Summary: Researchers report that adults with major depressive disorder who experienced childhood trauma show persistent abnormalities in resting-state brain network connectivity.
Source: University of Pennsylvania
Overview
A team at Penn Medicine has identified a link between childhood trauma and lasting differences in brain network connectivity among adults diagnosed with major depressive disorder (MDD). Published in Proceedings of the National Academy of Sciences (PNAS), this data-driven study is the first to demonstrate symptom-specific, system-level changes in resting-state network connectivity associated with MDD and a history of childhood maltreatment.
“With estimates that a substantial portion of children in the United States experience abuse or neglect, understanding how maltreatment affects brain development and later function is essential,” said Yvette I. Sheline, MD, McLure Professor of Psychiatry, Radiology, and Neurology, and director of the Center for Neuromodulation in Depression and Stress (CNDS) at the Perelman School of Medicine, University of Pennsylvania. Sheline emphasizes that the study not only reinforces the relationship between childhood trauma and major depression but also connects specific trauma histories with distinct functional brain network abnormalities, suggesting an environmental contribution to neurobiological symptoms.
Background
Major depressive disorder is a common and often disabling psychiatric condition characterized by persistent low mood, loss of interest or pleasure, low energy, changes in sleep (insomnia or hypersomnia), and other symptoms that interfere with daily functioning and raise suicide risk. Childhood trauma—including physical, sexual, or emotional abuse and physical or emotional neglect—has long been associated with the development and persistence of depressive and anxiety disorders. Despite this known association, the neurobiological mechanisms that link early trauma and adult depression remain incompletely understood.
Study design and methods
The investigators used functional magnetic resonance imaging (fMRI) to examine resting-state brain networks in adults. The study included 189 participants diagnosed with MDD and 39 healthy control participants. First author Meichen Yu, a postdoctoral fellow at CNDS, led statistical analyses that explored how temporal correlations of connectivity within and between ten well-established large-scale resting-state networks (RSNs) related to clinical measures. Clinical assessments included both retrospective reports of childhood trauma and current symptom profiles—depression, anxiety, and suicidality—measured across 213 item-level survey questions.
Key findings
Compared with healthy controls, people with MDD showed a pattern of altered connectivity across multiple networks. Specifically, the study identified reduced within-network connectivity in task-positive networks such as the frontoparietal network (FPN), the dorsal attention network (DAN), and the cingulo-opercular network (CON). At the same time, several intrinsic or internally focused networks, including the default mode network (DMN) and the salience network (SAN), displayed increased within-network connectivity. Sensory networks—sensorimotor (SMN) and visual (VIS)—also showed higher within-network connectivity in the patient group. In addition to these within-network differences, the researchers observed altered connectivity between multiple networks.
Among participants with MDD, a history of childhood trauma and current clinical symptom measures were associated with a specific multivariate pattern that involved seven different within- and between-network connectivities. Networks implicated in these trauma- and symptom-related patterns included the DAN, FPN, CON, subcortical regions, ventral attention network (VAN), auditory network (AUD), VIS, and SMN. Notably, the strongest correlations tied abnormal connectivity patterns to childhood trauma, though current depressive symptoms also correlated with connectivity changes. Participants were not preselected for trauma history, and brain imaging in many cases occurred decades after the traumatic events, yet prior trauma remained detectable in functional connectivity differences.
Implications
These results suggest that resting-state network connectivity captures neurobiological signatures associated with both childhood trauma and the symptom dimensions of major depressive disorder. As such, RSN connectivity profiles may help elucidate mechanisms underlying varied depressive symptoms and hold promise as candidate biomarkers for identifying depression subtypes or “biotypes.” Improved biomarker-based classification could support more targeted diagnostic approaches and, eventually, more personalized treatment strategies.
About this research
Source:
University of Pennsylvania
Media contact:
Yvette I. Sheline – University of Pennsylvania
Image source:
The image is in the public domain.
Original research (open access):
“Childhood trauma history is linked to abnormal brain connectivity in major depression” — Meichen Yu, Kristin A. Linn, Russell T. Shinohara, Desmond J. Oathes, Philip A. Cook, Romain Duprat, Tyler M. Moore, Maria A. Oquendo, Mary L. Phillips, Melvin McInnis, Maurizio Fava, Madhukar H. Trivedi, Patrick McGrath, Ramin Parsey, Myrna M. Weissman, and Yvette I. Sheline. Proceedings of the National Academy of Sciences (PNAS), published ahead of print April 8, 2019. DOI: 10.1073/pnas.1900801116
Abstract summary
The study reports that patients with major depressive disorder exhibit consistent disruptions in resting-state networks: reduced connectivity within certain task-positive networks (FPN, DAN, CON), increased connectivity within intrinsic networks (DMN, SAN), and elevated connectivity in sensory networks (SMN, VIS). Inter-network connectivity was also altered. Across patients, a multivariate connectivity pattern linked childhood trauma history and current symptom measures to connectivity changes involving multiple networks and subcortical regions. These findings indicate that traumatic childhood experiences and dimensional symptom measures are associated with abnormal network architecture in MDD and suggest that RSN connectivity could inform diagnostic biomarkers.