King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, Centre for Affective Disorders, London, United Kingdom; University of Zurich, Institute of Psychology, Clinical Psychology and Psychotherapy, Zurich, Switzerland.
University of Zurich, Institute of Psychology, Clinical Psychology and Psychotherapy, Zurich, Switzerland; University of Zurich, University Research Priority Program (URPP) Dynamics of Healthy Aging, Zurich, Switzerland.
Neurosci Biobehav Rev. 2019 Jan;96:182-196. doi: 10.1016/j.neubiorev.2018.11.009. Epub 2018 Nov 19.
Around 50% of depressed patients do not respond to antidepressants. Evidence from familial studies suggests a genetic component to this. This study investigated whether patients with polymorphisms in genes related to the hypothalamic-pituitary-adrenal (HPA) axis were less likely to respond to antidepressants.
EMBASE, MEDLINE, PsycINFO, and the Cochrane Library were searched. Inclusionary criteria were: 1) patients with depression, 2) study of HPA axis-related candidate genes, 3) at least four weeks of antidepressants, and 4) assessment of depressive symptoms dividing patients into non-responders and responders.
Nineteen studies were identified. Non-responders and responders did not differ in single nucleotide polymorphisms (SNPs) in genes encoding arginine vasopressin. Findings were equivocal regarding genes encoding the FK506 binding protein 5 and glucocorticoid and mineralocorticoid receptors. Specific SNPs and haplotypes within genes related to corticotropin-releasing hormone (CRHBP, CRHR1) and melanocortins (POMC) predicted non-responder status.
Replication studies and additional investigations exploring gene x environment and drug x environment interactions are necessary before pharmacological treatments may be adjusted based on a patient's genetic profile.
约 50%的抑郁症患者对抗抑郁药没有反应。家族研究的证据表明，这与遗传因素有关。本研究调查了与下丘脑-垂体-肾上腺 (HPA) 轴相关的基因多态性患者是否不太可能对抗抑郁药产生反应。
检索了 EMBASE、MEDLINE、PsycINFO 和 Cochrane 图书馆。纳入标准为：1）抑郁症患者，2）研究 HPA 轴相关候选基因，3）使用抗抑郁药至少四周，4）评估抑郁症状将患者分为无反应者和有反应者。
确定了 19 项研究。在编码血管加压素的基因中的单核苷酸多态性 (SNP) 中，无反应者和有反应者没有差异。关于编码 FK506 结合蛋白 5 和糖皮质激素和盐皮质激素受体的基因，结果存在争议。与促肾上腺皮质激素释放激素 (CRHBP、CRHR1) 和黑色素皮质素 (POMC) 相关基因内的特定 SNP 和单倍型预测了无反应状态。
在根据患者的遗传特征调整药物治疗之前，有必要进行复制研究和进一步的研究，以探索基因 x 环境和药物 x 环境的相互作用。
