Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remain uncer­tain. We conducted a “meta-umbrella” systematic synthesis of umbrella reviews, which are systematic reviews of meta-analyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on non-purely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convincing), class II (highly suggestive), class III (suggestive), class IV (weak). Sensitivity analyses were conducted on prospective studies to test for temporality (reverse causation), TRANSD criteria were applied to test transdiagnosticity of factors, and A Measurement Tool to Assess Systematic Reviews (AMSTAR) was employed to address the quality of meta-analyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 meta-analyses and 1,180 associations between putative risk or protective factors and mental disorders. We included 176 class I to III evidence associations, relating to 142 risk/protective factors. The most robust risk factors (class I or II, from prospective designs) were 21. For dementia, they included type 2 diabetes mellitus (risk ratio, RR from 1.54 to 2.28), depression (RR from 1.65 to 1.99) and low frequency of social contacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For non-organic psychotic disorders, the most robust risk factors were clinical high risk state for psychosis (OR=9.32), cannabis use (OR=3.90), and childhood adversities (OR=2.80). For depressive disorders, they were widowhood (RR=5.59), sexual dysfunction (OR=2.71), three (OR=1.99) or four-five (OR=2.06) metabolic factors, childhood physical (OR=1.98) and sexual (OR=2.42) abuse, job strain (OR=1.77), obesity (OR=1.35), and sleep disturbances (RR=1.92). For autism spectrum disorder, the most robust risk factor was maternal overweight pre/during pregnancy (RR=1.28). For attention-deficit/hyperactivity disorder (ADHD), they were maternal pre-pregnancy obesity (OR=1.63), maternal smoking during pregnancy (OR=1.60), and maternal overweight pre/during pregnancy (OR=1.28). Only one robust protective factor was detected: high physical activity (hazard ratio, HR=0.62) for Alzheimer’s disease. In all, 32.9% of the associations were of high quality, 48.9% of medium quality, and 18.2% of low quality. Transdiagnostic class I-III risk/protective factors were mostly involved in the early neurodevelopmental period. The evidence-based atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expanding early intervention and preventive strategies for mental disorders.

中文翻译：

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遗传以外的精神障碍的风险和保护因素：循证图谱


数十年的研究揭示了遗传以外的许多精神障碍危险因素，但其一致性和严重程度仍不确定。我们通过检索从成立到 2021 年 1 月 1 日的国际数据库，对伞式综述进行了“元伞”系统综合，这些伞式综述是对个别研究的荟萃分析的系统综述。我们纳入了关于非纯粹遗传风险或保护性的伞式综述。任何 ICD/DSM 精神障碍的因素，应用证据可信度的既定分类：I 类（令人信服）、II 类（高度暗示性）、III 类（暗示性）、IV 类（弱）。对前瞻性研究进行敏感性分析以测试时间性（反向因果关系），应用 TRANSD 标准来测试因素的跨诊断性，并采用评估系统评价的测量工具（AMSTAR）来解决荟萃分析的质量。检索了 14 篇符合条件的总体综述，总结了 390 项荟萃分析以及假定的风险或保护因素与精神障碍之间的 1,180 种关联。我们纳入了 176 个 I 至 III 级证据关联，涉及 142 个风险/保护因素。最稳健的危险因素（I 类或 II 类，来自前瞻性设计）为 21 个。对于痴呆症，它们包括 2 型糖尿病（风险比，RR 从 1.54 到 2.28）、抑郁症（RR 从 1.65 到 1.99）和低频率社会交往（RR=1.57）。对于阿片类药物使用障碍，最有力的危险因素是吸烟（比值比，OR=3.07）。对于非器质性精神病，最重要的危险因素是精神病的临床高风险状态（OR=9.32）、大麻使用（OR=3.90）和童年不幸（OR=2.80）。对于抑郁症，她们是丧偶（RR = 5。59)、性功能障碍(OR=2.71)、三项(OR=1.99)或四五项(OR=2.06)代谢因素、儿童身体虐待(OR=1.98)和性虐待(OR=2.42)、工作压力(OR= 1.77）、肥胖（OR=1.35）和睡眠障碍（RR=1.92）。对于自闭症谱系障碍，最强有力的危险因素是母亲怀孕前/怀孕期间超重（RR = 1.28）。对于注意力缺陷/多动障碍（ADHD），它们是母亲孕前肥胖（OR=1.63）、母亲怀孕期间吸烟（OR=1.60）和母亲孕前/怀孕期间超重（OR=1.28）。仅检测到一种强有力的保护因素：阿尔茨海默病的高体力活动（风险比，HR=0.62）。总体而言，高质量的协会占 32.9%，中等质量的协会占 48.9%，低质量的协会占 18.2%。跨诊断I-III类风险/保护因素主要涉及神经发育早期。本研究中确定的关键风险和保护因素的循证图谱为推进临床特征和研究以及扩大精神障碍的早期干预和预防策略提供了基准。