Lurasidone has demonstrated efficacy for schizophrenia and bipolar depression in adults.

To identify a tolerated dose range of lurasidone for pediatric studies.

To characterize PK and tolerability profiles of lurasidone in a pediatric population.

Patients aged 6 to 17 years diagnosed with ADHD and conduct disorder/disruptive behavior disorder, bipolar disorder, schizophrenia, Tourette syndrome, or autism spectrum disorder were assigned to 1 of 5 open-label lurasidone dosing cohorts (20, 40, 80, 120, or 160 mg/d). If a dose level was tolerated, the next dose cohort was initiated. In the single-dose phase, blood was collected predose and for 48 hours postdose. In the multiple-dose phase, patients received once-daily lurasidone for 7 to 9 days; blood was collected before and for 24 hours after the final dose. Lurasidone PK parameters, including maximum serum concentration and area under the concentration-time curve, were calculated.

In 105 patients, the observed lurasidone PK were consistent with a PK model of adult exposure at steady state. The most common AEs were somnolence (42%), sedation (18%), and nausea (17%); incidence of AEs was generally dose-dependent across the 20-160 mg/d dose range. All 6- to 9-year-old patients experienced somnolence at 120 mg/d. Two serious AEs (parkinsonism, dystonia) were reported, both at 80 mg/d.

The PK and AE profiles of lurasidone in this heterogeneous pediatric population were consistent with data observed in adult populations. Based on this study, doses of lurasidone 20-80 mg/d are selected for evaluation in pediatric clinical trials.

Sunovion Pharmaceuticals Inc.

Deep learning using convolutional neural networks represents a form of artificial intelligence where computers recognise patterns and make predictions based upon provided datasets. This study aimed to determine if a convolutional neural network could be trained to differentiate the location of the anterior ethmoidal artery as either adhered to the skull base or within a bone ‘mesentery’ on sinus computed tomography scans.

Coronal sinus computed tomography scans were reviewed by two otolaryngology residents for anterior ethmoidal artery location and used as data for the Google Inception-V3 convolutional neural network base. The classification layer of Inception-V3 was retrained in Python (programming language software) using a transfer learning method to interpret the computed tomography images.

A total of 675 images from 388 patients were used to train the convolutional neural network. A further 197 unique images were used to test the algorithm; this yielded a total accuracy of 82.7 per cent (95 per cent confidence interval = 77.7–87.8), kappa statistic of 0.62 and area under the curve of 0.86.

Convolutional neural networks demonstrate promise in identifying clinically important structures in functional endoscopic sinus surgery, such as anterior ethmoidal artery location on pre-operative sinus computed tomography.

Interpersonal difficulties in borderline personality disorder (BPD) could be related to the disturbed self-views of BPD patients. This study investigates affective and neural responses to positive and negative social feedback (SF) of BPD patients compared with healthy (HC) and low self-esteem (LSE) controls and how this relates to individual self-views.

BPD (N = 26), HC (N = 32), and LSE (N = 22) performed a SF task in a magnetic resonance imaging scanner. Participants received 15 negative, intermediate and positive evaluative feedback words putatively given by another participant and rated their mood and applicability of the words to the self.

BPD had more negative self-views than HC and felt worse after negative feedback. Applicability of feedback was a less strong determinant of mood in BPD than HC. Increased precuneus activation was observed in HC to negative compared with positive feedback, whereas in BPD, this was similarly low for both valences. HC showed increased temporoparietal junction (TPJ) activation to positive v. negative feedback, while BPD showed more TPJ activation to negative feedback. The LSE group showed a different pattern of results suggesting that LSE cannot explain these findings in BPD.

The negative self-views that BPD have, may obstruct critically examining negative feedback, resulting in lower mood. Moreover, where HC focus on the positive feedback (based on TPJ activation), BPD seem to focus more on negative feedback, potentially maintaining negative self-views. Better balanced self-views may make BPD better equipped to deal with potential negative feedback and more open to positive interactions.

The treatment gap between the number of people with mental disorders and the number treated represents a major public health challenge. We examine this gap by socio-economic status (SES; indicated by family income and respondent education) and service sector in a cross-national analysis of community epidemiological survey data.

Data come from 16 753 respondents with 12-month DSM-IV disorders from community surveys in 25 countries in the WHO World Mental Health Survey Initiative. DSM-IV anxiety, mood, or substance disorders and treatment of these disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI).

Only 13.7% of 12-month DSM-IV/CIDI cases in lower-middle-income countries, 22.0% in upper-middle-income countries, and 36.8% in high-income countries received treatment. Highest-SES respondents were somewhat more likely to receive treatment, but this was true mostly for specialty mental health treatment, where the association was positive with education (highest treatment among respondents with the highest education and a weak association of education with treatment among other respondents) but non-monotonic with income (somewhat lower treatment rates among middle-income respondents and equivalent among those with high and low incomes).

The modest, but nonetheless stronger, an association of education than income with treatment raises questions about a financial barriers interpretation of the inverse association of SES with treatment, although future within-country analyses that consider contextual factors might document other important specifications. While beyond the scope of this report, such an expanded analysis could have important implications for designing interventions aimed at increasing mental disorder treatment among socio-economically disadvantaged people.

The U.S. Army uses universal preventives interventions for several negative outcomes (e.g. suicide, violence, sexual assault) with especially high risks in the early years of service. More intensive interventions exist, but would be cost-effective only if targeted at high-risk soldiers. We report results of efforts to develop models for such targeting from self-report surveys administered at the beginning of Army service.

21 832 new soldiers completed a self-administered questionnaire (SAQ) in 2011–2012 and consented to link administrative data to SAQ responses. Penalized regression models were developed for 12 administratively-recorded outcomes occurring by December 2013: suicide attempt, mental hospitalization, positive drug test, traumatic brain injury (TBI), other severe injury, several types of violence perpetration and victimization, demotion, and attrition.

The best-performing models were for TBI (AUC = 0.80), major physical violence perpetration (AUC = 0.78), sexual assault perpetration (AUC = 0.78), and suicide attempt (AUC = 0.74). Although predicted risk scores were significantly correlated across outcomes, prediction was not improved by including risk scores for other outcomes in models. Of particular note: 40.5% of suicide attempts occurred among the 10% of new soldiers with highest predicted risk, 57.2% of male sexual assault perpetrations among the 15% with highest predicted risk, and 35.5% of female sexual assault victimizations among the 10% with highest predicted risk.

Data collected at the beginning of service in self-report surveys could be used to develop risk models that define small proportions of new soldiers accounting for high proportions of negative outcomes over the first few years of service.

Civilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate.

The joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009.

There were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2–39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2–22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1–4.1], less so when previously deployed (OR 1.6, 95% CI 1.1–2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8–1.8). Adjustment for a differential ‘healthy warrior effect’ cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status.

Efforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.

Cross-national population data from the WHO World Mental Health surveys are used to compare role attainments and role impairments associated with binge-eating disorder (BED) and bulimia nervosa (BN).

Community surveys assessed 23 000 adults across 12 countries for BED, BN and ten other DSM-IV mental disorders using the WHO Composite International Diagnostic Interview. Age-of-onset was assessed retrospectively. Ten physical disorders were assessed using standard conditions checklists. Analyses examined reciprocal time-lagged associations of eating disorders (EDs) with education, associations of early-onset (i.e., prior to completing education) EDs with subsequent adult role attainments and cross-sectional associations of current EDs with days of role impairment.

BED and BN predicted significantly increased education (females). Student status predicted increased risk of subsequent BED and BN (females). Early-onset BED predicted reduced odds of current (at time of interview) marriage (females) and reduced odds of current employment (males). Early-onset BN predicted increased odds of current work disability (females and males). Current BED and BN were both associated with significantly increased days of role impairment (females and males). Significant BED and BN effects on adult role attainments and impairments were explained by controls for comorbid disorders.

Effects of BED on role attainments and impairments are comparable with those of BN. The most plausible interpretation of the fact that these associations are explained by comorbid disorders is that causal effects of EDs are mediated through secondary disorders. Controlled treatment effectiveness studies are needed to trace out long-term effects of BED–BN on secondary disorders.