Groenman Annabeth P, Greven Corina U, van Donkelaar Marjolein M J, Schellekens Arnt, van Hulzen Kimm J E, Rommelse Nanda, Hartman Catharina A, Hoekstra Pieter J, Luman Marjolein, Franke Barbara, Faraone Stephen V, Oosterlaan Jaap, Buitelaar Jan K
Department of Clinical Neuropsychology, VU University Amsterdam, The Netherlands.
Department of Cognitive Neuroscience, Radboud University Medical Centre Nijmegen, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, The Netherlands.
Addict Biol. 2016 Jul;21(4):915-23. doi: 10.1111/adb.12230. Epub 2015 Mar 6.
Individuals with attention deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders (SUDs) and nicotine dependence. The co-occurrence of ADHD and SUDs/nicotine dependence may in part be mediated by shared genetic liability. Several neurobiological pathways have been implicated in both ADHD and SUDs, including dopamine and serotonin pathways. We hypothesized that variations in dopamine and serotonin neurotransmission genes were involved in the genetic liability to develop SUDs/nicotine dependence in ADHD. The current study included participants with ADHD (n = 280) who were originally part of the Dutch International Multicenter ADHD Genetics study. Participants were aged 5-15 years and attending outpatient clinics at enrollment in the study. Diagnoses of ADHD, SUDs, nicotine dependence, age of first nicotine and substance use, and alcohol use severity were based on semi-structured interviews and questionnaires. Genetic risk scores were created for both serotonergic and dopaminergic risk genes previously shown to be associated with ADHD and SUDs and/or nicotine dependence. The serotonin genetic risk score significantly predicted alcohol use severity. No significant serotonin × dopamine risk score or effect of stimulant medication was found. The current study adds to the literature by providing insight into genetic underpinnings of the co-morbidity of ADHD and SUDs. While the focus of the literature so far has been mostly on dopamine, our study suggests that serotonin may also play a role in the relationship between these disorders.
患有注意力缺陷/多动障碍（ADHD）的个体患物质使用障碍（SUDs）和尼古丁依赖的风险增加。ADHD与SUDs/尼古丁依赖的共病现象可能部分由共同的遗传易感性介导。ADHD和SUDs均涉及多种神经生物学途径，包括多巴胺和5-羟色胺途径。我们假设多巴胺和5-羟色胺神经传递基因的变异与ADHD患者发生SUDs/尼古丁依赖的遗传易感性有关。本研究纳入了最初作为荷兰国际多中心ADHD遗传学研究一部分的ADHD患者（n = 280）。参与者年龄在5至15岁之间，研究入组时在门诊就诊。ADHD、SUDs、尼古丁依赖、首次使用尼古丁和物质的年龄以及酒精使用严重程度的诊断基于半结构化访谈和问卷。为先前已证明与ADHD和SUDs和/或尼古丁依赖相关的5-羟色胺能和多巴胺能风险基因创建了遗传风险评分。5-羟色胺遗传风险评分显著预测了酒精使用严重程度。未发现显著的5-羟色胺×多巴胺风险评分或兴奋剂药物的影响。本研究通过深入了解ADHD和SUDs共病的遗传基础，为文献增添了内容。虽然迄今为止文献的重点主要是多巴胺，但我们的研究表明5-羟色胺在这些疾病之间的关系中也可能起作用。
