Testing the 'Extreme Female Brain' Theory of Psychosis in Adults with Autism Spectrum Disorder with or without Co-Morbid Psychosis.

INTRODUCTION: Males and females in the general population differ, on average, in their drive for empathizing (higher in females) and systemizing (higher in males). People with autism spectrum disorder (ASD) show a drive for systemizing over empathizing, irrespective of sex, which led to the conceptualisation of ASD as an 'extreme of the typical male brain'. The opposite cognitive profile, an 'extreme of the typical female brain', has been proposed to be linked to conditions such as psychosis and mania/hypomania. METHODS: We compared an empathizing-over-systemizing bias (for short 'empathizing bias') in individuals with ASD, who had experienced psychotic illness (N = 64) and who had not (N = 71). RESULTS: There were overall differences in the distribution of cognitive style. Adults with ASD who had experienced psychosis were more likely to show an empathizing bias than adults with ASD who had no history of psychosis. This was modulated by IQ, and the group-difference was driven mainly by individuals with above-average IQ. In women with ASD and psychosis, the link between mania/hypomania and an empathizing bias was greater than in men with ASD. CONCLUSIONS: The bias for empathizing over systemizing may be linked to the presence of psychosis in people with ASD. Further research is needed in a variety of clinical populations, to understand the role an empathizing bias may play in the development and manifestation of mental illness.FVL was supported by the Medical Research Council (MRC) UK and the Baily Thomas Charitable Trust. M-CL was supported by the William Binks Autism Neuroscience Fellowship, the European Autism Interventions—A Multicentre Study for Developing New Medications (EU-AIMS), and Wolfson College, Cambridge. APW and AJH received support from the NIHR Collaboration for Leadership in Applied Health Research and Care East of England at the Cambridgeshire and Peterborough NHS Foundation Trust during the preparation of this manuscript. SB-C was supported by the MRC, EU-AIMS, and the Autism Research Trust.This is the final version. It was first published by PLOS at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128102#abstract0

Psychosis in autism: comparison of the features of both conditions in a dually affected cohort.

BackgroundThere is limited information on the presentation and characteristics of psychotic illness experienced by people with autism spectrum disorder (ASD).AimsTo describe autistic and psychotic phenomenology in a group of individuals with comorbid ASD and psychosis (ASD-P) and compare this group with populations affected by either, alone.MethodWe studied 116 individuals with ASD-P. We compared features of their ASD with people with ASD and no comorbid psychosis (ASD-NP), and clinical characteristics of psychosis in ASD-P with people with psychosis only.ResultsIndividuals with ASD-P had more diagnoses of atypical psychosis and fewer of schizophrenia compared with individuals with psychosis only. People with ASD-P had fewer stereotyped interests/behaviours compared with those with ASD-NP.ConclusionsOur data show there may be a specific subtype of ASD linked to comorbid psychosis. The results support findings that psychosis in people with ASD is often atypical, particularly regarding affective disturbance.Medical Research Council (PhD studentship, Autism Imaging Multicentre Study (MRC AIMS) Consortium), Baily Thomas Charitable Trust, Health Foundation, University of Cambridge (William Binks Autism Neuroscience Fellowship), Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health and The Hospital for Sick Children, Toronto (O’Brien Scholars Program), Autism Research Trust, National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East of England at the Cambridgeshire & Peterborough NHS Foundation TrustThis is the final version of the article. It first appeared from The Royal College of Psychiatrists via https://doi.org/10.1192/bjp.bp.116.18768

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Adding a Dimension to the Dichotomy: Affective Processes Are Implicated in the Relationship Between Autistic and Schizotypal Traits

Introduction: There is a recognized increase in vulnerability to psychosis in autistic people (AP). However, the construct of psychosis (particularly schizophrenia) contains several distinct factors, making understanding the relationship between autism and psychosis complex. Previous research has suggested that affective lability may be particularly related to psychotic experiences for AP who have experienced psychosis (AP-P). There is also a suggestion that psychosis might be a state of extreme (over)empathizing, perhaps related to emotional processes. Method: We recruited three groups: AP-P (N = 23), a group of AP who had not experienced psychosis (AP-NP; N = 59) and a neurotypical control group (NC, N = 41). Participants completed measures of autistic traits, schizotypal traits (as a proxy for psychosis-proneness), emotional processes, and perspective taking (as a proxy for the type of empathizing most theoretically likely to be linked to psychosis). As well as comparisons between groups, regression analyses were used to understand the influence of dependent variables on schizotypal traits. Results: We found that AP-P had significantly higher rates of schizotypy (positive and disorganized), as well as higher rates of emotional difficulties. Across all groups, affective lability had a positive and significant association with positive and disorganized schizotypal traits. Differences in perspective taking between groups were small and generally non-significant, particularly in adjusted comparisons; additionally, its impact on schizotypy was small and non-significant. Discussion: Our findings suggest that positive and disorganized schizotypy, in particular, have a relationship with affective lability. This, in turn, supports the idea of emotional processes as related to the development of schizotypal traits and psychosis across all individuals, regardless of autism diagnostic status. We found no evidence of empathy relating to any subscale of schizotypy, or the total schizotypy score. We contend that emotional processes should be considered in exploration of the relationship between autism and schizotypy in future. This may help to explain some of the findings of overlap between these constructs in previous research. Factors known to affect neurodevelopment of emotion systems such as history of early trauma, challenges during pregnancy and birth, and early childhood experiences of adversity during critical windows of development need further consideration in future research

Regression model fit to empathizing bias (EB) within the psychotic group (N = 59 given the missing values on FSIQ–see Table 3).

<p>Interaction is denoted by ‘×’.</p><p>† Male taken as reference level.</p><p>‡ Presence of no mania taken as reference level. FSIQ = full scale IQ.</p><p>Regression model fit to empathizing bias (EB) within the psychotic group (N = 59 given the missing values on FSIQ–see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128102#pone.0128102.t003" target="_blank">Table 3</a>).</p

Raw differences between those with and without mania/hypomania, within the psychotic group.

<p>† N = 36, due to missing data.</p><p>‡ N = 23, due to missing data. FSIQ = full-scale IQ. EB = empathizing bias. SD = standard deviation. Dif = difference. CI = confidence interval.</p><p>Raw differences between those with and without mania/hypomania, within the psychotic group.</p

Raw differences between ASD-P and ASD-NP groups.

<p>† N = 59, due to missing data.</p><p>ASD = autism spectrum disorder. FSIQ = full-scale IQ. EB = empathizing bias. SD = standard deviation. Dif = difference. CI = confidence interval.</p><p>Raw differences between ASD-P and ASD-NP groups.</p

Differences in the distribution of categorical drives for empathizing/systemizing, by group (ASD-P vs ASD-NP).

<p>Differences in the distribution of categorical drives for empathizing/systemizing, by group (ASD-P vs ASD-NP).</p

Regression model fit to empathizing bias (EB), across both groups (N = 130, given the missing values on FSIQ–see Table 1).

<p>Interaction is denoted by ‘×’.</p><p>† Male taken as reference level.</p><p>‡ ASD-P taken as reference level. FSIQ = full scale IQ.</p><p>Regression model fit to empathizing bias (EB), across both groups (N = 130, given the missing values on FSIQ–see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128102#pone.0128102.t001" target="_blank">Table 1</a>).</p