Childhood Trauma History Is Linked To Abnormal Brain Connectivity In Major Depression

Yu, Meichen; Linn, Kristin A.; Shinohara, Russell T.; Oathes, Desmond J.; Cook, Philip A.; Duprat, Romain; Moore, Tyler M.; Oquendo, Maria A.; Phillips, Mary L.; McInnis, Melvin; Fava, Maurizio; Trivedi, Madhukar H.; McGrath, Patrick; Parsey, Ramin; Weissman, Myrna M.; Sheline, Yvette I.

Patients with major depressive disorder (MDD) present with heterogeneous symptom profiles, while neurobiological mechanisms are still largely unknown. Brain network studies consistently report disruptions of resting-state networks (RSNs) in patients with MDD, including hypoconnectivity in the frontoparietal network (FPN), hyperconnectivity in the default mode network (DMN), and increased connection between the DMN and FPN. Using a large, multisite fMRI dataset ( n = 189 patients with MDD, n = 39 controls), we investigated network connectivity differences within and between RSNs in patients with MDD and healthy controls. We found that MDD could be characterized by a network model with the following abnormalities relative to controls: ( i ) lower within-network connectivity in three task-positive RSNs [FPN, dorsal attention network (DAN), and cingulo-opercular network (CON)], ( ii ) higher within-network connectivity in two intrinsic networks [DMN and salience network (SAN)], and ( iii ) higher within-network connectivity in two sensory networks [sensorimotor network (SMN) and visual network (VIS)]. Furthermore, we found significant alterations in connectivity between a number of these networks. Among patients with MDD, a history of childhood trauma and current symptoms quantified by clinical assessments were associated with a multivariate pattern of seven different within- and between-network connectivities involving the DAN, FPN, CON, subcortical regions, ventral attention network (VAN), auditory network (AUD), VIS, and SMN. Overall, our study showed that traumatic childhood experiences and dimensional symptoms are linked to abnormal network architecture in MDD. Our results suggest that RSN connectivity may explain underlying neurobiological mechanisms of MDD symptoms and has the potential to serve as an effective diagnostic biomarker.


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Proceedings of the National Academy of Sciences

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February 1, 2022