Objective

Fundamental questions in biological psychiatry concern the mechanisms that mediate between genetic liability and psychiatric symptoms. Genetic liability for many common psychiatric disorders often confers transdiagnostic risk to develop a wide variety of psychopathological symptoms through yet unknown pathways. This study examined the psychological and cognitive pathways that might mediate the relationship between genetic liability (indexed by polygenic scores; PS) and broad psychopathology (indexed by p factor and its underlying dimensions).

Method

First, which of the common psychiatric PSs (major depressive disorder [MDD], attention-deficit/hyperactivity disorder [ADHD], anxiety, bipolar disorder, schizophrenia, autism) that were associated with p factor were identified. Then focused was shifted to 3 pathways: punishment sensitivity (reflected by behavioral inhibition system), reward sensitivity (reflected by behavioral activation system), and cognitive abilities (reflected by g factor based on 10 neurocognitive tasks). We applied structural equation modeling on the Adolescent Brain Cognitive Development (ABCD) Study dataset (n = 4,814; 2,263 girls; 9-10 years old).

Results

MDD and ADHD PSs were associated with p factor. The association between MDD PS and psychopathology was partially mediated by punishment sensitivity and cognitive abilities (proportion mediated = 22.35%). Conversely, the influence of ADHD PS on psychopathology was partially mediated by reward sensitivity and cognitive abilities (proportion mediated = 30.04%). The mediating role of punishment sensitivity was specific to emotional/internalizing. The mediating role of both reward sensitivity and cognitive abilities was specific to behavioral/externalizing and neurodevelopmental dimensions of psychopathology.

Conclusion

This study provides a better understanding of how genetic risks for MDD and ADHD confer risks for psychopathology and suggests potential prevention/intervention targets for children at risk.

中文翻译：

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动机和认知能力作为多基因评分与儿童精神病理学之间的中介

客观的

生物精神病学中的基本问题涉及在遗传责任和精神症状之间调解的机制。许多常见精神疾病的遗传责任通常会带来跨诊断风险，以通过未知途径发展出多种精神病理学症状。本研究检查了可能介导遗传责任（由多基因评分；PS）和广泛的精神病理学（由p因子及其潜在维度索引）之间关系的心理和认知途径。

方法

首先，确定了哪些与p因子相关的常见精神病学 PS（重度抑郁症 [MDD]、注意力缺陷/多动障碍 [ADHD]、焦虑、双相情感障碍、精神分裂症、自闭症）。然后将注意力转移到3个途径：惩罚敏感性（由行为抑制系统反映）、奖励敏感性（由行为激活系统反映）和认知能力（由基于10个神经认知任务的g因子反映）。我们将结构方程模型应用于青少年大脑认知发展 (ABCD) 研究数据集（n = 4,814；2,263 名女孩；9-10 岁）。

结果

MDD 和 ADHD PSs 与p因子相关。MDD PS与精神病理学之间的关联部分由惩罚敏感性和认知能力介导（比例介导= 22.35％）。相反，ADHD PS 对精神病理学的影响部分由奖励敏感性和认知能力介导（比例介导 = 30.04%）。惩罚敏感性的中介作用特定于情绪化/内化。奖励敏感性和认知能力的中介作用特定于精神病理学的行为/外化和神经发育维度。

结论

这项研究提供了对 MDD 和 ADHD 的遗传风险如何赋予精神病理学风险的更好理解，并为处于风险中的儿童提出了潜在的预防/干预目标。