Showing papers in "Archives of General Psychiatry in 2005"

Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication

Abstract: Context Little is known about lifetime prevalence or age of onset of DSM-IV disorders. Objective To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. Design and Setting Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Participants Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. Main Outcome Measures Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. Results Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. Conclusions About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.

Prevalence, Severity, and Comorbidity of 12-Month DSM-IV Disorders in the National Comorbidity Survey Replication

Abstract: Background Little is known about the general population prevalence or severity of DSM-IV mental disorders. Objective To estimate 12-month prevalence, severity, and comorbidity of DSM-IV anxiety, mood, impulse control, and substance disorders in the recently completed US National Comorbidity Survey Replication. Design and Setting Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using a fully structured diagnostic interview, the World Health Organization World Mental Health Survey Initiative version of the Composite International Diagnostic Interview. Participants Nine thousand two hundred eighty-two English-speaking respondents 18 years and older. Main Outcome Measures Twelve-month DSM-IV disorders. Results Twelve-month prevalence estimates were anxiety, 18.1%; mood, 9.5%; impulse control, 8.9%; substance, 3.8%; and any disorder, 26.2%. Of 12-month cases, 22.3% were classified as serious; 37.3%, moderate; and 40.4%, mild. Fifty-five percent carried only a single diagnosis; 22%, 2 diagnoses; and 23%, 3 or more diagnoses. Latent class analysis detected 7 multivariate disorder classes, including 3 highly comorbid classes representing 7% of the population. Conclusion Although mental disorders are widespread, serious cases are concentrated among a relatively small proportion of cases with high comorbidity.

Twelve-Month Use of Mental Health Services in the United States Results From the National Comorbidity Survey Replication

Abstract: Background Dramatic changes have occurred in mental health treatments during the past decade. Data on recent treatment patterns are needed to estimate the unmet need for services. Objective To provide data on patterns and predictors of 12-month mental health treatment in the United States from the recently completed National Comorbidity Survey Replication. Design and Setting Nationally representative face-to-face household survey using a fully structured diagnostic interview, the World Health Organization’s World Mental Health Survey Initiative version of the Composite International Diagnostic Interview, carried out between February 5, 2001, and April 7, 2003. Participants A total of 9282 English-speaking respondents 18 years and older. Main Outcome Measures Proportions of respondents with 12-monthDSM-IVanxiety, mood, impulse control, and substance disorders who received treatment in the 12 months before the interview in any of 4 service sectors (specialty mental health, general medical, human services, and complementary and alternative medicine). Number of visits and proportion of patients who received minimally adequate treatment were also assessed. Results Of 12-month cases, 41.1% received some treatment in the past 12 months, including 12.3% treated by a psychiatrist, 16.0% treated by a nonpsychiatrist mental health specialist, 22.8% treated by a general medical provider, 8.1% treated by a human services provider, and 6.8% treated by a complementary and alternative medical provider (treatment could be received by >1 source). Overall, cases treated in the mental health specialty sector received more visits (median, 7.4) than those treated in the general medical sector (median, 1.7). More patients in specialty than general medical treatment also received treatment that exceeded a minimal threshold of adequacy (48.3% vs 12.7%). Unmet need for treatment is greatest in traditionally underserved groups, including elderly persons, racial-ethnic minorities, those with low incomes, those without insurance, and residents of rural areas. Conclusions Most people with mental disorders in the United States remain either untreated or poorly treated. Interventions are needed to enhance treatment initiation and quality.

Epidemiology of Major Depressive Disorder: Results From the National Epidemiologic Survey on Alcoholism and Related Conditions

Abstract: Objective:To present nationally representative data on 12-month and lifetime prevalence, correlates, and comorbidity of DSM-IV major depressive disorder (MDD) among adults in the United States. Design/Setting/Participants:Face-to-face survey of more than 43000 adults aged 18 years and older residinginhouseholdsandgroupquartersintheUnitedStates. Main Outcome Measures: Prevalence and associationsofMDDwithsociodemographiccorrelatesandAxis I and II disorders. Results:Theprevalenceof12-monthandlifetimeDSM-IV MDD was 5.28% (95% confidence interval, 4.98-5.57) and 13.23% (95% confidence interval, 12.64-13.81), respectively. Being female; Native American; middleaged; widowed, separated, or divorced; and low income increased risk, and being Asian, Hispanic, or black decreased risk (P.05). Women were significantly more likely to receive treatment than men. Both current and lifetimeMDDweresignificantlyassociatedwithotherspecific psychiatric disorders, notably substance dependence, panic and generalized anxiety disorder, and several personality disorders. Conclusions:This large survey suggests a higher prevalence of MDD in the US population than large-sample estimates from the 1980s and 1990s. The shift in highest lifetime risk from young to middle-aged adults is an important transformation in the distribution of MDD in the United States and specificity in risk for an ageperiodcohort.AssociationsbetweenMDDandAxisIand II disorders were strong and significant, with variation within broad categories by specific diagnoses signaling the need for attention to the genetic and environmental reasons for such variation, as well as the implications for treatment response. Arch Gen Psychiatry. 2005;62:1097-1106

Association Between Duration of Untreated Psychosis and Outcome in Cohorts of First-Episode Patients: A Systematic Review

Abstract: Context Duration of untreated psychosis (DUP) is the time from manifestation of the first psychotic symptom to initiation of adequate treatment. It has been postulated that a longer DUP leads to a poorer prognosis. If so, outcome might be improved through earlier detection and treatment. Objectives To establish whether DUP is associated with prognosis and to determine whether any association is explained by confounding with premorbid adjustment. Data Sources The CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, and PsychLIT databases were searched from their inception dates to May 2004. Study Selection Eligible studies reported the relationship between DUP and outcome in prospective cohorts recruited during their first episode of psychosis. Twenty-six eligible studies involving 4490 participants were identified from 11 458 abstracts, each screened by 2 reviewers. Data Extraction Data were extracted independently and were checked by double entry. Sensitivity analyses were conducted excluding studies that had follow-up rates of less than 80%, included affective psychoses, or did not use a standardized assessment of DUP. Data Synthesis Independent meta-analyses were conducted of correlational data and of data derived from comparisons of long and short DUP groups. Most data were correlational, and these showed a significant association between DUP and several outcomes at 6 and 12 months (including total symptoms, depression/anxiety, negative symptoms, overall functioning, positive symptoms, and social functioning). Long vs short DUP data showed an association between longer DUP and worse outcome at 6 months in terms of total symptoms, overall functioning, positive symptoms, and quality of life. Patients with a long DUP were significantly less likely to achieve remission. The observed association between DUP and outcome was not explained by premorbid adjustment. Conclusions There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.

Failure and Delay in Initial Treatment Contact After First Onset of Mental Disorders in the National Comorbidity Survey Replication

Abstract: Context An understudied crucial step in the help-seeking process is making prompt initial contact with a treatment provider after first onset of a mental disorder. Objective To provide data on patterns and predictors of failure and delay in making initial treatment contact after first onset of a mental disorder in the United States from the recently completed National Comorbidity Survey Replication. Design and Setting Nationally representative face-to-face household survey carried out between February 2001 and April 2003. Participants A total of 9282 respondents aged 18 years and older. Main Outcome Measures LifetimeDSM-IVdisorders were assessed with the World Mental Health (WMH) Survey Initiative version of the World Health Organization Composite International Diagnostic Interview (WMH-CIDI), a fully structured interview designed to be administered by trained lay interviewers. Information about age of first professional treatment contact for each lifetimeDSM-IV/WMH-CIDI disorder assessed in the survey was collected and compared with age at onset of the disorder to study typical duration of delay. Results Cumulative lifetime probability curves show that the vast majority of people with lifetime disorders eventually make treatment contact, although more so for mood (88.1%-94.2%) disorders than for anxiety (27.3%-95.3%), impulse control (33.9%-51.8%), or substance (52.7%-76.9%) disorders. Delay among those who eventually make treatment contact ranges from 6 to 8 years for mood disorders and 9 to 23 years for anxiety disorders. Failure to make initial treatment contact and delay among those who eventually make treatment contact are both associated with early age of onset, being in an older cohort, and a number of socio-demographic characteristics (male, married, poorly educated, racial/ethnic minority). Conclusions Failure to make prompt initial treatment contact is a pervasive aspect of unmet need for mental health care in the United States. Interventions to speed initial treatment contact are likely to reduce the burdens and hazards of untreated mental disorder.

The lifetime risk of suicide in schizophrenia: a reexamination.

Abstract: Background The psychiatry literature routinely quotes a lifetime schizophrenia suicide prevalence of 10% based on 1 meta-analysis and 2 studies of chronic schizophrenics. Objectives To build a methodology for extrapolating lifetime suicide prevalence estimates from published cohorts and to apply this approach to studies that meet inclusion criteria. Data sources We began with a MEDLINE search (1966-present) for articles that observed cohorts of schizophrenic patients. Exhaustive bibliography searching of each identified article brought the total number of articles reviewed to 632. Study selection Studies included in the meta-analysis observed a cohort of schizophrenic patients for at least 2 years, with at least 90% follow-up, and reported suicides. Articles are excluded for systematic age bias (ie, adolescents). Data extraction Extracted data included sample size, number of deaths, number of suicides, percentage of follow-up, and diagnostic system used. Data were extracted independently by 2 of us, and differences were resolved by consensus after re-review. Data synthesis Studies were divided into 2 groups: 32 studies of schizophrenics enrolled at various illness points (25 578 subjects) and 29 studies of schizophrenics identified at either illness onset or first admission (22 598 subjects). Regression models of the intersection of proportionate mortality (the percentage of the dead who died by suicide) and case fatality (the percentage of the total sample who died by suicide) were used to calculate suicide risk in each group. The estimate of lifetime suicide prevalence in those observed from first admission or illness onset was 5.6% (95% confidence interval, 3.7%-8.5%). Mixed samples showed a rate of 1.8% (95% confidence interval, 1.4%-2.3%). Case fatality rates showed no significant differences when studies of patients diagnosed with the use of newer systems were compared with studies of patients diagnosed under older criteria. Conclusion This study estimates that 4.9% of schizophrenics will commit suicide during their lifetimes, usually near illness onset.

Cognitive therapy vs medications in the treatment of moderate to severe depression.

Abstract: Background There is substantial evidence that antidepressant medications treat moderate to severe depression effectively, but there is less data on cognitive therapy’s effects in this population. Objective To compare the efficacy in moderate to severe depression of antidepressant medications with cognitive therapy in a placebo-controlled trial. Design Random assignment to one of the following: 16 weeks of medications (n = 120), 16 weeks of cognitive therapy (n = 60), or 8 weeks of pill placebo (n = 60). Setting Research clinics at the University of Pennsylvania, Philadelphia, and Vanderbilt University, Nashville, Tenn. Patients Two hundred forty outpatients, aged 18 to 70 years, with moderate to severe major depressive disorder. Interventions Some study subjects received paroxetine, up to 50 mg daily, augmented by lithium carbonate or desipramine hydrochloride if necessary; others received individual cognitive therapy. Main Outcome Measure The Hamilton Depression Rating Scale provided continuous severity scores and allowed for designations of response and remission. Results At 8 weeks, response rates in medications (50%) and cognitive therapy (43%) groups were both superior to the placebo (25%) group. Analyses based on continuous scores at 8 weeks indicated an advantage for each of the active treatments over placebo, each with a medium effect size. The advantage was significant for medication relative to placebo, and at the level of a nonsignificant trend for cognitive therapy relative to placebo. At 16 weeks, response rates were 58% in each of the active conditions; remission rates were 46% for medication, 40% for cognitive therapy. Follow-up tests of a site × treatment interaction indicated a significant difference only at Vanderbilt University, where medications were superior to cognitive therapy. Site differences in patient characteristics and in the relative experience levels of the cognitive therapists each appear to have contributed to this interaction. Conclusion Cognitive therapy can be as effective as medications for the initial treatment of moderate to severe major depression, but this degree of effectiveness may depend on a high level of therapist experience or expertise.

A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder.

Abstract: Background: Previous functional neuroimaging studies have demonstrated exaggerated amygdala responses and diminished medial prefrontal cortex responses during the symptomatic state in posttraumatic stress disorder (PTSD). Objectives: To determine whether these abnormalities also occur in response to overtly presented affective stimuli unrelated to trauma; to examine the functional relationship between the amygdala and medial prefrontal cortex and their relationship to PTSD symptom severity in response to these stimuli; and to determine whether responsivity of these regions habituates normally across repeated stimulus presentations in PTSD.

A Susceptibility Gene for Affective Disorders and the Response of the Human Amygdala

Abstract: Background: A common regulatory variant (5HTTLPR) in the human serotonin transporter gene (SLC6A4), resulting in altered transcription and transporter availability, has been associated with vulnerability for affective disorders, including anxiety and depression. A recent functional magnetic resonance imaging study suggested that this association may be mediated by 5-HTTLPR effects on the response bias of the human amygdala—a brain region critical for emotional and social behavior—to environmental threat. Objectives and Design: To examine the effects of 5-HTTLPR genotype on the reactivity of the human amygdala to salient environmental cues with functional magnetic resonance imaging in a large (N=92) cohort of volunteers carefully screened for past and present medical or psychiatric illness, and to explore the effects of 5-HTTLPR genotype as well as amygdala reactivity on harm avoidance, a putative personality measure related to trait anxiety. Results: We now confirm the finding of 5-HTTLPR short allele–driven amygdala hyperreactivity in a large independent cohort of healthy subjects with no history of psychiatric illness or treatment. Furthermore, we demonstrate that these genotype effects on amygdala function are consistent with a dominant short allele effect and are equally prominent in men and women. However, neither 5-HTTLPR genotype, amygdala reactivity, nor genotype-driven variability in this reactivity was reflected in harm avoidance scores. Conclusions: Our results reveal a potent modulatory effect of the 5-HTTLPR on amygdala reactivity to environmental threat. Since this genetically driven effect exists in healthy subjects, it does not, in and of itself, predict dimensions of mood or temperament. As such, the 5-HTTLPR may represent a classic susceptibility factor for affective disorders by biasing the functional reactivity of the human amygdala in the context of stressful life experiences and/or deficient cortical regulatory input. Arch Gen Psychiatry. 2005;62:146-152

Somatization increases medical utilization and costs independent of psychiatric and medical comorbidity

Abstract: Context Somatoform disorders are an important determinant of medical care utilization, but their independent effect on utilization is difficult to determine because somatizing patients frequently have psychiatric and medical comorbidity Objectives To assess the extent of the overlap of somatization with other psychiatric disorders; to compare the medical utilization of somatizing and nonsomatizing patients; and to determine the independent contribution of somatization alone to utilization Design Patients were surveyed with self-report questionnaires assessing somatization and psychiatric disorder Medical care utilization was obtained from automated encounter data for the year preceding the index visit Medical morbidity was indexed with a computerized medical record audit Setting Two hospital-affiliated primary care practices Participants Consecutive adults making scheduled visits to their primary care physicians on randomly chosen days In all, 2668 questionnaires were distributed, and 1914 (717%) were returned Of these, 1546 (808%) contained complete data and met eligibility criteria Main Outcome Measures Medical care utilization and costs within our hospital system in the preceding 12 months Results Two hundred ninety-nine patients (205%) received a provisional diagnosis of somatization; 423% of these patients had no comorbid depressive or anxiety disorder Somatizing patients, when compared with nonsomatizing patients, had more primary care visits (mean [SE], 490 [032] vs 343 [011]; P P P P P P P = 04), more specialist visits ( P = 002), more emergency department visits ( P P P P P Conclusions Patients with somatization had approximately twice the outpatient and inpatient medical care utilization and twice the annual medical care costs of nonsomatizing patients Adjusting the findings for the presence of psychiatric and medical comorbidity had relatively little effect on this association

Strategy for investigating interactions between measured genes and measured environments.

Abstract: The purpose of this article is to promote research that tests hypotheses of measured gene-environment interaction (GxE). A GxE occurs when the effect of exposure to an environmental pathogen on health is conditional on a person's genotype (or conversely, when environmental experience moderates genes' effects on health). Gene-environment interactions were thought to be rare in psychiatry, but empirical findings of measured GxEs are now emerging. However, the current high level of curiosity about GxE is accompanied by uncertainty about the feasibility of GxE research and by pragmatic questions about how to carry out good GxE studies. First, we summarize emerging evidence about GxE in psychiatric disorders. Second, we describe 7 strategic steps that may be used to organize further hypothesis-driven studies of GxE. Third, we explain the potential benefits of the measured-GxE approach for basic neuroscience and for gene hunting. We suggest that in psychiatric genetics, ignoring nurture handicaps the field's capacity to make new discoveries about nature.

The current state of cognitive therapy: a 40-year retrospective.

Abstract: The basic framework of the cognitive theory of psychopathology and cognitive therapy of specific psychiatric disorders was developed more than 40 years ago. Since that time, there has been continuing progress in the development of cognitive theory and therapy and in the empirical testing of both. A substantial body of research supports the cognitive model of depression and, to a somewhat lesser extent, the various anxiety disorders. Cognitive therapy (CT), often labeled as the generic term cognitive behavior therapy , has been shown to be effective in reducing symptoms and relapse rates, with or without medication, in a wide variety of psychiatric disorders. Suggestions for future research and applications are presented.

Subthreshold Depression in Adolescence and Mental Health Outcomes in Adulthood

Abstract: Background There is increasing interest in the extent to which individuals with subthreshold depression face increased risks of subsequent major depression and other disorders. Objective To examine linkages between the extent of depressive symptoms (asymptomatic, subthreshold, major depression) at ages 17 to 18 years and mental health outcomes up to age 25 years in a New Zealand birth cohort. Design Data were gathered during the Christchurch Health and Development Study, a 25-year longitudinal study of a birth cohort of 1265 New Zealand children (635 males, 630 females). Setting General community sample. Participants The analysis was based on 1006 participants who represented 80% of the original cohort. Main Outcome Measures Diagnostic and Statistical Manual of Mental Disorders, Fourth Editionsymptom criteria for major depression and anxiety disorder, treatment-seeking, suicidal ideation, and suicide attempt. Results There were significant associations (P Conclusions Findings suggest that sample members with subthreshold depression are a group with elevated risks of later depression and suicidal behaviors. Current diagnostic procedures, which classify people with subthreshold depression into complex discrete groups, might obscure the fact that depressive symptoms are dimensional and range from none to severe.

Antipsychotic drug effects on brain morphology in first-episode psychosis

Abstract: Background Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described. Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome. This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia. Objective To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patientsandthat gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition. Design Longitudinal, randomized, controlled, multisite, double-blind study. Patients treated and followed up for up to 104 weeks. Neurocognitive and magnetic resonance imaging (MRI) assessments performed at weeks 0 (baseline), 12, 24, 52, and 104. Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI, psychopathologic, and neurocognitive outcomes. Setting Fourteen academic medical centers (United States, 11; Canada, 1; Netherlands, 1; England, 1). Participants Patients with first-episode psychosis (DSM-IV) and healthy volunteers. Interventions Random allocation to a conventional antipsychotic, haloperidol (2-20 mg/d), or an atypical antipsychotic, olanzapine (5-20 mg/d). Main Outcome Measures Brain volume changes assessed by MRI. Results Of 263 randomized patients, 161 had baseline and at least 1 postbaseline MRI evaluation. Haloperidol-treated patients exhibited significant decreases in gray matter volume, whereas olanzapine-treated patients did not. A matched sample of healthy volunteers (n = 58) examined contemporaneously showed no change in gray matter volume. Conclusions Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes. Haloperidol was associated with significant reductions in gray matter volume, whereas olanzapine was not. Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated. The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine.

Anxiety Disorders and Risk for Suicidal Ideation and Suicide Attempts A Population-Based Longitudinal Study of Adults

Abstract: Context Controversy exists whether anxiety disorders are independently associated (ie, after adjusting for comorbid mental disorders) with suicidal ideation and suicide attempts. Objective To examine whether anxiety disorders are risk factors for suicidal ideation and suicide attempts in a large population-based longitudinal study. Methods Data come from the Netherlands Mental Health Survey and Incidence Study, a prospective population-based survey with a baseline and 2 follow-up assessments over a 3-year period. The Composite International Diagnostic Interview was used to assess DSM-III-R mental disorders. Lifetime diagnoses of anxiety disorders (social phobia, simple phobia, generalized anxiety disorder, panic disorder, agoraphobia, obsessive-compulsive disorder) were assessed at baseline. Multiple logistic regression analyses were used to examine whether anxiety disorders were associated with suicidal ideation and attempts at baseline (n = 7076) and whether anxiety disorders were risk factors for subsequent onset of suicidal ideation and attempts (n = 4796). Results After adjusting for sociodemographic factors and all other mental disorders assessed in the survey, baseline presence of any anxiety disorder was significantly associated with suicidal ideation and suicide attempts in both the cross-sectional analysis (adjusted odds ratio for suicidal ideation, 2.29; 95% confidence interval, 1.85-2.82; adjusted odds ratio for suicidal attempts, 2.48; 95% confidence interval, 1.70-3.62) and longitudinal analysis (adjusted odds ratio for suicidal ideation, 2.32; 95% confidence interval, 1.31-4.11; adjusted odds ratio for suicide attempts, 3.64; 95% confidence interval, 1.70-7.83). Further analyses demonstrated that the presence of any anxiety disorder in combination with a mood disorder was associated with a higher likelihood of suicide attempts in comparison with a mood disorder alone. Conclusions This is the first study to demonstrate that a preexisting anxiety disorder is an independent risk factor for subsequent onset of suicidal ideation and attempts. Moreover, the data clearly demonstrate that comorbid anxiety disorders amplify the risk of suicide attempts in persons with mood disorders. Clinicians and policymakers need to be aware of these findings, and further research is required to delineate whether treatment of anxiety disorders reduces the risk of subsequent suicidal behavior.

Deficient Fear Conditioning in Psychopathy A Functional Magnetic Resonance Imaging Study

Abstract: Context Psychopaths belong to a larger group of persons with antisocial personality disorder and are characterized by an inability to have emotional involvement and by the repeated violation of the rights of others. It was hypothesized that this behavior might be the consequence of deficient fear conditioning. Objective To study the cerebral, peripheral, and subjective correlates of fear conditioning in criminal psychopaths and healthy control subjects. Design An aversive differential pavlovian delay conditioning paradigm with slides of neutral faces serving as conditioned and painful pressure as unconditioned stimuli. Setting The Department of Medical Psychology at the University of Tubingen, Tubingen, Germany. Participants Ten male psychopaths as defined by the Hare Psychopathy Checklist–Revised and 10 age- and education-matched healthy male controls. The psychopaths were criminal offenders on bail and waiting for their trial or were on parole. The healthy controls were recruited from the community. Main Outcome Measures Brain activation based on functional magnetic resonance imaging, electrodermal responses, emotional valence, arousal, and contingency ratings. Results The healthy controls showed enhanced differential activation in the limbic-prefrontal circuit (amygdala, orbitofrontal cortex, insula, and anterior cingulate) during the acquisition of fear and successful verbal and autonomic conditioning. The psychopaths displayed no significant activity in this circuit and failed to show conditioned skin conductance and emotional valence ratings, although contingency and arousal ratings were normal. Conclusion This dissociation of emotional and cognitive processing may be the neural basis of the lack of anticipation of aversive events in criminal psychopaths.

Prevention of relapse following cognitive therapy vs medications in moderate to severe depression.

Abstract: Background Antidepressant medication prevents the return of depressive symptoms, but only as long as treatment is continued. Objectives To determine whether cognitive therapy (CT) has an enduring effect and to compare this effect against the effect produced by continued antidepressant medication. Design Patients who responded to CT in a randomized controlled trial were withdrawn from treatment and compared during a 12-month period with medication responders who had been randomly assigned to either continuation medication or placebo withdrawal. Patients who survived the continuation phase without relapse were withdrawn from all treatment and observed across a subsequent 12-month naturalistic follow-up. Setting Outpatient clinics at the University of Pennsylvania and Vanderbilt University. Patients A total of 104 patients responded to treatment (57.8% of those initially assigned) and were enrolled in the subsequent continuation phase; patients were initially selected to represent those with moderate to severe depression. Interventions Patients withdrawn from CT were allowed no more than 3 booster sessions during continuation; patients assigned to continuation medication were kept at full dosage levels. Main Outcome Measures Relapse was defined as a return, for at least 2 weeks, of symptoms sufficient to meet the criteria for major depression or Hamilton Depression Rating Scale scores of 14 or higher during the continuation phase. Recurrence was defined in a comparable fashion during the subsequent naturalistic follow-up. Results Patients withdrawn from CT were significantly less likely to relapse during continuation than patients withdrawn from medications (30.8% vs 76.2%; P = .004), and no more likely to relapse than patients who kept taking continuation medication (30.8% vs 47.2%; P = .20). There were also indications that the effect of CT extends to the prevention of recurrence. Conclusions Cognitive therapy has an enduring effect that extends beyond the end of treatment. It seems to be as effective as keeping patients on medication.

Two-Year Outcomes for Interpersonal and Social Rhythm Therapy in Individuals With Bipolar I Disorder

Abstract: Context Numerous studies have pointed to the failure of prophylaxis with pharmacotherapy alone in the treat ment of bipolar I disorder. Recent investigations have demonstrated benefits from the addition of psychoeducation or psychotherapy to pharmacotherapy in this population. Objective To compare 2 psychosocial interventions: interpersonal and social rhythm therapy (IPSRT) and an intensive clinical management (ICM) approach in the treatment of bipolar I disorder. Design Randomized controlled trial involving 4 treatment strategies: acute and maintenance IPSRT (IPSRT/IPSRT), acute and maintenance ICM (ICM/ICM), acute IPSRT followed by maintenance ICM (IPSRT/ICM), or acute ICM followed by maintenance IPSRT (ICM/IPSRT). The preventive maintenance phase lasted 2 years. Setting Research clinic in a university medical center. Participants One hundred seventy-five acutely ill individuals with bipolar I disorder recruited from inpatient and outpatient settings, clinical referral, public presentations about bipolar disorder, and other public information activities. Interventions Interpersonal and social rhythm therapy, an adaptation of Klerman and Weissman’s interpersonal psychotherapy to which a social rhythm regulation component has been added, and ICM. Main Outcome Measures Time to stabilization in the acute phase and time to recurrence in the maintenance phase. Results We observed no difference between the treatment strategies in time to stabilization. After controlling for covariates of survival time, we found that participants assigned to IPSRT in the acute treatment phase survived longer without a new affective episode ( P = .01), irrespective of maintenance treatment assignment. Participants in the IPSRT group had higher regularity of social rhythms at the end of acute treatment ( P P = .05). Conclusion Interpersonal and social rhythm therapy appears to add to the clinical armamentarium for the management of bipolar I disorder, particularly with respect to prophylaxis of new episodes.

Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years.

Abstract: Context While the neuroanatomical basis of autism is not yet known, evidence suggests that brain enlargement may be characteristic of this disorder. Inferences about the timing of brain enlargement have recently come from studies of head circumference (HC). Objectives To examine brain volume and HC in individuals with autism as compared with control individuals. Design A cross-sectional study of brain volume was conducted at the first time point in an ongoing longitudinal magnetic resonance imaging study of brain development in autism. Retrospective longitudinal HC measurements were gathered from medical records on a larger sample of individuals with autism and local control individuals. Setting Clinical research center. Participants The magnetic resonance imaging study included 51 children with autism and 25 control children between 18 and 35 months of age (the latter included both developmentally delayed and typically developing children). Retrospective, longitudinal HC data were examined from birth to age 3 years in 113 children with autism and 189 local control children. Main Outcome Measures Cerebral cortical (including cortical lobes) and cerebellar gray and white matter magnetic resonance imaging brain volumes as well as retrospective HC data from medical records were studied. Results Significant enlargement was detected in cerebral cortical volumes but not cerebellar volumes in individuals with autism. Enlargement was present in both white and gray matter, and it was generalized throughout the cerebral cortex. Head circumference appears normal at birth, with a significantly increased rate of HC growth appearing to begin around 12 months of age. Conclusions Generalized enlargement of gray and white matter cerebral volumes, but not cerebellar volumes, are present at 2 years of age in autism. Indirect evidence suggests that this increased rate of brain growth in autism may have its onset postnatally in the latter part of the first year of life.

Hostile Marital Interactions, Proinflammatory Cytokine Production, and Wound Healing

Abstract: Context A growing epidemiological literature has suggested that marital discord is a risk factor for morbidity and mortality. In addition, depression and stress are associated with enhanced production of proinflammatory cytokines that influence a spectrum of conditions associated with aging. Objective To assess how hostile marital behaviors modulate wound healing, as well as local and systemic proinflammatory cytokine production. Design and Setting Couples were admitted twice to a hospital research unit for 24 hours in a crossover trial. Wound healing was assessed daily following research unit discharge. Participants Volunteer sample of 42 healthy married couples, aged 22 to 77 years (mean [SD], 37.04 [13.05]), married a mean (SD) of 12.55 (11.01) years. Interventions During the first research unit admission, couples had a structured social support interaction, and during the second admission, they discussed a marital disagreement. Main Outcome Measures Couples’ interpersonal behavior, wound healing, and local and systemic changes in proinflammatory cytokine production were assessed during each research unit admission. Results Couples’ blister wounds healed more slowly and local cytokine production (IL-6, tumor necrosis factor α, and IL-1β) was lower at wound sites following marital conflicts than after social support interactions. Couples who demonstrated consistently higher levels of hostile behaviors across both their interactions healed at 60% of the rate of low-hostile couples. High-hostile couples also produced relatively larger increases in plasma IL-6 and tumor necrosis factor α values the morning after a conflict than after a social support interaction compared with low-hostile couples. Conclusions These data provide further mechanistic evidence of the sensitivity of wound healing to everyday stressors. Moreover, more frequent and amplified increases in proinflammatory cytokine levels could accelerate a range of age-related diseases. Thus, these data also provide a window on the pathways through which hostile or abrasive relationships affect physiological functioning and health.

Suicide risk in relation to psychiatric hospitalization : evidence based on longitudinal registers

Abstract: Background Persons with a history of admission to a psychiatric hospital are at high risk for suicide, but little is known about how this is influenced by factors related to psychiatric hospitalization. Objective To explore suicide risk according to time since admission, diagnosis, length of hospital treatment, and number of prior hospitalizations. Design Nested case-control design. Setting Individual data are drawn from various Danish longitudinal registers. Participants All 13 681 male and 7488 female suicides committed in Denmark from January 1, 1981, to December 31, 1997, and 423 128 population control subjects matched for sex, age, and calendar time of suicide. Main Outcome Measure Risk of suicide is estimated by conditional logistic regression. Data are adjusted for socioeconomic factors. Results This study demonstrates that there are 2 sharp peaks of risk for suicide around psychiatric hospitalization, one in the first week after admission and another in the first week after discharge; suicide risk is significantly higher in patients who received less than the median duration of hospital treatment; affective disorders have the strongest impact on suicide risk in terms of its effect size and population attributable risk; and suicide risk associated with affective and schizophrenia spectrum disorders declines quickly after treatment and recovery, while the risk associated with substance abuse disorders declines relatively slower. This study also indicates that an admission history increases suicide risk relatively more in women than in men; and suicide risk is substantial for substance disorders and for multiple admissions in women but not in men. Conclusions Suicide risk peaks in periods immediately after admission and discharge. The risk is particularly high in persons with affective disorders and in persons with short hospital treatment. These findings should lead to systematic evaluation of suicide risk among inpatients before discharge and corresponding outpatient treatment, and family support should be initiated immediately after the discharge.

Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia.

Abstract: Background Two brain regions often implicated in schizophrenia are the dorsolateral prefrontal cortex (DLPFC) and the hippocampal formation (HF). It has been hypothesized that the pathophysiology of the disorder might involve an alteration of functional interactions between medial temporal and prefrontal areas. Methods We used neuroimaging data acquired during a working memory challenge and a sensorimotor control task in 22 medication-free schizophrenic patients and 22 performance-, age-, and sex-matched healthy subjects to investigate “functional connectivity” between HF and DLPFC in schizophrenia. The HF blood flow, measured with positron emission tomography, was assessed within a probabilistic template. Brain areas whose activity was positively or negatively coupled to HF were identified using voxelwise analysis of covariance throughout the entire brain and analyzed using a random effects model. Results During working memory, patients showed reduced activation of the right DLPFC and left cerebellum. In both groups, inverse correlations were observed between the HF and the contralateral DLPFC and inferior parietal lobule. While these did not differ between diagnostic groups during the control task, the working memory challenge revealed a specific abnormality in DLPFC-HF functional connectivity—while the right DLPFC was significantly coupled to the left HF in both groups during the control task, this correlation was not seen in healthy subjects during working memory but persisted undiminished in patients, resulting in a significant task-by-group interaction. Conclusions Our results suggest a regionally specific alteration of HF-DLPFC functional connectivity in schizophrenia that manifests as an unmodulated persistence of an HF-DLPFC linkage during working memory activation. Thus, a mechanism by which HF dysfunction may manifest in schizophrenia is by inappropriate reciprocal modulatory interaction with the DLPFC.

Psychosocial Disability in the Course of Bipolar I and II Disorders A Prospective, Comparative, Longitudinal Study

Abstract: Context Evidence of psychosocial disability in bipolar disorder is based primarily on bipolar I disorder (BP-I) and does not relate disability to affective symptom severity and polarity or to bipolar II disorder (BP-II). Objective To provide detailed data on psychosocial disability in relation to symptom status during the long-term course of BP-I and BP-II. Design A naturalistic study with 20 years of prospective, systematic follow-up. Setting Inpatient and outpatient treatment facilities at 5 US academic centers. Patients One hundred fifty-eight patients with BP-I and 133 patients with BP-II who were followed up for a mean (SD) of 15 (4.8) years in the National Institute of Mental Health Collaborative Depression Study. Main Outcome Measures The relationship, by random regression, between Range of Impaired Functioning Tool psychosocial impairment scores and affective symptom status in 1-month periods during the long-term course of illness from 6-month and yearly Longitudinal Interval Follow-up Evaluation interviews. Results Psychosocial impairment increases significantly with each increment in depressive symptom severity for BP-I and BP-II and with most increments in manic symptom severity for BP-I. Subsyndromal hypomanic symptoms are not disabling in BP-II, and they may even enhance functioning. Depressive symptoms are at least as disabling as manic or hypomanic symptoms at corresponding severity levels and, in some cases, significantly more so. At each level of depressive symptom severity, BP-I and BP-II are equally impairing. When asymptomatic, patients with bipolar disorder have good psychosocial functioning, although it is not as good as that of well controls. Conclusions Psychosocial disability fluctuates in parallel with changes in affective symptom severity in BP-I and BP-II. Important findings for clinical management are the following: (1) depressive episodes and symptoms, which dominate the course of BP-I and BP-II, are equal to or more disabling than corresponding levels of manic or hypomanic symptoms; (2) subsyndromal depressive symptoms, but not subsyndromal manic or hypomanic symptoms, are associated with significant impairment; and (3) subsyndromal hypomanic symptoms appear to enhance functioning in BP-II.

Crime Victimization in Adults With Severe Mental Illness: Comparison With the National Crime Victimization Survey

Abstract: Context Since deinstitutionalization, most persons with severe mental illness (SMI) now live in the community, where they are at great risk for crime victimization. Objectives To determine the prevalence and incidence of crime victimization among persons with SMI by sex, race/ethnicity, and age, and to compare rates with general population data (the National Crime Victimization Survey), controlling for income and demographic differences between the samples. Design Epidemiologic study of persons in treatment. Independent master’s-level clinical research interviewers administered the National Crime Victimization Survey to randomly selected patients sampled from 16 randomly selected mental health agencies. Setting Sixteen agencies providing outpatient, day, and residential treatment to persons with SMI in Chicago, Ill. Participants Randomly selected, stratified sample of 936 patients aged 18 or older (483 men, 453 women) who were African American (n = 329), non-Hispanic white (n = 321), Hispanic (n = 270), or other race/ethnicity (n = 22). The comparison group comprised 32 449 participants in the National Crime Victimization Survey. Main Outcome Measure National Crime Victimization Survey, developed by the Bureau of Justice Statistics. Results More than one quarter of persons with SMI had been victims of a violent crime in the past year, a rate more than 11 times higher than the general population rates even after controlling for demographic differences between the 2 samples ( P P Conclusions Crime victimization is a major public health problem among persons with SMI who are treated in the community. We recommend directions for future research, propose modifications in public policy, and suggest how the mental health system can respond to reduce victimization and its consequences.

Instability of the DSM-IV Subtypes of ADHD From Preschool Through Elementary School

Abstract: Context The DSM-IV definition of attention-deficit/hyperactivity disorder (ADHD) distinguished 3 subtypes that had not been extensively studied. Objective To determine whether the ADHD subtypes are stable enough over time to be valid. Design Longitudinal study with a greater-than 89% retention rate in 7 assessments over 8 years. Setting Outpatient clinics. Participants Volunteer sample of 118 4- to 6-year-olds who met DSM-IV criteria for ADHD, including impairment in 2 settings in at least 1 assessment. Main Outcome Measure Meeting DSM-IV criteria for the subtypes of ADHD during years 2 through 8. Results The number of children who met criteria for ADHD declined over time, but most persisted. Children who met criteria for the combined subtype (CT, n = 83) met criteria for ADHD in more subsequent assessments than children in the predominantly hyperactive-impulsive subtype (HT, n = 23). Thirty-one (37%) of 83 CT children and 6 (50%) of 12 children in the predominantly inattentive subtype (IT) met criteria for a different subtype at least twice in the next 6 assessments. Children of the HT subtype were even more likely to shift to a different subtype over time, with HT children who persisted in ADHD mostly shifting to CT in later assessments. The subtypes exhibited consistently different mean levels of hyperactive-impulsive symptoms during years 2 through 8 that corresponded with their initial subtype classifications, but initial subtype differences in inattention symptoms diminished in later years. Conclusions In younger children, the CT and IT may be stable enough to segregate groups for research, but they seem too unstable for use in the clinical assessment of individual children. Children rarely remain in the HT classification over time; rather, they sometimes desist from ADHD but mostly shift to CT in later years. Using continuous ratings of hyperactivity-impulsivity symptoms as a diagnostic qualifier should be considered as an alternative to classifying nominal subtypes of ADHD in DSM-V .

Neighborhood Residence and Mental Health Problems of 5- to 11-Year-Olds

Abstract: Context Little research has investigated possible effects of neighborhood residence on mental health problems in children such as depression, anxiety, and withdrawal. Objective To examine whether children’s mental health is associated with neighborhood structural characteristics (concentrated disadvantage, immigrant concentration, and residential stability) and whether neighborhood social processes (collective efficacy and organizational participation) underlie such effects. Design and Setting The Project on Human Development in Chicago Neighborhoods is a multilevel, longitudinal study of a representative sample of children aged 5 to 11 years in the late 1990s recruited from 80 neighborhoods. A community survey assessing neighborhood social processes was conducted with an independent sample of adult residents in these 80 neighborhoods and is used in conjunction with US census data to assess neighborhood conditions. Participants A total of 2805 children (18.1% European American, 33.8% African American, and 48.1% Latino) and their primary caregivers were seen twice. Main Outcome Measures Child Behavior Checklist total raw and clinical cutoff scores for internalizing behavior problems (depression, anxiety, withdrawal, and somatic problems). Results The percentages of children above the clinical threshold were 21.5%, 18.3%, and 11.5% in neighborhoods of low, medium, and high socioeconomic status, respectively. A substantial proportion of variance in children’s total internalizing scores (intraclass correlation, 11.1%) was attributable to between-neighborhood differences. Concentrated disadvantage was associated with more mental health problems and a higher number of children in the clinical range, after accounting for family demographic characteristics, maternal depression, and earlier child mental health scores. Neighborhood collective efficacy and organizational participation were associated with better mental health, after accounting for neighborhood concentrated disadvantage. Collective efficacy mediated the effect of concentrated disadvantage. Conclusions A large number of children in poor neighborhoods have mental health problems. The mechanism through which neighborhood economic effects operated was community social control and cohesion, which may be amenable to intervention.

Alcohol Use Disorders Among US College Students and Their Non–College-Attending Peers

Abstract: Background Heavy/binge drinking among college students has become a major public health problem. There is consistent evidence suggesting that young adults in college are drinking more than their non–college-attending peers, but it is still not clear whether they are more likely to suffer from clinically significant alcohol use disorders. Objective To compare the prevalence of alcohol use disorders and alcohol use disorder symptoms in college-attending young adults with their non–college-attending peers within the same study in a large and representative US national sample. Design Cross-sectional survey. Setting Civilian, noninstitutionalized US population. Participants Young adults (n = 6352) from the 2001 National Household Survey on Drug Abuse (19-21 years of age, 51% female, 66% white, 14% African American, 14% Hispanic). Main Outcome Measures Lifetime, past-year, and past-month drinking, past-year and past-month weekly drinking, past-month weekly binge drinking, past-month daily drinking, typical quantity consumed in the past month, and past-year DSM-IV alcohol dependence and abuse diagnoses. Results Eighteen percent of US college students (24% of men, 13% of women) suffered from clinically significant alcohol-related problems in the past year, compared with 15% of their non–college-attending peers (22% of men, 9% of women; overall odds ratio = 1.32). The association between past-year alcohol use disorder and college attendance was stronger among women (odds ratio = 1.70) than men (odds ratio = 1.14). College students were more likely to receive a diagnosis of DSM-IV alcohol abuse than their peers not attending college; despite the fact that those in college were drinking more, they were not more likely to receive a diagnosis of DSM-IV alcohol dependence. Conclusions College students suffer from some clinically significant consequences of their heavy/binge drinking, but they do not appear to be at greater risk than their non–college-attending peers for the more pervasive syndrome of problems that is characteristic of alcohol dependence.

Effects of Antidepressant Medication on Morbidity and Mortality in Depressed Patients After Myocardial Infarction

Abstract: Background Depression after myocardial infarction (MI) is associated with higher morbidity and mortality. Although antidepressants are effective in reducing depression, their use in patients with cardiovascular disease remains controversial. Objective To undertake a secondary analysis to determine the effects of using antidepressants on morbidity and mortality in post-MI patients who participated in the Enhancing Recovery in Coronary Heart Disease study. Design Observational secondary analysis. Setting Eight academic sites. Patients The Enhancing Recovery in Coronary Heart Disease clinical trial randomized 2481 depressed and/or socially isolated patients from October 1, 1996, to October 31, 1999. Depression was diagnosed using a structured clinical interview. This analysis was conducted on the 1834 patients enrolled with depression (849 women and 985 men). Intervention Use of antidepressant medication. Main Outcome Measures Event-free survival was defined as the absence of death or recurrent MI. All-cause mortality was also examined. To relate exposure to antidepressants to subsequent morbidity and mortality, the data were analyzed using a time-dependent covariate model. Results During a mean follow-up of 29 months, 457 fatal and nonfatal cardiovascular events occurred. The risk of death or recurrent MI was significantly lower in patients taking selective serotonin reuptake inhibitors (adjusted hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.38-0.84), as were the risk of all-cause mortality (adjusted HR, 0.59; 95% CI, 0.37-0.96) and recurrent MI (adjusted HR, 0.53; 95% CI, 0.32-0.90), compared with patients who did not use selective serotonin reuptake inhibitors. For patients taking non–selective serotonin reuptake inhibitor antidepressants, the comparable HRs (95% CIs) were 0.72 (0.44-1.18), 0.64 (0.34-1.22), and 0.73 (0.38-1.38) for risk of death or recurrent MI, all-cause mortality, or recurrent MI, respectively, compared with nonusers. Conclusions Use of selective serotonin reuptake inhibitors in depressed patients who experience an acute MI might reduce subsequent cardiovascular morbidity and mortality. A controlled trial is needed to examine this important issue.

Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity

Abstract: CONTEXT Hyperactivity and inattention are common symptoms in children with autistic disorder and related pervasive developmental disorders, but studies of stimulants in these conditions have been inconclusive. OBJECTIVES To determine the efficacy and safety of methylphenidate hydrochloride in children with pervasive developmental disorders and hyperactivity. DESIGN Double-blind, placebo-controlled, crossover trial followed by open-label continuation. SETTING Five academic outpatient clinics. PARTICIPANTS Seventy-two drug-free children, aged 5 to 14 years, with pervasive developmental disorders accompanied by moderate to severe hyperactivity. INTERVENTIONS Prior to randomization, subjects entered a 1-week test-dose phase in which each subject received placebo for 1 day followed by increasing doses of methylphenidate (low, medium, and high doses) that were each given for 2 days. The low, medium, and high doses of methylphenidate hydrochloride were based on weight, and they ranged from 7.5 mg/d to 50.0 mg/d in divided doses. Subjects who tolerated the test dose (n = 66) were assigned to receive placebo for 1 week and then 3 methylphenidate doses in random order during a double-blind, crossover phase. Children responding to methylphenidate then entered 8 weeks of open-label treatment at the individually determined best dose. MAIN OUTCOME MEASURES The primary outcome measure was the teacher-rated hyperactivity subscale of the Aberrant Behavior Checklist. Response was defined as \"much improved\" or \"very much improved\" on the Clinical Global Impressions Improvement item coupled with considerable reductions in the parent-rated and/or teacher-rated Aberrant Behavior Checklist hyperactivity subscale score. RESULTS Methylphenidate was superior to placebo on the primary outcome measure, with effect sizes ranging from 0.20 to 0.54 depending on dose and rater. Thirty-five (49%) of 72 enrolled subjects were classified as methylphenidate responders. Adverse effects led to the discontinuation of study medication in 13 (18%) of 72 subjects. CONCLUSIONS Methylphenidate was often efficacious in treating hyperactivity associated with pervasive developmental disorders, but the magnitude of response was less than that seen in typically developing children with attention-deficit/hyperactivity disorder. Adverse effects were more frequent.