Cahill Stephanie, Chandola Tarani, Hager Reinmar
Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom.
Faculty of Humanities, Cathie Marsh Institute for Social Research, The University of Manchester, Manchester, United Kingdom.
Front Psychiatry. 2022 May 20;13:840120. doi: 10.3389/fpsyt.2022.840120. eCollection 2022.
Resilience is broadly defined as the ability to maintain or regain functioning in the face of adversity and is influenced by both environmental and genetic factors. The identification of specific genetic factors and their biological pathways underpinning resilient functioning can help in the identification of common key factors, but heterogeneities in the operationalisation of resilience have hampered advances. We conducted a systematic review of genetic variants associated with resilience to enable the identification of general resilience mechanisms. We adopted broad inclusion criteria for the definition of resilience to capture both human and animal model studies, which use a wide range of resilience definitions and measure very different outcomes. Analyzing 158 studies, we found 71 candidate genes associated with resilience. OPRM1 (Opioid receptor mu 1), NPY (neuropeptide Y), CACNA1C (calcium voltage-gated channel subunit alpha1 C), DCC (deleted in colorectal carcinoma), and FKBP5 (FKBP prolyl isomerase 5) had both animal and human variants associated with resilience, supporting the idea of shared biological pathways. Further, for OPRM1, OXTR (oxytocin receptor), CRHR1 (corticotropin-releasing hormone receptor 1), COMT (catechol-O-methyltransferase), BDNF (brain-derived neurotrophic factor), APOE (apolipoprotein E), and SLC6A4 (solute carrier family 6 member 4), the same allele was associated with resilience across divergent resilience definitions, which suggests these genes may therefore provide a starting point for further research examining commonality in resilience pathways.
复原力被广泛定义为在面对逆境时维持或恢复功能的能力,它受到环境和遗传因素的影响。确定支撑复原力功能的特定遗传因素及其生物学途径有助于识别共同的关键因素,但复原力操作定义的异质性阻碍了进展。我们对与复原力相关的基因变异进行了系统综述,以确定一般的复原力机制。我们对复原力的定义采用了广泛的纳入标准,以涵盖人类和动物模型研究,这些研究使用了广泛的复原力定义并测量了非常不同的结果。通过分析158项研究,我们发现了71个与复原力相关的候选基因。μ阿片受体1(OPRM1)、神经肽Y(NPY)、电压门控钙通道亚基α1C(CACNA1C)、结直肠癌缺失基因(DCC)和FK506结合蛋白5(FKBP5)既有与复原力相关的动物变异,也有人类变异,这支持了共享生物学途径的观点。此外,对于OPRM1、催产素受体(OXTR)、促肾上腺皮质激素释放激素受体1(CRHR1)、儿茶酚-O-甲基转移酶(COMT)、脑源性神经营养因子(BDNF)、载脂蛋白E(APOE)和溶质载体家族6成员4(SLC6A4),相同的等位基因在不同的复原力定义中都与复原力相关,这表明这些基因可能因此为进一步研究复原力途径的共性提供了一个起点。