Acute cortisol reactivity attenuates engagement of fronto-parietal and striatal regions during emotion processing in negative mood disorders

Abstract

Objective Depression and bipolar disorder (negative mood disorders, NMD) are associated with dysregulated hypothalamic-pituitary-adrenal (HPA)-axis function and disrupted emotion processing. The neural networks involved in attenuation of HPA-axis reactivity overlap with the circuitry involved in perception and modulation of emotion; however, direct links between these systems are understudied. This study investigated whether cortisol activity prior to undergoing fMRI was related to neural processing of emotional information in participants with NMD. Methods Forty-one adults (Mage=40.33, SD=15.57) with major depression (n=29) or bipolar disorder (n=12) and 23 healthy control comparisons (Mage=36.43, SD=17.33) provided salivary cortisol samples prior to completing a facial emotion perception test during 3-Tesla fMRI. Results Overall, pre-scan cortisol level was positively associated with greater engagement of the dorsal anterior cingulate (dACC), inferior parietal lobule, insula, putamen, precuneus, middle and medial frontal and postcentral gyri, posterior cingulate, and inferior temporal gyrus during emotion processing of all faces. NMD status moderated this effect; in NMD participants’ pre-scan cortisol was associated with attenuated activation of the insula, postcentral gyrus, precuneus, and putamen for fearful faces and the medial frontal gyrus for angry faces relative to HCs. Cortisol-related attenuation of activation among NMD participants was also observed for facial identification in the dACC, putamen, middle temporal gyrus, precuneus, and caudate. Conclusions Across all participants, cortisol was associated with greater activation in several regions involved in the perception and control of emotion. However, cortisol responsivity was associated with hypoactivation of several of these regions in the NMD group, suggesting that HPA-axis activity may selectively interfere with the potentially adaptive recruitment of circuits supporting emotion perception, processing and/or regulation in mood disorders.

A tumultuous transition to motherhood: Altered brain and hormonal responses in mothers with postpartum depression

“…Among the most studied in this regard are cortisol's preferential actions on the salience and reward network (ie, prefrontal and limbic structures) via glucocorticoid receptors. Heightened endogenous cortisol has been associated with attenuated activations of key fronto‐limbic regions of the salience and reward network (eg, mPFC, ACC, insula, amygdala, caudate, putamen) in non‐postpartum depression during a wide range of cognitive and emotional tasks (eg, facial recognition, emotion processing, cognitive encoding) . This is in contrast to the observed association between heightened cortisol and heightened fronto‐limbic activation in healthy controls and is consistent with the proposal that affective state at the time of glucocorticoid elevations alters the effect of cortisol on brain functions .…”

“…It would be of interest for future research to investigate whether an intranasal administration of oxytocin would similarly mitigate or reverse some of the altered BOLD responses that have been documented in mothers with PPD, as has been reviewed in the earlier sections above.The literature on non-postpartum depression has yet to fully clarify the complex ways in which hormones, including oxytocin and cortisol, and the brain intersect to influence and perpetuate depressive symptoms. Among the most studied in this regard are cortisol's preferential actions on the salience and reward network (ie, prefrontal and limbic structures) via glucocorticoid receptors.Heightened endogenous cortisol has been associated with attenuated activations of key fronto-limbic regions of the salience and reward network (eg, mPFC, ACC, insula, amygdala, caudate, putamen) in non-postpartum depression during a wide range of cognitive and emotional tasks (eg, facial recognition, emotion processing, cognitive encoding) [115][116][117]. This is in contrast to the observed association between heightened cortisol and heightened fronto-limbic activation in healthy controls and is consistent with the proposal that affective state at the time of glucocorticoid elevations alters the effect of cortisol on brain functions 118.…”

Redefining the Endophenotype Concept to Accommodate Transdiagnostic Vulnerabilities and Etiological Complexity

“…This state of affairs is depicted in Figure 2 . Low midbrain DA activity and reactivity to incentives – neural vulnerabilities to both ADHD and unipolar depression [ 11 ] – emerge from interactions among numerous etiological inputs including normal allelic variation [ 42–44 ], heritable CNVs [ 45 , 46 ], de novo mutations [ 47 ], epigenetic changes in receptor function [ 48 ], neurotoxic environmental risk exposures [ 48 ] and neurohormonal influences [ 49 , 50 ], among other factors [ 12 ]. These influences aggregate and interact to induce an anhedonic and irritable mood state that confers vulnerability to both externalizing disorders and unipolar depression.…”

Translational Functional Neuroimaging in the Explanation of Depression

“…In both groups, cortisol was associated with greater activation in several regions involved in the perception and control of emotion (dorsal anterior cingulate, inferior parietal lobule, insula, putamen, precuneus, middle and medial frontal and postcentral gyri, posterior cingulate, and inferior temporal gyrus during emotion processing of all faces). However, in the patient group, cortisol responsivity was associated with hypoactivation of the insula, postcentral gyrus, precuneus, and putamen for fearful faces and the medial frontal gyrus for angry faces ( 75 ).…”