title: A functional polymorphism of the brain derived neurotrophic factor gene and cortical anatomy in autism spectrum disorder.
abstract: Autism Spectrum Disorder (ASD) is associated with both (i) post-mortem and neuroimaging evidence of abnormal cortical development, and (ii) altered signalling in Brain Derived Neurotrophic Factor (BDNF) pathways - which regulate neuroproliferative and neuroplastic processes. In healthy controls genotype at a single nucleotide polymorphism that alters BDNF signalling (Val66met) has been related to regional cortical volume. It is not known however if this influence on brain development is intact in ASD. Therefore we compared the relationship between genotype and cortical anatomy (as measured using in vivo Magnetic Resonance Imaging) in 41 people with ASD and 30 healthy controls. We measured cortical volume, and its two sole determinants - cortical thickness and surface area - which reflect differing neurodevelopmental processes. We found "Group-by-Genotype" interactions for cortical volume in medial (caudal anterior cingulate, posterior cingulate) and lateral (rostral middle, lateral orbitofrontal, pars orbitalis and pars triangularis) frontal cortices. Furthermore, within (only) these regions "Group-by-Genotype" interactions were also found for surface area. No effects were found for cortical thickness in any region. Our preliminary findings suggest that people with ASD have differences from controls in the relationship between BDNF val66met genotype and regional (especially frontal) cortical volume and surface area, but not cortical thickness. Therefore alterations in the relationship between BDNF val66met genotype and surface area in ASD may drive the findings for volume. If correct, this suggests ASD is associated with a distorted relationship between BDNF val66met genotype and the determinants of regional cortical surface area - gyrification and/or sulcal positioning.
authors.affiliation: Department of Child and Adolescent Psychiatry, Institute of Psychiatry (IOP), Kings College London (KCL), 16 De Crespigny Park, London, SE5 8AF, UK, armin.raznahan@iop.kcl.ac.uk.
authors.forename: Armin
authors.initials: A
authors.lastname: Raznahan
authors.forename: Roberto
authors.initials: R
authors.lastname: Toro
authors.forename: Petra
authors.initials: P
authors.lastname: Proitsi
authors.forename: John
authors.initials: J
authors.lastname: Powell
authors.forename: Tomas
authors.initials: T
authors.lastname: Paus
authors.forename: Patrick
authors.initials: P
authors.lastname: F Bolton
authors.forename: Declan G M
authors.initials: DG
authors.lastname: Murphy