Department of Psychiatry, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Department of Psychological Sciences, University of Missouri, Columbia, MO, USA.
Psychol Med. 2024 Jun;54(8):1533-1543. doi: 10.1017/S0033291723003367. Epub 2023 Nov 29.
Dual-systems models, positing an interaction between two distinct and competing systems (i.e. top-down self-control, and bottom-up reward- or emotion-based drive), provide a parsimonious framework for investigating the interplay between cortical and subcortical brain regions relevant to impulsive personality traits (IPTs) and their associations with psychopathology. Despite recent developments in multivariate analysis of genome-wide association studies (GWAS), molecular genetic investigations of these models have not been conducted.
Using IPT GWAS, we conducted confirmatory genomic structural equation models (GenomicSEM) to empirically evaluate dual-systems models of the genetic architecture of IPTs. Genetic correlations between dual-systems factors and relevant cortical and subcortical neuroimaging phenotypes (regional/structural volume, cortical surface area, cortical thickness) were estimated and compared.
GenomicSEM dual-systems models underscored important sources of shared and unique genetic variance between top-down and bottom-up constructs. Specifically, a dual-systems genomic model consisting of sensation seeking and lack of self-control factors demonstrated distinct but related sources of genetic influences ( = 0.60). Genetic correlation analyses provided evidence of differential associations between dual-systems factors and cortical neuroimaging phenotypes (e.g. lack of self-control negatively associated with cortical thickness, sensation seeking positively associated with cortical surface area). No significant associations were observed with subcortical phenotypes.
Dual-systems models of the genetic architecture of IPTs tested were consistent with study hypotheses, but associations with relevant neuroimaging phenotypes were mixed (e.g. no associations with subcortical volumes). Findings demonstrate the utility of dual-systems models for studying IPT genetic influences, but also highlight potential limitations as a framework for interpreting IPTs as endophenotypes for psychopathology.
双系统模型假设两个不同且相互竞争的系统（即自上而下的自我控制和自下而上的奖励或情绪驱动）之间存在相互作用，为研究与冲动人格特质（IPT）相关的皮质和皮质下脑区之间的相互作用及其与精神病理学的关联提供了一个简洁的框架。尽管全基因组关联研究（GWAS）的多元分析有了最近的发展，但这些模型的分子遗传学研究尚未进行。
使用 IPT GWAS，我们进行了确认性基因组结构方程模型（GenomicSEM），以实证评估 IPT 遗传结构的双系统模型。双系统因素与相关皮质和皮质下神经影像学表型（区域/结构体积、皮质表面积、皮质厚度）之间的遗传相关性进行了估计和比较。
GenomicSEM 双系统模型强调了自上而下和自下而上结构之间共享和独特遗传方差的重要来源。具体来说，由感觉寻求和缺乏自我控制因素组成的双系统基因组模型显示出不同但相关的遗传影响来源（ = 0.60）。遗传相关分析提供了证据，表明双系统因素与皮质神经影像学表型之间存在差异关联（例如，缺乏自我控制与皮质厚度呈负相关，感觉寻求与皮质表面积呈正相关）。与皮质下表型没有观察到显著关联。
所测试的 IPT 遗传结构的双系统模型与研究假设一致，但与相关神经影像学表型的关联是混合的（例如，与皮质下体积没有关联）。研究结果表明，双系统模型在研究 IPT 遗传影响方面具有实用性，但也突出了作为解释 IPT 作为精神病理学的内表型的框架的潜在局限性。
