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.

BackgroundWhite matter (WM) integrity may represent a shared biomarker for emotional disorders (ED). Aims: To identify transdiagnostic biomarkers of reduced WM by meta-analysis of findings across multiple EDs.MethodWeb of Science was searched systematically for studies of whole brain analysis of fractional anisotropy (FA) in adults with major depressive disorder, bipolar disorder, social anxiety disorder, obsessive-compulsive disorder or posttraumatic stress disorder compared with a healthy control (HC) group. Peak MNI coordinates were extracted from 37 studies of voxel-based analysis (892 HC and 962 with ED) and meta-analyzed using seed-based d Mapping (SDM) Version 4.31. Separate meta-analyses were also conducted for each disorder.ResultsIn the transdiagnostic meta-analysis, reduced FA was identified in ED studies compared to HCs in the left inferior fronto-occipital fasciculus, forceps minor, uncinate fasciculus, anterior thalamic radiation, superior corona radiata, bilateral superior longitudinal fasciculi, and cerebellum. Disorder-specific meta-analyses revealed the OCD group had the most similarities in reduced FA to other EDs, with every cluster of reduced FA overlapping with at least one other diagnosis. The PTSD group was the most distinct, with no clusters of reduced FA overlapping with any other diagnosis. The BD group were the only disorder to show increased FA in any region, and showed a more bilateral pattern of WM changes, compared to the other groups which tended to demonstrate a left lateralized pattern of FA reductions.ConclusionsDistinct diagnostic categories of ED show commonalities in WM tracts with reduced FA when compared to HC, which links brain networks involved in cognitive and affective processing. This meta-analysis facilitates an increased understanding of the biological markers that are shared by these ED.

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.

Background Recent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes. Method Resting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted. Results Young adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN. Conclusions This is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness.

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