Emotion-Dependent Functional Connectivity of the Default Mode Network in Adolescent Depression

Abstract

Background Functional magnetic resonance imaging (fMRI) research suggests that both adult and adolescent major depressive disorder (MDD) is marked by aberrant connectivity of the default mode network (DMN) during resting-state. However, emotional dysresgulation is also a key feature of MDD. No studies to date have examined emotion-related DMN pathology in adolescent depression. Comprehensively understanding the dynamics of DMN connectivity across brain states in depressed individuals with short disease histories could provide insight into the etiology of MDD. Methods We collected fMRI data during an emotion identification task and also during resting-state from 26 medication-free adolescents (13-17 years) with MDD and 37 wellmatched healthy controls (HCL). We examined between-group differences in blood oxygenation level-dependent task responses, emotion-dependent, and resting-state functional connectivity of the two primary nodes of the DMN: medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC). Additionally, we examined between-group differences in DMN functional connectivity and its relationship to depression severity. Results Relative to HCL, unmedicated MDD adolescents demonstrated reduced mPFC and PCC emotion-related deactivation and greater mPFC and PCC emotion-dependent functional connectivity with precuneus, cingulate gyrus, and striatum/subcallosal cingulate gyrus. Importantly, PCC-subcallosal cingulate connectivity remained inflexibly elevated in MDD versus HCL during resting-state. Lastly, stronger PCC emotion-dependent functional connectivity was associated with greater depression severity and an earlier age of depression onset. Conclusions Adolescent depression is associated with inflexibly elevated DMN connections. Given recent evidence of DMN maturation throughout adolescence, our findings suggest that early-onset depression adversely impacts normal development of functional brain networks.

Enhanced default mode network connectivity with ventral striatum in subthreshold depression individuals

“…In addition, the DMN is more notable at the MPFC in our study, the Bluhm et al study used precunus/PCC as seed. The two sub-DMN networks may be associated with different functions (Ho, Connolly, 2014, Li, Liu, 2013). Thus, we speculate that the difference may represent different neuropathologies at different stages of depression.…”

“…Previous studies (Bluhm et al, 2009, Greicius et al, 2007, Hamilton et al, 2013, Ho et al, 2014, Li et al, 2013, Liston et al, 2014, Posner et al, 2013, Wang et al, 2012, Wu et al, 2013, Zhu et al, 2012) have found disrupted DMN functional connectivity (FC) in MDD patients, and these changes are associated with psychiatric measurements such as rumination score in MDD patients. Yet one question that remains unanswered is whether DMN FC changes can be observed in StD patients.…”

Orbitofrontal Cortex Activity and Connectivity Predict Future Depression Symptoms in Adolescence

“…Relatively less is known about functional and effective connectivity of OFC in adult depression, with studies showing greater connectivity of OFC with insula (30), amygdala (31), and a distributed network including prefrontal and cingulate cortices (32), and this enhanced connectivity is associated with more severe depression symptoms (30, 32). Despite prefrontal maturation during adolescence (33), adolescents and adults with and at risk for MDD show a similar pattern of prefrontal resting-state connectivity (34, 35). However, it is unclear whether attenuated OFC activity and/or enhanced OFC connectivity during rewards and losses represents a premorbid risk that precedes the onset of symptoms or is the result of depression onset or treatment exposure, indicating a need for longitudinal research on OFC functioning prior to depression onset.…”

10.3 Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression

“…The lack of typical anticorrelation between the DMN and supramarginal gyrus / inferior parietal lobule, an important attention control region (56,57), in at-risk children is consistent with cognitive control deficits in depressed adult patients (58,59) and reduced DMN deactivation during an emotional identification task in depressed adolescents (3). Greater anticorrelation between DMN and cognitive control networks in healthy adults has been linked to better performance in cognitive control and working memory tasks (60,61) and may reflect an individual's capacity to switch between internally and externally focused attention (62).…”

“…Table 2 Between-group connectivity differences from default mode network (DMN), right dorsolateral prefrontal cortex (DLPFC), left DLPFC, and right amygdala. BA, Brodmann area; k, cluster size in mm 3 . Peak coordinates (x y z) based on MNI (Montreal Neurologic Institute) brain.…”