Showing papers in "The Journal of Clinical Psychiatry in 2010"

Reliability and validity of the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID).

Abstract: Objective To investigate the concurrent validity and reliability of the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), a short structured diagnostic interview for DSM-IV and ICD-10 psychiatric disorders in children and adolescents. Method Participants were 226 children and adolescents (190 outpatients and 36 controls) aged 6 to 17 years. To assess the concurrent validity of the MINI-KID, participants were administered the MINI-KID and the Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) by blinded interviewers in a counterbalanced order on the same day. Participants also completed a self-rated measure of disability. In addition, interrater (n = 57) and test-retest (n = 83) reliability data (retest interval, 1-5 days) were collected, and agreement between the parent version of the MINI-KID and the standard MINI-KID (n = 140) was assessed. Data were collected between March 2004 and January 2008. Results Substantial to excellent MINI-KID to K-SADS-PL concordance was found for syndromal diagnoses of any mood disorder, any anxiety disorder, any substance use disorder, any ADHD or behavioral disorder, and any eating disorder (area under curve [AUC] = 0.81-0.96, kappa = 0.56-0.87). Results were more variable for psychotic disorder (AUC = 0.94, kappa = 0.41). Sensitivity was substantial (0.61-1.00) for 15/20 individual DSM-IV disorders. Specificity was excellent (0.81-1.00) for 18 disorders and substantial (> 0.73) for the remaining 2. The MINI-KID identified a median of 3 disorders per subject compared to 2 on the K-SADS-PL and took two-thirds less time to administer (34 vs 103 minutes). Interrater and test-retest kappas were substantial to almost perfect (0.64-1.00) for all individual MINI-KID disorders except dysthymia. Concordance of the parent version (MINI-KID-P) with the standard MINI-KID was good. Conclusions The MINI-KID generates reliable and valid psychiatric diagnoses for children and adolescents and does so in a third of the time as the K-SADS-PL.

Twelve-Month Prevalence of and Risk Factors for Suicide Attempts in the World Health Organization World Mental Health Surveys

Abstract: Objective: Although suicide is a leading cause of death worldwide, clinicians and researchers lack a data-driven method to assess the risk of suicide attempts. This study reports the results of an analysis of a large cross-national epidemiologic survey database that estimates the 12-month prevalence of suicidal behaviors, identifies risk factors for suicide attempts, and combines these factors to create a risk index for 12-month suicide attempts separately for developed and developing countries. Method: Data come from the World Health Organization (WHO) World Mental Health (WMH) Surveys (conducted 2001–2007), in which 108,705 adults from 21 countries were interviewed using the WHO Composite International Diagnostic Interview. The survey assessed suicidal behaviors and potential risk factors across multiple domains, including sociodemographic characteristics, parent psychopathology, childhood adversities, DSM-IV disorders, and history of suicidal behavior. Results: Twelve-month prevalence estimates of suicide ideation, plans, and attempts are 2.0%, 0.6%, and 0.3%, respectively, for developed countries and 2.1%, 0.7%, and 0.4%, respectively, for developing countries. Risk factors for suicidal behaviors in both developed and developing countries include female sex, younger age, lower education and income, unmarried status, unemployment, parent psychopathology, childhood adversities, and presence of diverse 12-month DSMIV mental disorders. Combining risk factors from multiple domains produced risk indices that accurately predicted 12-month suicide attempts in both developed and developing countries (area under the receiver operating characteristic curve = 0.74–0.80). Conclusions: Suicidal behaviors occur at similar rates in both developed and developing countries. Risk indices assessing multiple domains can predict suicide attempts with fairly good accuracy and may be useful in aiding clinicians in the prediction of these behaviors.

Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder.

Abstract: Objective—Suicidal ideation is a medical emergency, especially when severe. Little research has been done on pharmacological interventions that could address this problem. Ketamine, an Nmethyl-D-aspartate (NMDA) antagonist, has been reported to have antidepressant effects within hours. We examined the effects of a single dose of ketamine on suicidal ideation in subjects with treatment-resistant major depressive disorder (MDD). Method—Thirty-three subjects with DSM-IV-diagnosed MDD received a single open-label infusion of ketamine (0.5 mg/kg) and rated at baseline, 40, 80, 120, and 230 minutes post-infusion with the Scale for Suicide Ideation (SSI), the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Rating Scale (HDRS), and the Beck Depression Inventory (BDI). Results—Suicidal ideation scores decreased significantly on the SSI as well as on the suicide subscales of other rating instruments within 40 minutes; these decreases remained significant through the first four hours post-infusion (p<.001). Ten subjects (30%) had a SSI score 4 at baseline, and all dropped below a score of 4 (nine by 40 minutes and one by 80 minutes). For those starting below a score of 4 on the SSI, only one reached a score of 4. Depression, anxiety, and hopelessness were significantly improved at all time points (p<.001). Conclusion—Suicidal ideation in the context of MDD improved within 40 minutes of a ketamine infusion and remained improved for up to four hours post-infusion. Future studies with ketamine in suicidal ideation are warranted due to its potential impact on public health.

Should we expand the toolbox of psychiatric treatment methods to include Repetitive Transcranial Magnetic Stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders.

Abstract: Objective: Repetitive transcranial magnetic stimulation (rTMS) is a safe treatment method with few side effects However, efficacy for various psychiatric disorders is currently not clear Data sources: A literature search was performed from 1966 through October 2008 using PubMed, Ovid Medline, Embase Psychiatry, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and PsycINFO The following search terms were used transcranial magnetic stimulation, TMS, repetitive TMS, psychiatry, mental disorder, psychiatric disorder, anxiety disorder, attention-deficit hyperactivity disorder, bipolar disorder, catatonia, mama, depression, obsessive-compulsive disorder, psychosis, posttraumatic stress disorder, schizophrenia, Tourette's syndrome, bulimia nervosa, and addiction. Study selection: Data were obtained from randomized, sham-controlled studies of rTMS treatment for depression (34 studies), auditory verbal hallucinations (AVH, 7 studies), negative symptoms in schizophrenia (7 studies), and obsessive-compulsive disorder (OCD, 3 studies) Studies of rTMS versus electroconvulsive treatment (ECT, 6 studies) for depression were meta-analyzed. Data extraction: Standardized mean effect sizes of rTMS versus sham were computed based on pretreatment-posttreatment comparisons Data synthesis: The mean weighted effect size of rTMS versus sham for depression was 0.55 (P <001). Monotherapy with rTMS was more effective than rTMS as adjunctive to antidepressant medication. ECT was superior to rTMS in the treatment of depression (mean weighted effect size -0 47, P = 004) In the treatment of AVH, rTMS was superior to sham treatment, with a mean weighted effect size of 0.54 (P <001) The mean weighted effect size for rTMS versus sham in the treatment of negative symptoms in schizophrenia was 0.39 (P = 11) and for OCD, 0 15 (P = .52) Side effects were mild, yet more prevalent with high-frequency rTMS at frontal locations Conclusions: It is time to provide rTMS as a clinical treatment method for depression, for auditory verbal hallucinations, and possibly for negative symptoms We do not recommend rTMS for the treatment of OCD J Clin Psychiatry 2010,71(7).873-884 (C) Copyright 2010 Physicians Postgraduate Press, Inc

Antidepressants and Body Weight: A Comprehensive Review and Meta-Analysis

Abstract: Objective: Psychotropic drugs often induce weight gain, leading to discomfort and discontinuation of treatment and, more importantly, increasing the risk of obesity-related illnesses such as diabetes mellitus, hypertension, and coronary heart disease. There is evidence that antidepressant drugs may induce a variable amount of weight gain, but results are sparse and often contradictory. Data Sources: We performed a literature search using the MEDLINE, ISI Web of Knowledge, and Cochrane research databases for all publications available to January 2009. We used the following keywords: antidepressant, psychotropic drugs, body weight, weight gain, obesity, overweight, adverse event, side effects, SSRIs, tricyclic antidepressants, and the name of each antidepressant active compound together with body weight or other keywords. Studies reporting body weight changes during treatment with different antidepressants were selected for eligibility. Finally, 116 studies were included in the analysis. Data Extraction: Weight change mean and standard deviation and size of each group were recorded. Missing means and standard deviations were directly calculated by using information available in the article when possible. Non-placebo-controlled studies were compared to a virtual placebo sample, whose mean and standard deviation were derived by the weighted mean of means and standard deviations of all placebo samples. Methodological quality of studies, heterogeneity, publication bias, and effect of treatment duration were systematically controlled. Data Synthesis: Quantitative results evidenced that amitriptyline, mirtazapine, and paroxetine were associated with a greater risk of weight gain. In contrast, some weight loss occurs with fluoxetine and bupropion, although the effect of fluoxetine appears to be limited to the acute phase of treatment. Other compounds have no transient or negligible effect on body weight in the short term. However, the effect of each antidepressant may vary greatly depending on an individual's characteristics and generally became more evident in the long term to a variable degree across compounds. Conclusions: Despite the fact that some analyses were done on only a few studies due to the difficulty of finding reliable information in literature, to our knowledge, this is the first comprehensive meta-analysis to allow comparison of different antidepressants as regards their impact on body weight. Data presented may be helpful for a more accurate treatment selection in patients at risk of obesity or related medical illness.

A Double-Blind, Randomized Study of Minocycline for the Treatment of Negative and Cognitive Symptoms in Early-Phase Schizophrenia

Abstract: BACKGROUND Current antipsychotics have only a limited effect on 2 core aspects of schizophrenia: negative symptoms and cognitive deficits. Minocycline is a second-generation tetracycline that has a beneficial effect in various neurologic disorders. Recent findings in animal models and human case reports suggest its potential for the treatment of schizophrenia. These findings may be linked to the effect of minocycline on the glutamatergic system, through inhibition of nitric oxide synthase and blocking of nitric oxide-induced neurotoxicity. Other proposed mechanisms of action include effects of minocycline on the dopaminergic system and its inhibition of microglial activation. OBJECTIVE To examine the efficacy of minocycline as an add-on treatment for alleviating negative and cognitive symptoms in early-phase schizophrenia. METHOD A longitudinal double-blind, randomized, placebo-controlled design was used, and patients were followed for 6 months from August 2003 to March 2007. Seventy early-phase schizophrenia patients (according to DSM-IV) were recruited and 54 were randomly allocated in a 2:1 ratio to minocycline 200 mg/d. All patients had been initiated on treatment with an atypical antipsychotic < or = 14 days prior to study entry (risperidone, olanzapine, quetiapine, or clozapine; 200-600 mg/d chlorpromazine-equivalent doses). Clinical, cognitive, and functional assessments were conducted, with the Scale for the Assessment of Negative Symptoms (SANS) as the primary outcome measure. RESULTS Minocycline was well tolerated, with few adverse events. It showed a beneficial effect on negative symptoms and general outcome (evident in SANS, Clinical Global Impressions scale). A similar pattern was found for cognitive functioning, mainly in executive functions (working memory, cognitive shifting, and cognitive planning). CONCLUSIONS Minocycline treatment was associated with improvement in negative symptoms and executive functioning, both related to frontal-lobe activity. Overall, the findings support the beneficial effect of minocycline add-on therapy in early-phase schizophrenia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00733057.

A Comparison of the Efficacy of Medications for Adult Attention-Deficit/Hyperactivity Disorder Using Meta-Analysis of Effect Sizes

Abstract: OBJECTIVES Medications used to treat attention-deficit/hyperactivity disorder (ADHD) in adults have been well researched, but comparisons among drugs are hindered by the absence of direct comparative trials. Our objectives were to (1) estimate the effect size of the medications used to treat adult ADHD, (2) determine if differences in the designs of studies confound comparisons of medication efficacy, (3) quantify the evidence for differences in effect sizes among medications, and (4) see if features of study design influence estimates of efficacy. DATA SOURCES The following search engines were used: PubMed, Ovid, ERIC, CINAHL, MEDLINE, PREMEDLINE, the Cochrane database, e-psyche, and Social Sciences Abstracts. Presentations from the American Psychiatric Association and American Academy of Child and Adolescent Psychiatry meetings were reviewed. STUDY SELECTION A literature search was conducted to identify double-blind, placebo-controlled studies of ADHD in adults published in English after 1979. Only trials that used DSM-III, -III-R, or -IV ADHD criteria and followed subjects for > or = 2 weeks were selected. DATA EXTRACTION Meta-analysis regression assessed the influence of medication type and study design features on medication effects. RESULTS Nineteen trials met criteria and were included in this meta-analysis. These trials studied 13 drugs using 18 different outcome measures of hyperactive, inattentive, or impulsive behavior. After trials were stratified on the class of drug studied (short-acting stimulant vs long-acting stimulant vs nonstimulant), significant differences in effect size were observed between stimulant and nonstimulant medications (P = .006 and P = .0001, respectively, for short- and long-acting stimulants vs nonstimulants), but the effect for short-acting stimulants was not significant after correcting for study design features. The effect sizes for each drug class were similar in magnitude to what we previously reported for medication treatment studies of children with ADHD. We found significant heterogeneity of effect sizes for short-acting stimulants (P < .001) but not for other medication groups. CONCLUSIONS Although both stimulant and nonstimulant medications are effective for treating ADHD in adults, stimulant medications show greater efficacy for the short durations of treatment characteristic of placebo-controlled studies. We found no significant differences between short- and long-acting stimulant medications. Study design features vary widely among studies and can confound indirect comparisons unless addressed statistically as we have done in this study.

A Double-Blind, Placebo-Controlled Study of Quetiapine and Lithium Monotherapy in Adults in the Acute Phase of Bipolar Depression (EMBOLDEN I)

Abstract: OBJECTIVE The aim of this study was to compare the efficacy and tolerability of quetiapine and lithium monotherapy with that of placebo for a major depressive episode in bipolar disorder. METHOD 802 patients with DSM-IV-defined bipolar disorder (499 bipolar I, 303 bipolar II) were randomly allocated to quetiapine 300 mg/d (n = 265), quetiapine 600 mg/d (n = 268), lithium 600 to 1800 mg/d (n = 136), or placebo (n = 133) for 8 weeks. Primary endpoint was the change in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The study was conducted from August 2005 to May 2007. RESULTS Mean MADRS total score change from baseline at week 8 was -15.4 for quetiapine 300 mg/d, -16.1 for quetiapine 600 mg/d, -13.6 for lithium, and -11.8 for placebo (P < .001 for both quetiapine doses, P = .123 for lithium, vs placebo). Quetiapine 600 mg/d was significantly more effective than lithium in improving MADRS total score at week 8 (P = .013). Quetiapine-treated (both doses), but not lithium-treated, patients showed significant improvements (P < .05) in MADRS response and remission rates, Hamilton Depression Rating Scale (HDRS), Clinical Global Impressions-Bipolar-Severity of Illness and -Change, and Hamilton Anxiety Rating Scale (HARS) scores at week 8 versus placebo. Both quetiapine doses were more effective than lithium at week 8 on the HDRS and HARS. The most common adverse events were somnolence, dry mouth, and dizziness with quetiapine (both doses) and nausea with lithium. CONCLUSIONS Quetiapine (300 or 600 mg/d) was more effective than placebo for the treatment of episodes of acute depression in bipolar disorder. Lithium did not significantly differ from placebo on the main measures of efficacy. Both treatments were generally well tolerated. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00206141.

Early-onset bipolar disorder and treatment delay are risk factors for poor outcome in adulthood

Abstract: Objective We examined the influence of age at onset of illness and the delay in time to first treatment on morbidity in adulthood Method 529 adult outpatients with a mean age of 42 years, who entered our research network from 1996 through 2001 and who were diagnosed with bipolar disorder according to DSM-IV criteria, were rated prospectively on a daily basis with the National Institute of Mental Health-Life Chart Method during naturalistic treatment for up to 4 years Results Fifty percent of patients had illness onset in childhood ( Conclusions These data converge with other evidence that onset of bipolar disorder in childhood is common and often associated with extraordinarily long delays to first pharmacologic treatment Both childhood onset and treatment delay were associated with a persistently more adverse course of illness rated prospectively in adults These data should help foster efforts to ensure earlier and more effective treatment of bipolar illness in children and adolescents It is hoped that appropriate early intervention would result in a more benign illness and a better prognosis in adulthood

The pharmacologic treatment of anxiety disorders: a review of progress.

Abstract: Anxiety disorders, as a group, are among the most common mental health conditions and frequently cause significant functional impairment. Both psychotherapeutic and pharmacologic techniques are recognized to be effective management strategies. This review provides a discussion of the major classes of psychotropic medications investigated in clinical trials of the following anxiety disorders: panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, and obsessive-compulsive disorder. Findings suggest that both selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are useful first-line agents for most of the anxiety disorders, particularly given the frequent comorbidity with mood disorders. Highly serotonergic agents are preferred for obsessive-compulsive disorder. Other antidepressants, such as tricyclic antidepressants or monoamine oxidase inhibitors, are generally reserved as second- and third-line strategies due to tolerability issues. Evidence for other agents, including anticonvulsants and atypical antipsychotics, suggests that they may have an adjunctive role to antidepressants in cases of treatment resistance, while azapirones have been used effectively for generalized anxiety disorder, and a substantial body of evidence supports benzodiazepine use in panic disorder and generalized anxiety disorder. Despite notable advances, many patients with anxiety disorders fail to adequately respond to existing pharmacologic treatments. Increased research attention should be focused on systematizing pharmacologic and combined pharmacologic-psychosocial strategies to address treatment resistance and developing novel treatments for anxiety disorders.

Major Depressive Disorder Treatment Guidelines in America and Europe

Abstract: The various major American and European guidelines for the treatment of depression provide similar basic principles of treatment, which include individualizing the treatment plan, preparing the patient for potential long-term treatment, providing measurement-based care, and treating to remission. While the guidelines are all evidence-based, certain factors can influence differences in specific recommendations, such as the consensus group's composition, underlying mandates, and cultural attitudes. The similarities and differences among 6 sets of guidelines from Europe and the Americas published in the past decade are reviewed here (American Psychiatric Association, British Association for Psychopharmacology, Canadian Network for Mood and Anxiety Treatments, National Institute for Health and Clinical Excellence, Texas Medication Algorithm Project, and World Federation of Societies of Biological Psychiatry). In the guidelines, mild depression has the most variance in treatment recommendations; some, but not all, guidelines suggest that it may resolve with exercise or watchful waiting, but psychotherapy or antidepressants could be used if initial efforts fail. Moderate and severe major depression carry broadly similar recommendations among the guidelines. First-line treatment recommendations for moderate major depressive disorder include antidepressant monotherapy, psychotherapy, and the combination of both. Severe depression may require the combination of an antidepressant and an antipsychotic, electroconvulsive therapy, or the combination of an antidepressant and psychotherapy. Benzodiazepines play a very limited role in the treatment of depression; if the patient has catatonic depression, acutely suicidal depression, or depression with symptoms of anxiety, agitation, or insomnia, benzodiazepines are recommended by some guidelines for short-term treatment only.

A double-blind, placebo-controlled study of quetiapine and paroxetine as monotherapy in adults with bipolar depression (EMBOLDEN II)

Abstract: Objective The aim of this study was to evaluate the efficacy and tolerability of quetiapine and paroxetine monotherapy for major depression in bipolar disorder. Method 740 patients (478 bipolar I, 262 bipolar II) with major depressive episodes (DSM-IV) were randomly assigned to quetiapine 300 mg/d (n = 245), quetiapine 600 mg/d (n = 247), paroxetine 20 mg/d (n = 122), or placebo (n = 126) for 8 weeks. The primary end point was the change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The study was conducted from May 2005 to May 2007. Results Mean MADRS score change from baseline at 8 weeks was -16.19 for quetiapine 300 mg, -16.31 for quetiapine 600 mg, -13.76 for paroxetine, and -12.60 for placebo (P Conclusions Quetiapine (300 or 600 mg/d), but not paroxetine, was more effective than placebo for treating acute depressive episodes in bipolar I and II disorder. Quetiapine treatment was generally well tolerated. Trial registration clinicaltrials.gov Identifier: NCT00119652.

Loss of Control Over Eating Predicts Outcomes in Bariatric Surgery Patients: A Prospective, 24-Month Follow-Up Study

Abstract: Objective This study examined the clinical significance of loss of control over eating (LOC) in bariatric surgery over 24 months of prospective multi-wave follow-ups.

Telemedicine for Anger Management Therapy in a Rural Population of Combat Veterans With Posttraumatic Stress Disorder: A Randomized Noninferiority Trial

Abstract: OBJECTIVE: To demonstrate the noninferiority of a telemedicine modality, videoteleconferencing, compared to traditional in-person service delivery of a group psychotherapy intervention for rural combat veterans with posttraumatic stress disorder (PTSD). METHOD: A randomized controlled noninferiority trial of 125 male veterans with PTSD (according to DSM criteria on the Clinician-Administered PTSD Scale) and anger difficulties was conducted at 3 Veterans Affairs outpatient clinics. Participants were randomly assigned to receive anger management therapy delivered in a group setting with the therapist either in-person (n = 64) or via videoteleconferencing (n = 61). Participants were assessed at baseline, midtreatment (3 weeks), posttreatment (6 weeks), and 3 and 6 months posttreatment. The primary clinical outcome was reduction of anger difficulties, as measured by the anger expression and trait anger subscales of the State-Trait Anger Expression Inventory-2 (STAXI-2) and by the Novaco Anger Scale total score (NAS-T). Data were collected from August 2005 to October 2008. RESULTS: Participants in both groups showed significant and clinically meaningful reductions in anger symptoms, with posttreatment and 3 and 6 months posttreatment effect sizes ranging from .12 to .63. Using a noninferiority margin of 2 points for STAXI-2 subscales anger expression and trait anger and 4 points for NAS-T outcomes, participants in the videoteleconferencing condition demonstrated a reduction in anger symptoms similar ("non-inferior") to symptom reductions in the in-person groups. Additionally, no significant between-group differences were found on process variables, including attrition, adherence, satisfaction, and treatment expectancy. Participants in the in-person condition reported significantly higher group therapy alliance. CONCLUSIONS: Clinical and process outcomes indicate delivering cognitive-behavioral group treatment for PTSD-related anger problems via videoteleconferencing is an effective and feasible way to increase access to evidence-based care for veterans residing in rural or remote locations.

Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms.

Abstract: Background It is generally believed that selective serotonin reuptake inhibitor (SSRI) drugs increase the risk of abnormal bleeding and decrease the risk of ischemic heart disease events by blocking the uptake of serotonin into platelets, leading to an impairment in the platelet hemostatic response. Objective To perform a detailed qualitative review of existing literature on the association of abnormal bleeding with the use of SSRIs. Data sources We conducted a PubMed search during June 2009 using the search terms antidepressants and SSRIs (including the names of individual SSRIs: fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram) in association with bleeding, platelets, hemostasis, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, antiplatelet drugs, proton pump inhibitors, peptic ulcer, premenstrual dysphoric disorder, menstruation, pregnancy, postpartum hemorrhage, surgery, tooth extraction, dental bleeding, stroke, ischemic heart disease, and other terms related to the field. We then searched the reference lists of identified studies. Study selection We provide a qualitative discussion of all studies that would inform clinicians about the mechanisms of bleeding and bleeding risks associated with these drugs in different clinical contexts. Results Epidemiologic studies show that SSRI use is associated with roughly doubled odds of upper gastrointestinal (GI) bleeding; bleeding at other sites has been less commonly described, as has a possibly increased risk of bleeding associated with surgical procedures. The risk of SSRI-associated GI bleeding is increased with the concurrent use of NSAIDs, anticoagulants, and antiplatelet agents and is decreased by concurrent proton pump inhibitors. The risk of bleeding is increased in patients with cirrhosis of the liver or liver failure. There is, curiously, little literature on use of SSRIs and menstrual or postpartum blood loss. Selective serotonin reuptake inhibitors appear protective against ischemic heart disease events. The data are too limited to allow interpretations about influences on ischemic and hemorrhagic stroke. Conclusions On the basis of the findings of our literature search, we suggest that SSRI-induced increase in gastric acid secretion may explain the GI bleeding risk and that SSRI-related effects on platelet reactivity, endothelial reactivity, and inflammatory markers may explain the ischemic heart disease protective effect. Because the absolute risk of GI bleeds with SSRIs is low, precautions are probably necessary only in high-risk patients, such as those with acid-peptic disease and those with a history of bleeds. We discuss management issues and areas for future research.

Adjuvant Aspirin Therapy Reduces Symptoms of Schizophrenia Spectrum Disorders : Results From a Randomized, Double-Blind, Placebo-Controlled Trial

Abstract: Objective: Inflammatory processes may play a role in the pathophysiology of schizophrenia. The aim of this study was to determine the efficacy of adjuvant treatment with aspirin (acetylsalicylic acid) in schizophrenia spectrum disorders. Method: This randomized, double-blind, placebo-controlled study was conducted between May 2004 and August 2007. Seventy antipsychotictreated inpatients and outpatients from 10 psychiatric hospitals in The Netherlands with a DSM-IV–diagnosed schizophrenia spectrum disorder were included. Patients were randomized to adjuvant treatment with aspirin 1000 mg/d or placebo. During a 3-month follow-up, psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). Other assessments included cognitive tests and immune function. The primary efficacy outcome was the change in total PANSS score. Secondary outcomes were changes in the PANSS subscales and cognitive test results. Results: Mixed-effect models showed a 4.86-point (95% CI, 0.91 to 8.80) and 1.57-point (95% CI, 0.06 to 3.07) larger decrease in the aspirin group compared to the placebo group on the total and positive PANSS score, respectively. Similar but not statistically significant results were observed for the other PANSS subscale scores. Treatment efficacy on total PANSS score was substantially larger in patients with the more altered immune function (P = .018). Aspirin did not significantly affect cognitive function. No substantial side effects were recorded. Conclusion: Aspirin given as adjuvant therapy to regular antipsychotic treatment reduces the symptoms of schizophrenia spectrum disorders. The reduction is more pronounced in those with the more altered immune function. Inflammation may constitute a potential new target for antipsychotic drug development. Trial Registration: controlled-trials.com

Efficacy of the Novel Antidepressant Agomelatine on the Circadian Rest-Activity Cycle and Depressive and Anxiety Symptoms in Patients With Major Depressive Disorder: A Randomized, Double-Blind Comparison With Sertraline

Abstract: OBJECTIVE This study evaluates the efficacy of agomelatine, the first antidepressant to be an agonist at MT(1)/MT(2) receptors and an antagonist at 5-HT(2C) receptors, versus sertraline with regard to the amplitude of the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder (MDD). METHOD Outpatients with DSM-IV-TR-defined MDD received either agomelatine 25 to 50 mg (n = 154) or sertraline 50 to 100 mg (n = 159) during a 6-week, randomized, double-blind treatment period. The study was conducted from 2005 to 2006. The main outcome measure was the relative amplitude of the individual rest-activity cycles, expressed as change from baseline to week 6 and collected from continuous records using wrist actigraphy and sleep logs. Secondary outcome measures were sleep efficiency and sleep latency, both derived from actigraphy, and efficacy on depression symptoms (17-Item Hamilton Depression Rating Scale total score and Clinical Global Impressions scale scores) and anxiety symptoms (Hamilton Anxiety Rating Scale total score and subscores). RESULTS A significant difference in favor of agomelatine compared to sertraline on the relative amplitude of the circadian rest-activity cycle was observed at the end of the first week (P = .01). In parallel, a significant improvement of sleep latency (P <.001) and sleep efficiency (P <.001) from week 1 to week 6 was observed with agomelatine as compared to sertraline. Over the 6-week treatment period, depressive symptoms improved significantly more with agomelatine than with sertraline (P <.05), as did anxiety symptoms (P <.05). CONCLUSIONS The favorable effect of agomelatine on the relative amplitude of the circadian rest-activity/sleep-wake cycle in depressed patients at week 1 reflects early improvement in sleep and daytime functioning. Higher efficacy results were observed with agomelatine as compared to sertraline on both depressive and anxiety symptoms over the 6-week treatment period, together with a good tolerability profile. These findings indicate that agomelatine offers promising benefits for MDD patients. TRIAL REGISTRATION www.isrctn.org: ISRCTN49376288.

Identifying depressive subtypes in a large cohort study: results from the Netherlands Study of Depression and Anxiety (NESDA).

Abstract: Objective: The heterogeneity of depression in the current classification system remains a point of discussion in the psychiatric field, despite previous efforts to subclassify depressive disorders. Data-driven techniques may help to come to a more empirically based classification. This study aimed to identify depressive subtypes within a large cohort of subjects with depression. Method: Baseline data from 818 persons with a DSM-IV diagnosis of current major depressive disorder or minor depression who participated in the Netherlands Study of Depression and Anxiety were used. Respondents were recruited in the community, in primary care, and in specialized mental health care from September 2004 through February 2007. Latent classes were derived from latent class analysis using 16 depressive symptoms from the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology. Classes were characterized using demographic, clinical psychiatric, psychosocial, and physical health descriptors. Results: Three classes were identified: a severe melancholic class (prevalence, 46.3%), a severe atypical class (prevalence, 24.6%), and a class of moderate severity (prevalence, 29.1%). Both severe classes were characterized by more neuroticism (melancholic OR=1.05 [95% CI, 1.01-1.10]; atypical OR=1.07 [95% Cl, 1.03-1.12]), more disability (melancholic OR=1.07 [95% Cl, 1.05-1.09]; atypical OR=1.06 [95% CI, 1.04-1.07]), and less extraversion (melancholic OR=0.95 [95% CI, 0.92-0.99]; atypical OR=0.95 [95% CI, 0.92-0.99] than the moderate class. Comparing the melancholic class with the atypical class revealed that the melancholic class had more smokers (atypical OR=0.57 [95% CI, 0.39-0.84]) and more childhood trauma (atypical OR=0.86 [95% CI, 0.74-1.00]), whereas the atypical class had more women (atypical OR=1.52 [95% CI, 0.99-2.32]), a higher body mass index (atypical OR=1.13 [95% CI, 1.09-1.17]), and more metabolic syndrome (atypical OR=2.17 [95% CI, 1.38-3.42]). Conclusions: Both depression severity (moderate vs severe) and the nature of depressive symptoms (melancholic vs atypical) were found to be important differentiators between subtypes. Higher endorsement rates of somatic symptoms and more metabolic syndrome in the atypical class suggest the involvement of a metabolic component. J Clin Psychiatry 2010;71(12):1582-1589 (C) Copyright 2010 Physicians Postgraduate Press, Inc.

Prevalence of negative symptoms in outpatients with schizophrenia spectrum disorders treated with antipsychotics in routine clinical practice: findings from the CLAMORS study.

Abstract: Objective To analyze the prevalence of negative symptoms in antipsychotic-treated outpatients with schizophrenia spectrum disorders. Method A cross-sectional, retrospective multicenter study was carried out between May 2004 and April 2005 in 1,704 adult psychiatric outpatients meeting DSM-IV criteria for schizophrenia, schizophreniform, or schizoaffective disorder. We used 5 items of the Positive and Negative Syndrome Scale (PANSS) negative symptoms subscale to individually determine the presence of a negative symptom when the score on the item was > 3. Primary negative symptoms were considered present when patients fulfilled all of the following: > 3 score on the corresponding item; Results A total of 1,452 evaluable patients (863 men, 60.9%), 40.7 +/- 12.2 (mean +/- SD) years of age, were included. One or more negative symptoms were present in 57.6% of patients, with primary negative symptoms in 12.9% of subjects. The most frequent negative symptom items were social withdrawal (45.8%), emotional withdrawal (39.1%), poor rapport (35.8%), and blunted affect (33.1%). Negative symptoms (1-blunted affect, 2-emotional withdrawal, 3-poor rapport, 4-social withdrawal, 5-verbal fluency) were most associated with maleness (symptom 4); age > 40/45 years (men/women; symptoms 1,2,4); single/unmarried status (symptoms 2-4); unemployment (symptoms 3,4); higher score on the Clinical Global Impressions (CGI) scale and PANSS total score (symptoms 1-5); lower score on the PANSS positive symptoms subscale (symptoms 1,3); more than 52 weeks of treatment (symptoms 1-3,5); and high antipsychotic dose (symptom 2). Conclusions The prevalence of negative symptoms in patients with schizophrenia spectrum disorders treated with antipsychotics in routine clinical practice not only is still considerably high but also seems to be related to poorer functioning, unemployment, greater severity, and less positive symptomatology and higher antipsychotic dose.

Past and present progress in the pharmacologic treatment of schizophrenia.

Abstract: Despite treatment advances over the past decades, schizophrenia remains one of the most severe psychiatric disorders that is associated with a chronic relapsing course and marked functional impairment in a substantial proportion of patients. In this article, a historical overview of the pharmacologic advances in the treatment of schizophrenia over the past 50 years is presented. This is followed by a review of the current developments in optimizing the treatment and outcomes in patients with schizophrenia. Methodological challenges, potential solutions, and areas of particular need for further research are highlighted. Although treatment goals of response, remission, and recovery have been defined more uniformly, a good "effectiveness" measure mapping onto functional outcomes is still lacking. Moreover, the field must advance in transferring measurement-based approaches from research to clinical practice. There is an ongoing debate regarding whether and which first- or second-generation antipsychotics should be used. However, especially when considering individual adverse effect profiles, the differentiation into first- and second-generation antipsychotics as unified classes cannot be upheld, and a more differentiated view and treatment selection are required. The desired, individualized treatment approach needs to consider current symptoms, comorbid conditions, past therapeutic response, and adverse effects, as well as patient choice and expectations. Acute and long-term goals and effects of medication treatment should be balanced. To date, clozapine is the only evidence-based treatment for refractory patients, and the role of antipsychotic polypharmacy and other augmentation strategies remains unclear, at best. To discover novel treatments with enhanced/broader efficacy and improved tolerability, and to enable personalized treatment, the mechanisms underlying illness development and progression, symptomatic improvement, and side effect development need to be elucidated.

Insomnia and Sleep Duration in a Large Cohort of Patients With Major Depressive Disorder and Anxiety Disorders

Abstract: Objective: Disturbed sleep has a high impact on daily functioning and has been correlated with psychopathology. We investigated the extent to which insomnia and sleep duration were associated with both current and remitted depressive and anxiety disorders in a large-scale epidemiologic study, taking sociodemographics, health factors, and medication use into account. Method: Data of 2,619 individuals from the Netherlands Study of Depression and Anxiety (NESDA) were analyzed. Psychopathology was classified as no, current, or remitted DSM-IV-based diagnosis of major depressive or anxiety disorder. Outcome measures were insomnia (Women's Health Initiative Insomnia Rating Scale score >= 9) and sleep duration ( Results: Both current and remitted depressive disorder and current anxiety disorder were associated with insomnia and short sleep duration with odds ratios (ORs) for insomnia ranging from 1.42 to 3.23 and for short sleep duration ranging from 1.41 to 2.53. Associations were stronger for current than for remitted diagnoses and stronger for depressive than for anxiety disorders. Also long sleep duration was associated with current depressive disorder and anxiety disorders (OR range, 1.53-2.66). Sociodemographic factors, health indicators, and psychotropic medication use did contribute to sleep outcomes but could not explain much of the psychopathology and sleep associations. Conclusion: Depressive disorder but also anxiety disorder is strongly associated with sleep disturbances. Insomnia and short sleep duration persist after remittance of these disorders, suggesting that these are residual symptoms or possibly trait markers. Also, long sleep duration is associated with current depressive or anxiety disorders. J Clin Psychiatry 2010;71(3):239-246 (C) Copyright 2010 Physicians Postgraduate Press, Inc.

The EPPIC follow-up study of first-episode psychosis: longer-term clinical and functional outcome 7 years after index admission.

Abstract: Objective: To describe the longer-term clinical and functional outcome of a large, epidemiologic representative cohort of individuals experiencing a first episode of psychosis. Method: A naturalistic, prospective follow-up of an epidemiologic sample of 723 consecutive first-episode psychosis patients, followed between January 1998 and April 2005, at a median of 7.4 years after initial presentation to the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne, Australia. EPPIC is a frontline public mental health early psychosis program, servicing a geographically defined catchment area with a population of about 800,000 people. The main outcome measures included the Brief Psychiatric Rating Scale, the Schedule for the Assessment of Negative Symptoms, the Beck Depression Inventory, the Global Assessment of Functioning Scale, the Social and Occupational Functioning Assessment Scale, the Quality of Life Scale, and the remission criteria developed by the Remission in Schizophrenia Working Group. Results: Follow-up information was collected on up to 90.0% (n = 651) of the baseline cohort of 723 participants, with 66.9% (n = 484) interviewed. In the last 2 years, 57% of individuals with schizophrenia/ schizophreniform, 54% with schizoaffective disorder, 62% with affective psychosis, and 68% with other psychotic disorders reported some paid employment. Depending upon the criteria applied, symptomatic remission at follow-up was observed in 37%-59% of the cohort. Social/vocational recovery was observed in 31% of the cohort. Approximately a quarter achieved both symptomatic remission and social/vocational recovery. Conclusion: The relatively positive outcomes are consistent with a beneficial effect of specialized early intervention programs; however it is premature to draw firm conclusions. There was no control group and there are many differences between the relevant comparison studies and the present one. Although difficult to conduct, large scale controlled health services research trials are required to definitively determine the impact and optimal duration of specialized early psychosis programs.

Incidence of tardive dyskinesia with atypical versus conventional antipsychotic medications: a prospective cohort study.

Abstract: When the atypical antipsychotics became available, it was hoped that they would be associated with a lower risk of tardive dyskinesia (TD) than the older conventional antipsychotics. A 2004 systematic review of early conventional-controlled and other studies indicated that the evidence seemed to support the idea that this hope had been realized.1 As noted in the review, however, few of the existing studies were designed to focus on TD and its accurate identification. It is possible that a limited focus on TD diagnosis could have introduced bias in favor of atypicals.2 The primary aim of the current study was to compare the incidence of TD among users of atypical and conventional antipsychotics. Methods were similar to those from a previous TD incidence study conducted at our site during the conventional antipsychotic era. 3, 4

The neurobiology of the switch process in bipolar disorder: a review.

Abstract: Objective The singular phenomenon of switching from depression to its opposite state of mania or hypomania, and vice versa, distinguishes bipolar disorder (BPD) from all other psychiatric disorders. Despite the fact that it is a core aspect of the clinical presentation of BPD, the neurobiology of the switch process is still poorly understood. In this review we summarize the clinical evidence regarding somatic interventions associated with switching, with a particular focus on the biological underpinnings presumably involved in the switch process.

Noninvasive brain stimulation with high-frequency and low-intensity repetitive transcranial magnetic stimulation treatment for posttraumatic stress disorder.

Abstract: Posttraumatic stress disorder (PTSD) is an incapacitating anxiety disorder characterized by intrusive thoughts, hyperarousal, flashbacks, nightmares, sleep disturbances, emotional numbing, and withdrawal, among other clinical symptoms (as classified by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]).1 Posttraumatic stress disorder has a lifetime prevalence of about 6.8% and may develop in susceptible individuals after exposure to a terrifying ordeal that involved physical harm or the threat of physical harm.2 This severe anxiety disorder affects about 7.7 million people each year and remains challenging to treat, with persistent symptoms leading to considerable social, occupational, and interpersonal dysfunction.3 Although selective serotonin reuptake inhibitors (SSRIs)—among other antidepressants—have resulted in various degrees of improvement in patients with PTSD, there is no definitive pharmacotherapy available to date for the treatment of this debilitating disorder. A review of 37 clinical trials of pharmacotherapies4 found inadequate evidence to determine the value of antidepressants, benzodiazepines, anticonvulsants, α-blockers, and second-generation antipsychotics for the treatment of PTSD. Even so, according to an American Psychiatric Association guideline,5 SSRIs remain the first line of treatment for PTSD. In addition, due to the complex nature of this disorder, individuals with PTSD also seem to benefit from 10 to 12 sessions of cognitive-behavioral therapy, prolonged-exposure therapy, or cognitive-processing therapy. Nevertheless, many individuals respond inadequately to currently available therapies, and research for more effective treatment paradigms is ongoing. Most recently, repetitive transcranial magnetic stimulation (rTMS)—a method of noninvasive neuromodulation—has been emerging as a potentially effective technique in the treatment of PTSD. Indeed, rTMS has already been shown to be highly effective in the treatment of medically refractory depression6 and is now a clinically available form of treatment in certain settings. Similarly, there is evidence that rTMS can also be effective for the treatment of PTSD. In a prior open-label study,7 a single session of low-frequency (0.3 Hz) transcranial magnetic stimulation (TMS) applied to the left and right motor cortex was found to be transiently effective in lowering the core PTSD symptom of avoidance as well as somatization and symptoms of anxiety and depression. Stimulation with 10 Hz rTMS to the right DLPFC was then shown to generate even greater effects with an especially marked improvement in symptoms of re-experiencing and avoidance; these effects lasted for at least 2 weeks after the end of stimulation.8 Furthermore, 2 case studies suggest that stimulation of the right DLPFC with 1 Hz rTMS can, in fact, normalize the right frontal and paralimbic metabolic hyperactivity that is associated with PTSD as measured with positron emission tomography studies.9 In sum, these previous studies suggest that modulation of prefrontal activity, perhaps particularly on the right frontal cortex, with rTMS holds promise as a form of therapy in the treatment of PTSD. Therefore, in this study, we aimed to investigate the clinical efficacy of high-frequency rTMS in the relief of core PTSD symptoms (such as hyperarousal, flashbacks, vigilance, intrusive thoughts, emotional numbness, and withdrawal) as well as PTSD-associated symptoms of anxiety and depression. In contrast to previous studies, here we investigate treatment with 20 Hz rTMS (higher frequency than previous studies), as there is evidence that higher-frequency stimulation may result in more substantial effects. In addition, we compare the effects of treatment of either right or left DLPFC (“left rTMS” and “right rTMS”), since rTMS is known to have side-specific effects. For example, in patients with major depression, rTMS can induce antidepressant effects either by enhancing left DLPFC excitability via high-frequency stimulation or by decreasing right DLPFC excitability via low-frequency stimulation.10 Finally, our study here also offers a longer follow-up period of 3 months’ duration and an inclusion of an extensive battery of neuropsychological assessments. The main goal of this study was to evaluate the effects of high-frequency rTMS of right and left DLPFC, as compared to sham stimulation, on the clinical symptoms of PTSD. As secondary aims, we explored whether the clinical effects of stimulation were long lasting and associated with any cognitive changes as indexed by a battery of neuropsychological tests.

Does Inclusion of a Placebo Arm Influence Response to Active Antidepressant Treatment in Randomized Controlled Trials? Results From Pooled and Meta-Analyses

Abstract: OBJECTIVE To determine if the inclusion of a placebo arm and/or the number of active comparators in antidepressant trials influences the response rates of the active medication and/or placebo. DATA SOURCES Searches of MEDLINE, PsycINFO, and pharmaceutical Web sites for published trials or trials conducted but unpublished between January 1996 and October 2007. STUDY SELECTION 2,275 citations were reviewed, 285 studies were retrieved, and 90 were included in the analysis. Trials reporting response and/or remission rates in adult subjects treated with an antidepressant monotherapy for unipolar major depression were included. DATA EXTRACTION The primary investigator recorded the number of responders and/or remitters in the intent-to-treat population of each study arm or computed these numbers using the quoted rates. DATA SYNTHESIS Poisson regression analyses demonstrated that mean response rate for the active medication was higher in studies comparing 2 or more active medications without a placebo arm than in studies comparing 2 or more active medications with a placebo arm (65.4% vs 57.7%, P < .0001) or in studies comparing only 1 active medication with placebo (65.4% vs 51.7%, P = .0005). Mean response rate for placebo was significantly lower in studies comparing 1 rather than 2 or more active medications (34.3% vs 44.6%, P = .003). Mean remission rates followed a similar pattern. Meta-analysis confirmed results from the pooled analysis. CONCLUSIONS These data suggest that antidepressant response rates in randomized control trials may be influenced by the presence of a placebo arm and by the number of treatment arms and that placebo response rates may be influenced by the number of active treatment arms in a study.

Bipolar disorder: new perspectives in health care and prevention.

Abstract: Medical and research findings, along with health economic data, support a more modern view of bipolar disorder as a chronic, progressive, multisystem disorder. This new comprehensive framework should guide the search to identify biomarkers and etiologic factors and should help design a new policy for health care, including prevention, diagnosis, treatment, and training.

Increased Risk for Suicidal Behavior in Comorbid Bipolar Disorder and Alcohol Use Disorders: Results From the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)

Abstract: OBJECTIVE: Bipolar disorder is associated with a high rate of suicide attempt, and alcohol use disorders have also been associated with elevated risk for suicidal behavior. Whether risk for suicidal behavior is elevated when these conditions are comorbid has not been addressed in epidemiologic studies. METHOD: 1,643 individuals with a DSM-IV lifetime diagnosis of bipolar disorder were identified from 43,093 general-population respondents who were interviewed in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Assessments were made using the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV). Lifetime prevalence of reported history of suicide attempt and suicidal thoughts among bipolar disorder respondents with and without DSM-IV lifetime alcohol use disorders (abuse or dependence) was assessed using chi2 and adjusted odds ratios with confidence intervals. Logistic regression was used to test the relevance of other comorbid clinical conditions to suicide risk in bipolar respondents with and without comorbid alcohol use disorders. RESULTS: More than half of the respondents (54%) who met criteria for bipolar disorder also reported alcohol use disorder. Bipolar individuals with comorbid alcohol use disorder were at greater risk for suicide attempt than those individuals without alcohol use disorder (adjusted odds ratio=2.25; 95% CI, 1.61-3.14) and were more likely to have comorbid nicotine dependence and drug use disorders. Nicotine dependence and drug use disorders did not increase risk for suicidal behavior among those with bipolar disorder, nor did they confer additional risk among bipolar respondents who also reported alcohol use disorder. Despite greater psychopathological burden, individuals with comorbid bipolar disorder and alcohol use disorder did not receive more treatment or more intensive treatment. CONCLUSIONS: Suicidal behavior is more likely to occur in bipolar respondents who also suffer from alcohol use disorder. Interventions to reduce suicide risk in bipolar disorder need to address the common and high-risk comorbidity with alcohol use disorders. Language: en

Reduced Anterior Cingulate and Orbitofrontal Volumes in Child Abuse–Related Complex PTSD

Abstract: OBJECTIVE: Classic posttraumatic stress disorder (PTSD) is associated with smaller hippocampus, amygdala, and anterior cingulate cortex (ACC) volumes. We investigated whether child abuse-related complex PTSD-a severe form of PTSD with affect dysregulation and high comorbidity-showed similar brain volume reductions. METHOD: We used voxel-based morphometry to measure gray matter concentrations in referred outpatients with child abuse-related complex PTSD (n = 31) compared to matched healthy nontraumatized controls (n = 28). Complex PTSD was diagnosed using the Structured Clinical Interview for DSM-IV-TR and the Structured Clinical Interview for Disorders of Extreme Stress. All respondents were scanned on a 1.5-T magnetic resonance system at the VU Medical Center, Amsterdam, The Netherlands, between September 2005 and February 2006. RESULTS: As was hypothesized, patients with child abuse-related complex PTSD showed reductions in gray matter concentration in right hippocampus (P(SVC corrected) = .04) and right dorsal ACC (P(SVC corrected) = .02) compared to controls. In addition, a reduction in gray matter concentration in the right orbitofrontal cortex (OFC) was found. Severity of child abuse and PTSD-hyperarousal correlated negatively with ACC volume. Impulsivity correlated negatively with hippocampus volume, and anger, with hippocampus and OFC volume. Comorbidity of borderline personality disorder-compared to comorbid cluster C personality disorder-accounted for more extensive reductions in the ACC and OFC volume. CONCLUSIONS: In complex PTSD, not only the hippocampus and the ACC but also the OFC seem to be affected, even in the absence of comorbid borderline personality disorder. These results suggest that neural correlates of complex PTSD are more severe than those of classic PTSD. Language: en

Obesity and onset of significant depressive symptoms: results from a prospective community-based cohort study of older men and women

Abstract: Objective Although several cross-sectional studies have linked obesity and depression, less is known about their longitudinal association and about the relative influence of obesity subtypes We prospectively examined whether obesity (specifically, abdominal) increased the risk of onset of depression in a population-based sample of older persons Method Participants were 2,547 nondepressed, well-functioning white and black persons, aged 70-79 years, enrolled in the Health, Aging, and Body Composition Study, an ongoing prospective community-based cohort study Baseline measurements were conducted between April 1997 and June 1998 Overall obesity was assessed by body mass index (BMI) and percent body fat (measured by dual energy x-ray absorptiometry), whereas abdominal obesity measures included waist circumference, sagittal diameter, and visceral fat (measured by computer tomography) Onset of significant depressive symptoms was defined as a Center for Epidemiologic Studies Depression 10-item score > or = 10 at any annual follow-up over 5 years and/or new antidepressant medication use Persistent depression was defined as depression at 2 consecutive follow-up visits Results Over 5 years, significant depressive symptoms emerged in 237% of initially nondepressed persons In men, both overall (BMI: hazard ratio [HR] per SD increase = 120; 95% CI, 103-140) and abdominal obesity (visceral fat: HR per SD increase = 119; 95% CI, 107-133) predicted onset of depressive symptoms after adjustment for sociodemographics When BMI and visceral fat were adjusted for each other, only visceral fat was significantly associated with depression onset (HR = 118; 95% CI, 104-134) Stronger associations were found for persistent depressive symptoms No associations were found in women Conclusion This study shows that obesity, in particular visceral fat, increases the risk of onset of significant depressive symptoms in men These results suggest that specific mechanisms might relate visceral fat to the onset of depression