305 US Army soldiers from 4 Active Component and 2 National Guard infantry brigade combat teams. Interventions Between 2004 and 2007, anonymous mental health surveys were collected at 3 and 12 months following deployment. Main Outcome Measures Current PTSD, depression, functional impairment, alcohol misuse, and aggressive behavior. Results Prevalence rates for PTSD or depression with serious functional impairment ranged between 8.5% and 14.0%, with some impairment between 23.2% and 31.1%. Alcohol misuse or aggressive behavior comorbidity was present in approximately half of the cases. Rates remained stable for the Active Component soldiers but increased across all case definitions from the 3- to 12-month time point for National Guard soldiers. Conclusions The prevalence rates of PTSD and depression after returning from combat ranged from 9% to 31% depending on the level of functional impairment reported. The high comorbidity with alcohol misuse and aggression highlights the need for comprehensive postdeployment screening. Persistent or increased prevalence rates at 12 months compared with 3 months postdeployment illustrate the persistent effects of war zone service and provide important data to guide postdeployment care.

A Randomized Add-on Trial of an N-methyl-d-aspartate Antagonist in Treatment-Resistant Bipolar Depression

Abstract: Context Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects—for instance, within a few hours or days—would have an enormous impact on patient care and public health. Objective To determine whether anN-methyl-D-aspartate–receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression. Design A randomized, placebo-controlled, double-blind, crossover, add-on study conducted from October 2006 to June 2009. Setting Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland. Patients Eighteen subjects withDSM-IVbipolar depression (treatment-resistant). Interventions Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery-Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion. Main Outcome Measures Change in Montgomery-Asberg Depression Rating Scale primary efficacy measure scores. Results Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d = 0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d = 0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point. Conclusion In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of anN-methyl-D-aspartate antagonist. Trial Registration clinicaltrials.gov Identifier:NCT00088699

Long-chain ω-3 fatty acids for indicated prevention of psychotic disorders: A randomized, placebo-controlled trial

Abstract: Context: The use of antipsychotic medication for the prevention of psychotic disorders is controversial. Longchain-3 (omega-3) polyunsaturated fatty acids (PUFAs) may be beneficial in a range of psychiatric conditions, including schizophrenia. Given that-3 PUFAs are generally beneficial to health and without clinically relevant adverse effects, their preventive use in psychosis merits investigation. Objective: To determine whether -3 PUFAs reduce the rate of progression to first-episode psychotic disorder in adolescents and young adults aged 13 to 25 years with subthreshold psychosis. Design: Randomized, d ouble-blind, p lacebocontrolled trial conducted between 2004 and 2007. Setting: Psychosis detection unit of a large public hospital in Vienna, Austria. Participants: Eighty-one individuals at ultra-high risk of psychotic disorder. Interventions: A 12-week intervention period of 1.2g/d -3 PUFA or placebo was followed by a 40-week monitoring period; the total study period was 12 months. Main Outcome Measures: The primary outcome measure was transition to psychotic disorder. Secondary outcomes included symptomatic and functional changes. The ratio of -6 to -3 fatty acids in erythrocytes was used to index pretreatment vs posttreatment fatty acid composition. Results: Seventy-six of 81 participants (93.8%) completed the intervention. By study’s end (12 months), 2 of 41 individuals (4.9%) in the -3 group and 11 of 40 (27.5%) in the placebo group had transitioned to psychotic disorder (P = .007). The difference between the groups in the cumulative risk of progression to fullthreshold psychosis was 22.6% (95% confidence interval, 4.8-40.4). -3 Polyunsaturated fatty acids also significantly reduced positive symptoms (P=.01), negative symptoms (P=.02), and general symptoms (P=.01) and improved functioning (P = .002) compared with placebo. The incidence of adverse effects did not differ between the treatment groups. Conclusions: Long-chain-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states. Trial Registration: clinicaltrials.gov Identifier: NCT00396643

Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial

Abstract: CONTEXT: Daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) has been studied as a potential treatment for depression, but previous work had mixed outcomes and did not adequately mask sham conditions. OBJECTIVE: To test whether daily left prefrontal rTMS safely and effectively treats major depressive disorder. DESIGN: Prospective, multisite, randomized, active sham-controlled (1:1 randomization), duration-adaptive design with 3 weeks of daily weekday treatment (fixed-dose phase) followed by continued blinded treatment for up to another 3 weeks in improvers. SETTING: Four US university hospital clinics. PATIENTS: Approximately 860 outpatients were screened, yielding 199 antidepressant drug-free patients with unipolar nonpsychotic major depressive disorder. INTERVENTION: We delivered rTMS to the left prefrontal cortex at 120% motor threshold (10 Hz, 4-second train duration, and 26-second intertrain interval) for 37.5 minutes (3000 pulses per session) using a figure-eight solid-core coil. Sham rTMS used a similar coil with a metal insert blocking the magnetic field and scalp electrodes that delivered matched somatosensory sensations. MAIN OUTCOME MEASURE: In the intention-to-treat sample (n = 190), remission rates were compared for the 2 treatment arms using logistic regression and controlling for site, treatment resistance, age, and duration of the current depressive episode. RESULTS: Patients, treaters, and raters were effectively masked. Minimal adverse effects did not differ by treatment arm, with an 88% retention rate (90% sham and 86% active). Primary efficacy analysis revealed a significant effect of treatment on the proportion of remitters (14.1% active rTMS and 5.1% sham) (P = .02). The odds of attaining remission were 4.2 times greater with active rTMS than with sham (95% confidence interval, 1.32-13.24). The number needed to treat was 12. Most remitters had low antidepressant treatment resistance. Almost 30% of patients remitted in the open-label follow-up (30.2% originally active and 29.6% sham). CONCLUSION: Daily left prefrontal rTMS as monotherapy produced statistically significant and clinically meaningful antidepressant therapeutic effects greater than sham. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00149838. Language: en

Randomized clinical trial comparing family-based treatment with adolescent-focused individual therapy for adolescents with anorexia nervosa.

Abstract: means. Secondary outcome measures included partial remission rates (85% of expected weight for height plus those who were in full remission) and changes in body mass index percentile and eating-related psychopathology. Results: There were no differences in full remission between treatments at EOT. However, at both the 6- and 12month follow-up, FBT was significantly superior to AFT on this measure. Family-based treatment was significantly superior for partial remission at EOT but not at follow-up. In addition, body mass index percentile at EOT was significantly superior for FBT, but this effect was not found at follow-up. Participants in FBT also had greater changes in Eating Disorder Examination score at EOT than those in AFT, but there were no differences at follow-up. Conclusion: Although both treatments led to considerable improvement and were similarly effective in producing full remission at EOT, FBT was more effective in facilitating full remission at both follow-up points. Trial Registration: clinicaltrials.gov Identifier: NCT00149786.

Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study

Abstract: Context Indicated prevention is currently regarded as the most promising strategy to attenuate, delay, or even avert psychosis. Existing criteria need improvement in terms of specificity and individual risk assessment to allow for better targeted and earlier interventions. Objective To develop a differential predictive clinical model of transition to first-episode psychosis. Design Prospective multicenter, naturalistic field study with a total follow-up time of 18 months. Setting Six early-detection outpatient centers in Germany, Finland, the Netherlands, and England. Participants Two hundred forty-five help-seeking patients in a putatively prodromal state of psychosis according to either ultra-high-risk (UHR) criteria or the basic symptom–based criterion cognitive disturbances (COGDIS). Main Outcome Measure Incidence of transition to psychosis. Results At 18-month follow-up, the incidence rate for transition to psychosis was 19%. Combining UHR and COGDIS yielded the best sensitivity. A prediction model was developed and included positive symptoms, bizarre thinking, sleep disturbances, a schizotypal disorder, level of functioning in the past year, and years of education. With a positive likelihood ratio of 19.9, an area under the curve of 80.8%, and a positive predictive value of 83.3%, diagnostic accuracy was excellent. A 4-level prognostic index further classifying the general risk of the whole sample predicted instantaneous incidence rates of up to 85% and allowed for an estimation of time to transition. Conclusions The prediction model identified an increased risk of psychosis with appropriate prognostic accuracy in our sample. A 2-step risk assessment is proposed, with UHR and cognitive disturbance criteria serving as first-step criteria for general risk and the prognostic index as a second-step tool for further risk classification of each patient. This strategy will allow clinicians to target preventive measures and will support efforts to unveil the biological and environmental mechanisms underlying progression to psychosis.

Childhood adversities and adult psychopathology in the National Comorbidity Survey Replication (NCS-R) II: Associations with persistence of DSM-IV disorders

Abstract: Significant associations between retrospectively reported childhood adversities (CAs) and a wide variety of adult mental disorders have been documented in numerous community epidemiological surveys.1-4 These associations are substantial, with over 30% of adult mental disorders estimated to be directly related to CAs.5, 6 Previous studies have suggested that the associations of CAs with adult disorders are due to increased stress sensitivity that persists into adulthood, making individuals with a history of CAs especially vulnerable to episode onsets of mental disorders triggered by adult stressors.7-9 If this is the case, we would expect that CAs would be associated with disorder persistence, as the majority of episode onsets in adulthood are recurrences rather than first onsets of mental disorders.10-12 However, previous epidemiological studies of the associations between CAs and adult psychopathology have largely focused on prevalent disorders1, 13-15 or on lifetime disorders.15-17 No attempt was made in these studies to distinguish associations of CAs with first onset versus persistence of disorders. It would be useful to make this distinction in order to advance our understanding of the associations of CAs with adult mental disorders and to evaluate the intervention implications of these associations. A companion paper to this one6 takes a first step in doing this by analyzing data from the National Comorbidity survey Replication (NCS-R)18 and showing that a number of CAs are, in fact, associated with first onsets of a wide range of DSM-IV disorders throughout the life course. The current report takes the next logical step in this line of investigation by examining associations of CAs with persistence of the same DSM-IV disorders in the NCS-R. Although a handful of previous studies have examined the associations of CAs with illness course, the results have been inconsistent. Some of these studies found significant associations of CAs with illness course,10, 11, 19, 20 while other did not.3, 21 A limitation of these studies is that they used relatively primitive methods to measure and analyze these associations and generally focused on a single mental health outcome. We address the first limitation in two ways. First, we use a novel statistical approach to examine the separate and joint associations of CAs with disorder persistence6 to address the fact that CAs are highly co-occurring22-24 and that multivariate associations of co-occurring CAs are generally nonadditive.25 Second, we use an innovative approach to measure illness course based on a special class of survival models known as backward recurrence models.26, 27 These models allow us to study the associations of CAs with illness course more sensitively than in previous retrospective studies. We address the second limitation by examining associations of CAs with persistence of a wide range of DSM-IV disorders.

Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder.

Abstract: Context Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder that affects 2% of the general population. Even when the best available treatments are applied, approximately 10% of patients remain severely afflicted and run a long-term deteriorating course of OCD. Objective To determine whether bilateral deep brain stimulation of the nucleus accumbens is an effective and safe treatment for treatment-refractory OCD. Design The study consisted of an open 8-month treatment phase, followed by a double-blind crossover phase with randomly assigned 2-week periods of active or sham stimulation, ending with an open 12-month maintenance phase. Setting Academic research. Patients Sixteen patients (age range, 18-65 years) with OCD according to DSM-IV criteria meeting stringent criteria for refractoriness to treatment were included in the study. Interventions Treatment with bilateral deep brain stimulation of the nucleus accumbens. Main Outcome Measures Primary efficacy was assessed by score change from baseline on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Responders were defined by a score decrease of at least 35% on the Y-BOCS. Results In the open phase, the mean (SD) Y-BOCS score decreased by 46%, from 33.7 (3.6) at baseline to 18.0 (11.4) after 8 months ( P P = .004). Depression and anxiety decreased significantly. Except for mild forgetfulness and word-finding problems, no permanent adverse events were reported. Conclusion Bilateral deep brain stimulation of the nucleus accumbens may be an effective and safe treatment for treatment-refractory OCD. Clinical Trial Registration isrctn.org Identifier:ISRCTN23255677

High Occurrence of Mood and Anxiety Disorders Among Older Adults: The National Comorbidity Survey Replication

Abstract: Context Little is known about prevalence rates of DSM-IV disorders across age strata of older adults, including common conditions such as individual and coexisting mood and anxiety disorders Objective To determine nationally representative estimates of 12-month prevalence rates of mood, anxiety, and comorbid mood-anxiety disorders across young-old, mid-old, old-old, and oldest-old community-dwelling adults Design The National Comorbidity Survey Replication (NCS-R) is a population-based probability sample of 9282 participants 18 years and older, conducted between February 2001 and April 2003 The NCS-R survey used the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview Setting Continental United States Participants We studied the 2575 participants 55 years and older who were part of NCS-R (43%, 55-64 years; 32%, 65-74 years; 20%, 75-84 years; 5%, ≥85 years) This included only noninstitutionalized adults, as all NCS-R participants resided in households within the community Main Outcome Measures Twelve-month prevalence of mood disorders (major depressive disorder, dysthymia, bipolar disorder), anxiety disorders (panic disorder, agoraphobia, specific phobia, social phobia, generalized anxiety disorder, posttraumatic stress disorder), and coexisting mood-anxiety disorder were assessed using DSM-IV criteria Prevalence rates were weighted to adjust for the complex design to infer generalizability to the US population Results The likelihood of having a mood, anxiety, or combined mood-anxiety disorder generally showed a pattern of decline with age ( P Conclusion Prevalence rates of DSM-IV mood and anxiety disorders in late life tend to decline with age, but remain very common, especially in women These results highlight the need for intervention and prevention strategies

Psychosocial Risk Factors Associated With Cyberbullying Among Adolescents: A Population-Based Study

Abstract: Context To our knowledge, no population study examining psychosocial and psychiatric risk factors associated with cyberbullying among adolescents exists. Objective To study cross-sectional associations between cyberbullying and psychiatric and psychosomatic problems among adolescents. Design Population-based cross-sectional study. Setting Finland. Participants The sample consists of 2215 Finnish adolescents aged 13 to 16 years with complete information about cyberbullying and cybervictimization. Main Outcome Measures Self-reports of cyberbullying and cybervictimization during the past 6 months. Results In the total sample, 4.8% were cybervictims only, 7.4% were cyberbullies only, and 5.4% were cyberbully-victims. Cybervictim-only status was associated with living in a family with other than 2 biological parents, perceived difficulties, emotional and peer problems, headache, recurrent abdominal pain, sleeping difficulties, and not feeling safe at school. Cyberbully-only status was associated with perceived difficulties, hyperactivity, conduct problems, low prosocial behavior, frequent smoking and drunkenness, headache, and not feeling safe at school. Cyberbully-victim status was associated with all of these risk factors. Among cybervictims, being cyberbullied by a same-sex or opposite-sex adult, by an unknown person, and by a group of people were associated with fear for safety, indicating possible trauma. Conclusions Both cyberbullying and cybervictimization are associated with psychiatric and psychosomatic problems. The most troubled are those who are both cyberbullies and cybervictims. This indicates the need for new strategies for cyberbullying prevention and intervention.

Prediction of dementia by subjective memory impairment: effects of severity and temporal association with cognitive impairment.

Abstract: Context Subjective memory impairment (SMI) is receiving increasing attention as a pre-mild cognitive impairment (MCI) condition in the course of the clinical manifestation of Alzheimer disease (AD). Objectives To determine the risk for conversion to any dementia, dementia in AD, or vascular dementia by SMI, graded by the level of SMI-related worry and by the temporal association of SMI and subsequent MCI. Design Longitudinal cohort study with follow-up examinations at 1½ and 3 years after baseline. Setting Primary care medical record registry sample. Participants A total of 2415 subjects without cognitive impairment 75 years or older in the German Study on Aging, Cognition and Dementia in Primary Care Patients. Main Outcome Measures Conversion to any dementia, dementia in AD, or vascular dementia at follow-up 1 or follow-up 2 predicted by SMI with or without worry at baseline and at follow-up 2 predicted by different courses of SMI at baseline and MCI at follow-up 1. Results In the first analysis, SMI with worry at baseline was associated with greatest risk for conversion to any dementia (hazard ratio [HR], 3.53; 95% confidence interval [CI], 2.07-6.03) or dementia in AD (6.54; 2.82-15.20) at follow-up 1 or follow-up 2. The sensitivity was 69.0% and the specificity was 74.3% conversion to dementia in AD. In the second analysis, SMI at baseline and MCI at follow-up 1 were associated with greatest risk for conversion to any dementia (odds ratio [OR], 8.92; 95% CI, 3.69-21.60) or dementia in AD (19.33; 5.29-70.81) at follow-up 2. Furthermore, SMI at baseline and amnestic MCI at follow-up 1 increased the risk for conversion to any dementia (OR, 29.24; 95% CI, 8.75-97.78) or dementia in AD (60.28; 12.23-297.10), with a sensitivity of 66.7% and a specificity of 98.3% for conversion to dementia in AD. Conclusion The prediction of dementia in AD by SMI with subsequent amnestic MCI supports the model of a consecutive 3-stage clinical manifestation of AD from SMI via MCI to dementia.

Hippocampal Plasticity in Response to Exercise in Schizophrenia

Abstract: Context Hippocampal volume is lower than expected in patients with schizophrenia; however, whether this represents a fixed deficit is uncertain. Exercise is a stimulus to hippocampal plasticity. Objective To determine whether hippocampal volume would increase with exercise in humans and whether this effect would be related to improved aerobic fitness. Design Randomized controlled study. Setting Patients attending a day hospital program or an outpatient clinic. Patients or Other Participants Male patients with chronic schizophrenia and matched healthy subjects. Interventions Aerobic exercise training (cycling) and playing table football (control group) for a period of 3 months. Main Outcome Measures Magnetic resonance imaging of the hippocampus. Secondary outcome measures were magnetic resonance spectroscopy, neuropsychological (Rey Auditory Verbal Learning Test, Corsi block-tapping test), and clinical (Positive and Negative Syndrome Scale) features. Results Following exercise training, relative hippocampal volume increased significantly in patients (12%) and healthy subjects (16%), with no change in the nonexercise group of patients (−1%). Changes in hippocampal volume in the exercise group were correlated with improvements in aerobic fitness measured by change in maximum oxygen consumption ( r = 0.71; P = .003). In the schizophrenia exercise group (but not the controls), change in hippocampal volume was associated with a 35% increase in the N -acetylaspartate to creatine ratio in the hippocampus. Finally, improvement in test scores for short-term memory in the combined exercise and nonexercise schizophrenia group was correlated with change in hippocampal volume ( r = 0.51; P Conclusion These results indicate that in both healthy subjects and patients with schizophrenia hippocampal volume is plastic in response to aerobic exercise.

Increased synaptic dopamine function in associative regions of the striatum in schizophrenia.

Abstract: Context A long-standing version of the dopamine hypothesis of schizophrenia postulates that hyperactivity of dopaminergic transmission at D 2 receptors in the limbic striatum is associated with the illness and that blockade of mesolimbic D 2 receptors is responsible for the antipsychotic action of D 2 receptor antagonists. Objective To localize dopaminergic hyperactivity within the striatum in schizophrenia. Design Case-control study. Setting Inpatient research unit. Participants Eighteen untreated patients with schizophrenia and 18 healthy control subjects matched for age, sex, ethnicity, parental socioeconomic status, cigarette smoking, and weight. Main Outcome Measures Percentage change in dopamine D 2 receptor availability in striatal subregions within each subject measured by positron emission tomography with carbon 11–labeled raclopride before and during pharmacologically induced dopamine depletion. Results In the associative striatum, acute dopamine depletion resulted in a larger increase in D 2 receptor availability in patients with schizophrenia (mean [SD], 15% [7%]) than in control subjects (10% [7%], P = .045), suggesting higher synaptic dopamine concentration. Within the associative striatum, this effect was most pronounced in the precommissural dorsal caudate (15% [8%] in patients vs 9% [8%] in controls, P = .03). No between-group differences were observed in the limbic and sensorimotor striatum. Conclusions These findings suggest that schizophrenia is associated with elevated dopamine function in associative regions of the striatum. Because the precommissural dorsal caudate processes information from the dorsolateral prefrontal cortex, this observation also suggests that elevated subcortical dopamine function might adversely affect performance of the dorsolateral prefrontal cortex in schizophrenia. On the other hand, the absence of a group difference in the limbic striatum brings into question the therapeutic relevance of the mesolimbic selectivity of second-generation antipsychotic drugs.

Posttraumatic stress disorder and risk of dementia among US veterans.

Abstract: Context Posttraumatic stress disorder (PTSD) is highly prevalent among US veterans because of combat and may impair cognition. Objective To determine whether PTSD is associated with the risk of developing dementia among older US veterans receiving treatment in the Department of Veterans Affairs medical centers. Design A stratified, retrospective cohort study conducted using the Department of Veterans Affairs National Patient Care Database. Setting Department of Veterans Affairs medical centers in the United States. Participants A total of 181 093 veterans 55 years or older without dementia from fiscal years 1997 through 2000 (53 155 veterans with and 127 938 veterans without PTSD). Main Outcome Measures During the follow-up period between October 1, 2000, and December 31, 2007, 31 107 (17.2%) veterans were ascertained to have newly diagnosed dementia according to International Classification of Diseases, Ninth Revision, Clinical Modification codes. Results The mean baseline age of the veterans was 68.8 years, and 174 806 (96.5%) were men. Veterans with PTSD had a 7-year cumulative incident dementia rate of 10.6%, whereas those without had a rate of 6.6% ( P Conclusions In a predominantly male veteran cohort, those diagnosed as having PTSD were at a nearly 2-fold-higher risk of developing dementia compared with those without PTSD. Mechanisms linking these important disorders need to be identified with the hope of finding ways to reduce the increased risk of dementia associated with PTSD.

Psychological Treatments of Binge Eating Disorder

Abstract: Context Interpersonal psychotherapy (IPT) is an effective specialty treatment for binge eating disorder (BED). Behavioral weight loss treatment (BWL) and guided self-help based on cognitive behavior therapy (CBTgsh) have both resulted in short-term reductions in binge eating in obese patients with BED. Objective To test whether patients with BED require specialty therapy beyond BWL and whether IPT is more effective than either BWL or CBTgsh in patients with a high negative affect during a 2-year follow-up. Design Randomized, active control efficacy trial. Setting University outpatient clinics. Participants Two hundred five women and men with a body mass index between 27 and 45 who met DSM-IV criteria for BED. Intervention Twenty sessions of IPT or BWL or 10 sessions of CBTgsh during 6 months. Main Outcome Measures Binge eating assessed by the Eating Disorder Examination. Results At 2-year follow-up, both IPT and CBTgsh resulted in greater remission from binge eating than BWL ( P P P Conclusions Interpersonal psychotherapy and CBTgsh are significantly more effective than BWL in eliminating binge eating after 2 years. Guided self-help based on cognitive behavior therapy is a first-line treatment option for most patients with BED, with IPT (or full cognitive behavior therapy) used for patients with low self-esteem and high eating disorder psychopathology. Trial Registration clinicaltrials.gov Identifier:NCT00060762

National Trends in Psychotropic Medication Polypharmacy in Office-Based Psychiatry

Abstract: Context Psychotropic medication polypharmacy is common in psychiatric outpatient settings and, in some patient groups, may have increased in recent years. Objective To examine patterns and recent trends in psychotropic polypharmacy among visits to office-based psychiatrists. Design Annual data from the 1996-2006 cross-sectional National Ambulatory Medical Care Surveys were analyzed to examine patterns and trends in psychotropic polypharmacy within nationally representative samples of 13 079 visits to office-based psychiatrists. Setting Office-based psychiatry practices in the United States. Participants Outpatients with mental disorder diagnoses visiting office-based psychiatrists. Main Outcome Measure Number of medications prescribed in each visit and specific medication combinations. Results There was an increase in the number of psychotropic medications prescribed across years; visits with 2 or more medications increased from 42.6% in 1996-1997 to 59.8% in 2005-2006; visits with 3 or more medications increased from 16.9% to 33.2% (both P Conclusions There has been a recent significant increase in polypharmacy involving antidepressant and antipsychotic medications. While some of these combinations are supported by clinical trials, many are of unproven efficacy. These trends put patients at increased risk of drug-drug interactions with uncertain gains for quality of care and clinical outcomes.

Depression care in the United States: too little for too few.

Abstract: Objective To determine the prevalence and adequacy of depression care among different ethnic and racial groups in the United States. Design Collaborative Psychiatric Epidemiology Surveys (CPES) data were analyzed to calculate nationally representative estimates of depression care. Setting The 48 coterminous United States. Participants Household residents 18 years and older (N = 15 762) participated in the study. Main Outcome Measures Past-year depression pharmacotherapy and psychotherapy using American Psychiatric Association guideline-concordant therapies. Depression severity was assessed with the Quick Inventory of Depressive Symptomatology Self-Report. Primary predictors were major ethnic/racial groups (Mexican American, Puerto Rican, Caribbean black, African American, and non-Latino white) and World Mental Health Composite International Diagnostic Interview criteria for 12-month major depressive episode. Results Mexican American and African American individuals meeting 12-month major depression criteria consistently and significantly had lower odds for any depression therapy and guideline-concordant therapies despite depression severity ratings not significantly differing between ethnic/racial groups. All groups reported higher use of any past-year psychotherapy and guideline-concordant psychotherapy compared with pharmacotherapy; however, Caribbean black and African American individuals reported the highest proportions of this use. Conclusions Few Americans with recent major depression have used depression therapies and guideline-concordant therapies; however, the lowest rates of use were found among Mexican American and African American individuals. Ethnic/racial differences were found despite comparable depression care need. More Americans with recent major depression used psychotherapy over pharmacotherapy, and these differences were most pronounced among Mexican American and African American individuals. This report underscores the importance of disaggregating ethnic/racial groups and depression therapies in understanding and directing efforts to improve depression care in the United States.

Incidence and risk patterns of anxiety and depressive disorders and categorization of generalized anxiety disorder.

Abstract: Context: Controversy surrounds the diagnostic categorization of generalized anxiety disorder (GAD). Objectives: To examine the incidence, comorbidity, and risk patterns for anxiety and depressive disorders and to test whether developmental features of GAD more strongly support a view of this condition as a depressive as opposed to an anxiety disorder. Design: Face-to-face, 10-year prospective longitudinal and family study with as many as 4 assessment waves. The DSM-IV Munich Composite International Diagnostic Interview was administered by clinically trained interviewers. Setting: Munich, Germany. Participants: A community sample of 3021 individuals aged 14 to 24 years at baseline and 21 to 34 years at last follow-up. Main Outcome Measures: Cumulative incidence of GAD, other anxiety disorders (specific phobias, social phobia, agoraphobia, and panic disorder), and depressive disorders (major depressive disorder, and dysthymia). Results: Longitudinal associations between GAD and depressive disorders are not stronger than those between GAD and anxiety disorders or between other anxiety and depressive disorders. Survival analyses reveal that the factors associated with GAD overlap more strongly with those specific to anxiety disorders than those specific to depressive disorders. In addition, GAD differs from anxiety and depressive disorders with regard to family climate and personality profiles. Conclusions: Anxiety and depressive disorders appear to differ with regard to risk constellations and temporal longitudinal patterns, and GAD is a heterogeneous disorder that is, overall, more closely related to other anxiety disorders than to depressive disorders. More work is needed to elucidate the potentially unique aspects of pathways and mechanisms involved in the etiopathogenesis of GAD. Grouping GAD with depressive disorders, as suggested by cross-sectional features and diagnostic comorbidity patterns, minimizes the importance of longitudinal data on risk factors and symptom trajectories.

Mitochondrial complex I activity and oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder.

Abstract: Context Accumulating evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of bipolar disorder and schizophrenia. It remains unclear whether mitochondrial dysfunction, specifically complex I impairment, is associated with increased oxidative damage and, if so, whether this relationship is specific to bipolar disorder. Objective To evaluate whether decreased levels of the electron transport chain complex I subunit NDUFS7 are associated with complex I activity and increased oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder, schizophrenia, or major depressive disorder. Design Postmortem prefrontal cortex from patients and controls were assessed using immunoblotting, spectrophotometric, competitive enzyme immunoassay to identify group differences in expression and activity of complex I, and in oxidative damage in mitochondria. Setting University of British Columbia, Vancouver, Canada. Patients Forty-five patients with a psychiatric disorder (15 each with bipolar disorder, schizophrenia, and major depressive disorder) and 15 nonpsychiatric control subjects were studied. Main Outcome Measures Oxidative damage to proteins and mitochondrial complex I activity. Results Levels of NDUFS7 and complex I activity were decreased significantly in patients with bipolar disorder but were unchanged in those with depression and schizophrenia compared with controls. Protein oxidation, as measured by protein carbonylation, was increased significantly in the bipolar group but not in the depressed or schizophrenic groups compared with controls. We observed increased levels of 3-nitrotyrosine in the bipolar disorder and schizophrenia groups. Conclusions Impairment of complex I may be associated with increased protein oxidation and nitration in the prefrontal cortex of patients with bipolar disorder. Therefore, complex I activity and mitochondrial dysfunction may be potential therapeutic targets for bipolar disorder.

Effect of a purpose in life on risk of incident Alzheimer disease and mild cognitive impairment in community-dwelling older persons.

Abstract: Context: Emerging data suggest that psychological and experiential factors are associated with risk of Alzheimer disease (AD), but the association of purpose in life with incident AD is unknown. Objective: To test the hypothesis that greater purpose in life is associated with a reduced risk of AD. Design: Prospective, longitudinal epidemiologic study of aging.

Antidepressant Monotherapy vs Sequential Pharmacotherapy and Mindfulness-Based Cognitive Therapy, or Placebo, for Relapse Prophylaxis in Recurrent Depression

Abstract: Relapse and recurrence following recovery from Major Depressive Disorder (MDD) are common and debilitating outcomes that carry enormous person, familial and societal costs1. Maintenance antidepressant monotherapy (M-ADM), the current standard for depressive relapse prophylaxis2 is effective as long as it is continued, yet in practice, this plan is compromised by rates of patient noncompliance that can reach 40%3,4. Alternatives to long term antidepressant monotherapy, especially those that address mood outcomes in a broader context of well-being, may appeal to patients wary of continued intervention. One such approach involves the use of sequenced, phase-specific depression treatments within an envelope spanning both acute phase and post-remission care5. Such models involve treating patients to remission pharmacologically and then providing psychotherapy aimed at preventing relapse by teaching affect regulation and self-management skills to be used during recovery. Implicit here is the view that the mechanisms underlying the onset of a depressive episode differ from those responsible for its return6 and that unique interventions are required to address each. Prevention outcomes from the sequential treatment of mood disorders are largely supportive of the approach. Fava7,8 reported lower relapse rates at 4 year follow up and fewer multiple relapses for remitted patients who discontinued medication and received CBT, compared to clinical management. Frank et al.,9 found that time to recurrence was greater for patients who discontinued antidepressants at remission and received Interpersonal Therapy (IPT) or IPT and pill placebo (PLA) versus PLA alone. Similar findings have been obtained with Mindfulness-Based Cognitive Therapy (MBCT), a group intervention designed to train recovered, recurrently depressed patients to disengage from dysphoria-activated depressogenic thinking that increases risk for relapse/recurrence. In addition, MBCT’s emphasis on the daily practice of health enhancing behaviours such as meditation or yoga is a positive incentive for the type of long term engagement required by any maintenance therapy. To date, this intervention designed to be suitable for patients achieving remission via antidepressant treatment, has been evaluated in 3 RCTs with outcomes suggesting a 50% reduction in relapse for patients receiving MBCT compared to treatment as usual10,11 or no difference in survival compared to maintenance pharmacotherapy12. These data, while encouraging, do not address the frequently encountered clinical scenario where a remitted patient wishes, whether for reasons of preference13, side effect burden14 or suitability15, (e.g. pregnancy) to discontinue antidepressant treatment but requires additional prophylactic care. Although previous studies have enrolled patients who were already in remission, no study has explicitly treated patients to remission pharmacologically with the aim of testing MBCT’s prevention effects directly following discontinuation, against active treatment or a placebo (PLA) control. Addressing this question would help determine MBCT’s generalizability to real world clinical settings and evaluate, more broadly, the sequential staging through which both treatments are delivered. The present study was designed to test the relative efficacy of MBCT and M-ADM (versus PLA and clinical management) for prevention of relapse in patients with recurrent depression who have achieved remission through antidepressant pharmacotherapy. We predicted that both MBCT and M-ADM would offer effective protection when compared against PLA and that the level of protection achieved by MBCT would not differ from that provided by M-ADM.

Neuropsychology of the Prodrome to Psychosis in the NAPLS Consortium: Relationship to Family History and Conversion to Psychosis

Abstract: Context Early detection and prospective evaluation of clinical high-risk (CHR) individuals who may develop schizophrenia or other psychotic disorders is critical for predicting psychosis onset and for testing preventive interventions. Objectives To elucidate the neuropsychology of the CHR syndrome, to determine the association of neuropsychological function with conversion to psychosis and family history of psychosis, and to examine whether baseline neuropsychological functioning predicts subsequent psychosis. Design Longitudinal study with 2½ years of follow-up. Setting Eight centers participating in the North American Prodrome Longitudinal Study. Participants Three hundred four prospectively identified CHR individuals meeting Structured Interview for Prodromal Syndromes criteria, 52 non-CHR persons with a family history of psychosis in first- or second-degree relatives (family high-risk group), and 193 normal controls with neither a family history of psychosis nor a CHR syndrome, all of whom underwent baseline neuropsychological evaluations. Main Outcome Measures A neurocognitive composite score, 8 individual neuropsychological measures, an IQ estimate, and high-risk status. Results Global (“composite”) neuropsychological functioning was comparably impaired in the CHR and family high-risk groups compared with controls, but profiles differed significantly between groups. Neuropsychological functioning in the CHR group was significantly lower in persons who progressed to psychosis than in those who did not and was worst in the subgroup with a family history of psychosis. Tests of processing speed and verbal learning and memory were most sensitive in discriminating CHR individuals from controls, although reductions were less severe than in established schizophrenia. Neuropsychological functioning did not contribute uniquely to the prediction of psychosis beyond clinical criteria, but worse verbal memory predicted more rapid conversion. Conclusions These findings document that CHR individuals have significant neuropsychological difficulties, particularly those who later develop psychosis. This dysfunction is generally of moderate severity but less than in first-episode schizophrenia, suggesting that further decline may occur after baseline CHR assessment.

Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease

Abstract: CONTEXT: Blood-based analytes may be indicators of pathological processes in Alzheimer disease (AD). OBJECTIVE: To identify plasma proteins associated with AD pathology using a combined proteomic and neuroimaging approach. DESIGN: Discovery-phase proteomics to identify plasma proteins associated with correlates of AD pathology. Confirmation and validation using immunodetection in a replication set and an animal model. SETTING: A multicenter European study (AddNeuroMed) and the Baltimore Longitudinal Study of Aging. PARTICIPANTS: Patients with AD, subjects with mild cognitive impairment, and healthy controls with standardized clinical assessments and structural neuroimaging. MAIN OUTCOME MEASURES: Association of plasma proteins with brain atrophy, disease severity, and rate of clinical progression. Extension studies in humans and transgenic mice tested the association between plasma proteins and brain amyloid. RESULTS: Clusterin/apolipoprotein J was associated with atrophy of the entorhinal cortex, baseline disease severity, and rapid clinical progression in AD. Increased plasma concentration of clusterin was predictive of greater fibrillar amyloid-beta burden in the medial temporal lobe. Subjects with AD had increased clusterin messenger RNA in blood, but there was no effect of single-nucleotide polymorphisms in the gene encoding clusterin with gene or protein expression. APP/PS1 transgenic mice showed increased plasma clusterin, age-dependent increase in brain clusterin, as well as amyloid and clusterin colocalization in plaques. CONCLUSIONS: These results demonstrate an important role of clusterin in the pathogenesis of AD and suggest that alterations in amyloid chaperone proteins may be a biologically relevant peripheral signature of AD.

Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder.

Abstract: Context Major depressive disorder (MDD) is associated with behavioral and neurophysiological evidence of mood-congruent processing biases toward explicitly presented, emotionally valenced stimuli. However, few studies have investigated such biases toward implicitly presented stimuli. Objective To investigate differential amygdala responses to sad, happy, and neutral faces presented below the level of explicit conscious awareness using a backward masking task in unmedicated participants with MDD and healthy controls (HCs). Design Initial cross-sectional design followed by a longitudinal treatment trial using functional magnetic resonance imaging. Setting Psychiatric outpatient clinic at the National Institute of Mental Health. Participants We studied 22 unmedicated, currently depressed people with MDD (dMDD), 16 unmedicated individuals with MDD in full remission (rMDD), and 25 HCs. Intervention Ten dMDD participants underwent 8 weeks of antidepressant treatment with the selective serotonin reuptake inhibitor sertraline hydrochloride. Main Outcome Measures Amygdala region-of-interest and whole-brain analyses evaluated the hemodynamic response during exposure to masked sad vs masked happy faces, to masked sad vs neutral faces, and to masked happy vs neutral faces. Results The dMDD participants showed greater amygdala responses than HCs to masked sad faces, whereas HCs showed greater amygdala responses to masked happy faces. The bias toward sad faces also was evident in rMDD participants relative to HCs and did not differ between dMDD and rMDD participants. This processing bias reversed toward the normative pattern in dMDD participants after sertraline treatment. Conclusions Emotional-processing biases occur in amygdala responses to sad faces presented below the level of conscious awareness in dMDD or rMDD individuals and to happy faces in HCs. By influencing the salience of social stimuli, mood-congruent processing biases in the amygdala may contribute to dysfunction in conscious perceptions and social interactions in MDD. Our data suggest, however, that the negative bias resolves and a positive bias develops in patients with MDD during selective serotonin reuptake inhibitor treatment.

Increased BDNF promoter methylation in the Wernicke area of suicide subjects.

Abstract: Context: Brain-derived neurotrophic factor (BDNF) plays a pivotal role in the pathophysiology of suicidal behavior andBDNF levels are decreased in the brain and plasma of suicide subjects. So far, the mechanisms leading to downregulation of BDNF expression are poorly understood. Objectives: To test the hypothesis that alterations of DNA methylation could be involved in the dysregulation of BDNF gene expression in the brain of suicide subjects. Design: Three independent quantitative methylation techniques were performed on postmortem samples of brain tissue. BDNF messenger RNA levels were determined by quantitative real-time polymerase chain reaction. Setting: Academic medical center. Patients or Other Participants: Forty-four suicide completers and 33 nonsuicide control subjects of white ethnicity.

Meta-analytical Comparison of Voxel-Based Morphometry Studies in Obsessive-Compulsive Disorder vs Other Anxiety Disorders

Abstract: Context: Whether obsessive-compulsive disorder (OCD) is adequately classified as an anxiety disorder is a matter of considerable debate. Objectives: To quantitatively compare structural brain changes in OCD and other anxiety disorders using novel voxel-based meta-analytical methods and to generate an online database to facilitate replication and further analyses by other researchers. Data Sources: The PubMed, ScienceDirect, and Scopus databases were searched between 2001 (the date of the first voxel-based morphometry study in any anxiety disorder) and 2009. All voxel-based morphometry studies comparing patients with any anxiety disorder and healthy controls were retrieved. Manual searches were also conducted. Authors were contacted soliciting additional data. Study Selection: Thirty-seven data sets were identified, of which 26 (including 639 patients with anxiety disorders and 737 healthy controls) met inclusion criteria. Data Extraction: Coordinates were extracted from clusters of significant gray matter difference between patients and controls. Demographic, clinical, and methodological variables were extracted from each study or obtained from the authors. Data Synthesis: Patients with anxiety disorders (including OCD) showed decreased bilateral gray matter volumes in the dorsomedial frontal/anterior cingulate gyri. Individuals with OCD had increased bilateral gray matter volumes (vs healthy controls and vs individuals with other anxiety disorders) in the lenticular/caudate nuclei, while patients with other anxiety disorders (mainly panic and posttraumatic stress disorders) had decreased gray matter volumes in the left lenticular nucleus. The findings remained largely unchanged in quartile and jackknife sensitivity analyses. Controlling for potential confounders such as age or antidepressant medication had little impact on the results. Conclusions: The meta-analysis consistently revealed common as well as distinct neural substrates in OCD and other anxiety disorders. These results have implications for the current debate surrounding the classification of OCD in the DSM-V.

Regional brain volume in depression and anxiety disorders.

Abstract: Context Major depressive disorder (MDD), panic disorder, and social anxiety disorder are among the most prevalent and frequently co-occurring psychiatric disorders in adults and may have, at least in part, a common etiology. Objective To identify the unique and shared neuroanatomical profile of depression and anxiety, controlling for illness severity, medication use, sex, age of onset, and recurrence. Design Cross-sectional study. Setting Netherlands Study of Depression and Anxiety. Participants Outpatients with MDD (n = 68), comorbid MDD and anxiety (n = 88), panic disorder, and/or social anxiety disorder without comorbid MDD (n = 68) and healthy controls (n = 65). Main Outcome Measures Volumetric magnetic resonance imaging was conducted for voxel-based morphometry analyses. We tested voxelwise for the effects of diagnosis, age at onset, and recurrence on gray matter density. Post hoc, we studied the effects of use of medication, illness severity, and sex. Results We demonstrated lower gray matter volumes of the rostral anterior cingulate gyrus extending into the dorsal anterior cingulate gyrus in MDD, comorbid MDD and anxiety, and anxiety disorders without comorbid MDD, independent of illness severity, sex, and medication use. Furthermore, we demonstrated reduced right lateral inferior frontal volumes in MDD and reduced left middle/superior temporal volume in anxiety disorders without comorbid MDD. Also, patients with onset of depression before 18 years of age showed lower volumes of the subgenual prefrontal cortex. Conclusions Our findings indicate that reduced volume of the rostral-dorsal anterior cingulate gyrus is a generic effect in depression and anxiety disorders, independent of illness severity, medication use, and sex. This generic effect supports the notion of a shared etiology and may reflect a common symptom dimension related to altered emotion processing. Specific involvement of the inferior frontal cortex in MDD and lateral temporal cortex in anxiety disorders without comorbid MDD, on the other hand, may reflect disorder-specific symptom clusters. Early onset of depression is associated with a distinct neuroanatomical profile that may represent a vulnerability marker of depressive disorder.