Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, ADHD Clinical Research Network, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany.
Eur Neuropsychopharmacol. 2013 Jun;23(6):479-91. doi: 10.1016/j.euroneuro.2012.07.013. Epub 2012 Aug 30.
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with impairments across the lifespan. The persistence of ADHD is associated with considerable liability to neuropsychiatric co-morbidity such as depression, anxiety and substance use disorder. The substantial heritability of ADHD is well documented and recent genome-wide analyses for risk genes revealed synaptic adhesion molecules (e.g. latrophilin-3, LPHN3; fibronectin leucine-rich repeat transmembrane protein-3, FLRT3), glutamate receptors (e.g. metabotropic glutamate receptor-5, GRM5) and mediators of intracellular signalling pathways (e.g. nitric oxide synthase-1, NOS1). These genes encode principal components of the molecular machinery that connects pre- and postsynaptic neurons, facilitates glutamatergic transmission, controls synaptic plasticity and empowers intersecting neural circuits to process and refine information. Thus, identification of genetic variation affecting molecules essential for the formation, specification and function of excitatory synapses is refocusing research efforts on ADHD pathogenesis to include the long-neglected glutamate system.
注意缺陷多动障碍（ADHD）是一种常见的神经发育障碍，其影响贯穿整个生命周期。ADHD 的持续存在与神经精神共病（如抑郁症、焦虑症和物质使用障碍）有很大的关联性。ADHD 的大量遗传性已得到充分证明，最近针对风险基因的全基因组分析显示了突触黏附分子（例如拉普罗林-3，LPHN3；纤维连接蛋白富含亮氨酸重复跨膜蛋白-3，FLRT3）、谷氨酸受体（例如代谢型谷氨酸受体-5，GRM5）和细胞内信号通路的介质（例如一氧化氮合酶-1，NOS1）。这些基因编码了连接前突触和后突触神经元、促进谷氨酸能传递、控制突触可塑性并使交叉神经网络能够处理和完善信息的分子机制的主要成分。因此，识别影响形成、特异性和兴奋性突触功能的关键分子的遗传变异，将重新聚焦 ADHD 发病机制的研究，包括长期被忽视的谷氨酸系统。
