Reliability, Convergent Validity and Time Invariance of Default Mode Network Deviations in Early Adult Major Depressive Disorder

Abstract

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.

Developmental changes in resting-state functional networks among individuals with and without internalizing psychopathologies

“…Subsets of these samples have been reported in prior work, including from MH091811 awarded to Langenecker (Bessette et al, 2018;Bhaumik et al, 2017;DelDonno et al, 2017;Jacobs et al, 2014Jacobs et al, , 2016Jenkins et al, 2017;Rao et al, 2016;Stange et al, 2017), MH086517 awarded to Monk and Phan (Hamm et al, 2014;Wu et al, 2016), UIC CCTS UL1TR000050, Mind and Life Foundation, and Klingenstein Third Generation Foundation Fellowship awarded to Jacobs Peters et al, 2016). Data is also present from MH101487 (awarded to Langenecker).…”

“…We have previously shown that within the CCN, adolescents (ages 12–17) with a history of depression exhibit increased connectivity (Peters, Burkhouse, Feldhaus, Langenecker, & Jacobs, 2016), whereas the opposite pattern is found among remitted depressed young adults ranging in age from 18 to 23 (Stange et al, 2017). Moreover, when examining cross-network connectivity patterns, remitted depressed adolescents exhibited increased connectivity between the SEN and DMN (Peters et al, 2016), while young adults in remission from MDD exhibited stable and reliable hyperconnectivities of the DMN and SEN with the CCN (Bessette et al, 2018; Jacobs et al, 2014). Thus, taken together, these previous studies suggest that developmental stage may impact the pattern of network connectivity among individuals with a history of depressive and anxiety disorders.…”

Intrinsic neural circuitry of depression in adolescent females

“…The optimal scan time depends on multiple factors, including the metrics of RSFC, the scope of the connectivity (ranging from voxel-wise to whole-brain connectivity), the tradeoff between the quantity of data and participant-related factors such as fatigue, motion, and sleepiness (Tomasi, Shokri-Kojori, & Volkow, 2017). Studies have recommended a single scan session between 7 (Tomasi et al, 2017) to 13 min (Bessette et al, 2018;Birn et al, 2013) for obtaining reliable resting-state data.…”

Pre-scan cortisol is differentially associated with enhanced connectivity to the cognitive control network in young adults with a history of depression

“…First, PCC connectivity was somewhat attenuated to the CCN and enhanced to the SN, compared to other seeds, particularly the antHPF. Perhaps this pattern reflects that cortisol is differentially relevant to ventral and dorsal sub-components of the DMN (Bessette et al, 2018;Buckner et al, 2008). The antHPF seeds may more closely mirror results from the amygdala and sgACC because of density in MR and GR receptors, which are more sparsely distributed in the PCC (Sapolsky, 2000;Tsigos and Chrousos, 2002).…”