ObjectiveFunctional connectivity MRI (fcMRI) studies of individuals currently diagnosed with major depressive disorder (MDD) document hyperconnectivities within the default mode network (DMN) and between the DMN and salience networks (SN) with regions of the cognitive control network (CCN). Studies of individuals in the remitted state are needed to address whether effects derive from trait, and not state or chronic burden features of MDD.MethodfcMRI data from two 3.0 Tesla GE scanners were collected from 30 unmedicated (47% medication naïve) youth (aged 18–23, modal depressive episodes = 1, mean age of onset = 16.2, SD = 2.6) with remitted MDD (rMDD; modal years well = 4) and compared with data from 23 healthy controls (HCs) using four bilateral seeds in the DMN and SN (posterior cingulate cortex (PCC), subgenual anterior cingulate (sgACC), and amygdala), followed by voxel-based comparisons of the whole brain.ResultsCompared to HCs, rMDD youth exhibited hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CCN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among rMDD youth. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/NoGo task, one positively and one inversely.ConclusionsFindings document hyperconnectivities of the DMN and SN with the CCN (BA 8/10), which were related to rumination and sustained attention. Given these cognitive markers are known predictors of response and relapse, hyperconnectivities may increase relapse risk or represent compensatory mechanisms.

The aim of the current study was to use fMRI to examine the neural correlates of engaging in rumination among a sample of remitted depressed adolescents, a population at high risk for future depressive relapse. A rumination induction task was used to assess differences in patterns of neural activation during rumination as compared with a distraction condition among 26 adolescents in remission from major depressive disorder (rMDD) and 15 healthy control adolescents. Self-report depression and rumination as well as clinician-rated depression were also assessed among all participants. All participants recruited regions in the default mode network (DMN), including the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), inferior parietal lobe (IPL), and medial temporal gyrus (MTG) during rumination. Increased activation in these regions during rumination was correlated with increased self-report rumination and symptoms of depression across all participants. Adolescents with rMDD also exhibited greater activation in regions involved in visual, somatosensory, and emotion processing when compared to healthy peers. The current findings suggest that during ruminative thought, adolescents with rMDD are characterized by increased recruitment of regions within the DMN and in areas involved in visual, somatosensory, and emotion processing.

Many individuals with major depressive disorder (MDD) experience cognitive dysfunction including impaired cognitive control and negative cognitive styles. Functional connectivity MRI studies of individuals with current MDD have documented altered resting-state connectivity within the default-mode network and across networks. However, no studies to date have evaluated the extent to which impaired connectivity within the cognitive control network (CCN) may be present in remitted MDD (rMDD), nor have studies examined the temporal stability of such attenuation over time. This represents a major gap in understanding stable, trait-like depression risk phenotypes. In the present study, resting-state functional connectivity data were collected from 52 unmedicated young adults with rMDD and 47 demographically-matched healthy controls, using three bilateral seeds in the CCN (dorsolateral prefrontal cortex, inferior parietal lobule, and dorsal anterior cingulate cortex). Mean connectivity within the entire CCN was attenuated among individuals with rMDD, was stable and reliable over time, and was most pronounced from the right dorsolateral prefrontal cortex and right inferior parietal lobule to the three bilateral CCN seeds. Attenuated connectivity in rMDD appeared to be specific to the CCN as opposed to representing attenuated within-network coherence in other networks (e.g., default-mode, salience). In addition, attenuated connectivity within the CCN mediated relationships between rMDD status and cognitive risk factors for depression, including ruminative brooding, pessimistic attributional style, and negative automatic thoughts. Given that these cognitive markers are known predictors of relapse, these results suggest that attenuated connectivity within the CCN could represent a biomarker for trait phenotypes of depression risk.

Objective Previous studies have found that family-based psychosocial treatments are effective adjuncts to pharmacotherapy among adults and adolescents with bipolar disorder (BD). The objective of this study was to compare the efficacy of adjunctive Child- and Family-Focused Cognitive Behavioral Therapy (CFF-CBT) to psychotherapy as usual (control) for mood symptom severity and global functioning in children with BD. Method Sixty-nine youth, aged 7–13 (M = 9.19, SD = 1.61) with DSM-IV-TR bipolar I, II, or not otherwise specified (NOS) disorder were randomly assigned to CFF-CBT or control groups. Both treatments consisted of 12 weekly sessions followed by 6 monthly booster sessions delivered over a total of 9 months. Independent evaluators assessed participants at baseline, week 4, week 8, week 12 (posttreatment), and week 39 (6-month follow-up). Results Participants in CFF-CBT attended more sessions, were less likely to drop out, and reported greater satisfaction with treatment than controls. CFF-CBT demonstrated efficacy compared to the control in reducing parent-reported mania at posttreatment and depression symptoms at posttreatment and follow-up. Global functioning did not differ at posttreatment but was higher among CFF-CBT participants at follow-up. Conclusion CFF-CBT may be efficacious in reducing acute mood symptoms and improving long-term psychosocial functioning among children with BD.

This pilot randomized control trial was designed to examine whether Rumination-Focused Cognitive Behavior Therapy (RFCBT) reduces rumination and residual depressive symptoms among adolescents with a history of Major Depressive Disorder (MDD) who are at risk for relapse. We also examined whether these changes in symptoms were associated with changes in functional connectivity of the posterior cingulate cortex (PCC), a key node in the default mode network (DMN). Thirty-three adolescents (ages 12–18) were randomized to eight weeks of RFCBT or an assessment only (AO) control. Twenty two adolescents successfully completed fMRI scans pre- and post-intervention. Adolescents were recruited from the clinic and community and met criteria for at least one previous episode of MDD and were currently in full or partial remission. An Independent Evaluator interviewed parent and child before and after the eight-week intervention. The left PCC (-5, -50, 36) seed was used to probe resting state functional connectivity of the DMN. Adolescents who received RFCBT demonstrated reduced rumination (F = -2.76, df = 112, p < .01, 95% CI [-4.72,-0.80]) and self-report depression across eight weeks (F = -2.58, df = 113, p < .01, 95% CI [-4.21, -0.94]). Youth who received RFCBT also demonstrated significant decreases in connectivity between the left PCC and the right inferior frontal gyrus (IFG) and bilateral inferior temporal gyri (ITG). Degree of change in connectivity was correlated with changes in self-report depression and rumination. These data suggest that rumination can be reduced over eight weeks and that this reduction is associated with parallel decreases in residual depressive symptoms and decreased functional connectivity of the left PCC with cognitive control nodes. These changes may enhance the ability of vulnerable youth to stay well during the transition to adulthood.Trial Registration: ClinicalTrials.gov NCT01905267