title: Sex differences in frontal lobe connectivity in adults with autism spectrum conditions.
abstract: Autism spectrum conditions (ASC) are more prevalent in males than females. The biological basis of this difference remains unclear. It has been postulated that one of the primary causes of ASC is a partial disconnection of the frontal lobe from higher-order association areas during development (that is, a frontal 'disconnection syndrome'). Therefore, in the current study we investigated whether frontal connectivity differs between males and females with ASC. We recruited 98 adults with a confirmed high-functioning ASC diagnosis (61 males: aged 18-41 years; 37 females: aged 18-37 years) and 115 neurotypical controls (61 males: aged 18-45 years; 54 females: aged 18-52 years). Current ASC symptoms were evaluated using the Autism Diagnostic Observation Schedule (ADOS). Diffusion tensor imaging was performed and fractional anisotropy (FA) maps were created. Mean FA values were determined for five frontal fiber bundles and two non-frontal fiber tracts. Between-group differences in mean tract FA, as well as sex-by-diagnosis interactions were assessed. Additional analyses including ADOS scores informed us on the influence of current ASC symptom severity on frontal connectivity. We found that males with ASC had higher scores of current symptom severity than females, and had significantly lower mean FA values for all but one tract compared to controls. No differences were found between females with or without ASC. Significant sex-by-diagnosis effects were limited to the frontal tracts. Taking current ASC symptom severity scores into account did not alter the findings, although the observed power for these analyses varied. We suggest these findings of frontal connectivity abnormalities in males with ASC, but not in females with ASC, have the potential to inform us on some of the sex differences reported in the behavioral phenotype of ASC.
authors.affiliation: Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: E A
authors.initials: EA
authors.lastname: Zeestraten
authors.affiliation: Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: M C
authors.initials: MC
authors.lastname: Gudbrandsen
authors.affiliation: Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Daly
authors.affiliation: Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: M T
authors.initials: MT
authors.lastname: de Schotten
authors.affiliation: Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Catani
authors.affiliation: Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: F
authors.initials: F
authors.lastname: Dell'Acqua
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.|Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health and The Hospital for Sick Children, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: M-C
authors.initials: MC
authors.lastname: Lai
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: A N V
authors.initials: AN
authors.lastname: Ruigrok
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.|Department of Psychology and Center for Applied Neuroscience, University of Cyprus, Nicosia, Cyprus.
authors.forename: M V
authors.initials: MV
authors.lastname: Lombardo
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.|School of Psychology and Clinical Language Sciences, Centre for Integrative Neuroscience and Neurodynamics, University of Reading, Reading, UK.
authors.forename: B
authors.initials: B
authors.lastname: Chakrabarti
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.|CLASS Clinic, Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Baron-Cohen
authors.affiliation: Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Ecker
authors.affiliation: Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, King's College London, London, UK.
authors.forename: D G M
authors.initials: DG
authors.lastname: Murphy
authors.affiliation: Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|National Autism Unit, Bethlem Royal Hospital, SLAM NHS Foundation Trust, London, UK.
authors.forename: M C
authors.initials: MC
authors.lastname: Craig
mesh_terms: D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000000981:diagnostic imaging* / Q000473:pathology*; D016022:Case-Control Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging* / Q000473:pathology*; D012737:Sex Factors; D055815:Young Adult