Shared and Distinct Brain Regions in Anxiety, Depression, and Neuroticism: A Multi-Phenotypic Approach Using Data from the UK Biobank

BackgroundAnxiety and depression are highly comorbid and share common clinical symptoms and etiological factors, particularly through overlapping genetic and environmental risk. Neuroticism strongly correlates with both anxiety and depression, and genetic studies suggest it accounts for a significant portion of the shared genetic risk between these disorders. MethodsThis study used data from 46,541 participants from the UK Biobank with available imaging data including 4,355 with a lifetime anxiety disorder and 8,559 with major depressive disorder to investigate the neuroanatomical correlates of anxiety, depression, and neuroticism with a focus on identifying shared and distinct associated brain regions across these phenotypes. Using structural MRI data, we examined cortical thickness (CT), surface area (SA), and subcortical volume associations with both subscale-specific and full measures of neuroticism and these disorders. ResultsFindings revealed significant associations between anxiety disorders and thinner CT in the left insula, posterior cingulate, and several frontal and temporal regions. Depression was associated with increased right caudate volume, decreased SA in the pericalcarine and cuneus, and thinner lateral occipital and posterior cingulate CT. Neuroticism and its subscales showed more widespread brain involvement, with significant associations in areas including the bilateral caudate, medial orbitofrontal cortex, and precentral gyrus. Notably, neuroticism measures demonstrated stronger associations than diagnosis-specific outcomes, emphasizing the utility of dimensional approaches. Only one significant association (thinner left posterior cingulate) was shared between anxiety and depression, but several trends were observed. ConclusionsOur findings further support a partial neurobiological sharing between anxiety and depression with neuroticism providing a nuanced framework for their connections.