Fabbri Chiara, Serretti Alessandro
Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Clin Psychopharmacol Neurosci. 2020 Nov 30;18(4):484-492. doi: 10.9758/cpn.2020.18.4.484.
Depression is the single largest contributor to non-fatal health loss and affects 322 million people globally. The clinical heterogeneity of this disorder shows biological correlates and it makes the personalization of antidepressant prescription an important pillar of treatment. There is increasing evidence of genetic overlap between depression, other psychiatric and non-psychiatric disorders, which varies across depression subtypes. Therefore, the first step of clinical evaluation should include a careful assessment of psychopathology and physical health, not limited to previously diagnosed disorders. In part of the patients indeed the pathogenesis of depression may be strictly linked to inflammatory and metabolic abnormalities, and the treatment should target these as much as the depressive symptoms themselves. When the evaluation of the symptom and drug tolerability profile, the concomitant biochemical abnormalities and physical conditions is not enough and at least one pharmacotherapy failed, the genotyping of variants in (cytochromes responsible for antidepressant metabolism) should be considered. Individuals with altered metabolism through one of these enzymes may benefit from some antidepressants rather than others or need dose adjustments. Finally, if available, the polygenic predisposition towards cardio-metabolic disorders can be integrated with non-genetic risk factors to tune the identification of patients who should avoid medications associated with this type of side effects. A sufficient knowledge of the polygenic risk of complex medical and psychiatric conditions is becoming relevant as this information can be obtained through direct-to-consumer genetic tests and in the future it may provided by national health care systems.
抑郁症是导致非致命性健康损失的最大单一因素，全球有3.22亿人受其影响。这种疾病的临床异质性显示出生物学相关性，这使得抗抑郁药处方的个性化成为治疗的重要支柱。越来越多的证据表明，抑郁症与其他精神疾病和非精神疾病之间存在基因重叠，且这种重叠在不同的抑郁症亚型中有所不同。因此，临床评估的第一步应包括对精神病理学和身体健康的仔细评估，而不仅限于先前诊断出的疾病。实际上，部分患者抑郁症的发病机制可能与炎症和代谢异常密切相关，治疗应在针对抑郁症状本身的同时，尽可能针对这些异常。当对症状和药物耐受性、伴随的生化异常和身体状况的评估不足，且至少一种药物治疗失败时，应考虑对（负责抗抑郁药代谢的细胞色素）变体进行基因分型。通过这些酶之一代谢发生改变的个体可能从某些抗抑郁药中获益更多，而对其他药物则不然，或者需要调整剂量。最后，如果可行，可以将心血管代谢疾病的多基因易感性与非基因风险因素相结合，以优化对应避免使用与此类副作用相关药物的患者的识别。随着可以通过直接面向消费者的基因检测获得此类信息，并且未来可能由国家医疗保健系统提供，充分了解复杂医学和精神疾病的多基因风险正变得越来越重要。
