Molecular Psychiatry: Altered Patterns of Brain Connectivity Associated with Depression Risk in Young Adults

Identifying the neural markers of pathophysiological processes underlying depression severity can provide targets to guide treatment choice for individuals with subsyndromal or syndromal-level depression. This approach is particularly important for young adults with depression due to the high incidence of affective disorders during this age range, and because the effectiveness of interventions can be maximized during this neurodevelopmental period. 

In a recent Molecular Psychiatry paper, team of investigators from the University of Pittsburgh, including Michele Bertocci, PhD (Assistant Professor of Psychiatry), Yvette Afriyie-Agyemang (doctoral candidate), Renata Rozovsky, PhD (postdoctoral associate), and Mary Phillips, MD, MD (Cantab) (Distinguished Professor of Psychiatry, Clinical and Translational Science, and Bioengineering, and Pittsburgh Foundation-Emmerling Endowed Chair in Psychotic Disorders) looked at the central executive network (which supports emotion regulation subcomponent processes such as working memory), the default mode network (which supports self-related information), and the salience network (which is associated with self-referential processing); interference among these networks during working memory may predispose to depressive disorders. 

In a sample of young adults ages 18-25, the investigators examined relationships among activity and functional connectivity in these networks and current depression severity. In addition, they studied the extent to whether these relationships were specific to depression versus mania/hypomania, whether findings could be replicated in a second sample, and whether such relationships also predicted depression at up to 12 months post scan and/or mania/hypomania severity.

In the first sample, current depression severity was robustly predicted by greater activity and greater positive functional connectivity among the central executive network, default mode network, and salience network during working memory and emotional regulation tasks. These findings were specific to depression, replicated in the independent sample, and predicted future depression severity.

“I think a strength of this work is the replication of dysfunctional patterns of internetwork coupling across independent at-risk samples,” said Dr. Bertocci, the study’s corresponding author. “Replication suggests that there is potential for these neural targets, that seem to disrupt normal attentional processes, to be used to inform, guide, and monitor treatments for mood disorders.”

Altered patterns of central executive, default mode and salience network activity and connectivity are associated with current and future depression risk in two independent young adult samples
Bertocci MA, Afriyie-Agyemang Y, Rozovsky R, Iyengar S, Stiffler R, Aslam HA, Bebko G, Phillips ML.

Molecular Psychiatry (2022).