Vedechkina Maria, Holmes Joni, Warrier Varun, Astle Duncan E
MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
School of Psychology, University of East Anglia, Norwich, UK.
Transl Psychiatry. 2025 Aug 21;15(1):305. doi: 10.1038/s41398-025-03513-1.
Not everyone is equally likely to experience mental illness. What is the contribution of an individual's genetic background and experiences of childhood adversity to that likelihood? And how do these risk factors interact at the level of the brain? This study explores these questions by investigating the relationship between genetic liability for mental illness, childhood adversity, and cortico-limbic connectivity in a large developmental sample drawn from the ABCD cohort (N = 6535). Canonical Correlation Analysis - a multivariate data-reduction technique - revealed two genetic dimensions of mental illness from the polygenic risk scores for ADHD, Anxiety, Depression, and Psychosis. The first dimension represented liability for broad psychopathology which was positively correlated with adversity. The second dimension represented neurodevelopmental-specific risk which negatively interacted with adversity, suggesting that neurodevelopmental symptoms may arise from unique combinations of genetic and environmental factors that differ from other symptom domains. Next, we investigated the cortico-limbic signature of adversity and genetic liability using Partial Least Squares. We found that the neural correlates of adversity broadly mirrored those of genetic liability, with adversity capturing most of the shared variance. These novel findings suggest that genetic and environmental risk overlap in the neural connections that underlie mental health symptomatology.
并非每个人患精神疾病的可能性都相同。个人的遗传背景和童年逆境经历对这种可能性有何影响？这些风险因素在大脑层面是如何相互作用的？本研究通过调查来自ABCD队列的大量发育样本（N = 6535）中精神疾病的遗传易感性、童年逆境和皮质-边缘连接性之间的关系，探讨了这些问题。典型相关分析——一种多元数据降维技术——从注意力缺陷多动障碍、焦虑症、抑郁症和精神病的多基因风险评分中揭示了精神疾病的两个遗传维度。第一个维度代表广泛精神病理学的易感性，与逆境呈正相关。第二个维度代表神经发育特异性风险，与逆境呈负相互作用，这表明神经发育症状可能源于与其他症状领域不同的遗传和环境因素的独特组合。接下来，我们使用偏最小二乘法研究了逆境和遗传易感性的皮质-边缘特征。我们发现，逆境的神经关联大致反映了遗传易感性的神经关联，逆境捕获了大部分共同方差。这些新发现表明，遗传和环境风险在构成心理健康症状学基础的神经连接中存在重叠。
