Background Exposure to psychosocial stress activates the HPA-axis (e.g., cortisol), induces changes in global brain networks, and is implicated in the development of Major Depression Disorder (MDD). The stress-related endocrine system is connected to the global brain network through the hypothalamus, which is part of the HPA axis. However, relationships between cortisol and brain functional connectivity in the aftermath of stress in MDD have not been well characterized. To fill this gap, we investigated the association between hypothalamus functional connectivity and individual differences in cortisol responses to psychosocial stress in MDD.
Methods Sixty-nine individuals with current MDD (27.42±5.94 years; 35 females) and 39 Healthy Controls (HC; 28.10±5.94 years; 19 females) participated in this study. They completed two study visits (Stress and Control), one involving a psychosocial stress task (Maastricht Acute Stress Test, MAST), the other a matched control task, each followed by a resting-state functional MRI (rs-fMRI) scan after stress/control task. Serial blood draws for assessment of cortisol were collected pre- (T0) and post-stress/control task (T20 min, T80 min, etc.). rs-fMRI data preprocessing and analysis were performed using CONN toolbox v19b.
Results During the Stress Visit compared to the Control visit, HC (p<0.001) showed increased, and MDD (p<0.001) showed decreased hypothalamus FC to cingulate gyrus. Additionally, HC showed decreased and MDD showed increased hypothalamus FC to SFG (HC: p<0.001; MDD: p=0.001), MFG (HC: p<0.001; MDD: p<0.001), and putamen (HC: p<0.001; MDD: p<0.001). For the Stress Visit, cortisol AUC was positively correlated with hypothalamus FC to putamen in HC (p=0.028), but not in MDD (p=0.35). In contrast, for the Control Visit, HC showed a negative correlation between cortisol AUC and hypothalamus FC to MFG (p=0.009); in MDD this relationship was not significant (p=0.87).
Conclusions These findings provide novel evidence of a dissociation between hypothalamus and default mode and executive network connectivity in MDD, highlighting new pathways to target for treatments of stress-related psychiatric conditions.
Live Zoom Session – March 9th
Hyeonmin Ahn, PhD, Julia Hall, BS, Jessica N. Busler, PhD, Jill M. Goldstein, PhD, Daniel G. Dillon, PhD, Diego A. Pizzagalli, PhD, Laura M. Holsen, PhD
Laura M. Holsen, PhD