Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea.
Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Apr 20;91:4-13. doi: 10.1016/j.pnpbp.2018.03.009. Epub 2018 Mar 10.
The etiology of depression is characterized by the interplay of genetic and environmental factors and brain structural alteration. Childhood adversity is a major contributing factor in the development of depression. Interactions between childhood adversity and candidate genes for depression could affect brain morphology via the modulation of neurotrophic factors, serotonergic neurotransmission, or the hypothalamus-pituitary-adrenal (HPA) axis, and this pathway may explain the subsequent onset of depression. Childhood adversity is associated with structural changes in the hippocampus, amygdala, anterior cingulate cortex (ACC), and prefrontal cortex (PFC), as well as white matter tracts such as the corpus callosum, cingulum, and uncinate fasciculus. Childhood adversity showed an interaction with the brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism, serotonin transporter-linked promoter region (5-HTTLPR), and FK506 binding protein 51 (FKBP5) gene rs1360780 in brain morphologic changes in patients with depression and in a non-clinical population. Individuals with the Met allele of BDNF Val66Met and a history of childhood adversity had reduced volume in the hippocampus and its subfields, amygdala, and PFC and thinner rostral ACC in a study of depressed patients and healthy controls. The S allele of 5-HTTLPR combined with exposure to childhood adversity or a poorer parenting environment was associated with a smaller hippocampal volume and subsequent onset of depression. The FKBP5 gene rs160780 had a significant interaction with childhood adversity in the white matter integrity of brain regions involved in emotion processing. This review identified that imaging genetic studies on childhood adversity may deepen our understanding on the neurobiological background of depression by scrutinizing complicated pathways of genetic factors, early psychosocial environments, and the accompanying morphologic changes in emotion-processing neural circuitry.
抑郁症的病因特点是遗传和环境因素相互作用以及大脑结构改变。童年逆境是抑郁症发展的主要促成因素。童年逆境与抑郁症候选基因之间的相互作用可能通过调节神经营养因子、5-羟色胺能神经传递或下丘脑-垂体-肾上腺 (HPA) 轴来影响大脑形态，并通过这种途径来解释随后发生的抑郁症。童年逆境与海马体、杏仁核、前扣带回皮质 (ACC) 和前额叶皮质 (PFC) 以及胼胝体、扣带和钩束等白质束的结构变化有关。童年逆境与脑源性神经营养因子 (BDNF) Val66Met 多态性、5-羟色胺转运体相关启动子区 (5-HTTLPR) 和 FK506 结合蛋白 51 (FKBP5) 基因 rs1360780 相互作用，影响抑郁患者和非临床人群的大脑形态变化。BDNF Val66Met 基因的 Met 等位基因和有童年逆境史的个体，其海马体及其亚区、杏仁核和前额叶皮质的体积减小，在抑郁患者和健康对照组中，额极 ACC 的前部变薄。5-HTTLPR 的 S 等位基因与童年逆境或较差的养育环境相结合，与海马体体积减小和随后发生的抑郁症有关。FKBP5 基因 rs160780 与童年逆境在参与情绪处理的脑区白质完整性方面存在显著相互作用。本综述认为，对童年逆境的影像学遗传学研究通过仔细研究遗传因素、早期心理社会环境和伴随的情绪处理神经回路的形态变化等复杂途径，可能加深我们对抑郁症神经生物学背景的理解。
