Pinto Rebecca, Rijsdijk Fruhling, Ouellet-Morin Isabelle, Asherson Philip, McLoughlin Grainne, Kuntsi Jonna
King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
School of Criminology, University of Montréal, Research Centre of the Montreal Mental Health University Institute and the Research Group on Child Maladjustment, Montreal, Canada.
J Neural Transm (Vienna). 2016 Aug;123(8):991-1000. doi: 10.1007/s00702-016-1534-5. Epub 2016 Apr 22.
Attention-deficit/hyperactivity disorder (ADHD) has been linked to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, indexed by salivary cortisol. The phenotypic and aetiological association of cortisol productivity with ADHD was investigated. A selected twin design using 68 male twin-pairs aged 12-15, concordant or discordant for high ADHD symptom scores, or control twin-pairs with low ADHD symptoms, based on developmentally stable parental ADHD ratings. A genetic growth curve model was applied to cortisol samples obtained across three points during a cognitive-electroencephalography assessment, to examine the aetiological overlap of ADHD affection status (high versus low ADHD symptom scores) with latent intercept and slope factors. A significant phenotypic correlation emerged between ADHD and the slope factor, with cortisol levels dropping faster for the group with high ADHD symptom scores. The analyses further suggested this overlap was mostly driven by correlated genetic effects. We identified change in cortisol activity over time as significantly associated with ADHD affection status, primarily explained by shared genetic effects, suggesting that blunted cortisol productivity can be a marker of genetic risk in ADHD.
注意力缺陷多动障碍(ADHD)与下丘脑-垂体-肾上腺(HPA)轴功能失调有关,唾液皮质醇可作为该轴功能失调的指标。本研究调查了皮质醇分泌与ADHD的表型及病因学关联。采用特定的双生子设计,选取了68对12至15岁的男性双生子,根据父母对其ADHD症状的稳定评估,分为ADHD症状评分高的同病或异病双生子对,以及ADHD症状低的对照双生子对。应用遗传生长曲线模型对认知脑电图评估期间三个时间点采集的皮质醇样本进行分析,以检验ADHD患病状态(高ADHD症状评分与低ADHD症状评分)与潜在截距和斜率因子的病因学重叠情况。ADHD与斜率因子之间出现了显著的表型相关性,ADHD症状评分高的组皮质醇水平下降更快。分析进一步表明,这种重叠主要由相关的遗传效应驱动。我们发现,随着时间推移皮质醇活性的变化与ADHD患病状态显著相关,主要由共享的遗传效应解释,这表明皮质醇分泌减弱可能是ADHD遗传风险的一个标志。