Abstract
Insomnia disorder, major depressive disorder and anxiety disorders are the most common mental health conditions, often co-occurring and sharing genetic risk factors, suggesting possible common brain mechanisms. Here we analyzed multimodal magnetic resonance imaging data from over 25,604 UK Biobank participants to identify shared versus symptom-specific brain features associated with symptom severity of these disorders. Smaller total cortical surface area, smaller thalamic volumes and weaker functional connectivity were linked to more severe symptoms of all three disorders. Disorder-specific symptom severity associations were also observed: smaller reward-related subcortical regions were associated with more severe insomnia symptoms; thinner cortices in language, reward and limbic regions with more severe depressive symptoms; and weaker amygdala reactivity and functional connectivity of dopamine-, glutamate- and histamine-enriched regions with more severe anxiety symptoms. These symptom-specific associations were often in parts of the amygdala-hippocampal-medial prefrontal circuit, highlighting the interconnectedness of these disorders and suggesting new pathways for research and treatment.