Institute of Population Health, Department of Psychology, University of Liverpool, Bedford Street South, Liverpool L69 7ZA, United Kingdom.
The Turner Institute for Brain and Mental Health, School of Psychological Sciences, and Monash Biomedical Imaging, Monash University, Melbourne, VIC, Australia.
Dev Cogn Neurosci. 2023 Apr;60:101229. doi: 10.1016/j.dcn.2023.101229. Epub 2023 Mar 15.
In adulthood, stress exposure and genetic risk heighten psychological vulnerability by accelerating neurobiological senescence. To investigate whether molecular and brain network maturation processes play a similar role in adolescence, we analysed genetic, as well as longitudinal task neuroimaging (inhibitory control, incentive processing) and early life adversity (i.e., material deprivation, violence) data from the Adolescent Brain and Cognitive Development study (N = 980, age range: 9-13 years). Genetic risk was estimated separately for Major Depressive Disorder (MDD) and Alzheimer's Disease (AD), two pathologies linked to stress exposure and allegedly sharing a causal connection (MDD-to-AD). Adversity and genetic risk for MDD/AD jointly predicted functional network segregation patterns suggestive of accelerated (GABA-linked) visual/attentional, but delayed (dopamine [D2]/glutamate [GLU5R]-linked) somatomotor/association system development. A positive relationship between brain maturation and psychopathology emerged only among the less vulnerable adolescents, thereby implying that normatively maladaptive neurodevelopmental alterations could foster adjustment among the more exposed and genetically more stress susceptible youths. Transcriptomic analyses suggested that sensitivity to stress may underpin the joint neurodevelopmental effect of adversity and genetic risk for MDD/AD, in line with the proposed role of negative emotionality as a precursor to AD, likely to account for the alleged causal impact of MDD on dementia onset.
在成年期，压力暴露和遗传风险通过加速神经生物学衰老加剧心理脆弱性。为了研究分子和大脑网络成熟过程是否在青少年时期发挥类似作用，我们分析了来自青少年大脑与认知发展研究（N=980，年龄范围：9-13 岁）的遗传、纵向任务神经影像学（抑制控制、激励处理）和早期生活逆境（即物质剥夺、暴力）数据。遗传风险分别针对重度抑郁症（MDD）和阿尔茨海默病（AD）进行估计，这两种病症都与压力暴露有关，据称存在因果关系（MDD 到 AD）。逆境和 MDD/AD 的遗传风险共同预测了功能网络分离模式，提示加速（GABA 相关）视觉/注意力，但延迟（多巴胺 [D2]/谷氨酸 [GLU5R] 相关）躯体运动/联想系统发育。只有在脆弱性较低的青少年中，大脑成熟与精神病理学之间才存在正相关关系，这表明规范上适应不良的神经发育改变可能会促进更多暴露和遗传上更易受压力影响的年轻人的适应。转录组分析表明，对压力的敏感性可能是逆境和 MDD/AD 遗传风险的共同神经发育效应的基础，这与负面情绪作为 AD 前兆的作用一致，可能解释了 MDD 对痴呆发病的所谓因果影响。
