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Autism may result from abnormalities in specific brain regions and a global lack of integration due to brain enlargement. Inconsistencies in the literature partly relate to differences in the age and IQ of study populations. Some regions may show abnormal growth trajectories.

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Siblings of individuals with autism have over 20 times the population risk of autism. Evidence of comparable, but less marked, cognitive and social communication deficits in siblings suggests a role for these traits in the search for biomarkers of familial risk. However, no neuroimaging biomarkers of familial risk have been identified to date. Here we show, for the first time, that the neural response to facial expression of emotion differs between unaffected siblings and healthy controls with no family history of autism. Strikingly, the functional magnetic resonance imaging (fMRI) response to happy versus neutral faces was significantly reduced in unaffected siblings compared with controls within a number of brain areas implicated in empathy and face processing. The response in unaffected siblings did not differ significantly from the response in autism. Furthermore, investigation of the response to faces versus fixation crosses suggested that, within the context of this study, an atypical response specifically to happy faces, rather than to faces in general, accounts for the observed sibling versus controls difference and is a clear biomarker of familial risk. Our findings suggest that an atypical implicit response to facial expression of emotion may form the basis of impaired emotional reactivity in autism and in the broader autism phenotype in relatives. These results demonstrate that the fMRI response to facial expression of emotion is a candidate neuroimaging endophenotype for autism, and may offer far-reaching insights into the etiology of autism.

Endophenotypes are heritable and quantifiable markers that may assist in the identification of the complex genetic underpinnings of psychiatric conditions. Here we examined global hypoconnectivity as an endophenotype of autism spectrum conditions (ASCs). We studied well-matched groups of adolescent males with autism, genetically-related siblings of individuals with autism, and typically-developing control participants. We parcellated the brain into 258 regions and used complex-network analysis to detect a robust hypoconnectivity endophenotype in our participant group. We observed that whole-brain functional connectivity was highest in controls, intermediate in siblings, and lowest in ASC, in task and rest conditions. We identified additional, local endophenotype effects in specific networks including the visual processing and default mode networks. Our analyses are the first to show that whole-brain functional hypoconnectivity is an endophenotype of autism in adolescence, and may thus underlie the heritable similarities seen in adolescents with ASC and their relatives.

BackgroundFemales and males differ significantly in the prevalence and presentation of autism spectrum conditions. One theory of this effect postulates that autistic traits lie on a sex-related continuum in the general population, and autism represents the extreme male end of this spectrum. This theory predicts that any feature of autism in males should 1) be present in autistic females, 2) differentiate between the sexes in the typical population, and 3) correlate with autistic traits. We tested these three predictions for default mode network (DMN) hypoconnectivity during the resting state, one of the most robustly found neurobiological differences in autism.MethodsWe analyzed a primary dataset of adolescents (N = 121, 12–18 years of age) containing a relatively large number of females and a replication multisite dataset including children, adolescents, and adults (N = 980, 6–58 years of age). We quantified the average connectivity between DMN regions and tested for group differences and correlation with behavioral performance using robust regression.ResultsWe found significant differences in DMN intraconnectivity between female controls and females with autism (p = .001 in the primary dataset; p = .009 in the replication dataset), and between female controls and male controls (p = .036 in the primary dataset; p = .002 in the replication dataset). We also found a significant correlation between DMN intraconnectivity and performance on a mentalizing task (p = .001) in the primary dataset.ConclusionsCollectively, these findings provide the first evidence for DMN hypoconnectivity as a behaviorally relevant neuroimaging phenotype of the sex-related spectrum of autistic traits, of which autism represents the extreme case.

A composite index for COPD prognosis (the COPD Prognostic Index) has been validated in data not used in its development and is capable of predicting not only mortality, but also hospitalizations and exacerbations. All factors included in the index are straightforward to obtain, which should make the index suitable for use in primary as well as secondary care settings.

ObjectivesTo examine links between clinical and other characteristics of people with Alzheimer's disease living in the community, likelihood of care home or hospital admission, and associated costs.DesignObservational data extracted from clinical records using natural language processing and Hospital Episode Statistics. Statistical analyses examined effects of cognition, physical health, mental health, sociodemographic factors and living circumstances on risk of admission to care home or hospital over 6 months and associated costs, adjusting for repeated observations.SettingCatchment area for South London and Maudsley National Health Service Foundation Trust, provider for 1.2 million people in Southeast London.ParticipantsEvery individual with diagnosis of Alzheimer's disease seen and treated by mental health services in the catchment area, with at least one rating of cognition, not resident in care home at time of assessment (n=3075).InterventionsUsual treatment.Main outcome measuresRisk of admission to, and days spent in three settings during 6-month period following routine clinical assessment: care home, mental health inpatient care and general hospital inpatient care.ResultsPredictors of probability of care home or hospital admission and/or associated costs over 6 months include cognition, functional problems, agitation, depression, physical illness, previous hospitalisations, age, gender, ethnicity, living alone and having a partner. Patterns of association differed considerably by destination.ConclusionsMost people with dementia prefer to remain in their own homes, and funding bodies see this as cheaper than institutionalisation. Better treatment in the community that reduces health and social care needs of Alzheimer's patients would reduce admission rates. Living alone, poor living circumstances and functional problems all raise admission rates, and so major cuts in social care budgets increase the risk of high-cost admissions which older people do not want. Routinely collected data can be used to reveal local patterns of admission and costs.