Laura B. Gabriel

Increased Coupling of Intrinsic Networks in Remitted Depressed Youth Predicts Rumination and Cognitive Control

Objective Functional 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. Method fcMRI 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. Results Compared 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. Conclusions Findings 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.

Domain-specific impairment in cognitive control among remitted youth with a history of major depression

Impairment in neuropsychological functioning is common in major depressive disorder (MDD), but it is not clear to what degree these deficits are related to risk (e.g. trait), scar, burden or state effects of MDD. The objective of this study was to use neuropsychological measures, with factor scores in verbal fluency, processing speed, attention, set‐shifting and cognitive control in a unique population of young, remitted, unmedicated, early course individuals with a history of MDD in hopes of identifying putative trait markers of MDD.

Decreased Fronto-Limbic Activation and Disrupted Semantic-Cued List Learning in Major Depressive Disorder.

OBJECTIVES Individuals with major depressive disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits. METHODS Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during functional magnetic resonance imaging. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event-related (Words Recalled) models. RESULTS MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD. CONCLUSIONS Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD.

Comorbid anxiety increases cognitive control activation in Major Depressive Disorder

Major Depressive Disorder (MDD) and anxiety disorders often co‐occur, with poorer treatment response and long‐term outcomes. However, little is known about the shared and distinct neural mechanisms of comorbid MDD and anxiety (MDD+Anx). This study examined how MDD and MDD+Anx differentially impact cognitive control.

Amygdala and dorsomedial hyperactivity to emotional faces in youth with remitted Major Depression

We present neuroimaging markers of the remitted state of major depressive disorder (rMDD) during facial emotion perception in 84 individuals during fMRI. Participants comprised 47 individuals (aged 18-23) diagnosed with rMDD and 37 healthy controls (HCs). Participants classified emotional faces or animals (control condition) in the Facial Emotion Perception Test (FEPT) during fMRI. Behavioural performance on the FEPT did not differ significantly between groups. During fMRI, both groups demonstrated significant blood oxygen level-dependent (BOLD) activity in bilateral inferior frontal gyri for the faces minus animals (F-A) contrast. The rMDD group additionally showed BOLD activity during F-A in numerous regions, including the bilateral paracingulate gyri, middle temporal gyri and right amygdala. The rMDD group exhibited significantly greater activity than the HC group in regions including the bilateral middle temporal gyri and left superior frontal gyrus. Although the rMDD group did not manifest the behavioural performance deficits on facial emotion recognition tasks that have been observed in actively depressed individuals, the rMDD group nevertheless showed increased BOLD activity compared with never-depressed controls during F-A in multiple posterior brain regions, suggesting that persistent effects of illness or possible trait vulnerabilities may distinguish individuals with rMDD from never-depressed controls.

Family support: A possible buffer against disruptive events for individuals with and without remitted depression.

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.