Neural signatures of major depressive, anxiety, and stress-related disorders

Some fascintating observation from Zhukovsky et al.,  (open source, nice graphics of brain imaging results) who find that major depressive and anxiety disorders share functional and structural neural signatures, but stress-related disorders are distinct from these. Also, better cognitive function is associated with lower connectivity of specific nodes of the default mode and frontoparietal networks.

Significance

Major depressive, anxiety, and stress-related disorders are highly comorbid and may affect similar neurocircuitry and cognitive processes. However, the neurocircuitry underlying shared dimensions of cognitive impairment is unclear and holds the promise of reimagining psychiatric nosology. Here we leverage population imaging data (n = 27,132) to show that while major depressive and anxiety disorders share functional and structural neural signatures, stress-related disorders are distinct from these two conditions. We report that better cognitive function is associated with lower connectivity of specific nodes of the default mode and frontoparietal networks. These findings provide population benchmarks for brain–cognition associations in healthy participants and those with lifetime major depressive and anxiety disorders, advancing our understanding of intrinsic brain networks underlying cognitive dysfunction.

Abstract

The extent of shared and distinct neural mechanisms underlying major depressive disorder (MDD), anxiety, and stress-related disorders is still unclear. We compared the neural signatures of these disorders in 5,405 UK Biobank patients and 21,727 healthy controls. We found the greatest case–control differences in resting-state functional connectivity and cortical thickness in MDD, followed by anxiety and stress-related disorders. Neural signatures for MDD and anxiety disorders were highly concordant, whereas stress-related disorders showed a distinct pattern. Controlling for cross-disorder genetic risk somewhat decreased the similarity between functional neural signatures of stress-related disorders and both MDD and anxiety disorders. Among cases and healthy controls, reduced within-network and increased between-network frontoparietal and default mode connectivity were associated with poorer cognitive performance (processing speed, attention, associative learning, and fluid intelligence). These results provide evidence for distinct neural circuit function impairments in MDD and anxiety disorders compared to stress disorders, yet cognitive impairment appears unrelated to diagnosis and varies with circuit function.