Effects of Cortisol Administration on Resting-State Functional Connectivity in Women with Depression.

Previous resting-state functional connectivity (rsFC) research has identified several brain networks impacted by depression and cortisol, including default mode (DMN), frontoparietal (FPN), and salience networks (SN). In the present study, we examined the effects of cortisol administration on rsFC of these networks in individuals varying in depression history and severity. We collected resting-state fMRI scans and self-reported depression symptom severity for 74 women with and without a history of depression after cortisol and placebo administration using a double-blind, crossover design. We conducted seed-based rsFC analyses for DMN, FPN, and SN seeds to examine rsFC changes after cortisol vs. placebo administration in relation to depression history group and severity. Results revealed a main effect of depression group, with lower left amygdala (SN)-middle temporal gyrus connectivity in women with a history of depression. Cortisol administration increased insula (SN)-inferior frontal gyrus and superior temporal gyrus connectivity. We also found that greater depression severity was associated with increased PCC (DMN)-cerebellum connectivity after cortisol. These results did not survive Bonferroni correction for seed ROIs and should be interpreted with caution. Our findings indicate that acute cortisol elevation may normalize aberrant connectivity of DMN and SN regions, which could help inform clinical treatments for depression.

Neural signal variability relates to maladaptive rumination in depression.

Rumination is a common feature of depression and predicts the onset and maintenance of depressive episodes. Maladaptive and adaptive subtypes of rumination contribute to distinct outcomes, with brooding worsening negative mood and reflection related to fewer depression symptoms in healthy populations. Neuroimaging studies have implicated several cortical midline and lateral prefrontal brain regions in rumination. Recent research indicates that blood oxygen level-dependent (BOLD) signal variability may be a novel predictor of cognitive flexibility. However, no prior studies have investigated whether brooding and reflection are associated with distinct patterns of BOLD signal variability in depression. We collected resting-state fMRI data for 79 women with different depression histories: no history, past history, and current depression. We examined differences in BOLD signal variability (BOLDSD) related to rumination subtypes for the following regions of interest previously implicated in rumination: amygdala, medial prefrontal, anterior cingulate, posterior cingulate, and dorsolateral prefrontal cortices (dlPFC). Rumination subtype was associated with BOLDSD in the dlPFC, with greater levels of brooding associated with lower BOLDSD in the dlPFC, even after controlling for depression severity. Depression history was related to BOLDSD in the dlPFC, with reduced BOLDSD in those with current depression versus no history of depression. These findings provide a novel demonstration of the neural circuitry associated with maladaptive rumination in depression and implicate decreased prefrontal neural signal variability in the pathophysiology of depression.