There is substantial variability across studies of default mode network (DMN) connectivity in major depressive disorder, and reliability and time-invariance are not reported. This study evaluates whether DMN dysconnectivity in remitted depression (rMDD) is reliable over time and symptom-independent, and explores convergent relationships with cognitive features of depression. A longitudinal study was conducted with 82 young adults free of psychotropic medications (47 rMDD, 35 healthy controls) who completed clinical structured interviews, neuropsychological assessments, and 2 resting-state fMRI scans across 2 study sites. Functional connectivity analyses from bilateral posterior cingulate and anterior hippocampal formation seeds in DMN were conducted at both time points within a repeated-measures analysis of variance to compare groups and evaluate reliability of group-level connectivity findings. Eleven hyper- (from posterior cingulate) and 6 hypo- (from hippocampal formation) connectivity clusters in rMDD were obtained with moderate to adequate reliability in all but one cluster (ICC's range = 0.50 to 0.76 for 16 of 17). The significant clusters were reduced with a principle component analysis (5 components obtained) to explore these connectivity components, and were then correlated with cognitive features (rumination, cognitive control, learning and memory, and explicit emotion identification). At the exploratory level, for convergent validity, components consisting of posterior cingulate with cognitive control network hyperconnectivity in rMDD were related to cognitive control (inverse) and rumination (positive). Components consisting of anterior hippocampal formation with social emotional network and DMN hypoconnectivity were related to memory (inverse) and happy emotion identification (positive). Thus, time-invariant DMN connectivity differences exist early in the lifespan course of depression and are reliable. The nuanced results suggest a ventral within-network hypoconnectivity associated with poor memory and a dorsal cross-network hyperconnectivity linked to poorer cognitive control and elevated rumination. Study of early course remitted depression with attention to reliability and symptom independence could lead to more readily translatable clinical assessment tools for biomarkers.

We investigated the ability of preferred classical music to activate the nucleus accumbens in patients with Major depressive disorder (MDD). Twelve males with MDD and 10 never mentally ill male healthy controls (HC) completed measures of anhedonia and depression severity, and listened to 90-second segments of preferred classical music during fMRI. Compared to HCs, individuals with MDD showed less activation of the left nucleus accumbens (NAcc). Individuals with MDD showed attenuation of the left NAcc response in later compared to earlier parts of the experiment, supporting theories that MDD involves an inability to sustain reward network activation. Counter intuitively, we found that NAcc activity during early music listening was associated with greater depression severity. In whole-brain analyses, anhedonia scores predicted activity in regions within the default mode network, supporting previous findings. Our results support theories that MDD involves an inability to sustain reward network activation. It also highlights that pleasant classical music can engage critical neural reward circuitry in MDD.

The current study sought to test the role of family support as a buffer of life stress for depressive symptoms in a sample of young adults at low- and high-risk for depression based on a previous history of depression. Ninety-seven young adults, 54 with remitted depression and 43 without prior history of depression, completed reports of family relationships, disruptive life events, and depressive symptoms at baseline and every 2 months for 10 months. Results revealed significant interactions between family environment and life events predicting Beck Depressive Inventory (BDI) scores at baseline, such that individuals with better family support were buffered from risk associated with life stress, and this was true even after accounting for a previous history of depression. Longitudinal analyses utilizing the Patient Health Questionnaire-9 (PHQ-9) as a depressive symptom measure did not find significant associations with family environment, but did find that more stressful events at baseline were associated with increasing levels of symptoms over time. Exploratory analyses suggest that discrepant findings for baseline versus longitudinal analyses may be due to differences in symptom measurement and to associations between family environment and cognitive features of depression. These findings provide qualified support for the continued relevance of families as stress buffers in young adulthood across a spectrum of risk for depression. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Background: We have previously demonstrated that pre-scan salivary cortisol is associated with attentuated frontal-subcortical brain activation during emotion processesing and semantic listlearning paradigms in depressed subjects. Additionally, altered functional connectivity is observed after remission of acute depression symptoms (rMDD). It is unknown whether cortisol also predicts altered functional connectivity during remission. Methods: Participants were 47 healthy controls (HC) and 73 rMDD, 18-30 years old who provided salivary cortisol samples before and after undergoing resting-state fMRI. We tested whether salivary cortisol by diagnosis interactions were associated with seed-based resting connectivity of the default mode (DMN) and salience and emotion (SN) networks using wholebrain, cluster-level corrected (p<.01) regression in SPM8. Results: Pre-scan cortisol predicted decreased (HC) and increased (rMDD) cross-network connectivity to the dorsal anterior cingulate, dorso-medial and lateral-prefrontal cortex, brain stem and cerebellum (all seeds) and precuneus (DMN seeds). By and large, pre/post-scan cortisol

There is evidence that CCN activity declines in rMDD and that there may be compensatory SEN activity in individuals with Comorbid rMDD and anxiety. Our findings support the identification of comorbid anxiety as a meaningful subtype of MDD that may obscure group differences between rMDD and HCs.