Dopamine (DA) neurons in the ventral tegmental area (VTA) help mediate stress susceptibility and resilience. However, upstream mechanisms controlling these neurons remain unknown. Noradrenergic (NE) neurons in the locus coeruleus, implicated in the pathophysiology of depression, have direct connections within the VTA. Here we demonstrate that NE neurons regulate vulnerability to social defeat through inhibitory control of VTA DA neurons.

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BACKGROUND: There is growing recognition that connectome architecture shapes cortical and subcortical gray matter atrophy across a spectrum of neurological and psychiatric diseases. Whether connectivity contributes to tissue volume loss in schizophrenia in the same manner remains unknown. METHODS: Here, we relate tissue volume loss in patients with schizophrenia to patterns of structural and functional connectivity. Gray matter deformation was estimated in a sample of 133 individuals with chronic schizophrenia (48 women, mean age 34.7 6 12.9 years) and 113 control subjects (64 women, mean age 23.5 6 8.4 years). Deformation-based morphometry was used to estimate cortical and subcortical gray matter deformation from T1-weighted magnetic resonance images. Structural and functional connectivity patterns were derived from an independent sample of 70 healthy participants using diffusion spectrum imaging and resting-state functional magnetic resonance imaging. RESULTS: We found that regional deformation is correlated with the deformation of structurally and functionally connected neighbors. Distributed deformation patterns are circumscribed by specific functional systems (the ventral attention network) and cytoarchitectonic classes (limbic class), with an epicenter in the anterior cingulate cortex. CONCLUSIONS: Altogether, the present study demonstrates that brain tissue volume loss in schizophrenia is conditioned by structural and functional connectivity, accounting for 25% to 35% of regional variance in deformation.