Dysfunctional Connectivity in the Depressed Adolescent Brain.

Aberration in the coordinated activity of large-scale brain networks, or functional connectivity, is a growing focus of depression research because it may be a key substrate underlying cognitive and emotional symptoms. Consistent with this assertion, numerous studies have shown that individuals with depression exhibit abnormal functional connectivity in brain systems previously implicated in socioemotional and cognitive processes relevant to depressive symptoms (1). These neural regions include midline cortical areas of the default network involved in self-referential and autobiographical thinking and prefrontal systems involved in higher order cognitive control or regulation of affect. However, although many studies examined functional connectivity either at rest when cognition is undirected or during tasks relevant to depressive symptoms, few studies have combined these modalities. This gap in our understanding of dysfunctional connectivity in depression gives rise to several important questions. First, to what extent are alterations in functional connectivity unique to specific cognitive or emotional processes? Second, what can the comparison of functional connectivity across multiple modalities reveal about markers of psychiatric illness? Finally, are abnormalities in functional connectivity malleable—do they change over development or normalize during treatment? Ho et al. (2) explore several of these questions in a study in the current issue of Biological Psychiatry. The authors collected functional magnetic resonance imaging data from adolescents with major depressive disorder (MDD) and healthy control subjects during two paradigms: an unconstrained period of rest and an emotion-identification task in which participants identified the emotional category of morphing faces (fearful, happy, sad). Critically, this design allowed the researchers to interrogate functional connectivity during directed emotional processing using psychophysiological interaction analyses and undirected thought using resting-state functional connectivity analyses. Several intriguing results emerged. First, when engaged in task-directed emotional processing, depressed adolescents exhibited greater functional connectivity than healthy youth in regions of the default network and between medial prefrontal and posterior cingulate “hubs” of the default network and cingulate or striatal regions involved in cognitive control or affective/salience processing. Second, during unconstrained rest, adolescents with depression and control subjects showed comparable functional connectivity among these regions. When inspecting the patterns of results across groups and connectivity modalities, both groups exhibited robust functional connectivity within the default network at rest; however, among youth with depression only, this network remained active and functionally connected during explicit