Default Mode Hypoconnectivity Underlies a Sex-Related Autism Spectrum.

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Ypma, Rolf JF 
Moseley, Rachel L 
Holt, Rosemary J 
Rughooputh, Naresh 
Floris, Dorothea L 

BACKGROUND: Females 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: Collectively, 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.

Autism, Connectomics, Default mode network, Extreme male brain theory, Functional connectivity, Neuroimaging
Journal Title
Biol Psychiatry Cogn Neurosci Neuroimaging
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Elsevier BV
Medical Research Council (G0600977)
Medical Research Council (G1000183)
Wellcome Trust (093875/Z/10/Z)
Medical Research Council (G0701919)
Medical Research Council (G0001354)
The authors thank the participants and their families for their participation and the autism support organizations who assisted with recruitment. We thank colleagues at the Brain Mapping Unit for methodological discussions. The present analysis was funded by a Rubicon Fellowship from the Netherlands Organization for Scientific Research (RJFY), a NARSAD Young Investigator award (MR) and by the Isaac Newton Trust (MR). Data collection was funded by a Clinical Scientist Fellowship from the UK Medical Research Council (MRC) (G0701919) to MDS, imaging data acquired from the depressed adolescents was from the MR-IMPACT study funded by the Medical Research Council. NR was supported by the Cambridge Trust; LRC was supported by the Gates Cambridge Scholarship Trust; RH was supported by the MRC and the Innovative Medicines Initiative (IMI) during the period of this work. The study was conducted in association with the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Cambridgeshire, and Peterborough National Health Service (NHS) Foundation Trust. The Brain Mapping Unit (RJFY, RLM, NR, JS, ETB and MR) is part of the Behavioral & Clinical Neuroscience Institute, which is funded by the MRC and the Wellcome Trust. High performance computing facilities were supported by the NIHR Cambridge Biomedical Research Centre.