精神药理影像遗传学研究进展及其临床应用前景

Research Progress and Clinical Application of Psychiatric Imaging Pharmacogenomics

精神疾病危害严重,其发病机制复杂难解,临床治疗效果不一,且存在明显的个体差异.近期精准医学研究发现精神药物作用于脑神经的生化过程受到遗传多态性的影响.本文从五羟色胺能、去甲肾上腺素能和多巴胺能三大系统入手,系统综述精神药理影像遗传学的相关研究进展,深入探讨精神药理的神经作用机制以及药物-基因-脑之间的交互作用.我们发现:SLC6A4、BDNF、FKBP5、COMT和多巴胺相关受体等基因多态性与多种精神疾病的发生发展及其治疗效果具有一定的相关性,可能成为相关精神疾病诊断的候选基因.杏仁核、海马、眶额叶、扣带回和前额叶等皮层与皮层下脑结构可能是不同神经递质相关的基因多态性影响精神药物生化作用过程的关键靶点脑区.在建立精神药物-基因-脑影像-行为的因果链中,仍然存在很多相互矛盾的结果和一定的局限性.因此,开展同质性强的临床试验、研究表观遗传作用等可以作为未来的研究发展趋势.

Although the harm of mental illness is serious, its pathogenesis remains unclear, clinical treatment is not effective, and there are obvious individual differences. Recent precision medical research has discovered the role of gene polymorphism in the individualized treatment of drugs. Based on the three major systems of serotonin, norepinephrine and dopaminergic, this article systematically reviewed the research progress of psychiatric pharmacogenomics and imaging pharmacogenomics studies, and explored in depth the mechanism of action of the brain, the mechanism of drug action, and gene-drug-brain interactions. We found that genetic polymorphisms such as SLC6A4, BDNF, FKBP5, COMT, and dopamine-related receptors were found to correlate with the occurrence of multiple mental disorders and the efficacy of antidepressant treatment, and consequently may be candidates for the diagnosis of related mental disorders. The cortical and subcortical brain regions including the amygdala, the hippocampus, the orbitofrontal cortex, the anterior cingulate cortex and the prefrontal lobe may be the key targets of the effect of different neurotransmitter gene polymorphisms on the biochemical process of psychotropic drugs. These related important brain areas may become biological markers for the diagnosis and treatment of related mental disorders. However, in the establishment of psychotropic drug-geneneuroimaging-behavior causal chain, there are still many contradictory results and limitations. Therefore, the studies on homogenous clinical trials and epigenetic effects can be recommended as future research trends.