Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznań, Poland.
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznań, Poland.
Pharmacol Rep. 2019 Feb;71(1):112-120. doi: 10.1016/j.pharep.2018.10.004. Epub 2018 Oct 11.
A contemporary model for the pathogenesis of mood disorders (bipolar and depressive disorders) involves gene-environmental interaction, with genetic predisposition, epigenetic regulation, and environmental effects. Among multiple environmental factors, the experience of childhood trauma can be connected with the pathogenesis, course and the treatment of mood disorders. Patients with mood disorders have the greater frequency of childhood trauma compared with the general population, and adverse childhood experiences can exert a negative impact on their clinical course. In this article, the neurobiological mechanisms of childhood trauma are presented. The influence of negative childhood experiences on the central nervous system can result in many structural and functional changes of the brain, including such structures as hippocampus and amygdala, associated with the development of bipolar and depressive illnesses. Interaction of several genes with childhood trauma to produce pathological, clinical phenomena in adulthood has been demonstrated, the most important in this respect being the serotonin transporter gene and the FKBP5 gene playing an important role in the pathogenesis of mood disorders. Neurobiological effects can also involve epigenetic mechanisms such as DNA methylation which can exert an effect on brain function over long-term periods. Somatic effects of childhood trauma include disturbances of stress axis and immune-inflammatory mechanisms as well as metabolic dysregulation. Negative childhood experiences may also bear implications for the treatment of mood disorders. In the article, the impact of such experiences on the treatment of mood disorders will be discussed, especially in the context of treatment -resistance to antidepressants and mood-stabilizing drugs.
当代心境障碍（双相及抑郁障碍）发病机制的模型涉及基因-环境相互作用，包括遗传易感性、表观遗传调控和环境影响。在多种环境因素中，童年创伤经历与心境障碍的发病机制、病程和治疗有关。心境障碍患者的童年创伤频率高于一般人群，不良的童年经历会对其临床病程产生负面影响。本文介绍了童年创伤的神经生物学机制。负面童年经历对中枢神经系统的影响可导致大脑的许多结构和功能发生变化，包括海马体和杏仁核等结构，这些变化与双相和抑郁障碍的发生发展有关。已经证明，一些基因与童年创伤相互作用会导致成年后出现病理性临床现象，其中最重要的是 5-羟色胺转运体基因和 FKBP5 基因，它们在心境障碍的发病机制中发挥着重要作用。神经生物学效应还涉及表观遗传机制，如 DNA 甲基化，它可以对大脑功能产生长期影响。童年创伤的躯体效应包括应激轴和免疫炎症机制以及代谢失调的紊乱。童年创伤经历也可能对心境障碍的治疗产生影响。本文将讨论这些经历对心境障碍治疗的影响，特别是在抗抑郁药和心境稳定剂治疗抵抗的背景下。
