Traumatic childhood experiences are associated with abnormal brain network architecture in patients with major depressive disorder (MDD), according to results from a brain network study published in the Proceedings of the National Academy of Sciences.

Investigators used a large, multisite functional magnetic resonance imaging dataset to investigate differences in brain network connectivity between patients with MDD (n=189) and healthy controls (n=39). Analysis concentrated on 10 well-established resting state networks (RSNs) associated with MDD in prior research. Within- and between-network connectivity was determined for each RSN and compared between participant groups. Among patients with depression, canonical correlation analysis was used to identify associations between network connectivity and clinical variables. Specifically, investigators tested for associations between RSN connectivity, childhood exposure to traumatic events, and “anxious misery,” an umbrella term for symptoms of depression, anhedonia, anxiety, neuroticism, and suicidality.

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MDD was strongly associated with the following network abnormalities relative to controls: (1) lower within-network connectivity in 3 task-positive RSNs (frontoparietal network, dorsal attention network, and cingulo-opercular network); (2) higher within-network connectivity in 2 intrinsic networks (default mode network and salience network); and (3) higher within-network connectivity in 2 sensory networks (sensorimotor network and visual network). Between-network abnormalities were also observed among patients with MDD, including hyperconnectivity in 7 pairs and hypoconnectivity in 3 pairs relative to controls.

Canonical correlation analyses identified childhood physical and emotional neglect or abuse and anxious misery as significantly associated with certain brain patterns (both P <.0001). Specifically, childhood trauma exposure and psychiatric symptoms were significantly associated with the within- and between-network connectivity of the following RSNs: dorsal attention network, frontoparietal network, cingulo-opercular network, subcortical regions, ventral attention network, auditory network, visual network, and sensorimotor network.

These data indicate that alterations in brain network connectivity may be associated with childhood trauma and psychiatric symptoms in patients with MDD. As such, RSN connectivity may have utility as a biomarker for MDD, researchers wrote, although additional research in larger patient samples is necessary to investigate this claim.


Yu M, Linn KA, Shinohara RT, et al. Childhood trauma history is linked to abnormal brain connectivity in major depression. Proc Natl Sci U S A. 2019;116(17):8582-8590.