Departments of Cognitive Neuroscience and Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 EN, Nijmegen, The Netherlands.
Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
Mol Psychiatry. 2022 Jan;27(1):38-48. doi: 10.1038/s41380-021-01031-2. Epub 2021 Feb 1.
Different psychiatric disorders and symptoms are highly correlated in the general population. A general psychopathology factor (or "P-factor") has been proposed to efficiently describe this covariance of psychopathology. Recently, genetic and neuroimaging studies also derived general dimensions that reflect densely correlated genomic and neural effects on behaviour and psychopathology. While these three types of general dimensions show striking parallels, it is unknown how they are conceptually related. Here, we provide an overview of these three general dimensions, and suggest a unified interpretation of their nature and underlying mechanisms. We propose that the general dimensions reflect, in part, a combination of heritable 'environmental' factors, driven by a dense web of gene-environment correlations. This perspective calls for an update of the traditional endophenotype framework, and encourages methodological innovations to improve models of gene-brain-environment relationships in all their complexity. We propose concrete approaches, which by taking advantage of the richness of current large databases will help to better disentangle the complex nature of causal factors underlying psychopathology.
在普通人群中,不同的精神障碍和症状高度相关。有人提出了一种一般精神病理学因素(或“P 因素”),以有效地描述精神病理学的这种协方差。最近,遗传和神经影像学研究也得出了反映行为和精神病理学上基因组和神经效应高度相关的一般维度。虽然这三种类型的一般维度显示出惊人的相似之处,但它们在概念上是如何相关的尚不清楚。在这里,我们概述了这三种一般维度,并提出了对其性质和潜在机制的统一解释。我们提出,一般维度在一定程度上反映了由密集的基因-环境相关网络驱动的可遗传“环境”因素的组合。这种观点要求更新传统的内表型框架,并鼓励采用创新的方法来改进所有复杂性的基因-大脑-环境关系模型。我们提出了具体的方法,通过利用当前大型数据库的丰富性,将有助于更好地区分精神病理学潜在因果因素的复杂性质。