Department of Child and Adolescent Psychiatry, Institute of Psychiatry (IOP), Kings College London (KCL), 16 De Crespigny Park, London, SE5 8AF, UK,
J Neurodev Disord. 2009 Sep;1(3):215-23. doi: 10.1007/s11689-009-9012-0. Epub 2009 May 14.
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.
自闭症谱系障碍（ASD）与（i）死后和神经影像学证据表明皮质发育异常，以及（ii）脑源性神经营养因子（BDNF）途径中的信号改变有关 - 这些途径调节神经增殖和神经可塑性过程。在健康对照组中，单核苷酸多态性改变 BDNF 信号（Val66met）的基因型与区域皮质体积有关。然而，目前尚不清楚这种对大脑发育的影响在 ASD 中是否完整。因此，我们比较了 41 名 ASD 患者和 30 名健康对照组的基因型与皮质解剖结构（通过体内磁共振成像测量）之间的关系。我们测量了皮质体积及其两个唯一决定因素 - 皮质厚度和表面积 - 它们反映了不同的神经发育过程。我们发现皮质体积在中线（尾侧前扣带回、后扣带回）和外侧（额中回、外侧眶额回、眶部和三角部）额叶皮质中存在“组 - 基因型”相互作用。此外，仅在这些区域中还发现了“组 - 基因型”相互作用的表面积。在任何区域都没有发现皮质厚度的影响。我们的初步研究结果表明，ASD 患者的 BDNF val66met 基因型与区域（特别是额叶）皮质体积和表面积之间的关系与对照组存在差异，但皮质厚度没有差异。因此，ASD 中 BDNF val66met 基因型与表面积之间关系的改变可能导致了体积的发现。如果正确，这表明 ASD 与 BDNF val66met 基因型与区域皮质表面积的决定因素（脑回和/或脑沟位置）之间的扭曲关系有关。
