Summary: Study finds an association between resting state network connectivity abnormalities in those with major depressive disorder who experienced childhood trauma.
Source: University of Pennsylvania
A study led by Penn Medicine researchers found that childhood trauma is linked to abnormal connectivity in the brain in adults with major depressive disorder (MDD). The paper, published this week in Proceedings of the National Academy of Sciences (PNAS), is the first data-driven study to show symptom-specific, system-level changes in brain network connectivity in MDD.
“With estimates of approximately 10 percent of all children in the United States having been subjected to child abuse, the significance of child maltreatment on brain development and function is an important consideration,” said Yvette I. Sheline, MD, McLure professor of Psychiatry, Radiology, and Neurology, and director of the Center for Neuromodulation in Depression and Stress (CNDS) in the Perelman School of Medicine at the University of Pennsylvania. “This study not only confirms the important relationship between childhood trauma and major depression but also links patients’ experiences of childhood trauma with specific functional brain network abnormalities. This suggests a possible environmental contributor to neurobiological symptoms.”
MDD is a common mental disorder characterized by a variety of symptoms — including persistently depressed mood, loss of interest, low energy, insomnia or hypersomnia, and more. These symptoms impair daily life and increase the risk of suicide. In addition, experiences of childhood trauma, including physical, sexual, or emotional abuse, as well as physical or emotional neglect, have been associated with the emergence and persistence of depressive and anxiety disorders. However, the neurobiological mechanisms underlying MDD are still largely unknown.
To address this challenge, a team led by Sheline utilized functional magnetic resonance imaging (fMRI) to investigate the brain networks and patterns that underlie the disorder. Researchers compared brain activity in 189 participants with MDD to activity of 39 healthy controls. First author Meichen Yu, a post-doctoral fellow in the CNDS, conducted statistical analyses to determine the associations between temporal correlations in connectivity within and between 10 well-established, large-scale resting state networks (RSNs) and clinical measures, including both past history of trauma and current clinical symptoms, such as depression, anxiety, suicidality. These symptoms were measured by 213 item-level survey questions.
The authors found that in patients with MDD, while the strongest correlations were with childhood trauma, abnormal network connectivity was also associated with current symptoms of depression. Even though participants in this study were not selected as participants based on a history of trauma, and the brain imaging took place decades after trauma occurred, prior trauma was evident in abnormal functional connectivity.
“These results suggest that resting-state network connectivity may point to some of the brain mechanisms underlying the symptoms of major depressive disorder,” Sheline explains. “It may have the potential to serve as an effective biomarker, aiding in the development of depression biotypes and opening up the possibility of targeted diagnosis.”
University of Pennsylvania
Yvette I. Sheline – University of Pennsylvania
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. PNAS published ahead of print April 8, 2019 doi:10.1073/pnas.1900801116
Childhood trauma history is linked to abnormal brain connectivity in major depression
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.