Categorical and Dimensional Approaches to Examining the Joint Effect of Autism and Schizotypal Personality Disorder on Sustained Attention.

Introduction: Accumulating evidence for the co-occurrence autism spectrum disorder (ASD) and schizotypal personality disorder (SPD) at both the diagnostic and symptom levels raises important questions about the nature of their association and the effect of their co-occurrence on the individual's phenotype and functional outcome. Research comparing adults with ASD and SPD, as well as the impact of their co-occurrence on outcomes is extremely limited. We investigated executive functioning in terms of response inhibition and sustained attention, candidate endophenotypes of both conditions, in adults with ASD, SPD, comorbid ASD and SPD, and neurotypical adults using both categorical and dimensional approaches.

Predictors of psychotic symptoms among young people with special educational needs.

Background: Psychotic symptoms and psychotic disorders occur at increased rates in adults with intellectual disability, including borderline intellectual functioning, compared with the general population. Little is known about the development of such symptoms in this population.AimsTo examine whether clinical factors predictive of psychotic disorder in a familial study of schizophrenia also apply to those with intellectual disability.

The development of antipsychotic drugs.

Antipsychotic drugs revolutionised psychiatric practice and provided a range of tools for exploring brain function in health and disease. Their development and introduction were largely empirical but based on long and honourable scientific credentials and remarkable powers of clinical observation. The class shares a common core action of attenuating central dopamine transmission, which underlies the major limitation to their use - high liability to disrupt extrapyramidal function - and also the most durable hypothesis of the basis of psychotic disorders, especially schizophrenia.

Reversal of proliferation deficits caused by chromosome 16p13.11 microduplication through targeting NFκB signaling: an integrated study of patient-derived neuronal precursor cells, cerebral organoids and in vivo brain imaging.

The molecular basis of how chromosome 16p13.11 microduplication leads to major psychiatric disorders is unknown. Here we have undertaken brain imaging of patients carrying microduplications in chromosome 16p13.

Dissociation of Brain Activation in Autism and Schizotypal Personality Disorder During Social Judgments.

Background: There are overlaps between autism and schizophrenia but these are particularly pronounced, especially in social domains, for higher functioning individuals with autism spectrum disorders (ASD) or schizotypal personality disorder (SPD). It is not known whether these overlapping social deficits result from shared or distinct brain mechanisms. We therefore compared social cognition in ASD and SPD using functional magnetic resonance imaging (fMRI).

Links between Autism Spectrum Disorder Diagnostic Status and Family Quality of Life.

Quality of life is often relatively lowered in families of children with additional needs, and this may be particularly the case where additional needs are accompanied by an autism spectrum disorder (ASD). Here we explore the effects of diagnostic status specifically, comparing families with children with an ASD diagnosis with others who a) have additional needs but no signs of ASD; and b) have additional needs and signs of ASD but no diagnosis. Mothers (n = 76) of children with additional needs completed standardised questionnaires about quality of life, stress, service provision, child behaviour and presence and severity of ASD traits.

Improved individualized prediction of schizophrenia in subjects at familial high risk, based on neuroanatomical data, schizotypal and neurocognitive features.

To date, there are no reliable markers for predicting onset of schizophrenia in individuals at high risk (HR). Substantial promise is, however, shown by a variety of pattern classification approaches to neuroimaging data. Here, we examined the predictive accuracy of support vector machine (SVM) in later diagnosing schizophrenia, at a single-subject level, using a cohort of HR individuals drawn from multiply affected families and a combination of neuroanatomical, schizotypal and neurocognitive variables.

Negative symptoms and longitudinal grey matter tissue loss in adolescents at risk of psychosis: preliminary findings from a 6-year follow-up study.

Background: Negative symptoms are perhaps the most disabling feature of schizophrenia. Their pathogenesis remains poorly understood and it has been difficult to assess their development over time with imaging techniques.

Aims: To examine, using tensor-based structural imaging techniques, whether there are regions of progressive grey matter volume change associated with the development of negative symptoms.

Charting the landscape of priority problems in psychiatry, part 1: classification and diagnosis.

Contemporary psychiatry faces major challenges. Its syndrome-based disease classification is not based on mechanisms and does not guide treatment, which largely depends on trial and error. The development of therapies is hindered by ignorance of potential beneficiary patient subgroups.

Charting the landscape of priority problems in psychiatry, part 2: pathogenesis and aetiology.

This is the second of two companion papers proposing priority problems for research on mental disorders. Whereas the first paper focuses on questions of nosology and diagnosis, this Personal View concerns pathogenesis and aetiology of psychiatric diseases. We hope that this (non-exhaustive and subjective) list of problems, nominated by scientists and clinicians from different fields and institutions, provides guidance and perspectives for choosing future directions in psychiatric science.

Grey matter networks in people at increased familial risk for schizophrenia.

Grey matter brain networks are disrupted in schizophrenia, but it is still unclear at which point during the development of the illness these disruptions arise and whether these can be associated with behavioural predictors of schizophrenia. We investigated if single-subject grey matter networks were disrupted in a sample of people at familial risk of schizophrenia. Single-subject grey matter networks were extracted from structural MRI scans of 144 high risk subjects, 32 recent-onset patients and 36 healthy controls.

Brief Report: The Association of Autistic Traits and Behavioural Patterns in Adolescents Receiving Special Educational Assistance.

Introduction: The study aim was to describe behaviours associated with autistic traits.

Methods: The Childhood Behaviour Checklist (CBCL) and Social Communication Questionnaire (SCQ) were used as measures of behaviour and autistic traits respectively in 331 adolescents receiving educational support. CBCL scores were compared between three groups defined by SCQ score: autism, pervasive developmental disorder (PDD) and non-PDD.

Hippocampal, amygdala and nucleus accumbens volume in first-episode schizophrenia patients and individuals at high familial risk: A cross-sectional comparison.

It is unknown whether brain changes occur prior to onset of schizophrenia or after it develops. Prospective familial high risk studies provide a good method to investigate this. In the Edinburgh High Risk Study, structural MRI scans of 150 young individuals at familial high risk of schizophrenia, 34 patients with first-episode schizophrenia and 36 matched controls were obtained.

Cortical Surface Area Differentiates Familial High Risk Individuals Who Go on to Develop Schizophrenia.

Background: Schizophrenia is associated with structural brain abnormalities that may be present before disease onset. It remains unclear whether these represent general vulnerability indicators or are associated with the clinical state itself.

Methods: To investigate this, structural brain scans were acquired at two time points (mean scan interval 1.

Computational neuropsychiatry - schizophrenia as a cognitive brain network disorder.

Computational modeling of functional brain networks in fMRI data has advanced the understanding of higher cognitive function. It is hypothesized that functional networks mediating higher cognitive processes are disrupted in people with schizophrenia. In this article, we review studies that applied measures of functional and effective connectivity to fMRI data during cognitive tasks, in particular working memory fMRI studies.

Cortical thickness in first-episode schizophrenia patients and individuals at high familial risk: a cross-sectional comparison.

Background: Schizophrenia is associated with cortical thickness reductions in the brain, but it is unclear whether these are present before illness onset, and to what extent they are driven by genetic factors.

Methods: In the Edinburgh High Risk Study, structural MRI scans of 150 young individuals at high familial risk for schizophrenia, 34 patients with first-episode schizophrenia and 36 matched controls were acquired, and clinical information was collected for the following 10 years for the high-risk and control group. During this time, 17 high-risk individuals developed schizophrenia, on average 2.

The application of nonlinear Dynamic Causal Modelling for fMRI in subjects at high genetic risk of schizophrenia.

Nonlinear Dynamic Causal Modelling (DCM) for fMRI provides computational modelling of gating mechanisms at the neuronal population level. It allows for estimations of connection strengths with nonlinear modulation within task-dependent networks. This paper presents an application of nonlinear DCM in subjects at high familial risk of schizophrenia performing the Hayling Sentence Completion Task (HSCT).

Longitudinal gray matter change in young people who are at enhanced risk of schizophrenia due to intellectual impairment.

Background: Existing studies of brain structural changes before the onset of schizophrenia have considered individuals with either familial risk factors or prodromal symptomatology. We aimed to determine whether findings from these studies are also applicable to those at enhanced risk of developing schizophrenia for another reason-intellectual impairment.

Methods: Participants with intellectual impairment (mean IQ: 78.

Social cognition, the male brain and the autism spectrum.

Behavioral studies have shown that, at a population level, women perform better on tests of social cognition and empathy than men. Furthermore Autism Spectrum Disorders (ASDs), which are characterized by impairments in social functioning and empathy, occur more commonly in males than females. These findings have led to the hypothesis that differences in the functioning of the social brain between males and females contribute to the greater vulnerability of males to ASD and the suggestion that ASD may represent an extreme form of the male brain.

Predicting first episode psychosis in those at high risk for genetic or cognitive reasons.

Structural and functional magnetic resonance imaging (MRI) of patients with psychosis has advanced to the point where there are clear abnormalities at a group level between patients and groups of healthy controls, and suggestions of different patterns of abnormalities between groups of patients. A major area of research endeavour is being able to translate these group differences into clinically relevant predictions at an individual patient level. Here, we briefly summarize our main findings in cohorts at high risk of psychosis because they come from families in which several members have schizophrenia or bipolar disorder, or have educational impairments.

Impact of a microRNA MIR137 susceptibility variant on brain function in people at high genetic risk of schizophrenia or bipolar disorder.

A recent 'mega-analysis' combining genome-wide association study data from over 40,000 individuals identified novel genetic loci associated with schizophrenia (SCZ) at genome-wide significance level. The strongest finding was a locus within an intron of a putative primary transcript for microRNA MIR137. In the current study, we examine the impact of variation at this locus (rs1625579, G/T; where T is the common and presumed risk allele) on brain activation during a sentence completion task that differentiates individuals with SCZ, bipolar disorder (BD), and their relatives from controls.

Evaluation of a screening instrument for autism spectrum disorders in prisoners.

Unlabelled: There have been concerns that individuals with autism spectrum disorders (ASDs) are over-represented but not recognised in prison populations. A screening tool for ASDs in prisons has therefore been developed.

Aims: We aimed to evaluate this tool in Scottish prisoners by comparing scores with standard measures of autistic traits (Autism Quotient (AQ)), neurodevelopmental history (Asperger Syndrome (and High-Functioning Autism) Diagnostic Interview (ASDI)), and social cognition (Ekman 60 Faces test).

Use of second-person pronouns and schizophrenia.

A masked analysis of videotaped assessments of people at high genetic risk of schizophrenia revealed that those who subsequently went on to develop schizophrenia used significantly more second-person pronouns. This was evident before diagnosis, at two separate assessments approximately 18 months apart. This supports the view that people who go on to develop schizophrenia may have an abnormality in the deictic frame of interpersonal communication - that is, the distinction between concepts being self-generated or from elsewhere may be blurred prior to the onset of a diagnosis of schizophrenia.

Effects of a mis-sense DISC1 variant on brain activation in two cohorts at high risk of bipolar disorder or schizophrenia.

Bipolar disorder and schizophrenia share a number of clinical features and genetic risk variants of small effect, suggesting overlapping pathogenic mechanisms. The effect of single genetic risk variants on brain function is likely to differ in people at high familial risk versus controls as these individuals have a higher overall genetic loading and are therefore closer to crossing a threshold of disease liability. Therefore, whilst the effects of genetic risk variants on brain function may be similar across individuals at risk of both disorders, they are hypothesized to differ compared to that seen in control subjects.