Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R(2) increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase.

Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Heritability and polygenic predictionIn the EUR sample, the SNP-based heritability (h 2 SNP ) (that is, the proportion of variance in liability attributable to all measured SNPs)

Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment.

No abstract

Existing literature on the profile of executive dysfunction in autism spectrum disorder showed inconsistent results. Age, comorbid attention-deficit/hyperactivity disorder (ADHD) and cognitive abilities appeared to play a role in confounding the picture. Previous meta-analyses have focused on a few components of executive functions. This meta-analysis attempted to delineate the profile of deficit in several components of executive functioning in children and adolescents with high-functioning autism spectrum disorder (HFASD). Ninety-eight English published case-control studies comparing children and adolescents with HFASD with typically developing controls using well-known neuropsychological measures to assess executive functions were included. Results showed that children and adolescents with HFASD were moderately impaired in verbal working memory (g = 0.67), spatial working memory (g = 0.58), flexibility (g = 0.59), planning (g = 0.62), and generativity (g = 0.60) except for inhibition (g = 0.41). Subgroup analysis showed that impairments were still significant for flexibility (g = 0.57-0.61), generativity (g = 0.52-0.68), and working memory (g = 0.49-0.56) in a sample of autism spectrum disorder (ASD) subjects without comorbid ADHD or when the cognitive abilities of the ASD group and the control group were comparable. This meta-analysis confirmed the presence of executive dysfunction in children and adolescents with HFASD. These deficits are not solely accounted for by the effect of comorbid ADHD and the general cognitive abilities. Our results support the executive dysfunction hypothesis and contribute to the clinical understanding and possible development of interventions to alleviate these deficits in children and adolescents with HFASD. Autism Res 2017, 10: 911-939. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Apart from attention to psychosocial risks, health and lifestyle factors are important considerations for mental health promotion. Service utilization for individuals with CMD in Hong Kong remains suboptimal, and would be enhanced by strengthening community primary care.

BackgroundNon-adherence to antipsychotic medication is commonly found in schizophrenia and other psychotic disorders, thus forming a major obstacle to long-term maintenance treatment and contributing to high relapse rates. With limited evidence on the success of interventions in enhancing medication adherence, this controlled trial was designed to test and evaluate the effectiveness of an adherence therapy (AT) for outpatients with schizophrenia spectrum disorders, based on a motivational interviewing approach over a six-month follow-up period.MethodsA single-blind, randomized controlled trial with a repeated-measures, two parallel groups design was conducted in a random sample of 114 participants with schizophrenia spectrum disorders in one community psychiatric nursing service. After pre-test, the participants were randomly assigned to either an eight-session course of AT plus usual care or usual psychiatric care (n = 57 per group). The main outcomes, including medication adherence, symptom severity, insight into treatment, hospitalization rate, and functioning, were measured at baseline and immediately and six months post-intervention.ResultsA total of 110 participants completed this trial and thus the attrition rate was 3.5 %. Results of repeated-measures analysis of variance followed by Helmert’s contrasts test indicated that the AT participants reported significantly greater improvements in their insight into illness and/or treatment, psychosocial functioning, symptom severity, number of re-hospitalizations, and medication adherence (F = 5.01 to 7.45, P = 0.007 to 0.030) over six months follow-up, when compared with usual care.ConclusionsMotivational interviewing-based AT for people with schizophrenia can be effective to reduce symptom severity and re-hospitalizations, and improve medication adherence, functioning, and insight into illness and/or treatment over a medium term (six months) period of follow-up. Further study on the effects of AT in people with psychotic disorders in terms of diverse sociodemographic and illness characteristics, and a longer term (for example, over 12 months) follow-up period is recommended.Trial registrationThe trial was registered at Clinicaltrials.gov (identifier: NCT01780116) on 6 July 2014.

No abstract