Showing papers in "JAMA Psychiatry in 2014"
TL;DR: The demographic composition of heroin users entering treatment has shifted over the last 50 years such that heroin use has changed from an inner-city, minority-centered problem to one that has a more widespread geographical distribution, involving primarily white men and women in their late 20s living outside of large urban areas.
Abstract: Importance Over the past several years, there have been a number of mainstream media reports that the abuse of heroin has migrated from low-income urban areas with large minority populations to more affluent suburban and rural areas with primarily white populations. Objective To examine the veracity of these anecdotal reports and define the relationship between the abuse of prescription opioids and the abuse of heroin. Design, Setting, and Participants Using a mixed-methods approach, we analyzed (1) data from an ongoing study that uses structured, self-administered surveys to gather retrospective data on past drug use patterns among patients entering substance abuse treatment programs across the country who received a primary ( DSM-IV ) diagnosis of heroin use/dependence (n = 2797) and (2) data from unstructured qualitative interviews with a subset of patients (n = 54) who completed the structured interview. Main Outcomes and Measures In addition to data on population demographics and current residential location, we used cross-tabulations to assess prevalence rates as a function of the decade of the initiation of abuse for (1) first opioid used (prescription opioid or heroin), (2) sex, (3) race/ethnicity, and (4) age at first use. Respondents indicated in an open-ended format why they chose heroin as their primary drug and the interrelationship between their use of heroin and their use of prescription opioids. Results Approximately 85% of treatment-seeking patients approached to complete the Survey of Key Informants’ Patients Program did so. Respondents who began using heroin in the 1960s were predominantly young men (82.8%; mean age, 16.5 years) whose first opioid of abuse was heroin (80%). However, more recent users were older (mean age, 22.9 years) men and women living in less urban areas (75.2%) who were introduced to opioids through prescription drugs (75.0%). Whites and nonwhites were equally represented in those initiating use prior to the 1980s, but nearly 90% of respondents who began use in the last decade were white. Although the “high” produced by heroin was described as a significant factor in its selection, it was often used because it was more readily accessible and much less expensive than prescription opioids. Conclusion and Relevance Our data show that the demographic composition of heroin users entering treatment has shifted over the last 50 years such that heroin use has changed from an inner-city, minority-centered problem to one that has a more widespread geographical distribution, involving primarily white men and women in their late 20s living outside of large urban areas.
1,040 citations
TL;DR: The analysis suggests that anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increased risks of adverse effects, and supports a proof-of-concept concerning the use of anti- inflammatory treatment in depression.
Abstract: with depression (SMD, −0.54; 95% CI, −1.08 to −0.01; I 2 = 68%) and depressive symptoms (SMD, −0.27; 95% CI, −0.53 to −0.01; I 2 = 68%). The heterogeneity of the studies was not explained by differences in inclusion of clinical depression vs depressive symptoms or use of NSAIDs vs cytokine inhibitors. Subanalyses emphasized the antidepressant properties of the selective cyclooxygenase 2 inhibitor celecoxib (SMD, −0.29; 95% CI, −0.49 to −0.08; I 2 =7 3%) on remission (OR, 7.89; 95% CI, 2.94 to 21.17; I 2 = 0%) and response (OR, 6.59; 95% CI, 2.24 to 19.42; I 2 = 0%). Among the 6 studies reporting on adverse effects, we found no evidence of an increased number of gastrointestinal or cardiovascular events after 6 weeks or infections after 12 weeks of anti-inflammatory treatment compared with placebo. All trials were associated with a high risk of bias owing to potentially compromised internal validity.
685 citations
TL;DR: Higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing depression and psychosis in young adulthood, and inflammatory pathways may provide important new intervention and prevention targets for these disorders.
Abstract: IMPORTANCE: Longitudinal studies have linked the systemic inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) with the risk of developing heart disease and diabetes mellitus, which are common comorbidities for depression and psychosis. Recent meta-analyses of cross-sectional studies have reported increased serum levels of these inflammatory markers in depression, first-episode psychosis, and acute psychotic relapse; however, the direction of the association has been unclear. OBJECTIVE: To test the hypothesis that higher serum levels of IL-6 and CRP in childhood would increase future risks for depression and psychosis. DESIGN, SETTING, AND PARTICIPANTS: The Avon Longitudinal Study of Parents and Children (ALSPAC)is a prospective general population birth cohort study based in Avon County, England. We have studied a subsample of approximately 4500 individuals from the cohort with data on childhood IL-6 and CRP levels and later psychiatric assessments. MEASUREMENT OF EXPOSURE: Levels of IL-6 and CRP were measured in nonfasting blood samples obtained in participants at age 9 years. MAIN OUTCOMES AND MEASURES: Participants were assessed at age 18 years. Depression was measured using the Clinical Interview Schedule-Revised (CIS-R) and Mood and Feelings Questionnaire (MFQ), thus allowing internal replication; psychotic experiences (PEs) and psychotic disorder were measured by a semistructured interview. RESULTS: After adjusting for sex, age, body mass index, ethnicity, social class, past psychological and behavioral problems, and maternal postpartum depression, participants in the top third of IL-6 values compared with the bottom third at age 9 years were more likely to be depressed (CIS-R) at age 18 years (adjusted odds ratio [OR], 1.55; 95% CI, 1.13-2.14). Results using the MFQ were similar. Risks of PEs and of psychotic disorder at age 18 years were also increased with higher IL-6 levels at baseline (adjusted OR, 1.81; 95% CI, 1.01-3.28; and adjusted OR, 2.40; 95% CI, 0.88-6.22, respectively). Higher IL-6 levels in childhood were associated with subsequent risks of depression and PEs in a dose-dependent manner. CONCLUSIONS AND RELEVANCE: Higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing depression and psychosis in young adulthood. Inflammatory pathways may provide important new intervention and prevention targets for these disorders. Inflammation might explain the high comorbidity between heart disease, diabetes mellitus, depression, and schizophrenia.
600 citations
TL;DR: The findings suggest that a multifeatured smartphone application may have significant benefit to patients in continuing care for alcohol use disorders.
Abstract: Importance Patients leaving residential treatment for alcohol use disorders are not typically offered evidence-based continuing care, although research suggests that continuing care is associated with better outcomes. A smartphone-based application could provide effective continuing care. Objective To determine whether patients leaving residential treatment for alcohol use disorders with a smartphone application to support recovery have fewer risky drinking days than control patients. Design, Setting, and Participants An unmasked randomized clinical trial involving 3 residential programs operated by 1 nonprofit treatment organization in the Midwestern United States and 2 residential programs operated by 1 nonprofit organization in the Northeastern United States. In total, 349 patients who met the criteria for DSM-IV alcohol dependence when they entered residential treatment were randomized to treatment as usual (n = 179) or treatment as usual plus a smartphone (n = 170) with the Addiction–Comprehensive Health Enhancement Support System (A-CHESS), an application designed to improve continuing care for alcohol use disorders. Interventions Treatment as usual varied across programs; none offered patients coordinated continuing care after discharge. A-CHESS provides monitoring, information, communication, and support services to patients, including ways for patients and counselors to stay in contact. The intervention and follow-up period lasted 8 and 4 months, respectively. Main Outcomes and Measures Risky drinking days—the number of days during which a patient’s drinking in a 2-hour period exceeded 4 standard drinks for men and 3 standard drinks for women, with standard drink defined as one that contains roughly 14 g of pure alcohol (12 oz of regular beer, 5 oz of wine, or 1.5 oz of distilled spirits). Patients were asked to report their risky drinking days in the previous 30 days on surveys taken 4, 8, and 12 months after discharge from residential treatment. Results For the 8 months of the intervention and 4 months of follow-up, patients in the A-CHESS group reported significantly fewer risky drinking days than did patients in the control group, with a mean of 1.39 vs 2.75 days (mean difference, 1.37; 95% CI, 0.46-2.27; P = .003). Conclusions and Relevance The findings suggest that a multifeatured smartphone application may have significant benefit to patients in continuing care for alcohol use disorders. Trial Registration clinicaltrials.gov Identifier:NCT01003119
566 citations
TL;DR: For individuals in aftercare following initial treatment for substance use disorders, RP and MBRP, compared with TAU, produced significantly reduced relapse risk to drug use and heavy drinking.
Abstract: Importance Relapse is highly prevalent following substance abuse treatments, highlighting the need for improved aftercare interventions. Mindfulness-based relapse prevention (MBRP), a group-based psychosocial aftercare, integrates evidence-based practices from mindfulness-based interventions and cognitive-behavioral relapse prevention (RP) approaches. Objective To evaluate the long-term efficacy of MBRP in reducing relapse compared with RP and treatment as usual (TAU [12-step programming and psychoeducation]) during a 12-month follow-up period. Design, Setting, and Participants Between October 2009 and July 2012, a total of 286 eligible individuals who successfully completed initial treatment for substance use disorders at a private, nonprofit treatment facility were randomized to MBRP, RP, or TAU aftercare and monitored for 12 months. Participants medically cleared for continuing care were aged 18 to 70 years; 71.5% were male and 42.1% were of ethnic/racial minority. Interventions Participants were randomly assigned to 8 weekly group sessions of MBRP, cognitive-behavioral RP, or TAU. Main Outcomes and Measures Primary outcomes included relapse to drug use and heavy drinking as well as frequency of substance use in the past 90 days. Variables were assessed at baseline and at 3-, 6-, and 12-month follow-up points. Measures used included self-report of relapse and urinalysis drug and alcohol screenings. Results Compared with TAU, participants assigned to MBRP and RP reported significantly lower risk of relapse to substance use and heavy drinking and, among those who used substances, significantly fewer days of substance use and heavy drinking at the 6-month follow-up. Cognitive-behavioral RP showed an advantage over MBRP in time to first drug use. At the 12-month follow-up, MBRP participants reported significantly fewer days of substance use and significantly decreased heavy drinking compared with RP and TAU. Conclusions and Relevance For individuals in aftercare following initial treatment for substance use disorders, RP and MBRP, compared with TAU, produced significantly reduced relapse risk to drug use and heavy drinking. Relapse prevention delayed time to first drug use at 6-month follow-up, with MBRP and RP participants who used alcohol also reporting significantly fewer heavy drinking days compared with TAU participants. At 12-month follow-up, MBRP offered added benefit over RP and TAU in reducing drug use and heavy drinking. Targeted mindfulness practices may support long-term outcomes by strengthening the ability to monitor and skillfully cope with discomfort associated with craving or negative affect, thus supporting long-term outcomes. Trial Registration clinicaltrials.gov Identifier:NCT01159535
527 citations
TL;DR: This study provides the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD, and may lead to novel approaches to the pharmacologic treatment of patients with this disabling condition.
Abstract: Importance Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition. Objective To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associated depressive symptoms in patients with chronic PTSD. Design, Setting, and Participants Proof-of-concept, randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, conducted at a single site (Icahn School of Medicine at Mount Sinai, New York, New York). Forty-one patients with chronic PTSD related to a range of trauma exposures were recruited via advertisements. Interventions Intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and midazolam (0.045 mg/kg). Main Outcomes and Measures The primary outcome measure was change in PTSD symptom severity, measured using the Impact of Event Scale–Revised. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression–Severity and –Improvement scales, and adverse effect measures, including the Clinician-Administered Dissociative States Scale, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale. Results Ketamine infusion was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale–Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms. Conclusions and Relevance This study provides the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with this disabling condition. Trial Registration clinicaltrials.gov Identifier:NCT00749203
427 citations
TL;DR: This nationwide study provides a first comprehensive assessment of the lifetime risks for treated mental disorders and the distinct signatures of the different mental disorders with respect to sex and age have important implications for service planning and etiologic research.
Abstract: RESULTS During the course of life, 37.66% of females (95% CI, 37.52%-37.80%) and 32.05% of males (31.91%-32.19%) received their first treatment in a psychiatric setting for any mental disorder. The occurrence of mental disorders varied markedly between diagnostic categories and by sex and age. The sex- and age-specific incidence rates for many mental disorders had a single peak incidence rate during the second and third decades of life. Some disorders had a second peak in the sex- and age-specific incidence rate later in life. CONCLUSIONS AND RELEVANCE This nationwide study provides a first comprehensive assessment of the lifetime risks for treated mental disorders. Approximately one-third of the Danish population received treatment for mental disorders. The distinct signatures of the different mental disorders with respect to sex and age have important implications for service planning and etiologic research.
426 citations
TL;DR: Compared with adultmental health care, the mental health care of young people has increased more rapidly and has coincided with increased psychotropic medication use.
Abstract: Importance Despite evidence of the increasing use of psychotropic medications, little is known about the broader changes in the delivery of outpatient mental health treatment to children, adolescents, and adults. Objective To assess national trends and patterns in the mental health care of children, adolescents, and adults in office-based medical practice. Design, Setting, and Participants Outpatient visits to physicians in office-based practice from the 1995-2010 National Ambulatory Medical Care Surveys (N = 446 542). Trends (1995-2010) in visits with mental health care indicators are first compared between youths ( Main Outcomes and Measures Visits resulting in mental disorder diagnoses, prescription of psychotropic medications, provision of psychotherapy, or psychiatrist care. Results Between 1995-1998 and 2007-2010, visits resulting in mental disorder diagnoses per 100 population increased significantly faster for youths (from 7.78 to 15.30 visits) than for adults (from 23.23 to 28.48 visits) (interaction: P P P = .13). While psychotherapy visits increased from 2.25 to 3.17 per 100 population for youths, they decreased from 8.37 to 6.36 for adults (interaction: P Conclusions and Relevance Compared with adult mental health care, the mental health care of young people has increased more rapidly and has coincided with increased psychotropic medication use. A great majority of mental health care in office-based medical practice to children, adolescents, and adults is provided by nonpsychiatrist physicians calling for increased consultation and communication between specialties.
365 citations
TL;DR: The study results support the view that cortical information processing is disrupted in psychosis and provides new evidence that disruptions within the frontoparietal control network may be a shared feature across both schizophrenia and affective psychosis.
Abstract: Importance Psychotic disorders (including schizophrenia, schizoaffective disorder, and psychotic bipolar disorder) are devastating illnesses characterized by breakdown in the integration of information processing. Recent advances in neuroimaging allow for the estimation of brain networks on the basis of intrinsic functional connectivity, but the specific network abnormalities in psychotic disorders are poorly understood. Objective To compare intrinsic functional connectivity across the cerebral cortex in patients with schizophrenia spectrum disorders or psychotic bipolar disorder and healthy controls. Design, Setting, and Participants We studied 100 patients from an academic psychiatric hospital (28 patients with schizophrenia, 32 patients with schizoaffective disorder, and 40 patients with bipolar disorder with psychosis) and 100 healthy controls matched for age, sex, race, handedness, and scan quality from December 2009 to October 2011. Main Outcomes and Measures Functional connectivity profiles across 122 regions that covered the entire cerebral cortex. Results Relative to the healthy controls, individuals with a psychotic illness had disruption across several brain networks, with preferential reductions in functional connectivity within the frontoparietal control network ( P Conclusions and Relevance Our study results support the view that cortical information processing is disrupted in psychosis and provides new evidence that disruptions within the frontoparietal control network may be a shared feature across both schizophrenia and affective psychosis.
335 citations
TL;DR: This pilot randomized clinical trial for P NES revealed significant seizure reduction and improved comorbid symptoms and global functioning with CBT-ip for PNES without and with sertraline and supports the use of manualized psychotherapy for Pnes and successful training of mental health clinicians in the treatment.
Abstract: Importance There is a paucity of controlled treatment trials for the treatment of conversion disorder, seizures type, also known as psychogenic nonepileptic seizures (PNES). Psychogenic nonepileptic seizures, the most common conversion disorder, are as disabling as epilepsy and are not adequately addressed or treated by mental health clinicians. Objective To evaluate different PNES treatments compared with standard medical care (treatment as usual). Design, Setting, and Participants Pilot randomized clinical trial at 3 academic medical centers with mental health clinicians trained to administer psychotherapy or psychopharmacology to outpatients with PNES. Thirty-eight participants were randomized in a blocked schedule among 3 sites to 1 of 4 treatment arms and were followed up for 16 weeks between September 2008 and February 2012; 34 were included in the analysis. Interventions Medication (flexible-dose sertraline hydrochloride) only, cognitive behavioral therapy informed psychotherapy (CBT-ip) only, CBT-ip with medication (sertraline), or treatment as usual. Main Outcomes and Measures Seizure frequency was the primary outcome; psychosocial and functioning measures, including psychiatric symptoms, social interactions, quality of life, and global functioning, were secondary outcomes. Data were collected prospectively, weekly, and with baseline, week 2, midpoint (week 8), and exit (week 16) batteries. Within-group analyses for each arm were performed on primary (seizure frequency) and secondary outcomes from treatment-blinded raters using an intention-to-treat analysis. Results The psychotherapy (CBT-ip) arm showed a 51.4% seizure reduction ( P = .01) and significant improvement from baseline in secondary measures including depression, anxiety, quality of life, and global functioning ( P P = .008) and significant improvements in some secondary measures, including global functioning ( P = .007). The sertraline-only arm did not show a reduction in seizures ( P = .08). The treatment as usual group showed no significant seizure reduction or improvement in secondary outcome measures ( P = .19). Conclusions and Relevance This pilot randomized clinical trial for PNES revealed significant seizure reduction and improved comorbid symptoms and global functioning with CBT-ip for PNES without and with sertraline. There were no improvements in the sertraline-only or treatment-as-usual arms. This study supports the use of manualized psychotherapy for PNES and successful training of mental health clinicians in the treatment. Future studies could assess larger-scale intervention dissemination. Trial Registration clinicaltrials.gov Identifier:NCT00835627
324 citations
TL;DR: The possibility of higher fatality rates among Army suicide attempts than among civilian suicide attempts highlights the potential importance of means control (ie, restricting access to lethal means [such as firearms]) as a suicide prevention strategy.
Abstract: Importance The suicide rate among US Army soldiers has increased substantially in recent years. Objectives To estimate the lifetime prevalence and sociodemographic, Army career, and psychiatric predictors of suicidal behaviors among nondeployed US Army soldiers. Design, Setting, and Participants A representative cross-sectional survey of 5428 nondeployed soldiers participating in a group self-administered survey. Main Outcomes and Measures Lifetime suicidal ideation, suicide plans, and suicide attempts. Results The lifetime prevalence estimates of suicidal ideation, suicide plans, and suicide attempts are 13.9%, 5.3%, and 2.4%. Most reported cases (47.0%-58.2%) had pre-enlistment onsets. Pre-enlistment onset rates were lower than in a prior national civilian survey (with imputed/simulated age at enlistment), whereas post-enlistment onsets of ideation and plans were higher, and post-enlistment first attempts were equivalent to civilian rates. Most reported onsets of plans and attempts among ideators (58.3%-63.3%) occur within the year of onset of ideation. Post-enlistment attempts are positively related to being a woman (with an odds ratio [OR] of 3.3 [95% CI, 1.5-7.5]), lower rank (OR = 5.8 [95% CI, 1.8-18.1]), and previously deployed (OR = 2.4-3.7) and are negatively related to being unmarried (OR = 0.1-0.8) and assigned to Special Operations Command (OR = 0.0 [95% CI, 0.0-0.0]). Five mental disorders predict post-enlistment first suicide attempts in multivariate analysis: pre-enlistment panic disorder (OR = 0.1 [95% CI, 0.0-0.8]), pre-enlistment posttraumatic stress disorder (OR = 0.1 [95% CI, 0.0-0.7]), post-enlistment depression (OR = 3.8 [95% CI, 1.2-11.6]), and both pre- and post-enlistment intermittent explosive disorder (OR = 3.7-3.8). Four of these 5 ORs (posttraumatic stress disorder is the exception) predict ideation, whereas only post-enlistment intermittent explosive disorder predicts attempts among ideators. The population-attributable risk proportions of lifetime mental disorders predicting post-enlistment suicide attempts are 31.3% for pre-enlistment onset disorders, 41.2% for post-enlistment onset disorders, and 59.9% for all disorders. Conclusions and Relevance The fact that approximately one-third of post-enlistment suicide attempts are associated with pre-enlistment mental disorders suggests that pre-enlistment mental disorders might be targets for early screening and intervention. The possibility of higher fatality rates among Army suicide attempts than among civilian suicide attempts highlights the potential importance of means control (ie, restricting access to lethal means [such as firearms]) as a suicide prevention strategy.
SUNY Downstate Medical Center1, North Shore-LIJ Health System2, Dartmouth College3, Boston University4, Yale University5, The Feinstein Institute for Medical Research6, University of Calgary7, University of North Carolina at Chapel Hill8, Nathan Kline Institute for Psychiatric Research9, National Institutes of Health10
TL;DR: In patients with FES, cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other.
Abstract: Importance The fact that individuals with schizophrenia have high cardiovascular morbidity and mortality is well established. However, risk status and moderators or mediators in the earliest stages of illness are less clear. Objective To assess cardiometabolic risk in first-episode schizophrenia spectrum disorders (FES) and its relationship to illness duration, antipsychotic treatment duration and type, sex, and race/ethnicity. Design, Setting, and Participants Baseline results of the Recovery After an Initial Schizophrenia Episode (RAISE) study, collected between July 22, 2010, and July 5, 2012, from 34 community mental health facilities without major research, teaching, or clinical FES programs. Patients were aged 15 to 40 years, had research-confirmed diagnoses of FES, and had less than 6 months of lifetime antipsychotic treatment. Exposure Prebaseline antipsychotic treatment was based on the community clinician’s and/or patient’s decision. Main Outcomes and Measures Body composition and fasting lipid, glucose, and insulin parameters. Results In 394 of 404 patients with cardiometabolic data (mean [SD] age, 23.6 [5.0] years; mean [SD] lifetime antipsychotic treatment, 47.3 [46.1] days), 48.3% were obese or overweight, 50.8% smoked, 56.5% had dyslipidemia, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome. Prediabetes (glucose based, 4.0%; hemoglobin A 1c based, 15.4%) and diabetes (glucose based, 3.0%; hemoglobin A 1c based, 2.9%) were less frequent. Total psychiatric illness duration correlated significantly with higher body mass index, fat mass, fat percentage, and waist circumference (all P P = .04]). Conversely, antipsychotic treatment duration correlated significantly with higher non–HDL-C, triglycerides, and triglycerides to HDL-C ratio and lower HDL-C and systolic blood pressure (all P ≤ .01). In multivariable analyses, olanzapine was significantly associated with higher triglycerides, insulin, and insulin resistance, whereas quetiapine fumarate was associated with significantly higher triglycerides to HDL-C ratio (all P ≤ .02). Conclusions and Relevance In patients with FES, cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other. Prevention of and early interventions for psychiatric illness and treatment with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases.
TL;DR: In the largest assessment of substance use among individuals with severe psychotic illness to date, the odds of smoking and alcohol and other substance use are found to be dramatically higher than recent estimates of Substance use in mild mental illness.
Abstract: Importance Although early mortality in severe psychiatric illness is linked to smoking and alcohol, to our knowledge, no studies have comprehensively characterized substance use behavior in severe psychotic illness. In particular, recent assessments of substance use in individuals with mental illness are based on population surveys that do not include individuals with severe psychotic illness. Objective To compare substance use in individuals with severe psychotic illness with substance use in the general population. Design, Setting, and Participants We assessed comorbidity between substance use and severe psychotic disorders in the Genomic Psychiatry Cohort. The Genomic Psychiatry Cohort is a clinically assessed, multiethnic sample consisting of 9142 individuals with the diagnosis of schizophrenia, bipolar disorder with psychotic features, or schizoaffective disorder, and 10 195 population control individuals. Main Outcomes and Measures Smoking (smoked >100 cigarettes in a lifetime), heavy alcohol use (>4 drinks/day), heavy marijuana use (>21 times of marijuana use/year), and recreational drug use. Results Relative to the general population, individuals with severe psychotic disorders have increased risks for smoking (odds ratio, 4.6; 95% CI, 4.3-4.9), heavy alcohol use (odds ratio, 4.0; 95% CI, 3.6-4.4), heavy marijuana use (odds ratio, 3.5; 95% CI, 3.2-3.7), and recreational drug use (odds ratio, 4.6; 95% CI, 4.3-5.0). All races/ethnicities (African American, Asian, European American, and Hispanic) and both sexes have greatly elevated risks for smoking and alcohol, marijuana, and drug use. Of specific concern, recent public health efforts that have successfully decreased smoking among individuals younger than age 30 years appear to have been ineffective among individuals with severe psychotic illness (interaction effect between age and severe mental illness on smoking initiation, P = 4.5 × 10 5 ). Conclusions and Relevance In the largest assessment of substance use among individuals with severe psychotic illness to date, we found the odds of smoking and alcohol and other substance use to be dramatically higher than recent estimates of substance use in mild mental illness.
TL;DR: Dendritic spine loss in the DLPFC was seen in both individuals with schizophrenia and individuals with bipolar disorder, suggesting that the 2 disorders may share some common pathophysiological features.
Abstract: Importance Prior studies have demonstrated reduced dendritic spine density in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia. However, it remains unclear how generalizable this finding is in schizophrenia and if it is seen in bipolar disorder, a historically distinct psychiatric condition. Objective To assess whether spine loss is present in the DLPFC of individuals with schizophrenia and individuals with bipolar disorder. Design, Setting, and Participants This study used postmortem human brain tissue from individuals with schizophrenia (n = 14), individuals with bipolar disorder (n = 9), and unaffected control participants (n = 19). Tissue samples containing the DLPFC (Brodmann area 46) were Golgi-stained, and basilar dendrites of pyramidal cells in the deep half of layer III were reconstructed. Main Outcomes and Measures The number of spines per dendrite, spine density, and dendrite length were compared across groups. We also assessed for the potential effects of clinical and demographic variables on dendritic parameters. Results The mean (SD) spine density was significantly reduced (ie, by 10.5%) in individuals with bipolar disorder (0.28 [0.04] spines/μm) compared with control participants (0.31 [0.05] spines/μm) ( P = .02). In individuals with schizophrenia, the mean (SD) spine density was also reduced (by 6.5%; 0.29 [0.03] spines/μm) but just missed significance when compared with control participants ( P = .06). There was a significant reduction in the mean (SD) number of spines per dendrite in both individuals with schizophrenia (72.8 [24.9] spines per dendrite) and individuals with bipolar disorder (68.9 [12.9] spines per dendrite) compared with controls (92.8 [31.1] spines per dendrite) (individuals with schizophrenia vs controls: 21.6% reduction [ P = .003]; individuals with bipolar disorder vs controls: 25.8% reduction [ P = .005]). In addition, both individuals with schizophrenia and individuals with bipolar disorder had a reduced mean (SD) dendrite length (246.5 [67.4] and 245.6 [29.8] μm, respectively) compared with controls (301.8 [75.1] μm) (individuals with schizophrenia vs controls: 18.3% reduction [ P = .005]; individuals with bipolar disorder vs controls: 18.6% reduction [ P = .005]). Conclusions and Relevance Dendritic spine loss in the DLPFC was seen in both individuals with schizophrenia and individuals with bipolar disorder, suggesting that the 2 disorders may share some common pathophysiological features.
TL;DR: Results suggest that a biologically informed temperament-based typology, developed with a discovery-based community detection algorithm, provides a superior description of heterogeneity in the ADHD population than does any current clinical nosologic criteria.
Abstract: Importance Psychiatric nosology is limited by behavioral and biological heterogeneity within existing disorder categories. The imprecise nature of current nosologic distinctions limits both mechanistic understanding and clinical prediction. We demonstrate an approach consistent with the National Institute of Mental Health Research Domain Criteria initiative to identify superior, neurobiologically valid subgroups with better predictive capacity than existing psychiatric categories for childhood attention-deficit/hyperactivity disorder (ADHD). Objective To refine subtyping of childhood ADHD by using biologically based behavioral dimensions (ie, temperament), novel classification algorithms, and multiple external validators. Design, Setting, and Participants A total of 437 clinically well-characterized, community-recruited children, with and without ADHD, participated in an ongoing longitudinal study. Baseline data were used to classify children into subgroups based on temperament dimensions and examine external validators including physiological and magnetic resonance imaging measures. One-year longitudinal follow-up data are reported for a subgroup of the ADHD sample to address stability and clinical prediction. Main Outcomes and Measures Parent/guardian ratings of children on a measure of temperament were used as input features in novel community detection analyses to identify subgroups within the sample. Groups were validated using 3 widely accepted external validators: peripheral physiological characteristics (cardiac measures of respiratory sinus arrhythmia and pre-ejection period), central nervous system functioning (via resting-state functional connectivity magnetic resonance imaging), and clinical outcomes (at 1-year longitudinal follow-up). Results The community detection algorithm suggested 3 novel types of ADHD, labeled as mild (normative emotion regulation), surgent (extreme levels of positive approach-motivation), and irritable (extreme levels of negative emotionality, anger, and poor soothability). Types were independent of existing clinical demarcations including DSM-5 presentations or symptom severity. These types showed stability over time and were distinguished by unique patterns of cardiac physiological response, resting-state functional brain connectivity, and clinical outcomes 1 year later. Conclusions and Relevance Results suggest that a biologically informed temperament-based typology, developed with a discovery-based community detection algorithm, provides a superior description of heterogeneity in the ADHD population than does any current clinical nosologic criteria. This demonstration sets the stage for more aggressive attempts at a tractable, biologically based nosology.
TL;DR: Acceptance rates for all types of insurance were significantly lower for psychiatrists than for physicians in other specialties, and these low rates of acceptance may pose a barrier to access to mental health services.
Abstract: Importance There have been recent calls for increased access to mental health services, but access may be limited owing to psychiatrist refusal to accept insurance. Objective To describe recent trends in acceptance of insurance by psychiatrists compared with physicians in other specialties. Design, Setting, and Participants We used data from a national survey of office-based physicians in the United States to calculate rates of acceptance of private noncapitated insurance, Medicare, and Medicaid by psychiatrists vs physicians in other specialties and to compare characteristics of psychiatrists who accepted insurance and those who did not. Main Outcomes and Measures Our main outcome variables were physician acceptance of new patients with private noncapitated insurance, Medicare, or Medicaid. Our main independent variables were physician specialty and year groupings (2005-2006, 2007-2008, and 2009-2010). Results The percentage of psychiatrists who accepted private noncapitated insurance in 2009-2010 was significantly lower than the percentage of physicians in other specialties (55.3% [95% CI, 46.7%-63.8%] vs 88.7% [86.4%-90.7%]; P P P P = .02). Conclusions and Relevance Acceptance rates for all types of insurance were significantly lower for psychiatrists than for physicians in other specialties. These low rates of acceptance may pose a barrier to access to mental health services.
TL;DR: Relteon administered nightly to elderly patients admitted for acute care may provide protection against delirium, and this finding supports a possible pathogenic role of melatonin neurotransmission inDelirium.
Abstract: Importance No highly effective interventions to prevent delirium have been identified. Objective To examine whether ramelteon, a melatonin agonist, is effective for the prevention of delirium. Design, Setting, and Participants A multicenter, rater-blinded, randomized placebo-controlled trial was performed in intensive care units and regular acute wards of 4 university hospitals and 1 general hospital. Eligible patients were 65 to 89 years old, newly admitted due to serious medical problems, and able to take medicine orally. Patients were excluded from the study if they had an expected stay or life expectancy of less than 48 hours. Interventions Sixty-seven patients were randomly assigned using the sealed envelope method to receive ramelteon (8 mg/d; 33 patients) or placebo (34 patients) every night for 7 days. Main Outcomes and Measures Incidence of delirium, as defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Results Ramelteon was associated with a lower risk of delirium (3% vs 32%; P = .003), with a relative risk of 0.09 (95% CI, 0.01-0.69). Even after risk factors were controlled for, ramelteon was still associated with a lower incidence of delirium ( P = .01; odds ratio, 0.07 [95% CI, 0.008-0.54]). The Kaplan-Meier estimates of time to development of delirium were 6.94 (95% CI, 6.82-7.06) days for ramelteon and 5.74 (5.05-6.42) days for placebo. Comparison by log-rank test showed that the frequency of delirium was significantly lower in patients taking ramelteon than in those taking placebo (χ 2 = 9.83; P = .002). Conclusions and Relevance Ramelteon administered nightly to elderly patients admitted for acute care may provide protection against delirium. This finding supports a possible pathogenic role of melatonin neurotransmission in delirium. Trial Registration University Hospital Medical Information Network Clinical Trials Registry Identifier:UMIN000005591
TL;DR: This article determined the effects of baseline plasma CRP concentration on postdeployment CAPS using zero-inflated negative binomial regression (ZINBR), a procedure designed for distributions, such as CAPS in this study, that have an excess of zeros in addition to being positively skewed.
Abstract: RESULTS We determined the effects of baseline plasma CRP concentration on postdeployment CAPS using zero-inflated negative binomial regression (ZINBR), a procedure designed for distributions, such as CAPS in this study, that have an excess of zeroes in addition to being positively skewed. Adjusting for the baseline CAPS score, trauma exposure, and other relevant covariates, we found baseline plasma CRP concentration to be a highly significant overall predictor of postdeployment CAPS scores (P = .002): each 10-fold increment in CRP concentration was associated with an odds ratio of nonzero outcome (presence vs absence of any PTSD symptoms) of 1.51 (95% CI, 1.15-1.97; P = .003) and a fold increase in outcome with a nonzero value (extent of symptoms when present) of 1.06 (95% CI, 0.99-1.14; P = .09).
TL;DR: The existence of a time trend in suicide risk among never-deployed soldiers argues indirectly against the view that exposure to combat-related trauma is the exclusive cause of the increase in Army suicides.
Abstract: Importance The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a multicomponent study designed to generate actionable recommendations to reduce Army suicides and increase knowledge of risk and resilience factors for suicidality. Objectives To present data on prevalence, trends, and basic sociodemographic and Army experience correlates of suicides and accident deaths among active duty Regular Army soldiers between January 1, 2004, and December 31, 2009, and thereby establish a foundation for future Army STARRS investigations. Design, Setting, and Participants Analysis of trends and predictors of suicide and accident deaths using Army and Department of Defense administrative data systems. Participants were all members of the US Regular Army serving at any time between 2004 and 2009. Main Outcomes and Measures Death by suicide or accident during active Army service. Results The suicide rate rose between 2004 and 2009 among never deployed and currently and previously deployed Regular Army soldiers. The accident death rate fell sharply among currently deployed soldiers, remained constant among the previously deployed, and trended upward among the never deployed. Increased suicide risk was associated with being a man (or a woman during deployment), white race/ethnicity, junior enlisted rank, recent demotion, and current or previous deployment. Sociodemographic and Army experience predictors were generally similar for suicides and accident deaths. Time trends in these predictors and in the Army’s increased use of accession waivers (which relaxed some qualifications for new soldiers) do not explain the rise in Army suicides. Conclusions and Relevance Predictors of Army suicides were largely similar to those reported elsewhere for civilians, although some predictors distinct to Army service emerged that deserve more in-depth analysis. The existence of a time trend in suicide risk among never-deployed soldiers argues indirectly against the view that exposure to combat-related trauma is the exclusive cause of the increase in Army suicides.
TL;DR: As adults approaching midlife, young suicide attempters were significantly more likely to have persistent mental health problems compared with nonattempters and to have physical health problems, and reported being lonelier and less satisfied with their lives.
Abstract: Importance Suicidal behavior has increased since the onset of the global recession, a trend that may have long-term health and social implications. Objective To test whether suicide attempts among young people signal increased risk for later poor health and social functioning above and beyond a preexisting psychiatric disorder. Design We followed up a cohort of young people and assessed multiple aspects of their health and social functioning as they approached midlife. Outcomes among individuals who had self-reported a suicide attempt up through age 24 years (young suicide attempters) were compared with those who reported no attempt through age 24 years (nonattempters). Psychiatric history and social class were controlled for. Setting and Participants The population-representative Dunedin Multidisciplinary Health and Development Study, which involved 1037 birth cohort members comprising 91 young suicide attempters and 946 nonattempters, 95% of whom were followed up to age 38 years. Main Outcomes and Measures Outcomes were selected to represent significant individual and societal costs: mental health, physical health, harm toward others, and need for support. Results As adults approaching midlife, young suicide attempters were significantly more likely to have persistent mental health problems (eg, depression, substance dependence, and additional suicide attempts) compared with nonattempters. They were also more likely to have physical health problems (eg, metabolic syndrome and elevated inflammation). They engaged in more violence (eg, violent crime and intimate partner abuse) and needed more social support (eg, long-term welfare receipt and unemployment). Furthermore, they reported being lonelier and less satisfied with their lives. These associations remained after adjustment for youth psychiatric diagnoses and social class. Conclusions and Relevance Many young suicide attempters remain vulnerable to costly health and social problems into midlife. As rates of suicidal behavior rise with the continuing global recession, additional suicide prevention efforts and long-term monitoring and after-care services are needed.
TL;DR: Impaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC have not previously been highlighted in depression and may be unique to adolescent MDD, suggesting potential mechanisms underlying both mood and vegetative symptoms.
Abstract: Importance Major depressive disorder (MDD) frequently emerges during adolescence and can lead to persistent illness, disability, and suicide. The maturational changes that take place in the brain during adolescence underscore the importance of examining neurobiological mechanisms during this time of early illness. However, neural mechanisms of depression in adolescents have been understudied. Research has implicated the amygdala in emotion processing in mood disorders, and adult depression studies have suggested amygdala-frontal connectivity deficits. Resting-state functional magnetic resonance imaging is an advanced tool that can be used to probe neural networks and identify brain-behavior relationships. Objective To examine amygdala resting-state functional connectivity (RSFC) in adolescents with and without MDD using resting-state functional magnetic resonance imaging as well as how amygdala RSFC relates to a broad range of symptom dimensions. Design, Setting, and Participants A cross-sectional resting-state functional magnetic resonance imaging study was conducted within a depression research program at an academic medical center. Participants included 41 adolescents and young adults aged 12 to 19 years with MDD and 29 healthy adolescents (frequency matched on age and sex) with no psychiatric diagnoses. Main Outcomes and Measures Using a whole-brain functional connectivity approach, we examined the correlation of spontaneous fluctuation of the blood oxygen level–dependent signal of each voxel in the whole brain with that of the amygdala. Results Adolescents with MDD showed lower positive RSFC between the amygdala and hippocampus, parahippocampus, and brainstem ( z >2.3, corrected P R = −.523, P = .01), dysphoria ( R = −.455, P = .05), and lassitude ( R = −.449, P = .05) and was positively correlated with well-being ( R = .470, P = .03). Patients also demonstrated greater (positive) amygdala-precuneus RSFC ( z >2.3, corrected P Conclusions and Relevance Impaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC have not previously been highlighted in depression and may be unique to adolescent MDD. These circuits are important for different aspects of memory and self-processing and for modulation of physiologic responses to emotion. The findings suggest potential mechanisms underlying both mood and vegetative symptoms, potentially via impaired processing of memories and visceral signals that spontaneously arise during rest, contributing to the persistent symptoms experienced by adolescents with depression.
TL;DR: The quality of the individual trials included in the pharmacotherapy and psychotherapy meta-analyses was assessed with the Cochrane risk of bias tool and effect sizes of psychotherapies vs placebo tended to be higher than those of medication, but direct comparisons did not reveal consistent differences.
Abstract: Importance There is debate about the effectiveness of psychiatric treatments and whether pharmacotherapy or psychotherapy should be primarily used. Objectives To perform a systematic overview on the efficacy of pharmacotherapies and psychotherapies for major psychiatric disorders and to compare the quality of pharmacotherapy and psychotherapy trials. Evidence Review We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Library (April 2012, with no time or language limit) for systematic reviews on pharmacotherapy or psychotherapy vs placebo, pharmacotherapy vs psychotherapy, and their combination vs either modality alone. Two reviewers independently selected the meta-analyses and extracted efficacy effect sizes. We assessed the quality of the individual trials included in the pharmacotherapy and psychotherapy meta-analyses with the Cochrane risk of bias tool. Findings The search yielded 45 233 results. We included 61 meta-analyses on 21 psychiatric disorders, which contained 852 individual trials and 137 126 participants. The mean effect size of the meta-analyses was medium (mean, 0.50; 95% CI, 0.41-0.59). Effect sizes of psychotherapies vs placebo tended to be higher than those of medication, but direct comparisons, albeit usually based on few trials, did not reveal consistent differences. Individual pharmacotherapy trials were more likely to have large sample sizes, blinding, control groups, and intention-to-treat analyses. In contrast, psychotherapy trials had lower dropout rates and provided follow-up data. In psychotherapy studies, wait-list designs showed larger effects than did comparisons with placebo. Conclusions and Relevance Many pharmacotherapies and psychotherapies are effective, but there is a lot of room for improvement. Because of the multiple differences in the methods used in pharmacotherapy and psychotherapy trials, indirect comparisons of their effect sizes compared with placebo or no treatment are problematic. Well-designed direct comparisons, which are scarce, need public funding. Because patients often benefit from both forms of therapy, research should also focus on how both modalities can be best combined to maximize synergy rather than debate the use of one treatment over the other.
TL;DR: Attention-deficit/hyperactivity disorder is associated with an increased risk of serious transport accidents, and this risk seems to be possibly reduced by ADHD medication, at least among male patients.
Abstract: Importance Studies have shown that attention-deficit/hyperactivity disorder (ADHD) is associated with transport accidents, but the magnitude of the association remains unclear. Most important, it is also unclear whether ADHD medication reduces this risk. Objectives To estimate the association between ADHD and the risk of serious transport accidents and to explore the extent to which ADHD medication influences this risk among patients with ADHD. Design, Setting, and Participants In total, 17 408 patients with a diagnosis of ADHD were observed from January 1, 2006, through December 31, 2009, for serious transport accidents documented in Swedish national registers. The association between ADHD and accidents was estimated with Cox proportional hazards regression. To study the effect of ADHD medication, we used stratified Cox regression to compare the risk of accidents during the medication period with the risk during the nonmedication period within the same patients. Main Outcomes and Measures Serious transport accident, identified as an emergency hospital visit or death due to transport accident. Results Compared with individuals without ADHD, male patients with ADHD (adjusted hazard ratio, 1.47; 95% CI, 1.32-1.63) and female patients with ADHD (1.45; 1.24-1.71) had an increased risk of serious transport accidents. In male patients with ADHD, medication was associated with a 58% risk reduction (hazard ratio, 0.42; 95% CI, 0.23-0.75), but there was no statistically significant association in female patients. Estimates of the population-attributable fractions suggested that 41% to 49% of the accidents in male patients with ADHD could have been avoided if they had been receiving treatment during the entire follow-up. Conclusions and Relevance Attention-deficit/hyperactivity disorder is associated with an increased risk of serious transport accidents, and this risk seems to be possibly reduced by ADHD medication, at least among male patients. This should lead to increased awareness among clinicians and patients of the association between serious transport accidents and ADHD medication.
TL;DR: Women with likely diagnoses of both PTSD and a major depressive episode are at a 4-fold increased risk of preterm birth; this risk is greater than, and independent of, antidepressant and benzodiazepine use and is not simply a function of mood or anxiety symptoms.
Abstract: Importance Posttraumatic stress disorder (PTSD) occurs in about 8% of pregnant women. Stressful conditions, including PTSD, are inconsistently linked to preterm birth. Psychotropic treatment has been frequently associated with preterm birth. Identifying whether the psychiatric illness or its treatment is independently associated with preterm birth may help clinicians and patients when making management decisions. Objective To determine whether a likely diagnosis of PTSD or antidepressant and benzodiazepine treatment during pregnancy is associated with risk of preterm birth. We hypothesized that pregnant women who likely had PTSD and women receiving antidepressant or anxiolytic treatment would be more likely to experience preterm birth. Design, Setting, and Participants Longitudinal, prospective cohort study of 2654 women who were recruited before 17 completed weeks of pregnancy from 137 obstetrical practices in Connecticut and Western Massachusetts. Exposures Posttraumatic stress disorder, major depressive episode, and use of antidepressant and benzodiazepine medications. Main Outcomes and Measures Preterm birth, operationalized as delivery prior to 37 completed weeks of pregnancy. Likely psychiatric diagnoses were generated through administration of the Composite International Diagnostic Interview and the Modified PTSD Symptom Scale. Data on medication use were gathered at each participant interview. Results Recursive partitioning analysis showed elevated rates of preterm birth among women with PTSD. A further split of the PTSD node showed high rates for women who met criteria for a major depressive episode, which suggests an interaction between these 2 exposures. Logistic regression analysis confirmed risk for women who likely had both conditions (odds ratio [OR], 4.08 [95% CI, 1.27-13.15]). For each point increase on the Modified PTSD Symptom Scale (range, 0-110), the risk of preterm birth increased by 1% to 2%. The odds of preterm birth are high for women who used a serotonin reuptake inhibitor (OR, 1.55 [95% CI, 1.02-2.36]) and women who used a benzodiazepine medication (OR, 1.99 [95% CI, 0.98-4.03]). Conclusions and Relevance Women with likely diagnoses of both PTSD and a major depressive episode are at a 4-fold increased risk of preterm birth; this risk is greater than, and independent of, antidepressant and benzodiazepine use and is not simply a function of mood or anxiety symptoms.
TL;DR: In the study population, advancing paternal age was associated with increased risk of some psychiatric disorders but decreased risk of the other indexes of morbidity, consistent with the hypothesis that new genetic mutations during spermatogenesis are causally related to offspring morbidity.
Abstract: RESULTS In the study population, advancing paternal age was associated with increased risk of some psychiatric disorders (eg, autism, psychosis, and bipolar disorders) but decreased risk of the other indexes of morbidity. In contrast, the sibling-comparison analyses indicated that advancing paternal age had a dose-response relationship with every index of morbidity, with the magnitude of the associations being as large or larger than the estimates in the entire population. Compared with offspring born to fathers 20 to 24 years old, offspring of fathers 45 years and older were at heightened risk of autism (hazard ratio [HR] = 3.45; 95% CI, 1.62-7.33), attention-deficit/hyperactivity disorder (HR = 13.13; 95% CI, 6.85-25.16), psychosis (HR = 2.07; 95% CI, 1.35-3.20), bipolar disorder (HR = 24.70; 95% CI, 12.12-50.31), suicide attempts (HR = 2.72; 95% CI, 2.08-3.56), substance use problems (HR = 2.44; 95% CI, 1.98-2.99), failing a grade (odds ratio [OR] = 1.59; 95% CI, 1.37-1.85), and low educational attainment (OR = 1.70; 95% CI, 1.50-1.93) in within-sibling comparisons. Additional analyses using several quasi-experimental designs obtained commensurate results, further strengthening the internal and external validity of the findings. CONCLUSIONS AND RELEVANCE Advancing paternal age is associated with increased risk of psychiatric and academic morbidity, with the magnitude of the risks being as large or larger than previous estimates. These findings are consistent with the hypothesis that new genetic mutations that occur during spermatogenesis are causally related to offspring morbidity.
TL;DR: Proactive aggression in youths with CU traits is linked to hypoactive amygdala responses to emotional distress cues, consistent with theories that externalizing behaviors in youngsters with these traits stem from deficient empathic responses to distress.
Abstract: Importance Among youths with conduct problems, callous-unemotional (CU) traits are known to be an important determinant of symptom severity, prognosis, and treatment responsiveness. But positive correlations between conduct problems and CU traits result in suppressor effects that may mask important neurobiological distinctions among subgroups of children with conduct problems. Objective To assess the unique neurobiological covariates of CU traits and externalizing behaviors in youths with conduct problems and determine whether neural dysfunction linked to CU traits mediates the link between callousness and proactive aggression. Design, Setting, and Participants This cross-sectional case-control study involved behavioral testing and neuroimaging that were conducted at a university research institution. Neuroimaging was conducted using a 3-T Siemens magnetic resonance imaging scanner. It included 46 community-recruited male and female juveniles aged 10 to 17 years, including 16 healthy control participants and 30 youths with conduct problems with both low and high levels of CU traits. Main Outcomes and Measures Blood oxygenation level–dependent signal as measured via functional magnetic resonance imaging during an implicit face-emotion processing task and analyzed using whole-brain and region of interest–based analysis of variance and multiple-regression analyses. Results Analysis of variance revealed no group differences in the amygdala. By contrast, consistent with the existence of suppressor effects, multiple-regression analysis found amygdala responses to fearful expressions to be negatively associated with CU traits ( x = 26, y = 0, z = −12; k = 1) and positively associated with externalizing behavior ( x = 24, y = 0, z = −14; k = 8) when both variables were modeled simultaneously. Reduced amygdala responses mediated the relationship between CU traits and proactive aggression. Conclusions and Relevance The results linked proactive aggression in youths with CU traits to hypoactive amygdala responses to emotional distress cues, consistent with theories that externalizing behaviors, particularly proactive aggression, in youths with these traits stem from deficient empathic responses to distress. Amygdala hypoactivity may represent an intermediate phenotype, offering new insights into effective treatment strategies for conduct problems.
TL;DR: Following extensive control for prospectively measured confounding factors, exposure to the Canterbury earthquakes was associated with a small to moderate increase in the risk for common mental health problems.
Abstract: Importance There has been growing research into the mental health consequences of major disasters. Few studies have controlled for prospectively assessed mental health. This article describes a natural experiment in which 57% of a well-studied birth cohort was exposed to a major natural disaster (the Canterbury, New Zealand, earthquakes in 2010-2011), with the remainder living outside of the earthquake area. Objective To examine the relationships between the extent of earthquake exposure and mental health outcomes following the earthquakes—net of adjustment for potentially confounding factors related to personal circumstances, prior mental health, and childhood family background. Design, Setting, and Participants Data were gathered from the Christchurch Health and Development Study, a 35-year longitudinal study of a birth cohort of New Zealand children (635 males and 630 females). This general community sample included 952 participants with available data on earthquake exposure and mental health outcomes at age 35 years. Exposures A composite measure of exposure to the events during and subsequent to the 4 major (Richter Scale >6.0) Canterbury earthquakes during the years 2010-2011. Main Outcomes and Measures DSM-IVsymptom criteria for major depression; posttraumatic stress disorder; anxiety disorder; suicidal ideation/attempt; nicotine dependence; alcohol abuse/dependence; and illicit drug abuse/dependence. Outcomes were measured approximately 20 to 24 months after the onset of exposure to the earthquakes and were assessed usingDSM-IVdiagnostic criteria and measures of subclinical symptoms. Results After covariate adjustment, cohort members with high levels of exposure to the earthquakes had rates of mental disorder that were 1.4 (95% CI, 1.1-1.7) times higher than those of cohort members not exposed. This increase was due to increases in the rates of major depression; posttraumatic stress disorder; other anxiety disorders; and nicotine dependence. Similar results were found using a measure of subclinical symptoms (incidence rate ratio, 1.4; 95% CI, 1.1-1.6). Estimates of attributable fraction suggested that exposure to the Canterbury earthquakes accounted for 10.8% to 13.3% of the overall rate of mental disorder in the cohort at age 35 years. Conclusions and Relevance Following extensive control for prospectively measured confounding factors, exposure to the Canterbury earthquakes was associated with a small to moderate increase in the risk for common mental health problems.
TL;DR: Individuals with UD and those with BD are differentiated by structural abnormalities in neural regions supporting emotion processing, and neuroimaging and multivariate pattern classification techniques are promising tools to differentiate UD from BD.
Abstract: Importance The structural abnormalities in the brain that accurately differentiate unipolar depression (UD) and bipolar depression (BD) remain unidentified. Objectives First, to investigate and compare morphometric changes in UD and BD, and to replicate the findings at 2 independent neuroimaging sites; second, to differentiate UD and BD using multivariate pattern classification techniques. Design, Setting, and Participants In a 2-center cross-sectional study, structural gray matter data were obtained at 2 independent sites (Pittsburgh, Pennsylvania, and Munster, Germany) using 3-T magnetic resonance imaging. Voxel-based morphometry was used to compare local gray and white matter volumes, and a novel pattern classification approach was used to discriminate between UD and BD, while training the classifier at one imaging site and testing in an independent sample at the other site. The Pittsburgh sample of participants was recruited from the Western Psychiatric Institute and Clinic at the University of Pittsburgh from 2008 to 2012. The Munster sample was recruited from the Department of Psychiatry at the University of Munster from 2010 to 2012. Equally divided between the 2 sites were 58 currently depressed patients with bipolar I disorder, 58 age- and sex-matched unipolar depressed patients, and 58 matched healthy controls. Main Outcomes and Measures Magnetic resonance imaging was used to detect structural differences between groups. Morphometric analyses were applied using voxel-based morphometry. Pattern classification techniques were used for a multivariate approach. Results At both sites, individuals with BD showed reduced gray matter volumes in the hippocampal formation and the amygdala relative to individuals with UD (Montreal Neurological Institute coordinates x = −22, y = −1, z = 20; k = 1938 voxels; t = 4.75), whereas individuals with UD showed reduced gray matter volumes in the anterior cingulate gyrus compared with individuals with BD (Montreal Neurological Institute coordinates x = −8, y = 32, z = 3; k = 979 voxels; t = 6.37; all corrected P P P Conclusions and Relevance Individuals with UD and those with BD are differentiated by structural abnormalities in neural regions supporting emotion processing. Neuroimaging and multivariate pattern classification techniques are promising tools to differentiate UD from BD and show promise as future diagnostic aids.
TL;DR: This methylome-wide association study of schizophrenia is one of the first MWASs of disease with a large sample size using a technology that provides good coverage of methylation sites across the genome and demonstratedone of the unique features ofmethylation studies that can capture signatures of environmental insults in peripheral tissues.
Abstract: Importance Epigenetic studies present unique opportunities to advance schizophrenia research because they can potentially account for many of its clinical features and suggest novel strategies to improve disease management. Objective To identify schizophrenia DNA methylation biomarkers in blood. Design, Setting, and Participants The sample consisted of 759 schizophrenia cases and 738 controls (N = 1497) collected in Sweden. We used methyl-CpG–binding domain protein-enriched genome sequencing of the methylated genomic fraction, followed by next-generation DNA sequencing. We obtained a mean (SD) number of 68 (26.8) million reads per sample. This massive data set was processed using a specifically designed data analysis pipeline. Critical top findings from our methylome-wide association study (MWAS) were replicated in independent case-control participants using targeted pyrosequencing of bisulfite-converted DNA. Main Outcomes and Measures Status of schizophrenia cases and controls. Results Our MWAS suggested a considerable number of effects, with 25 sites passing the highly conservative Bonferroni correction and 139 sites significant at a false discovery rate of 0.01. Our top MWAS finding, which was located in FAM63B , replicated with P = 2.3 × 10 −10 . It was part of the networks regulated by microRNA that can be linked to neuronal differentiation and dopaminergic gene expression. Many other top MWAS results could be linked to hypoxia and, to a lesser extent, infection, suggesting that a record of pathogenic events may be preserved in the methylome. Our findings also implicated a site in RELN , one of the most frequently studied candidates in methylation studies of schizophrenia. Conclusions and Relevance To our knowledge, the present study is one of the first MWASs of disease with a large sample size using a technology that provides good coverage of methylation sites across the genome. Our results demonstrated one of the unique features of methylation studies that can capture signatures of environmental insults in peripheral tissues. Our MWAS suggested testable hypotheses about disease mechanisms and yielded biomarkers that can potentially be used to improve disease management.
TL;DR: Differences in ACEs by era and sex lend preliminary support that enlistment may serve as an escape from adversity for some individuals, at least among men.
Abstract: Importance Adverse childhood experiences (ACEs) are associated with several adulthood health problems, such as self-directed violence. For some individuals, enlistment in the military may be an instrumental act to escape adverse household environments; however, to our knowledge prevalence of ACEs among persons with a history of military service has not been documented in the United States using population-based data. Objective To compare the prevalence of ACEs among individuals with and without a history of military service. Design, Setting, and Participants Data are from the 2010 Behavioral Risk Factor Surveillance System. Computer-assisted telephone interviews were conducted with population-based samples of noninstitutionalized US adults from January 1 through December 31, 2010. Analyses were limited to respondents who received the ACE module (n = 60 598). Participants were categorized by history of military service and whether a respondent was 18 years of age in 1973. Main Outcomes and Measures History of military service was defined by active duty service, veteran status, or training for the Reserves or National Guard. The ACE inventory assessed 11 negative experiences before the age of 18 years. Weighted χ 2 tests and multiple logistic regression analyses were used to examine differences in ACEs by history of military service, era of service, and sex. Results Those with military experience had greater odds of any difference in prevalence of ACEs. In the all-volunteer era, men with military service had a higher prevalence of ACEs in all 11 categories than men without military service. Notably, in the all-volunteer era, men with military service had twice the odds of reporting forced sex before the age of 18 years (odds ratio, 2.19; 95% CI, 1.34-3.57) compared with men without military service. In the draft era, the only difference among men was household drug use, in which men with a history of military service had a significantly lower prevalence than men without a history of military service (2.1% vs 3.3%; P = .003). Fewer differences were observed among women in the all-volunteer and draft eras. Conclusions and Relevance Differences in ACEs by era and sex lend preliminary support that enlistment may serve as an escape from adversity for some individuals, at least among men. Further research is needed to understand how best to support service members and veterans who may have experienced ACEs.