Abstract:
Schizophrenia is a severe psychiatric disorder, associated with a reduction in life expectancy of 15-20 years. Available treatments are at least partially effective in most affected individuals, and personal resources such as resilience (successful adaptation despite adversity) and coping abilities (strategies used to deal with stressful or threatening situations), are important determinants of disease outcomes and long-term sustained recovery. Published findings support the existence of a genetic background underlying resilience and coping, with variable heritability estimates. However, genome-wide analyses concerning the genetic determinants of these personal resources, especially in the context of schizophrenia, are lacking. Here, we performed a genome-wide association study coupled with accessory analyses to investigate potential genetic determinants of resilience, coping and self-esteem in 490 schizophrenia patients. Results revealed a complex genetic background partly overlapping with that of neuroticism, worry and schizophrenia itself and support the importance of social aspects in shapingthese psychological constructs. Hippocampal neurogenesis and lipid metabolism appear to be potentially relevant biological underpinnings, and specific miRNAs such as miR-124 and miR-137 may warrant further studies as potential biomarkers. In conclusion, this study represents an important first step in the identification of genetic and biological correlates shaping resilience, coping resources and self-esteem in schizophrenia.
摘要:
精神分裂症是一种严重的精神疾病,与预期寿命减少15-20年有关。可用的治疗方法对大多数受影响的个体至少部分有效,和个人资源,如韧性(成功适应逆境)和应对能力(用于应对压力或威胁情况的策略),是疾病结局和长期持续康复的重要决定因素。已发表的研究结果支持韧性和应对能力的遗传背景的存在,具有可变的遗传力估计。然而,关于这些个人资源的遗传决定因素的全基因组分析,尤其是在精神分裂症的背景下,缺乏。这里,我们进行了全基因组关联研究和辅助分析,以调查潜在的弹性遗传决定因素,490例精神分裂症患者的应对和自尊。结果表明,复杂的遗传背景与神经质的遗传背景部分重叠,担心和精神分裂症本身,并支持社会方面在塑造这些心理结构中的重要性。海马神经发生和脂质代谢似乎是潜在相关的生物学基础,和特定的miRNA,如miR-124和miR-137,可能需要进一步研究作为潜在的生物标志物。总之,这项研究代表了识别遗传和生物学相关因素形成弹性的重要的第一步,精神分裂症的应对资源和自尊。