From the Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; the Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands; the Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; the Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, the Netherlands; the Departments of Psychiatry and Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.; the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands; and the Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, the Netherlands.
Am J Psychiatry. 2015 Aug 1;172(8):768-75. doi: 10.1176/appi.ajp.2015.14081035. Epub 2015 May 22.
The serotonin transporter 5-HTTLPR genotype has been found to moderate the effect of stress on severity of attention deficit hyperactivity disorder (ADHD), with stronger effects of stress in carriers of the short allele than in individuals homozygous for the long allele. The underlying neurobiological mechanism of this gene-environment interaction in ADHD is unknown. The authors aimed to determine whether 5-HTTLPR moderates the effect of stress on brain gray matter volume and, if so, which brain regions mediate the effect of this gene-environment interaction on ADHD severity.
Structural MRI, 5-HTTLPR genotype, and stress exposure questionnaire data were available for 701 adolescents and young adults participating in the multicenter ADHD cohort NeuroIMAGE study (from 385 families; 291 with ADHD, 78 with subthreshold ADHD, 332 healthy comparison subjects; 55.8% male; average age: 17.0 years). ADHD symptom count was determined through multi-informant questionnaires. For the analysis, a whole-brain voxel-based morphometry approach was combined with mediation analysis.
Stress exposure was associated with significantly less gray matter volume in the precentral gyrus, middle and superior frontal gyri, frontal pole, and cingulate gyrus in S-allele carriers compared with participants homozygous for the l-allele. The association of this gene-environment interaction with ADHD symptom count was mediated by gray matter volume in the frontal pole and anterior cingulate gyrus.
5-HTTLPR genotype moderates the effect of stress on brain regions involved in social cognitive processing and cognitive control. Specifically, regions important for cognitive control link this gene-environment interaction to ADHD severity.
已发现 5-羟色胺转运体 5-HTTLPR 基因型可调节应激对注意缺陷多动障碍（ADHD）严重程度的影响，短等位基因携带者的应激影响大于长等位基因纯合子个体。ADHD 中这种基因-环境相互作用的潜在神经生物学机制尚不清楚。作者旨在确定 5-HTTLPR 是否调节应激对大脑灰质体积的影响，如果是，哪些脑区介导这种基因-环境相互作用对 ADHD 严重程度的影响。
结构磁共振成像、5-HTTLPR 基因型和应激暴露问卷数据可用于参加多中心 ADHD 队列神经影像研究的 701 名青少年和年轻人（来自 385 个家庭；291 名 ADHD，78 名亚临床 ADHD，332 名健康对照；55.8%为男性；平均年龄：17.0 岁）。ADHD 症状计数通过多信息问卷确定。对于分析，采用全脑基于体素的形态计量学方法结合中介分析。
应激暴露与 S-等位基因携带者的中央前回、额中回和额上回、额极和扣带回灰质体积明显减少相关，而与 l-等位基因纯合子参与者相比。这种基因-环境相互作用与 ADHD 症状计数的关联由额极和前扣带回的灰质体积介导。
5-HTTLPR 基因型调节应激对参与社会认知处理和认知控制的大脑区域的影响。具体来说，对认知控制很重要的区域将这种基因-环境相互作用与 ADHD 的严重程度联系起来。
