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Background and Hypothesis Quantitative acoustic and textual measures derived from speech (“speech features”) may provide valuable biomarkers for psychiatric disorders, particularly schizophrenia spectrum disorders (SSD). We sought to identify cross-diagnostic latent factors for speech disturbance with relevance for SSD and computational modeling. Study Design Clinical ratings for speech disturbance were generated across 14 items for a cross-diagnostic sample (N = 334), including SSD (n = 90). Speech features were quantified using an automated pipeline for brief recorded samples of free speech. Factor models for the clinical ratings were generated using exploratory factor analysis, then tested with confirmatory factor analysis in the cross-diagnostic and SSD groups. The relationships between factor scores and computational speech features were examined for 202 of the participants. Study Results We found a 3-factor model with a good fit in the cross-diagnostic group and an acceptable fit for the SSD subsample. The model identifies an impaired expressivity factor and 2 interrelated disorganized factors for inefficient and incoherent speech. Incoherent speech was specific to psychosis groups, while inefficient speech and impaired expressivity showed intermediate effects in people with nonpsychotic disorders. Each of the 3 factors had significant and distinct relationships with speech features, which differed for the cross-diagnostic vs SSD groups. Conclusions We report a cross-diagnostic 3-factor model for speech disturbance which is supported by good statistical measures, intuitive, applicable to SSD, and relatable to linguistic theories. It provides a valuable framework for understanding speech disturbance and appropriate targets for modeling with quantitative speech features.

To examine long-term effects of early intervention services (EIS) for first-episode psychosis, we compared Heinrichs-Carpenter Quality of Life (QLS) and Positive and Negative Syndrome Scale (PANSS) scores and inpatient hospitalization days over 5 years with data from the site-randomized RAISE-ETP trial that compared the EIS NAVIGATE (17 sites; 223 participants) and community care (CC) (17 sites; 181 participants). Inclusion criteria were: age 15–40 years; DSM-IV diagnoses of schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, or psychotic disorder not otherwise specified; first psychotic episode; antipsychotic medication taken for ≤6 months. NAVIGATE-randomized participants could receive NAVIGATE from their study entry date until NAVIGATE ended when the last-enrolled NAVIGATE participant completed 2 years of treatment. Assessments occurred every 6 months. 61% of participants had assessments conducted ≥2 years; 31% at 5 years. Median follow-up length was CC 30 months and NAVIGATE 38 months. Primary analyses assumed data were not-missing-at-random (NMAR); sensitivity analyses assumed data were missing-at-random (MAR). MAR analyses found no significant treatment-by-time interactions for QLS or PANSS. NMAR analyses revealed that NAVIGATE was associated with a 13.14 (95%CI:6.92,19.37) unit QLS and 7.73 (95%CI:2.98,12.47) unit PANSS better improvement and 2.53 (95%CI:0.59,4.47) fewer inpatient days than CC (all comparisons significant). QLS and PANSS effect sizes were 0.856 and 0.70. NAVIGATE opportunity length (mean 33.8 (SD = 5.1) months) was not associated (P = .72) with QLS outcome; duration of untreated psychosis did not moderate (P = .32) differential QLS outcome. While conclusions are limited by the low rate of five-year follow-up, the data support long-term benefit of NAVIGATE compared to community care.

Current research suggests that hundreds to thousands of single nucleotide polymorphisms (SNPs) with small to modest effect sizes contribute to the genetic basis of many disorders, a phenomenon labeled as polygenicity. Additionally, many such disorders demonstrate polygenic overlap, in which risk alleles are shared at associated genetic loci. A simple strategy to detect polygenic overlap between two phenotypes is based on rank-ordering the univariate p-values from two genome-wide association studies (GWASs). Although high-dimensional variable selection strategies such as Lasso and elastic nets have been utilized in other GWAS analysis settings, they are yet to be utilized for detecting shared polygenicity. In this paper, we illustrate how elastic nets, with polygenic scores as the dependent variable and with appropriate adaptation in selecting the penalty parameter, may be utilized for detecting a subset of SNPs involved in shared polygenicity. We provide theory to better understand our approaches, and illustrate their utility using synthetic datasets. Results from extensive simulations are presented comparing the elastic net approaches with the rank ordering approach, in various scenarios. Results from simulations studies exhibit one of the elastic net approaches to be superior when the correlations among the SNPs are high. Finally, we apply the methods on two real datasets to illustrate further the capabilities, limitations and differences among the methods.

Cognitive Load Theory has emerged as an important approach to improving instruction in the health professions workplace, including patient handovers. At the same time, there is growing recognition that emotion influences learning through numerous cognitive processes including motivation, attention, working memory, and long-term memory. This study explores how emotion influences the cognitive load experienced by trainees performing patient handovers. From January to March 2019, 693 (38.7%) of 1807 residents and fellows from a 24-hospital health system in New York city completed a survey after performing a handover. Participants rated their emotional state and cognitive load. The survey included questions about features of the learner, task, and instructional environment. The authors used factor analysis to identify the core dimensions of emotion. Regression analyses explored the relationship between the emotion factors and cognitive load types. Two emotion dimensions were identified representing invigoration and tranquility. In regression analyses, higher levels of invigoration, tranquility, and their interaction were independently associated with lower intrinsic load and extraneous load. The interaction of invigoration and tranquility predicted lower germane load. The addition of the emotion variables to multivariate models including other predictors of cognitive load types significantly increased the amount of variance explained. The study provides a model for measuring emotions in workplace learning. Because emotion appears to have a significant influence on cognitive load types, instructional designers should consider strategies that help trainees regulate emotion in order to reduce cognitive load and improve learning and performance.

Estimating the time lag between a pair of time series is of significance in many practical applications. In this article, we introduce a method to quantify such lags by adapting the visibility graph algorithm, which converts time series into a mathematical graph. Currently widely used method to detect such lags is based on cross-correlations, which has certain limitations. We present simulated examples where the new method identifies the lag correctly and unambiguously while as the cross-correlation method does not. The article includes results from an extensive simulation study conducted to better understand the scenarios where the new method performed better or worse than the existing approach. We also present a likelihood based parametric modeling framework and consider frameworks for quantifying uncertainty and hypothesis testing for the new approach. We apply the current and new methods to two case studies, one from neuroscience and the other from environmental epidemiology, to illustrate the methods further.

While antipsychotic medications have been utilized for decades, many patients experiencing psychosis do not demonstrate a satisfactory positive symptom response, even in the first episode of illness. Resting state functional magnetic resonance imaging (rs-fMRI) has increasingly been studied as a potential biomarker of antipsychotic treatment response, but studies to date remain limited in terms of sample size and brain regions examined. The present study examined fractional amplitude of low frequency fluctuations (fALFF) derived from rs-fMRI to search the whole brain, in a hypothesis-free manner, for regions that might predict response to 12 weeks of treatments with standard antipsychotic medications (risperidone or aripiprazole). To our knowledge, the present study represents the largest first episode psychosis treatment sample studied with rs-fMRI to date (N=126). At baseline, patients who would later meet strict criteria for clinical response demonstrated significantly greater baseline fALFF in bilateral orbitofrontal cortex compared to non-responders. In a subset of 62 patients who were scanned a second time at the end of treatment, responders and non-responders demonstrated significant increases in fALFF in differing brain regions. Specifically, responders demonstrated significant increases in fALFF, from baseline to follow-up, in bilateral dorsal prefrontal cortex; prefrontal changes were not observed in non-responders or in healthy individuals (n=45) scanned at two time points. Thus, spontaneous activity in orbitofrontal cortex may serve as a prognostic biomarker of antipsychotic treatment, while spontaneous activity in the dorsal prefrontal cortex may serve as a critical target of effective medication.

The risk of relapse after a successful acute course of treatment is a clinical challenge in electroconvulsive therapy (ECT) practice, particularly in patients with a history of marked resistance to previous treatments. Research suggests that a gradual decrease of ECT or its long-term continuation might be the best strategy. Notwithstanding, current studies do not address the role of continuation ECT in the truly refractory cases, that is, the clozapine-resistant patients. Our group published a randomized controlled trial of ECT augmentation of clozapine in clozapine-resistant patients with schizophrenia, where the augmentation was vastly superior in efficacy for the acute treatment. The aim of the current study is to evaluate the efficacy of continuation ECT for patients who showed response to the combination of acute ECT and clozapine for treatment-resistant schizophrenia.Continuation ECT was offered to all patients who completed the acute study and who met response criterion. We followed a tapered schedule of 4 weekly ECT sessions, followed by 4 ECT sessions every 2 weeks and 2 monthly ECT sessions for a total of 10 sessions.Patients sustained the gains achieved with the acute course of ECT, and no individual patient presented with clinically relevant worsening of symptoms. Moreover, the long-term use of ECT was not associated with added adverse effects.This is an open pilot study with a small sample size, and results should be interpreted accordingly, but this report offers a relevant starting point for much needed future studies.

PURPOSE/BACKGROUND Antidepressants are among the most frequently prescribed medications during pregnancy and may affect fetal weight. Associations between antenatal antidepressant use and ultrasonographic measures of fetal development have rarely been examined. We hypothesized that the prescription of an antenatal antidepressant would be associated with lower estimated fetal weight (EFW). METHODS/PROCEDURES A retrospective analysis of routine ultrasonographic data extracted from electronic medical records was performed on a cohort of pregnant women with psychiatric diagnoses and grouped according to the presence of an antenatal antidepressant prescription (n = 32 antidepressant-prescribed and n = 44 antidepressant prescription-free). After stratifying for gestational age, comparisons included 13 ultrasonographic parameters, frequency of oligohydramnios and polyhydramnios and growth deceleration, and maternal serum protein markers assessed per routine care, including α-fetoprotein, free β-human chorionic gonadotropin, and unconjugated estriol levels, using t tests, nonparametric and Fisher tests, and effect sizes (ESs) were computed. FINDINGS/RESULTS No statistically significant EFW differences between groups at any time point were detected (P > 0.05). Antenatal antidepressant prescription was associated with lower femur length at weeks 33 to 40 (P = 0.046, ES = 0.75) and greater left ventricular diameter at weeks 25 to 32 (P = 0.04, ES = 1.18). No differences for frequency of oligohydramnios or polyhydramnios or growth deceleration were observed (P > 0.05). We did not detect group differences for maternal proteins (P > 0.05). IMPLICATIONS/CONCLUSIONS Our evidence suggested a lack of association between antenatal antidepressant prescription and lower EFW but indicated an association with lower femur length and greater left ventricular diameter in mid-late gestation. Future research should examine the clinical implications of these findings.

ContextPatient handovers remain a significant patient safety challenge. Cognitive load theory (CLT) can be used to identify the cognitive mechanisms for handover errors. The ability to measure cognitive load types during handovers could drive the development of more effective curricula and protocols. No such measure currently exists.MethodsThe authors developed the Cognitive Load Inventory for Handoffs (CLIH) using a multi- step process, including expert interviews to enhance content validity and talk- alouds to optimise response process validity. The final version contained 28 items. From January to March 2019, we administered a cross- sectional survey to 1807 residents and fellows from a large health care system in the USA. Participants completed the CLIH following a handover. Exploratory factor analysis of data from one- third of respondents identified high- performing items; confirmatory factor analysis of data from the remaining sample assessed model fit. Model fit was evaluated using the comparative fit index (CFI) (>0.90), Tucker- Lewis index (TFI) (>0.80), standardised root mean square residual (SRMR) (

Cognitive Load Theory has emerged as an important approach to improving instruction in the health professions workplace, including patient handovers. At the same time, there is growing recognition that emotion influences learning through numerous cognitive processes including motivation, attention, working memory, and long-term memory. This study explores how emotion influences the cognitive load experienced by trainees performing patient handovers. From January to March 2019, 693 (38.7%) of 1807 residents and fellows from a 24-hospital health system in New York city completed a survey after performing a handover. Participants rated their emotional state and cognitive load. The survey included questions about features of the learner, task, and instructional environment. The authors used factor analysis to identify the core dimensions of emotion. Regression analyses explored the relationship between the emotion factors and cognitive load types. Two emotion dimensions were identified representing invigoration and tranquility. In regression analyses, higher levels of invigoration, tranquility, and their interaction were independently associated with lower intrinsic load and extraneous load. The interaction of invigoration and tranquility predicted lower germane load. The addition of the emotion variables to multivariate models including other predictors of cognitive load types significantly increased the amount of variance explained. The study provides a model for measuring emotions in workplace learning. Because emotion appears to have a significant influence on cognitive load types, instructional designers should consider strategies that help trainees regulate emotion in order to reduce cognitive load and improve learning and performance.

Dynamic correlation is the correlation between two time series across time. Two approaches that currently exist in neuroscience literature for dynamic correlation estimation are the sliding window method and dynamic conditional correlation. In this paper, we first show the limitations of these two methods especially in the presence of extreme values. We present an alternate approach for dynamic correlation estimation based on a weighted graph and show using simulations and real data analyses the advantages of the new approach over the existing ones. We also provide some theoretical justifications and present a framework for quantifying uncertainty and testing hypotheses.

Summary Background Most individuals with schizophrenia-spectrum disorders have relapses, which increase the risk of morbidity and mortality. Because non-adherence to antipsychotic maintenance treatment could affect more than half of individuals with schizophrenia-spectrum disorders, psychosis relapse can often be confounded by unnoticed treatment interruption. Research of relapse during confirmed antipsychotic exposure has basic clinical and neurobiological implications, but data are scarce. We aimed to generate reliable estimates of incidence and predictors of relapse during assured antipsychotic treatment. Methods We did a systematic review and individual participant data (IPD) meta-analysis of clinical trials of long-acting injectable antipsychotics (LAIs) for psychosis relapse-prevention, following IPD-PRISMA guidelines. Datasets were identified by searching relevant repositories from inception to Aug 1, 2019. Each LAI group was reanalysed as a separate cohort, further identifying subcohorts of individuals with and without prospectively determined symptom remission (PSR). Summary incidence rate of relapse, incidence rate ratios (IRRs) of relapse between individuals with and without PSR, hazard ratios (HRs) of covariates on risk of relapse, and standardised mean difference (SMDs) in changes in overall functioning associated with relapse were generated by pooling results from the harmonised reanalysis of each study. This study is registered with PROSPERO, number CRD42019137439. Findings 19 treatment cohorts consisting of 5130 individuals (2938 with PSR, 2192 without PSR), with 3959·53 observed participant-years, were meta-analysed. Pooled incidence of relapse was 22·97 per 100 participant-years (14·76 per 100 participant-years for the PSR subcohort, 31·51 per 100 participant-years for the non-PSR subcohort), with an IRR of 0·19 (95% CI 0·07 to 0·54). Relapse was associated with functional decline (overall SMD −0·76, 95% CI −1·14 to −0·37; PSR SMD −0·52, 95% CI −0·80 to −0·21; non-PSR SMD −0·72, 95% CI −1·18 to −0·26). The strongest predictor of relapse was tardive dyskinesia at treatment onset (HR 2·39, 95% CI 1·05 to 5·42). Interpretation Despite the established efficacy of antipsychotics in preventing relapse, these data indicate that these drugs might not prevent subsequent exacerbations for a proportion of individuals whose illness is stabilised on continuous antipsychotic treatment. Tardive dyskinesia in particular might have pathophysiological implications for relapse. Funding Northwell Health.

Ito’s lemma is a standard approach for calculating infinitesimal generators for stochastic process models. We present alternate ad-hoc methods based on elementary calculations for many commonly considered stochastic models. The only tools that we employ are binomial expansion, Taylor series expansion and solution methods for elementary differential equations. Our alternate approaches are especially useful for processes which cannot be expressed as stochastic differential equations, for which Ito’s lemma cannot be applied.

Genetic association studies are becoming an important component of medical research. To cite one instance, pharmacogenomics which is gaining prominence as a useful tool for personalized medicine is heavily reliant on results from genetic association studies. Meta-analysis of genetic association studies is being increasingly used to assess phenotypic differences between genotype groups. When the underlying genetic model is assumed to be dominant or recessive, assessing the phenotype differences based on summary statistics, reported for individual studies in a meta-analysis, is a valid strategy. However, when the genetic model is additive, a similar strategy based on summary statistics will lead to biased results. This fact about the additive model is one of the things that we establish in this paper, using simulations. The main goal of this paper is to present an alternate strategy for the additive model based on simulating data for the individual studies. We show that the alternate strategy is far superior to the strategy based on summary statistics.

Although applications of Bayesian analysis for numerical quadrature problems have been considered before, it's only very recently that statisticians have focused on the connections between statistics and numerical analysis of differential equations. In line with this very recent trend, we show how certain commonly used finite difference schemes for numerical solutions of ordinary and partial differential equations can be considered in a regression setting. Focusing on this regression framework, we apply a simple Bayesian strategy to obtain confidence intervals for the finite difference solutions. We apply this framework on several examples to show how the confidence intervals are related to truncation error and illustrate the utility of the confidence intervals for the examples considered.

Studies have examined the differences in sociodemographic/clinical characteristics between patients on long-acting injectable (LAI) versus oral medications. However, most studies did not focus specifically on patients for whom LAIs would clearly be indicated. We performed a chart review of patients with schizophrenia or schizoaffective disorder. Patients were categorized as having an ‘indication for an LAI’ or not on the basis of their adherence history. Patients for whom an LAI was indicated and prescribed on discharge were then compared with similar patients for whom an LAI was not prescribed. Of 305 charts reviewed, consisting of 279 unique patients, 27.2% were judged to have an indication for an LAI (n = 76), but only 32.9% of these (n = 25) were discharged on an LAI. In the multiregression model, being African American, residing in a psychiatric residence, having a previous history of an LAI trial, and being treated with a higher antipsychotic dose were predictive of LAI prescription. It is important to focus on the population who are not likely to receive an LAI, but who have such indications for treatment.

The interthalamic adhesion (ITA) is an understudied neuroanatomical structure that forms a bridge of tissue connecting the thalamus of each hemisphere across the midline whose functional significance remains largely unknown. The likelihood of ITA absence has been reported in some studies to be increased in males, but findings have been inconsistent. We used magnetic resonance imaging to investigate the size and absence of the ITA and their relationship to thalamic volume, putative indices of white matter integrity (fractional anisotropy and mean diffusivity) within the anterior thalamic radiation and neuropsychological functions in 233 (129M/104F) healthy volunteers (age range = 8 to 68). To ensure high reliability in this study 2 operators independently rated the absence of the ITA and measured its size for all individuals. The ITA was absent in 4% of all individuals with no sex differences in its absence. Females had greater ITA size compared to males overall with both groups demonstrating nonlinear age-associated changes across the age range examined. ITA size among females correlated significantly with thalamus volume and lower mean diffusivity in the anterior thalamic radiation. Path modeling indicated that ITA size statistically mediated the relationship between age and attention among females. Our findings provide evidence for sex differences in ITA size across the lifespan, which are associated with the surrounding thalamic anatomy and neuropsychological functions.

ImportancePsychiatric hospitalization is a major driver of cost in the treatment of schizophrenia. Symptom relapses are a frequent cause of hospitalization and both are primary source of burden to patients and their supporters.ObjectiveTo determine whether a novel, multicomponent, and technology-enhanced approach to relapse prevention in outpatients following a psychiatric hospitalization could reduce days spent in a hospital after discharge.DesignThe Improving Care and Reducing Cost (ICRC) study was a quasi-experimental clinical trial in outpatients with schizophrenia conducted between February 2013 and April 2015 at 10 different sites in the US. Data were obtained from 89 participants who received usual relapse prevention services, followed by a second cohort of 349 participants who received the technology-enhanced relapse prevention program. Both groups were followed for 6 months.SettingOutpatient setting.ParticipantsPatients were between 18 and 60 years old; had a diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified; and were currently hospitalized or had been hospitalized within the past 30 days.InterventionPatients received usual care or a technology-enhanced relapse prevention program during a 6-month period after discharge.Main Outcome(s) and Measure(s)Days spent in a psychiatric hospital during 6 months after discharge.ResultsThe study included 438 patients. Control participants (N = 89; 37 females) were enrolled first and received usual care for relapse prevention, and followed by 349 participants (128 females) who received technology-enhanced relapse prevention. Days of hospitalization were reduced by 4 days (Mean days: b = −4.25, 95% CI: −8.29; −0.21, P = 0.039) during follow-up in the intervention condition compared to control.Conclusions and RelevanceThe reduction in days spent in the hospital for participants in the technology-informed relapse prevention program compared to those who received usual care, and the previously reported high satisfaction and usability suggest that technology-enhanced relapse prevention is an effective and feasible way to reduce rehospitalization days among patients with schizophrenia.Key pointsQuestionCan rehospitalizations in schizophrenia be prevented at reduced cost by innovative mobile technology-delivered interventions?FindingsIn this clinical trial with 438 patients, a technology-enhanced relapse prevention program compared to usual services reduced an average of four days of hospitalization per patient during the first 6 months following an index hospitalization.MeaningRelapse prevention through a health technology may improve care while reducing costs associated with hospitalization.

Background Altered striatal development contributes to core deficits in motor and inhibitory control, impulsivity, and inattention associated with attention-deficit/hyperactivity disorder and may likewise play a role in deficient reward processing and emotion regulation in psychosis and depression. The maturation of striatal connectivity has not been well characterized, particularly as it relates to clinical symptomatology. Methods Resting-state functional connectivity with striatal subdivisions was examined for 926 participants (8–22 years of age, 44% male) from the general population who had participated in two large cross-sectional studies. Developing circuits were identified and growth charting of age-related connections was performed to obtain individual scores reflecting relative neurodevelopmental attainment. Associations of clinical symptom scales (attention-deficit/hyperactivity disorder, psychosis, depression, and general psychopathology) with the resulting striatal connectivity age-deviation scores were then tested using elastic net regression. Results Linear and nonlinear developmental patterns occurred across 231 striatal age-related connections. Both unique and overlapping striatal age-related connections were associated with the four symptom domains. Attention-deficit/hyperactivity disorder severity was related to age-advanced connectivity across several insula subregions, but to age-delayed connectivity with the nearby inferior frontal gyrus. Psychosis was associated with advanced connectivity with the medial prefrontal cortex and superior temporal gyrus, while aberrant limbic connectivity predicted depression. The dorsal posterior insula, a region involved in pain processing, emerged as a strong contributor to general psychopathology as well as to each individual symptom domain. Conclusions Developmental striatal pathophysiology in the general population is consistent with dysfunctional circuitry commonly found in clinical populations. Atypical age-normative connectivity may thereby reflect aberrant neurodevelopmental processes that contribute to clinical risk.

Up to 70% of patients with treatment-resistant schizophrenia do not respond to clozapine. Pharmacological augmentation to clozapine has been studied with unimpressive results. The authors examined the use of ECT as an augmentation to clozapine for treatment-refractory schizophrenia.In a randomized single-blind 8-week study, patients with clozapine-resistant schizophrenia were assigned to treatment as usual (clozapine group) or a course of bilateral ECT plus clozapine (ECT plus clozapine group). Nonresponders from the clozapine group received an 8-week open trial of ECT (crossover phase). ECT was performed three times per week for the first 4 weeks and twice weekly for the last 4 weeks. Clozapine dosages remained constant. Response was defined as ≥40% reduction in symptoms based on the psychotic symptom subscale of the Brief Psychiatric Rating Scale, a Clinical Global Impressions (CGI)-severity rating3, and a CGI-improvement rating ≤2.The intent-to-treat sample included 39 participants (ECT plus clozapine group, N=20; clozapine group, N=19). All 19 patients from the clozapine group received ECT in the crossover phase. Fifty percent of the ECT plus clozapine patients met the response criterion. None of the patients in the clozapine group met the criterion. In the crossover phase, response was 47%. There were no discernible differences between groups on global cognition. Two patients required the postponement of an ECT session because of mild confusion.The augmentation of clozapine with ECT is a safe and effective treatment option. Further research is required to determine the persistence of the improvement and the potential need for maintenance treatments.

OBJECTIVES To examine, in a large, nationally representative sample of high school students, the association between bullying victimization and carrying weapons to school and to determine to what extent past experience of 1, 2, or 3 additional indicators of peer aggression increases the likelihood of weapon carrying by victims of bullying (VoBs). METHODS National data from the 2015 Youth Risk Behavior Survey were analyzed for grades 9 to 12 (N = 15624). VoB groups were determined by self-report of being bullied at school and additional adverse experiences: fighting at school, being threatened or injured at school, and skipping school out of fear for one’s safety. Weapon carrying was measured by a dichotomized (ie, ≥ 1 vs 0) report of carrying a gun, knife, or club on school property. VoB groups were compared with nonvictims with respect to weapon carrying by logistic regression adjusting for sex, grade, and race/ethnicity. RESULTS When surveyed, 20.2% of students reported being a VoB in the past year, and 4.1% reported carrying a weapon to school in the past month. VoBs experiencing 1, 2, or 3 additional risk factors were successively more likely to carry weapons to school. The subset of VoBs who experienced all 3 additional adverse experiences were more likely to carry weapons to school compared with nonvictims (46.4% vs 2.5%, P < .001). CONCLUSIONS Pediatricians should recognize that VoBs, especially those who have experienced 1 or more indicators of peer aggression in conjunction, are at substantially increased risk of weapon carrying.

Objective:The primary aim of this study was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for implementation in the U.S. health care system, with community care on quality of life.Method:Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and ≤6 months of antipsychotic treatment (N=404) were enrolled and followed for ≥2 years. The primary outcome was the total score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in regular activities.Results:The 223 recipients of NAVIGATE remained in treatment longer, experienced greater ...

The original version of the article contained an error in the electronic supplementary material. The caption of the figure in the electronic supplementary material was omitted.

Parasympathetic arousal is associated with states of heightened attention and well-being. Arousal may affect widespread cortical and subcortical systems across the brain, however, little is known about its influence on cognitive task processing and performance. In the current study, healthy adult participants (n ​= ​20) underwent multi-band echo-planar imaging (TR ​= ​0.72 ​s) with simultaneous pulse oximetry recordings during performance of the Multi Source Interference Task (MSIT), the Oddball Task (OBT), and during rest. Processing speed on both tasks was robustly related to heart rate (HR). Participants with slower HR responded faster on both the MSIT (33% variance explained) and the OBT (25% variance explained). Within all participants, trial-to-trial fluctuations in processing speed were robustly related to the heartbeat-stimulus interval, a metric that is dependent both on the concurrent HR and the stimulus timing with respect to the heartbeat. Models examining the cardiac-BOLD response revealed that a distributed set of regions showed arousal-related activity that was distinct for different task conditions. Across these cortical regions, activity increased with slower HR. Arousal-related activity was distinct from task-evoked activity and it was robust to the inclusion of additional physiological nuisance regressors into the models. For the MSIT, such arousal-related activity occurred across visual and dorsal attention network regions. For the OBT, this activity occurred within fronto-parietal regions. For rest, arousal-related activity also occurred, but was confined to visual regions. The pulvinar nucleus of the thalamus showed arousal-related activity during all three task conditions. Widespread cortical activity, associated with increased parasympathetic arousal, may be propagated by thalamic circuits and contributes to improved attention. This activity is distinct from task-evoked activity, but affects cognitive performance and therefore should be incorporated into neurobiological models of cognition and clinical disorders.

Omega-3 treatment studies for multi-episode schizophrenia or clinical high risk for conversion to psychosis states have had variable, and often negative, results. To examine adjunctive omega-3 treatment for recent onset psychosis, participants aged 15–40 years with recent onset schizophrenia-spectrum (n = 46) or bipolar (n = 4) disorders and current psychotic symptoms were treated for 16 weeks with risperidone and randomly-assigned omega-3 (EPA 740 mg and DHA 400 mg daily) or matching placebo. The primary outcome measure was the Brief Psychiatric Rating Scale (BPRS) total score. Mean lifetime antipsychotic exposure was 18.1 days. Length of time in treatment, risperidone dose and number of omega-3/placebo capsules taken did not differ between conditions. Longitudinal analysis of the total BPRS score revealed a trend level (p = 0.0826) treatment effect favoring omega-3 treatment. Lorazepam was an allowed concomitant medication. Among the subgroup (N = 23) who did not receive lorazepam, the treatment effect on BPRS total scores favoring omega-3 was significant (p = 0.0406) and factor scores analyses revealed a substantial decrease in depression-anxiety with omega-3 but no change with placebo (treatment-by-time interaction, p = 0.0184). Motor side effects did not differ between conditions. Analysis of Systematic Assessment for Treatment Emergent Events assessments revealed fewer adverse events overall with omega-3 compared with placebo with the largest differences between conditions (all favoring omega-3) on confusion, anxiety, depression, irritability, and tiredness/fatigue. These results suggest that omega-3 adjuvant treatment is a potential option for depression and anxiety symptoms of people with recent onset psychosis. Further research is needed to confirm this potential. Clinical trial registration: NCT01786239

Identifying time-lag between two hydrogeological time series for planning and management of water resources has a long history and is of continuing research interest. Many hydrogeological studies in the past have used visual inspection and cross-correlogram techniques for quantifying the time lag. Cross-correlogram techniques, if not done under the transfer function framework, could lead to ambiguous results. In order to conduct cross-correlogram analysis under the transfer function framework, careful pre-processing steps have to be undertaken, which are often ignored in practice. In this paper, we propose a new approach to compare two sets of hydrogeological time series data using the visibility graph algorithm and show the advantages of using the new approach over the traditional approach. Application of the new approach is demonstrated by assessing the lags between rainfall and water level fluctuation in Lake Okeechobee, Florida. We also present simulation studies to better understand the performance of the method for different sample sizes, different underlying models and in the presence of missing values.

OBJECTIVES: To examine, in a large, nationally representative sample of high school students, the association between bullying victimization and carrying weapons to school and to determine to what extent past experience of 1, 2, or 3 additional indicators of peer aggression increases the likelihood of weapon carrying by victims of bullying (VoBs). METHODS: National data from the 2015 Youth Risk Behavior Survey were analyzed for grades 9 to 12 (N = 15 624). VoB groups were determined by self-report of being bullied at school and additional adverse experiences: fighting at school, being threatened or injured at school, and skipping school out of fear for one’s safety. Weapon carrying was measured by a dichotomized (ie, ≥1 vs 0) report of carrying a gun, knife, or club on school property. VoB groups were compared with nonvictims with respect to weapon carrying by logistic regression adjusting for sex, grade, and race/ethnicity. RESULTS: When surveyed, 20.2% of students reported being a VoB in the past year, and 4.1% reported carrying a weapon to school in the past month. VoBs experiencing 1, 2, or 3 additional risk factors were successively more likely to carry weapons to school. The subset of VoBs who experienced all 3 additional adverse experiences were more likely to carry weapons to school compared with nonvictims (46.4% vs 2.5%, P < .001). CONCLUSIONS: Pediatricians should recognize that VoBs, especially those who have experienced 1 or more indicators of peer aggression in conjunction, are at substantially increased risk of weapon carrying.

The presence of an anatomical connection between the orbitofrontal cortex and ventral striatum, forming a so-called reward network, is well established across species. This connection has important implications for reward processing and is relevant to a number of neuropsychiatric disorders. Moreover, white matter (WM) is known to continue to mature across adolescence and into early adulthood, and developmental change in the reward network is an important component of models of decision making and risk taking. Despite the importance of this connection, the underlying WM has only recently been characterized in humans histologically, and not yet in-vivo using brain imaging. Here, we implemented diffusion tensor imaging (DTI) in a large cross-sectional sample of 295 healthy individuals ages 8–68 to further characterize the WM of this connection and its development from childhood into adulthood. We demonstrate that the accumbofrontal tract, connecting the orbitofrontal cortex and nucleus accumbens, can be identified using standard DTI sequences. Using Poisson modeling, we show that the accumbofrontal tract undergoes significant change across the lifespan, with males showing a higher and earlier peak compared to females. Moreover, the change occurs in a pattern consistent with developmental models of decision-making. These findings support the hypothesis that developmental differences in WM integrity may be a contributing factor to the observed risk taking that occurs in adolescence. The accumbofrontal tract is not yet included in standard WM atlases, but may be important for inclusion in studies investigating fronto-striatal networks, as well as in investigations of substance abuse and decision making.

Research findings are particularly important for medication choice for first-episode patients as individual prior medication response to guide treatment decisions is unavailable. We describe the first large-scale double-masked randomized comparison with first-episode patients of aripiprazole and risperidone, 2 commonly used first-episode treatment agents. One hundred ninety-eight participants aged 15-40 years with schizophrenia, schizophreniform disorder, schizoaffective disorder or psychotic disorder Not Otherwise Specified, and who had been treated in their lifetime with antipsychotics for 2 weeks or less were randomly assigned to double-masked aripiprazole (5-30 mg/d) or risperidone (1-6 mg/d) and followed for 12 weeks. Positive symptom response rates did not differ (62.8% vs 56.8%) nor did time to response. Aripiprazole-treated participants had better negative symptom outcomes but experienced more akathisia. Body mass index change did not differ between treatments but advantages were found for aripiprazole treatment for total and low-density lipoprotein cholesterol, fasting glucose, and prolactin levels. Post hoc analyses suggested advantages for aripiprazole on depressed mood. Overall, if the potential for akathisia is a concern, low-dose risperidone as used in this trial maybe a preferred choice over aripiprazole. Otherwise, aripiprazole would be the preferred choice over risperidone in most situations based upon metabolic outcome advantages and some symptom advantages within the context of similar positive symptom response between medications.

Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability (“g”) in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals from a recent GWAS of cognition. A SNP (rs1906252) located at chromosome 6q16.1, previously associated with years of schooling, was significantly associated with g (P = 1.47 × 10−4) in COGENT. The first joint analysis of 43,381 non-overlapping individuals for this a priori-designated locus was strongly significant (P = 4.94 × 10−7), and the second joint analysis of 68,159 non-overlapping individuals was even more robust (P = 1.65 × 10−9). These results provide independent replication, in a large-scale dataset, of a genetic locus associated with cognitive function and education. As sample sizes grow, cognitive GWAS will identify increasing numbers of associated loci, as has been accomplished in other polygenic quantitative traits, which may be relevant to psychiatric illness. © 2015 Wiley Periodicals, Inc.

The corpus callosum (CC) is the largest interhemispheric white matter tract in the human brain, and is characterized by pronounced differences in morphology among individuals. There are limited data, however, regarding typical development, sex differences, and the neuropsychological correlates of individual differences within CC subregions. Magnetic resonance (MR) imaging exams were collected in a large cohort (N = 305) of healthy individuals (ages 8–68). We used a highly reliable program to automatically identify the midsagittal plane and obtain CC subregion measures according to approaches described by Witelson [1989]: Brain 112:799–835 and Hampel et al. [1998]: Arch Neurol 55:193–198 and a measure of whole CC shape (i.e., circularity). CC measurement parameters, including area, perimeter, length, circularity, and CC subregion area values were generally characterized by inverted U-shaped curves across the observed age range. Peak values for CC subregions were observed between ages 32 and 45, and descriptive linear correlations were consistent with sharper area changes in development. We also observed differing age-associated changes across the lifespan between males and females in the CC subregion corresponding to the genu (Witelson's subregion 2), as well as CC circularity. Mediation analysis using path modeling indicated that genu area mediated the relationship between age and processing speed for females, and the relationship between age and visual learning and executive functioning for males. Taken together, our findings implicate sex differences in CC morphology across the lifespan that are localized to the genu, which appear to mediate neuropsychological functions. Hum Brain Mapp 36:2691–2702, 2015. © 2015 Wiley Periodicals, Inc.

Patients with first-episode psychosis experience psychotic symptoms for a mean of up to 2 years prior to initiation of treatment, and long duration of untreated psychosis (DUP) is associated with poor clinical outcomes. Meanwhile, evidence compiled from numerous studies suggests that longer DUP is not associated with structural brain abnormalities. To date, few studies have examined the relationship between DUP and functional neuroimaging measures. In the present study, we used seed-based resting-state functional connectivity to examine the impact of DUP on corticostriatal circuitry. We included 83 patients with early phase schizophrenia and minimal exposure to antipsychotic drugs (