Showing papers in "The Journal of Clinical Psychiatry in 2011"

Comorbidity Patterns of Anxiety and Depressive Disorders in a Large Cohort Study: the Netherlands Study of Depression and Anxiety (NESDA)

Abstract: Background Comorbidity of depressive and anxiety disorders is common and has been shown to be a consistent predictor of chronicity. Comorbidity patterns among specific depressive and anxiety disorders have not been extensively reported. This study examines comorbidity patterns and temporal sequencing of separate depressive and anxiety disorders using data from a large psychiatric cohort. Method Baseline data (N = 1,783) of the Netherlands Study of Depression and Anxiety, collected between September 2004 and February 2007, were used. Current and lifetime comorbidity rates for depressive and anxiety disorders (DSM-IV-TR criteria) were calculated. Associations of comorbidity with sociodemographic, vulnerability, and clinical characteristics, and temporal sequencing of disorders were examined. Results Of those with a depressive disorder, 67% had a current and 75% had a lifetime comorbid anxiety disorder. Of persons with a current anxiety disorder, 63% had a current and 81% had a lifetime depressive disorder. Comorbidity of depressive and anxiety disorders was associated with more childhood trauma (OR = 1.19; 95% CI, 1.06-1.33), higher neuroticism (OR = 1.05; 95% CI, 1.02-1.08), earlier age at onset of first disorder (OR = 1.59; 95% CI, 1.22-2.07), longer duration of depressive and/or anxiety symptoms (OR = 1.01; 95% CI, 1.01-1.01), and higher symptom severity (ORs ranging from 1.01 to 1.03; all P values Conclusions Comorbidity rates in anxiety and depressive disorders were very high, indicating that it is advisable to assess both disorders routinely regardless of the primary reason for consultation. This is especially important since comorbid patients showed a specific vulnerability pattern, with more childhood trauma, neuroticism, and higher severity and duration of symptoms.

Meta-Analysis of the Effects of Eicosapentaenoic Acid (EPA) in Clinical Trials in Depression

Abstract: Objective—Randomized trials of omega-3 polyunsaturated fatty acid (PUFA) treatment for depression have differed in outcome. Recent meta-analyses ascribe discrepancies to differential effects of eicosapentaenoic acid (EPA) vs. docosahexaenoic acid (DHA) and to diagnostic heterogeneity. This meta-analysis tests the hypothesis that EPA is the effective component in PUFA treatment of major depressive episodes. Data Sources—PubMed was searched (1960 through June 2010) using terms “Fish Oils”[Mesh] AND (“Depressive Disorder”[Mesh] OR “Bipolar Depression”) AND “Randomized Controlled Trial”[Publication Type], for placebo-controlled trials of PUFA supplementation, a depressive episode as primary disorder, published in English, supplemented by manual bibliography review. Study Selection—The search yielded 15 trials involving 916 participants. Data Extraction—Sample sizes; PUFA doses; mean ages, baseline and endpoint depression ratings and standard deviations; and p values were extracted. Data Synthesis—In a mixed-effect model, percentage of EPA in the supplements was the fixedeffect predictor, dichotomized into two groups: EPA < 60% or EPA ≥ 60% of EPA + DHA. Secondary analyses explored relevance of treatment duration, age, and EPA dose. Results—Supplements with EPA ≥ 60% showed benefit on standardized mean depression scores (SMD, for EPA ≥ 60% = 0.558, 95% CI = (0.277, 0.838), z = 4.195, p = 0.001; for EPA < 60% = −0.026, 95% CI = (0.200, 0.148), z = −0.316, p =0.756), with negligible contribution of random effects or heteroscedasticity, and no effects of treatment duration or age. Supplements with EPA < 60% were ineffective. Exploratory analyses supported a non-linear model, with improvement determined by the dose of EPA in excess of DHA, within the range 200 to 2200 mg EPA. Conclusions—Supplements containing EPA ≥ 60%, in dose range 200 to 2200 mg EPA in excess of DHA, were effective against primary depression. Translational studies are needed to determine mechanisms of EPA’s therapeutic benefit.

The diagnostic challenge of psychiatric symptoms in neurodegenerative disease; rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease

Abstract: Objective To identify rates of and risk factors for psychiatric diagnosis preceding the diagnosis of neurodegenerative disease (ND).

The effect of exercise in clinically depressed adults: systematic review and meta-analysis of randomized controlled trials

Abstract: Objective To assess the effectiveness of exercise in adults with clinical depression. Data sources The databases CINAHL, Embase, Cochrane Database of Systematic reviews, Cochrane Controlled Trials Register, MEDLINE, and PsycINFO were searched (1806-2008) using medical subject headings (MeSH) and text word terms depression, depressive disorder and exercise, aerobic, non-aerobic, physical activity, physical fitness, walk*, jog*, run*, bicycling, swim*, strength, and resistance. Study selection Randomized trials including adults with clinical depression according to any diagnostic system were included. Data extraction Two investigators evaluated trials using a prepiloted structured form. Data synthesis Thirteen trials were identified that fulfilled the inclusion criteria. Eight had adequate allocation concealment, 6 had a blinded outcome, and 5 used intention-to-treat analyses. The pooled standardized mean difference (SMD) calculated using a random-effects model was -0.40 (95% CI, -0.66 to -0.14), with evidence of heterogeneity between trials (I(2) = 57.2%, P = .005). There was an inverse association between duration of intervention and the magnitude of the association of exercise with depression (P = .002). No other characteristics were related to between-study heterogeneity. Pooled analysis of 5 trials with long-term follow-up (ie, that examined outcomes beyond the end of the intervention) suggested no long-term benefit (SMD, -0.01; 95% CI, -0.28 to 0.26), with no strong evidence of heterogeneity in this pooled analysis (I(2) = 23.4%, P = .27). There was no strong statistical evidence for small study bias (P > .27). Only 3 studies were assessed as high quality (adequately concealed random allocation, blinded outcome assessment, and intention-to-treat analysis). When we pooled results from these, the estimated beneficial effect of exercise was more modest (SMD, -0.19; 95% CI, -0.70 to 0.31) than the pooled result for all 13 studies, with no strong evidence of benefit. Conclusions Our results suggest a short-term effect of exercise on depression: on average, depression scores 0.4 of a standard deviation lower in clinically depressed patients randomly assigned to an exercise intervention at the end of that intervention compared to those randomly assigned to a none exercise group. There is little evidence of a long-term beneficial effect of exercise in patients with clinical depression.

Meta-analysis of epidemiologic studies of pediatric bipolar disorder.

Abstract: Objective Meta-analyze all published epidemiologic studies reporting pediatric mania or bipolar disorder to investigate whether pediatric bipolar disorder is becoming more prevalent and whether rates vary significantly by country. Data sources Searches of PubMed and PsycInfo were conducted through the spring of 2010 using the following search terms: child, pediatric, young, adolescent, epidemiology, prevalence, bipolar, mania, suicide, and psychiatric. We also manually reviewed references in recent reviews of epidemiology of bipolar disorder. Study selection All studies reporting rates for mania or hypomania in community epidemiologic samples with participants up to 21 years of age. Data extraction All articles were coded to extract relevant variables. Prevalence rates were calculated from reported number of cases with bipolar disorders, then logit transformed. Twelve studies were included, enrolling 16,222 youths between the ages of 7 and 21 years during a period from 1985 to 2007. Six samples were from the United States; 6 were from other countries (the Netherlands, the United Kingdom, Spain, Mexico, Ireland, and New Zealand). Results The overall rate of bipolar disorder was 1.8% (95% CI, 1.1%-3.0%). There was no significant difference in the mean rates between US and non-US studies, but the US studies had a wider range of rates. The highest estimates came from studies that used broad definitions and included bipolar disorder not otherwise specified. Year of enrollment was negatively correlated with prevalence (r = -0.04) and remained nonsignificant when controlling for study methodological differences. Conclusions Mean rates of bipolar disorder were higher than commonly acknowledged and not significantly different in US compared to non-US samples, nor was there evidence of an increase in rates of bipolar disorder in the community over time. Differences in diagnostic criteria were a main driver of different rates across studies.

The Same or Different? A Phenomenological Comparison of Auditory Verbal Hallucinations in Healthy and Psychotic Individuals

Abstract: Objective: Whereas auditory verbal hallucinations (AVHs) are most characteristic of schizophrenia, their presence has frequently been described in a continuum, ranging from severely psychotic patients to schizotypal personality disorder patients to otherwise healthy participants. It remains unclear whether AVHs at the outer borders of this spectrum are indeed the same phenomenon. Furthermore, specific characteristics of AVHs may be important indicators of a psychotic disorder. Method: To investigate differences and similarities in AVHs in psychotic and nonpsychotic individuals, the phenomenology of AVHs in 118 psychotic outpatients was compared to that in 11 otherwise healthy individuals, both experiencing AVHs at least once a month. The study was performed between September 2007 and March 2010 at the University Medical Center, Utrecht, the Netherlands. Characteristics of AVHs were quantified using the Psychotic Symptoms Rating Scales Auditory Hallucinations subscale. Results: The perceived location of voices (inside/outside the head), the number of voices, loudness, and personification did not differentiate between psychotic and healthy individuals. The most prominent differences between AVHs in healthy and psychotic individuals were the emotional valence of the content, the frequency of AVHs, and the control subjects had over their AVHs (all P values <.001). Age at onset of AVHs was at a significantly younger age in the healthy individuals (P <.001). In our sample, the negative emotional valence of the content of AVHs could accurately predict the presence of a psychotic disorder in 88% of the participants. Conclusions: We cannot ascertain whether AVHs at the outer borders of the spectrum should be considered the same phenomenon, as there are both similarities and differences. The much younger age at onset of AVHs in the healthy subjects compared to that in psychotic patients may suggest a different pathophysiology. The high predictive value of the emotional content of voices implies that inquiring after the emotional content of AVHs may be a crucial step in the diagnosis of psychotic disorders in individuals hearing voices. J Clin Psychiatry 2011;72(3):320-325 (C) Copyright 2011 Physicians Postgraduate Press, Inc.

Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volume.

Abstract: Background Reduced brain-derived neurotrophic factor (BDNF) levels have been reported in the serum and plasma of patients with psychosis. The aim of this study was to investigate potential causes and consequences of reduced BDNF expression in these patients, by examining the association between BDNF levels and measures of stress, inflammation and hippocampal volume in first-episode psychosis.

Emotion Dysregulation and Negative Affect: Association With Psychiatric Symptoms

Abstract: Objective A growing body of research focuses on the development and correlates of emotion dysregulation, or deficits in the ability to regulate intense and shifting emotional states. Current models of psychopathology have incorporated the construct of emotion dysregulation, suggesting its unique and interactive contributions, along with childhood disruptive experiences and negative affect, in producing symptomatic distress. Some researchers have suggested that emotion dysregulation is simply a variant of high negative affect. The aim of this study was to assess the construct and incremental validity of self-reported emotion dysregulation over and above childhood trauma and negative affect in predicting a range of psychopathology.

Antidepressants for the Acute Treatment of Bipolar Depression: A Systematic Review and Meta-Analysis

Abstract: Objective: The role of antidepressants in the acute treatment of bipolar depression remains a contentious issue. A previous meta-analysis of randomized controlled trials (RCTs) concluded that antidepressants were effective and safe for bipolar depression. Several trials published since then suggest that antidepressants may not be as beneficial as previously concluded. The current systematic review and meta-analyses reexamine the efficacy and safety of antidepressant use for the acute treatment of bipolar depression. Data sources: EMBASE, MEDLINE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials databases were searched for double-blind RCTs published from 2003 to 2009 using the following diagnostic medical subject heading (MESH) terms: bipolar disorder, bipolar depression, bipolar I disorder, bipolar II disorder, bipolar III disorder, bipolar mania, cyclothymia, manic depressive psychosis, mixed mania and depression, and rapid cycling and bipolar disorder. Databases of trial registries were also searched for unpublished RCTs. These searches were supplemented by hand searches of relevant articles and review articles. Study selection: Trials that compared acute (< 16 wk) antidepressant treatment with either an active drug or a placebo comparator in adult bipolar patients, depressive phase were eligible for inclusion. Main outcome measures were clinical response, remission, and affective switch. Data synthesis: Six RCTs (N = 1,034) were identified since publication in 2004 of the first meta-analysis that assessed antidepressant use in the acute treatment of bipolar depression. These studies were combined with earlier studies for a total of 15 studies containing 2,373 patients. Antidepressants were not statistically superior to placebo or other current standard treatment for bipolar depression. Antidepressants were not associated with an increased risk of switch. Studies that employed more sensitive criteria to define switch did report elevated switch rates for antidepressants. Conclusions: Although antidepressants were found to be safe for the acute treatment of bipolar depression, their lack of efficacy may limit their clinical utility. Further high-quality studies are required to address the existing limitations in the literature.

Acute stress disorder as a predictor of posttraumatic stress disorder: a systematic review.

Abstract: Objective The utility of the acute stress disorder diagnosis to describe acute stress reactions and predict subsequent posttraumatic stress disorder (PTSD) was evaluated. Data sources A systematic search was conducted in the PsycINFO, MEDLINE, and PubMed databases for English-language articles published between 1994 and 2009 using keywords that combined acute stress disorder and posttraumatic stress disorder. Study selection Studies were selected that assessed for acute stress disorder within 1 month of trauma exposure and assessed at a later time for PTSD, using established measures of acute stress disorder and PTSD. Data extraction For each study, capacity of the acute stress disorder diagnosis to predict PTSD was calculated in terms of sensitivity, specificity, and positive and negative predictive power. For studies that reported subsyndromal acute stress disorder, the same analyses were calculated for cases that initially satisfied subsyndromal acute stress disorder criteria. Data synthesis Twenty-two studies were identified as suitable for analysis (19 with adults and 3 with children). Diagnosis of acute stress disorder resulted in half the rate of distressed people in the acute phase being identified relative to including cases with subsyndromal acute stress disorder. In terms of prediction, the acute stress disorder diagnosis had reasonable positive predictive power (proportion of people with acute stress disorder who later developed PTSD). In contrast, the sensitivity (proportion of people who developed PTSD who initially met criteria for acute stress disorder) was poor. Conclusions The acute stress disorder diagnosis does not adequately identify the majority of people who will eventually develop PTSD. There is a need to formally describe acute stress reactions, but this goal may be achieved more usefully by describing the broad range of initial reactions rather than by attempting to predict subsequent PTSD.

Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials.

Abstract: OBJECTIVE Late-life depression is an important public health issue, given the growing proportion of the elderly relative to the general population in the developed world. The purpose of this study was to examine the efficacy of antidepressants for the treatment of major depressive disorder (MDD) in elderly patients. DATA SOURCES PubMed/MEDLINE was searched for randomized, double-blind, placebo-controlled trials of antidepressants for treatment of both adult (nonelderly) MDD (patients aged < 65 years) and late-life MDD (patients aged ≥ 55 years). The search was limited to articles published between January 1, 1980, and March 3, 2010 (inclusive). The year 1980 was used as a cutoff in our search to decrease diagnostic variability, since the DSM-III was introduced in 1980. Our search cross-referenced the term placebo with each of the following antidepressants: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. We also reviewed the reference lists of all studies identified through the PubMed/MEDLINE search. STUDY SELECTION Articles were selected that reported on randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD and that met numerous a priori criteria pertaining to MDD diagnosis criteria, study duration, study design, drug formulation, original data, age thresholds, primary and secondary outcome measures, and exclusions of other disorders. Final inclusion of articles was determined by consensus between the authors. Seventy-four articles were found eligible for inclusion in our analysis (15 late-life MDD trials and 59 adult MDD trials). RESULTS Antidepressants were found to be efficacious for late-life MDD (age 55 and older; P < .0001), although there was evidence for heterogeneity across studies (Q22 = 67.302, P < .001). However, antidepressants were not found to be efficacious in the subset of studies using age thresholds of 65 years or older (older late-life MDD) (P = .265). Finally, when we controlled for study design characteristics, antidepressant but not placebo response rates were lower among late-life MDD patients than among adult MDD patients. CONCLUSIONS The present meta-analysis suggests that antidepressants are efficacious in late-life MDD, but significant study heterogeneity suggests that other factors may contribute to these findings. A secondary analysis raises the possibility that efficacy of these agents may be reduced in trials involving patients aged 65 years or older. Why antidepressants may be less efficacious in elderly versus younger subjects remains unclear.

Exercise as an augmentation treatment for nonremitted major depressive disorder: a randomized, parallel dose comparison.

Abstract: Objective: Most patients with major depressive disorder (MDD) require second-step treatments to achieve remission. The TReatment with Exercise Augmentation for Depression (TREAD) study was designed to test the efficacy of aerobic exercise as an augmentation treatment for MDD patients who had not remitted with antidepressant treatment. Method: Eligible participants in this randomized controlled trial were sedentary individuals (men and women aged 18–70 years) diagnosed with DSM-IV nonpsychotic MDD who had not remitted with selective serotonin reuptake inhibitor (SSRI) treatment. Participants were recruited through physician referrals and advertisements. A total of 126 participants were randomized to augmentation treatment with either 16 kcal per kg per week (KKW) or 4 KKW of exercise expenditure for 12 weeks while SSRI treatment was held constant. Supervised sessions were conducted at The Cooper Institute, Dallas, Texas, with additional home-based sessions as needed to fulfill the weekly exercise prescription. The primary outcome was remission (as determined by a score ≤ 12 on the Inventory of Depressive Symptomatology, ClinicianRated). The study took place between August 2003 and August 2007. Results: There were significant improvements over time for both groups combined (F1,121 = 39.9, P < .0001), without differential group effect (group effect: F1,134 = 3.2, P = .07; group-by-time effect: F1,119 = 3.8, P = .06). Adjusted remission rates at week 12 were 28.3% versus 15.5% for the 16-KKW and 4-KKW groups, respectively, leading to a number needed to treat (NNT) of 7.8 for 16 KKW versus 4 KKW. Men, regardless of family history of mental illness, and women without a family history of mental illness had higher remission rates by week 12 with higher-dose (women, 39.0%; men, 85.4%) than with lower-dose exercise (women, 5.6%; men, 0.1%) (women: t95 = 2.1, P = .04; men: t88 = 5.4, P < .0001) (NNT: women, 3.0; men, 1.2). Conclusions: There was a trend for higher remission rates in the higher-dose exercise group (P < .06), with a clinically meaningful NNT of 7.8 in favor of the high exercise dose. Significant differences between groups were found when the moderating effects of gender and family history of mental illness were taken into account and suggest that higher-dose exercise may be better for all men and for women without a family history of mental illness. Trial Registration: clinicaltrials.gov Identifier:

Exploratory analyses of efficacy data from major depressive disorder trials submitted to the US Food and Drug Administration in support of new drug applications.

Abstract: Objective There has been concern about a high rate of placebo response and a substantial failure rate in recent clinical trials in major depressive disorder (MDD). This report explores differences in efficacy data from placebo-controlled MDD trials submitted in support of new drug applications (NDAs) over a 25-year period. Method We compiled efficacy data from 81 randomized, double-blind clinical trials, with 21,611 evaluable patients, that were submitted to the US Food and Drug Administration as part of NDAs for an antidepressant claim between 1983 and 2008. Trial data were limited to completed, randomized, multicenter, double-blind, placebo-controlled clinical trials in adult patients diagnosed with MDD according to DSM-III or DSM-IV criteria. The database was further limited to patients who were involved in clinical trials for drugs widely viewed as effective antidepressants and for doses of these drugs also viewed as effective doses. Trials were rated as successful if they showed statistical superiority vs placebo for the investigational drug on change in Hamilton Depression Rating Scale (HDRS) score (last-observation-carried-forward data). (Trials with multiple investigational drug groups were successful if there was superiority in at least 1 drug group after adjustment for multiplicity.) In particular, we explored differences in effect size and success rate of these trials, based on when the studies were conducted, geographic location of the study sites (US vs non-US), trial duration, dosing regimen, study size, and baseline disease characteristics. Results Eighty-one percent of MDD patients were enrolled in US sites. Although the observed placebo and drug responses at non-US sites tended to be larger than at US sites, the treatment effect (drug-placebo difference) was similar (mean change from baseline of about -2.5 units in HDRS total score) in US and non-US trials. In both US and non-US trials, the placebo response showed a modest increase over the observation period (1983-2008). Treatment effect clearly diminished over this same period, at a similar rate for both US and non-US trials despite a marked increase in the sample size of the trials. Our analysis showed that 53% of all MDD trials in the last 25 years were successful. US trials had a higher success rate than non-US trials (58% vs 33%). Before 1995, the overall success rate was 55%, compared to 50% for trials in 1995 or later, and, in general, 6-week trials had a higher success rate than 8-week trials (55% vs 42%). It should be noted that the earlier trials were mostly 6 weeks, and the 6-week trials had higher mean baseline HDRS scores than the 8-week trials. Study size did not seem to influence trial success rates. Mean baseline HDRS total scores declined over the 25-year observation period for patients in both US and non-US trials, as did treatment effect in these trials, again, regardless of region. Fixed-dose trials had a numerically slightly greater success rate than flexible-dose trials (57% vs 51%), although on average treatment effect was numerically larger in the flexible-dose trials than in fixed-dose trials (mean of -2.9 vs -2.0 on HDRS units). Conclusions Treatment effect has declined over time in MDD trials, and there has been a high failure rate for these trials during the entire period, but the reasons for these findings remain elusive. Baseline disease severity seems to be a more important factor in study outcome than study duration, dosing regimen, sample size, time when studies were conducted, and regions where data were generated. Close attention is needed to a variety of factors in the design and conduct of these studies, including patient population, diagnostic considerations, patient assessment, and clinical practice differences. These considerations become increasingly important as globalization of clinical trials continues to increase.

A Randomized, Double-Blind, Placebo-Controlled Study of Light Therapy for Antepartum Depression

Abstract: Objective: Affective disorder during pregnancy is a common condition requiring careful judgment to treat the depression while minimizing risk to the fetus. Following up on promising pilot trials, we studied the efficacy of light therapy. Method: Twenty-seven pregnant women with nonseasonal major depressive disorder according to DSM-IV (outpatients, university polyclinic) were randomly assigned to 7,000 lux fluorescent bright white or 70 lux dim red (placebo) light administered at home in the morning upon awakening for 1 h/d in a 5-week double-blind trial carried out between October 2004 and October 2008. Clinical state was monitored weekly with the 29-item Structured Interview Guide for the Hamilton Depression Rating Scale (HDRS) with Atypical Depression Supplement (SIGH-ADS). Changes of rating scale scores over time were analyzed with the general linear model. Differences from baseline of SIGH-ADS and 17-item HDRS scores at every time point were the dependent variables, time was the within-subjects factor, and treatment was the between-subjects factor. The model also included baseline score of depression and gestational age at intervention start. Results: The superiority of bright light over dim light placebo was shown for both SIGH-ADS (R-2 = 0.251; F-3,F-23 = 3.91; P = 50% improvement) at week 5 was significantly greater for bright light (81.3%, n = 16) than for placebo light (45.5%, n = 11) (P < .05). Remission (final score 8) was attained by 68.6% versus 36.4%, respectively (P < .05). Expectation ratings did not differ significantly between groups. Conclusions: Bright white light treatment for 5 weeks improved depression during pregnancy significantly more than placebo dim red light. The study provides evidence that light therapy, a simple, cost-effective antidepressant modality with minimal side effects for the mother and no known risk for the unborn child, may be a useful non-pharmacologic approach in this difficult situation.

The association between social isolation and DSM-IV mood, anxiety, and substance use disorders: wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions.

Abstract: OBJECTIVE The objective of this study is to document the prevalence of social isolation from close friends and religious group members and to test the association of having infrequently contacted close friends and members of religious groups with the current DSM-IV mood, anxiety, and substance use disorders. METHOD We conducted a secondary data analysis based on a cross-sectional, population-based study conducted in 2004-2005 that consists of a nationally representative sample of 34,653 American community-dwelling adults aged 18 years and older. Mood, anxiety, and substance use disorders were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version. Due to missing values for social network characteristics, we focused on 33,368 subjects in this study. RESULTS We found that many Americans lacked frequently contacted close friends (10.1%; 95% CI, 9.6%-10.6%) or religious group members (58.7%; 95% CI, 57.5%-59.9%) in their social network. After adjusting for sociodemographic variables, lifetime diagnosis of the disorder in question, and social isolation in terms of 10 other social ties, we found that the absence of close friends was associated (P < .01) with an increased risk of major depressive disorder, dysthymic disorder, social phobia, and generalized anxiety disorder; the absence of frequently contacted religious group members in a network was positively related (P < .01) to alcohol abuse and dependence, drug abuse, and nicotine dependence. CONCLUSIONS These results suggest that social isolation is common in the United States and is associated with a higher risk of mental health problems. Results provide valuable information for prevention and treatment.

Pregnancy as a Major Determinant for Discontinuation of Antidepressants: An Analysis of Data From The Health Improvement Network

Abstract: Background: Potential adverse effects of antidepressants during pregnancy have caused concern about their use. There are, however, very limited detailed data on patterns of antidepressant prescribing in pregnancy. Objective: To examine secular trends in prescribing during pregnancy, to assess whether pregnancy is a major determinant for stopping antidepressants, and to identify characteristics of those who stopped antidepressants during pregnancy. Method: In this cohort study, we obtained data on 114,999 pregnant women (median age at delivery, 30.5 years [interquartile range, 26-34 years]) who had a live birth between 1992 and 2006 and 22,677 nonpregnant women from The Health Improvement Network primary care database, one of the largest sources of continuous anonymized primary care data in the United Kingdom and broadly representative of UK general practice. This database includes information on age, sex, medical diagnosis and symptoms, health promotion activities, referrals to secondary care, and prescriptions for each registered individual. The database also holds information about social deprivation as measured using quintiles of the Townsend score. We used Cox regression analysis to compare time to last prescription in pregnant versus nonpregnant women and to identify characteristics of those women who stopped antidepressants during pregnancy. Results: Antidepressant prescribing in pregnancy increased nearly 4-fold from 1992 to 2006 (relative risk = 3.87; 95% CI, 1.73-8.66; P < .001). Since 2001, approximately 3% of the cohort received antidepressants at some stage during pregnancy. Selective serotonin reuptake inhibitors accounted for approximately 80% of the prescribed antidepressants. Antidepressants were more likely to be stopped in pregnant than in nonpregnant women, in particular during the first 6 weeks of pregnancy (hazard ratio = 5.19; 95% CI, 4.85-5.56; P < .001). Only 10% of women treated before pregnancy still received antidepressants at the start of the third trimester. In contrast, 35% of nonpregnant women were still treated after a similar time period. Conclusions: Although antidepressant prescribing in pregnancy increased nearly 4-fold from 1992 to 2006, pregnancy was a major determinant of cessation of antidepressant medication, and most women did not receive further antidepressant prescriptions beyond 6 weeks of gestation. This finding may be explained by concerns about potential adverse effects of the medications, even though these concerns need to be balanced against the potential harm of inadequate treatment of depression during pregnancy. J Clin Psychiatry 2011;72(7):979-985 (C) Copyright 2011 Physicians Postgraduate Press, Inc.

An algorithm-based approach to first-episode schizophrenia: response rates over 3 prospective antipsychotic trials with a retrospective data analysis.

Abstract: Objective: Early, effective treatment in first-episode schizophrenia is advocated, although evidence based on a systematic approach over multiple antipsychotic trials is lacking. Employing a naturalistic design, we examined response rates over 3 circumscribed antipsychotic trials. Method: Between June 2003 and December 2008, 244 individuals with first-episode schizophrenia or schizoaffective disorder according to DSM-IV criteria were treated at the Centre for Addiction and Mental Health,Toronto, Ontario, Canada, following an algorithm that moved them through 2 antipsychotic trials, followed by a trial with clozapine. For the first 2 trials, treatment consisted of risperidone followed by olanzapine, or vice versa; each trial consisted of 3 stages (low-, full-, or high-dose) lasting up to 4 weeks at each level and adjusted according to response/tolerability. Clinical response was defined as a Clinical Global Impressions-Improvement score of 2 (much improved) or 1 (very much improved) and/or a Brief Psychiatric Rating Scale Thought Disorder subscale score <6. Data were analyzed retrospectively, and publication of anonymized clinical data was approved by the Research Ethics Board of the Centre for Addiction and Mental Health in May 2003. Results: In trial 1, 74.5% of individuals responded, with rates significantly higher for olanzapine (82.1 %, 115/140) versus risperidone (66.3%, 69/104; P=. 005 ). With trial 2, response rate dropped dramatically to 16.6% but again was significantly higher for olanzapine (25.7%, 9/35) compared to risperidone (4.0%, 1/25; P=.0 4 ). Response rate climbed above 70% once more, specifically 75.0% (21/28), in those individuals who agreed to a third trial with clozapine. Conclusions: Results confirm a high response rate (75%) to initial antipsychotic treatment in first-episode schizophrenia. A considerably lower response rate (< 20%) occurs with a second antipsychotic trial. Results here were specific to olanzapine and risperidone, suggesting clinical differences (ie, olanzapine more effective than risperidone). A subsequent trial with clozapine is clearly warranted, although it remains unclear whether outcome would be further enhanced if it were used earlier in the treatment algorithm.

Health-related quality of life across the anxiety disorders: results from the national epidemiologic survey on alcohol and related conditions (NESARC).

Abstract: Objective—Although clinical studies have documented that specific anxiety disorders are associated with impaired psychosocial functioning, little is known regarding their comparative effects on health-related quality of life within a general population. The current analysis compares health-related quality of life in a U.S. community-dwelling sample of adults with DSM-IV social anxiety disorder (SAD), generalized anxiety disorders (GAD), panic disorder (PD), and specific phobia (SP). Method—Face-to-face survey of a U.S. nationally representative sample of over 43,000 adults aged 18 years and older residing in households and group quarters. Prevalence of DSM-IV anxiety disorders and relative associations with health-related quality of life indicators were examined. Results—Roughly 9.8% of respondents met diagnostic criteria for at least one 12-month DSMIV anxiety disorder which, relative to the non-anxiety-disordered general population, were each associated with lower personal income, increased rates of 12-month physical conditions, and greater numbers of Axis I and Axis II DSM-IV psychiatric conditions. After adjusting for sociodemographic and clinical correlates including other anxiety disorders, GAD was associated with significant decrements in the SF-12 Mental Component Summary score. In similar models, GAD and to a lesser extent PD were significantly associated with impairment in social functioning, role emotional, and mental health SF subscales. Conclusion—GAD, followed by PD, appears to exact significant and independent tolls on health-related quality of life. Results underscore the importance of prompt and accurate clinical identification and improving access to effective interventions for these disorders. Anxiety disorders are the most prevalent class of mental health disorders 1 and collectively impose a substantial public health burden on society. Evidence of the burden of anxiety disorders is portrayed in reports of high health care utilization and costs, 2–5 losses of worker productivity, 6 elevated rates of general medical disorders, 7 frequent comorbid mental disorders, 1,8–13 and increased risk of suicide attempts and suicidal ideation. 14–16 Anxiety disorders are also associated with impaired health-related quality of life. 17 Yet epidemiologic surveys document long delays in treatment seeking 18 and low rates of treatment among individuals with anxiety disorders. 19

Lifetime prevalence of mood and anxiety disorders in fragile X premutation carriers

Abstract: OBJECTIVE The authors studied the lifetime prevalence of DSM-IV-TR psychiatric disorders in a population of adults with the fragile X premutation. METHOD The Structured Clinical Interview for DSM-IV was conducted, from 2007-2008, in 85 individuals with the fragile X premutation, 47 with the fragile X-associated tremor/ataxia syndrome (FXTAS; 33 male, 14 female; mean age = 66 years) and 38 without FXTAS (16 male, 22 female; mean age = 52 years). Lifetime prevalence for mood and anxiety disorders among carriers with and without FXTAS was compared to available age-specific population estimates from the National Comorbidity Survey Replication (NCS-R). RESULTS Among participants with FXTAS, 30 (65%) met lifetime DSM-IV-TR criteria for a mood disorder; 24 (52%) met lifetime DSM-IV-TR criteria for an anxiety disorder. Among the non-FXTAS participants, there were 15 instances of lifetime mood disorder (42%) and 18 of lifetime anxiety disorder (47%). When compared to age-specific NCS-R data, the lifetime prevalences of any mood disorder (P < .0001), major depressive disorder (P < .0001), any anxiety disorder (P < .0001), panic disorder (P = .006), specific phobia (P = .0003), and posttraumatic stress disorder (P = .004) were significantly higher in participants with FXTAS. The lifetime rates of social phobia in individuals with the premutation without FXTAS were significantly higher than NCS-R data (P = .001). CONCLUSIONS This sample of carriers of the fragile X premutation had a notably high lifetime risk of mood and anxiety disorders. Mood and anxiety disorders may be part of the clinical phenotype of the fragile X premutation conditions, especially in carriers with FXTAS. Clinicians encountering these patients are advised to consider FXTAS as a neuropsychiatric syndrome as well as a neurologic disorder.

An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method.

Abstract: Objective The lack of generally accepted diagnostic criteria for neuroleptic malignant syndrome (NMS) impedes research and clinical management of patients receiving antipsychotic medications. The purpose of this study was to develop NMS diagnostic criteria reflecting a broad consensus among clinical knowledge experts, represented by an international multispecialty physician panel. Participants Eleven psychiatrists, 2 neurologists, 2 anesthesiologists, and 2 emergency medicine specialists participated in a formal Delphi consensus procedure. Evidence A core bibliography consisting of 12 prominent, current reviews of the NMS literature was identified by an objective, comprehensive electronic search strategy. Each panel member was given a copy of these references and asked to examine them before commencing the survey process. Consensus process After reviewing the core bibliography, panel members were asked to list any clinical signs or symptoms or diagnostic studies that they believed, on the basis of their knowledge and clinical experience, were useful in making a diagnosis of NMS. In subsequent survey rounds, panel members assigned priority points to these items, and items that failed to receive a minimum priority score were eliminated from the next round. Information about individual panel member responses was fed back to the group anonymously in the form of the group median or mean and the number of members who had ranked or scored each survey item. The a priori consensus endpoint was defined operationally as a change of 10% or less in the mean priority score for any individual item, and an average absolute value change of 5% or less across all items, between consecutive rounds. The survey was conducted from January 2009 through September 2009. Results Consensus was reached on the fifth round regarding the following criteria: recent dopamine antagonist exposure, or dopamine agonist withdrawal; hyperthermia; rigidity; mental status alteration; creatine kinase elevation; sympathetic nervous system lability; tachycardia plus tachypnea; and a negative work-up for other causes. The panel also reached a consensus on the relative importance of these criteria and on the following critical values for quantitative criteria: hyperthermia, > 100.4°F or > 38.0°C on at least 2 occasions; creatine kinase elevation, at least 4 times the upper limit of normal; blood pressure elevation, ≥ 25% above baseline; blood pressure fluctuation, ≥ 20 mm Hg (diastolic) or ≥ 25 mm Hg (systolic) change within 24 hours; tachycardia, ≥ 25% above baseline; and tachypnea, ≥ 50% above baseline. Conclusions These diagnostic criteria significantly advance the field because they represent the consensus of an international multispecialty expert panel, include critical values, provide guidance regarding the relative importance of individual elements, and are less influenced by particular theoretical biases than most previously published criteria. They require validation before being applied in clinical settings.

Problematic Internet use and health in adolescents: data from a high school survey in Connecticut.

Abstract: OBJECTIVE This study aims to explore the prevalence and health correlates of problematic Internet use among high school students in the United States. METHOD A cross-sectional survey with a sample size of 3,560 students was conducted among high schools in Connecticut. Demographic data, characteristics of Internet use, health measures, and risk behaviors were assessed. Chi-square and logistic regression analyses were used to study the relationship between problematic Internet use and risk behaviors as well as related gender differences. RESULTS When problematic Internet use was diagnosed with criteria modeled after the Minnesota Impulsive Disorder Inventory that address core features of impulse-control disorder (strong urge, growing tension, and attempts to cut back), the overall prevalence was about 4%, with no significant difference between genders. Problematic Internet use was more common among Asian (7.86%) and Hispanic (6.07%) students. Even though boys spent significantly more time on the Internet (16.52% of boys spent over 20 hours per week vs 12.62% of girls; P = .0001) and more frequently missed important school or social activities as a result (8.97% of boys vs 5.85% of girls; P = .0004), girls more frequently self-reported measures of excessive use of the Internet (11.81% of girls thought that they had a problem vs 8.90% of boys; P = .0048). After adjustment of sociodemographic factors, problematic Internet use was found to associate significantly with substance use (P = .0014), depression (P < .0001), and aggression (P < .0001), with largely similar patterns of associations between genders. CONCLUSIONS Problematic Internet use may be present in about 4% of high school students in the United States. It may be associated with depression, substance use, and aggressive behaviors. High school boys, though, may have heavier Internet use and may be less self-aware of the related problems.

The epidemiology of the proposed DSM-5 hoarding disorder: exploration of the acquisition specifier, associated features, and distress.

Abstract: Objective: Compulsive hoarding, characterized by the acquisition of and failure to discard a large number of possessions, is increasingly recognized as a significant public health burden. Many facets of the phenomenology, including an understanding of the population prevalence and associated features, are not yet fully understood. There is growing evidence that hoarding may warrant its own diagnosis in DSM-5, and it is therefore imperative to investigate the proposed cardinal symptoms along with correlated features that may be diagnostically relevant. Method: The present investigation examined the point prevalence of hoarding disorder in a nationally representative sample from the German population (N = 2,512). The hoarding definition considered in this study was derived from the Hoarding Rating Scale (HRS) and informed by 3 of the proposed DSM-5 criteria. Several hypothesized core components of hoarding disorder were also assessed using questions from the HRS and the UCLA Hoarding Severity Scale, including types of acquisition, perfectionism, indecision, procrastination, distress, and impairment. Data were collected from May 16, 2009, to June 19, 2009. Results: Analyses revealed a current population estimate of 5.8%. Hoarding prevalence did not differ between men and women. Hoarders were significantly more likely to buy items, acquire free things, and steal items they did not need, compared to non-hoarders (P<.001). Perfectionism, indecision, and procrastination were all uniquely and significantly associated with hoarding status (P<.001). Relationships between the proposed core features and distress/impairment are also detailed. Conclusions: The current investigation identified the proposed hoarding disorder as a highly prevalent syndrome; however, it should be noted that we were not able to fully ascertain the DSM-5 criteria and that the current estimate may be higher than the actual population rate. Future research on the diagnostic criteria and associated features will be necessary to help clarify etiologic underpinnings, treatment efforts, and diagnostic nosology.

A national epidemic of unintentional prescription opioid overdose deaths: how physicians can help control it.

Abstract: Both the usage of prescription drugs such as opioid analgesics and benzodiazepines and overdoses involving them have increased dramatically in the United States since the 1990s. Patients using these drugs often have a combination of painful conditions, substance abuse, and other forms of mental illness. Psychiatrists and many primary care physicians might not be familiar with existing evidence-based guidelines for opioid prescribing or with programs designed to reduce the abuse of prescription drugs such as state prescription drug monitoring programs. Psychiatrists need to be informed regarding this problem to partner effectively with both pain specialists and primary care providers in their community.

Measurement-based care in psychiatric practice: a policy framework for implementation.

Abstract: This article describes the need for measurement-based care (MBC) in psychiatric practice and defines a policy framework for implementation. Although measurement in psychiatric treatment is not new, it is not standard clinical practice. Thus a gap exists between research and practice outcomes. The current standards of psychiatric clinical care are reviewed and illustrated by a case example, along with MBC improvements. Measurement-based care is defined for clinical practice along with limitations and recommendations. This article provides a policy top 10 list for implementing MBC into standard practice, including establishing clear expectations and guidelines, fostering practice-based implementation capacities, altering financial incentives, helping practicing doctors adapt to MBC, developing and expanding the MBC science base, and engaging consumers and their families. Measurement-based care as the standard of care could transform psychiatric practice, move psychiatry into the mainstream of medicine, and improve the quality of care for patients with psychiatric illness.

Randomized controlled trial of interventions for young people at ultra high risk for psychosis: 6-month analysis.

Abstract: OBJECTIVE: Cognitive therapy and/or low-dose antipsychotic administered during the prodromal phase of schizophrenia may prevent or delay the onset of full-blown illness. However, it is unclear which of these treatments are most effective, how long treatment should be given, and whether effects will be sustained over a prolonged period. METHOD: In order to examine these issues, we conducted a randomized controlled trial of cognitive therapy + risperidone; cognitive therapy + placebo; and supportive therapy + placebo in young people at ultra high risk for developing a psychotic disorder (that is, putatively prodromal). The main outcome was transition to psychotic disorder, with level of symptoms and functioning the secondary outcomes. This article reports the interim 6-month follow-up results. The study was conducted from August 2000 to May 2007. RESULTS: Of a possible 464 eligible ultra high risk individuals, 115 were recruited to the randomized controlled trial (cognitive therapy + risperidone, n = 43; cognitive therapy + placebo, n = 44; and supportive therapy + placebo, n = 28). An additional 78 individuals agreed to follow-up assessments but not to randomization ("monitoring group," n = 78). At 6 months, 8 of the 115 participants (7.0%) and 4 of the monitoring group (5.1%) had developed psychotic disorder. There were no significant differences between the 3 randomized groups (log rank test, P = .92) or between all 4 groups (log rank test, P = .93). There was also no difference between the 4 groups in secondary measures, with all groups showing a reduction in symptoms and increased functioning. CONCLUSIONS: Rates of transition to psychosis were lower than expected, particularly in the control supportive therapy + placebo group. This may have accounted for the negative finding, as the sample was therefore underpowered to find any difference between groups. Alternatively, it may be that all treatments were equally effective or equally ineffective at 6 months. TRIAL REGISTRATION: http://www.anzctr.org.au Identifier: ACTRN012605000247673.

Continuation of Quetiapine Versus Switching to Placebo or Lithium for Maintenance Treatment of Bipolar I Disorder (Trial 144: A Randomized Controlled Study)

Abstract: Objective: Quetiapine, combined with lithium or divalproex, demonstrates efficacy in the maintenance treatment of bipolar I disorder. This study investigated the efficacy and safety of quetiapine monotherapy as maintenance treatment in bipolar I disorder compared with switching to placebo or lithium. Method: Patients aged >= 18 years with DSM-IV-diagnosed bipolar I disorder and a current or recent manic, depressive, or mixed episode received open-label quetiapine (300-800 mg/d) for 4-24 weeks. Patients achieving stabilization were randomized to continue quetiapine or to switch to placebo or lithium (0.6-1.2 mEq/L) for up to 104 weeks in a double-blind trial. Outcome measures included times to recurrence of any mood event (primary outcome measure), manic event, or depressive event. Safety assessments included adverse events and laboratory values. The study was terminated early after planned interim analysis provided positive results. The study was conducted between March 2005 and July 2007. Results: Of 2,438 patients starting open-label quetiapine, 1,226(50.3%) were randomized to double-blind treatment, including 1,172 (95.6%) in the intent-to-treat population. Time to recurrence of any mood event was significantly longer for quetiapine versus placebo (hazard ratio [HR] = 0.29; 95% CI, 0.23-0.38; P <.0001) and for lithium versus placebo (HR = 0.46; 95% CI, 1136-0.59; P <.0001). Quetiapine and lithium significantly increased time to recurrence of both manic events (quetiapine: HR = 0.29; 95% CI, 0.21-0.40; P <.0001; lithium: HR = 0.37; 95% CI, 0.27-0.53; P <.0001) and depressive events (quetiapine: HR = 0.30; 95% CI, 0.20-0.44; P <.0001; lithium: HR = 0.59; 95% CI, 0.42-0.84; P <.004) compared with placebo. Overall rates of adverse events were generally similar between treatment groups, and safety findings for quetiapine were consistent with its known profile. Conclusions: In patients stabilized during acute quetiapine treatment, continuation of quetiapine significantly increased time to recurrence of any mood, manic, or depressive event compared with switching to placebo. Switching to lithium was also more effective than placebo for the prevention of manic and depressive events.

The efficacy of omega-3 supplementation for major depression: a randomized controlled trial.

Abstract: Objective To document the short-term efficacy of omega-3 supplementation in reducing depressive symptoms in patients experiencing a major depressive episode (MDE). Method Inclusive, double-blind, randomized, controlled, 8-week, parallel-group trial, conducted October 17, 2005 through January 30, 2009 in 8 Canadian academic and psychiatric clinics. Adult outpatients (N = 432) with MDE (Mini-International Neuropsychiatric Interview, version 5.0.0, criteria) lasting at least 4 weeks, including 40.3% taking antidepressants at baseline, were randomly assigned to 8 weeks of 1,050 mg/d of eicosapentaenoic acid (EPA) and 150 mg/d of docosahexaenoic acid (DHA) or matched sunflower oil placebo (2% fish oil). The primary outcome was the self-report Inventory of Depressive Symptomatology (IDS-SR(30)); the secondary outcome was the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS). Results The adjusted mean difference between treatment and placebo was 1.32 points (95% CI, -0.20 to 2.84; P = .088) on the IDS-SR(30) and 0.97 points (95% CI, -0.012 to 1.95; P = .053) on the MADRS. Planned subgroup analyses revealed a significant interaction of comorbid anxiety disorders and study group (P = .035). For patients without comorbid anxiety disorders (n = 204), omega-3 supplementation was superior to placebo, with an adjusted mean difference of 3.17 points on the IDS-SR(30) (95% CI, 0.89 to 5.45; P = .007) and 1.93 points (95% CI, 0.50 to 3.36; P = .008) on the MADRS. Conclusions In this heterogeneous sample of patients with MDE, there was only a trend toward superiority of omega-3 supplementation over placebo in reducing depressive symptoms. However, there was a clear benefit of omega-3 supplementation among patients with MDE without comorbid anxiety disorders. Trial registration controlled-trials.com Identifier: ISRCTN47431149.

Suicidality in obsessive-compulsive disorder: prevalence and relation to symptom dimensions and comorbid conditions.

Abstract: Background Suicidal thoughts and behaviors, also known as suicidality, are a fairly neglected area of study in patients with obsessive-compulsive disorder (OCD). Objective To evaluate several aspects of suicidality in a large multicenter sample of OCD patients and to compare those with and without suicidal ideation, plans, and attempts according to demographic and clinical variables, including symptom dimensions and comorbid disorders. Method This cross-sectional study included 582 outpatients with primary OCD (DSM-IV) recruited between August 2003 and March 2008 from 7 centers of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders. The following assessment instruments were used: the Yale-Brown Obsessive Compulsive Scale, the Dimensional Yale-Brown Obsessive Compulsive Scale, the Beck Depression and Anxiety Inventories, the Structured Clinical Interview for DSM-IV Axis I Disorders, and 6 specific questions to investigate suicidality. After univariate analyses, logistic regression analyses were performed to adjust the associations between the dependent and explanatory variables for possible confounders. Results Thirty-six percent of the patients reported lifetime suicidal thoughts, 20% had made suicidal plans, 11% had already attempted suicide, and 10% presented current suicidal thoughts. In the logistic regression, only lifetime major depressive disorder and posttraumatic stress disorder (PTSD) remained independently associated with all aspects of suicidal behaviors. The sexual/religious dimension and comorbid substance use disorders remained associated with suicidal thoughts and plans, while impulse-control disorders were associated with current suicidal thoughts and with suicide plans and attempts. Conclusions The risk of suicidal behaviors must be carefully investigated in OCD patients, particularly those with symptoms of the sexual/religious dimension and comorbid major depressive disorder, PTSD, substance use disorders, and impulse-control disorders.

Candidate gene analysis identifies a polymorphism in HLA-DQB1 associated with clozapine-induced agranulocytosis.

Abstract: Objective: Clozapine is considered to be the most efficacious drug to treat schizophrenia, although it is underutilized, partially due to a side effect of agranulocytosis. This analysis of 74 candidate genes was designed to identify an association between sequence variants and clozapine-induced agranulocytosis (CIA). Method: Blood and medical history were collected for 33 CIA cases and 54 clozapine-treated controls enrolled between April 2002 and December 2003. Significant markers from 4 genes were then assessed in an independently collected case-control cohort (49 CIA cases, 78 controls). Results: Sequence variants in 5 genes were found to be associated with CIA in the first cohort: HLA-DQB1, HLA-C, DRD1, NTSR1, and CSF2RB. Sequence variants in HLA-DQB1 were also found to be associated with CIA in the second cohort. After refinement analyses of sequence variants in HLA-DQB1, a single SNP (single nucleotide polymorphism), 6672G>C, was found to be associated with risk for CIA; the odds of CIA are 16.9 times greater in patients who carry this marker compared to those who do not. Conclusions: A sequence variant (6672G>C) in HLA-DQB1 is associated with increased risk for CIA. This marker identifies a subset of patients with an exceptionally high risk of CIA, 1,175 higher than the overall clozapine-treated population under the current blood-monitoring system. Assessing risk for CIA by testing for this and other genetic variants yet to be determined may be clinically useful when deciding whether to begin or continue treatment with clozapine. J Clin Psychiatry 2011;72(4):458-463 (C) Copyright 2010 Physicians Postgraduate Press, Inc.

Psychological characteristics of chronic depression: a longitudinal cohort study.

Abstract: Background: Few studies have investigated the importance of psychological characteristics for chronicity of depression. Knowledge about psychological differences between chronically depressed persons and nonchronically depressed persons may help to improve treatment of chronic depression. This is the first study to simultaneously compare in large samples various psychological characteristics between chronically depressed and nonchronically depressed adults. Method: Baseline data were drawn from the Netherlands Study of Depression and Anxiety (NESDA), an ongoing longitudinal cohort study aimed at examining the long-term course of depressive and anxiety disorders in different health care settings and phases of illness. Participants were aged 18 to 65 years at the baseline assessment in 2004-2007 and had a current diagnosis of DSM-IV major depressive disorder (N = 1,002). Chronicity of depression was defined as being depressed for 24 months or more in the past 4 to 5 years. The chronicity criterion was fulfilled by 31% (n = 312). The NEO Five-Factor Inventory measured the 5 personality domains, the Leiden Index of Depression Sensitivity-Revised was used to measure cognitive reactivity (eg, hopelessness, rumination), and the Mastery Scale measured external locus of control. Results: Compared to the nonchronically depressed persons, the chronically depressed persons reported significantly higher levels of neuroticism (OR = 1.81; 95% CI, 1.55-2.12; P <.001), external locus of control (OR = 1.94; 95% CI, 1.66-2.28; P <.001), and the following dimensions of cognitive reactivity: hopelessness (OR = 1.64; 95% CI, 1.43-1.88; P <.001), aggression (OR = 1.29; 95% CI, 1.131.48; P <.001), risk aversion (OR = 1.43; 95% CI, 1.24-1.63; P <.001), and rumination (OR = 1.55; 95% CI, 1.34-1.78; P <.001). They had significantly lower levels of extraversion (OR = 0.57; 95% CI, 0.49-0.67; P <.001), agreeableness (OR = 0.85; 95% CI, 0.74-0.97; P = .02), and conscientiousness (OR= 0.77; 95% CI, 0.67-0.88; P <.001). When testing these variables multivariably, the odds of chronic depression were significantly increased among those with low extraversion (OR = 0.73; 95% CI, 0.61-0.88; P = .001), high rumination (OR = 1.24; 95% CI, 1.01-1.53; P = .04), and high external locus of control (OR = 1.48; 95% CI, 1.21-1.80; P <.001). Controlling for severity of depressive symptoms, age at onset, comorbidity with anxiety disorders, medical illnesses, and treatment status did not change these results. Conclusions: Our findings suggest that extraversion, rumination, and external locus of control, but not neuroticism, are differentiating psychological characteristics for chronicity of depression. These findings provide suggestions for more specific interventions, focused on extraversion, rumination, and external locus of control, in the treatment of chronic depression. J Clin Psychiatry 2011;72(3):288-294 (C) Copyright 2011 Physicians Postgraduate Press,