Functional connectivity of hypothalamus is associated with ghrelin and cortisol in response to acute psychosocial stress

Hyeonmin Ahn, PhD

Brigham and Women’s Hospital
Functional connectivity of hypothalamus is associated with ghrelin and cortisol in response to acute psychosocial stress

Scientific Abstract

Background: Exposure to psychosocial stress activates the HPA-axis (e.g., cortisol), induces changes in resting state networks (salience and executive control), and is implicated in the development of psychiatric disorders. Recent data support the novel involvement of ghrelin, a hypothalamic orexigenic peptide, in the adaptation to stress. However, relationships between endogenous hormones and brain connectivity under stress have not been well characterized. To fill this gap, we investigated the association between hypothalamus functional connectivity and individual differences in cortisol and ghrelin responses to acute psychosocial stress.

Methods: 39 healthy adults (19F/20M) completed a study visit involving a laboratory psychosocial stress task (Maastricht Acute Stress Test, MAST), followed by a resting-state functional MRI (rs-fMRI) scan. Serial blood draws for assessment of cortisol and ghrelin were collected pre- (T0) and post-MAST (T20, T80). Area under the curve (AUC) for ghrelin and cortisol was calculated using the trapezoidal method. rs-fMRI data preprocessing and analysis were performed using CONN toolbox v19b.

Results: Post-stress ghrelin AUC and cortisol AUC were not significantly related (r=0.02, p= 0.89). Cortisol AUC was positively correlated with hypothalamus connectivity to regions in the salience network, including the nucleus accumbens (NAcc, pFDRcorr<0.05), amygdala (pFDRcorr<0.005), and hippocampus (pFDRcorr<0.01), but negatively correlated with hypothalamus connectivity to frontal regions, including the superior (pFDRcorr<0.05), middle (pFDRcorr<0.05), and inferior (pFDRcorr<0.05) frontal gyri. Ghrelin AUC showed a similar pattern: it was positively correlated with hypothalamus connectivity to the NAcc (pFDRcorr<0.05), amygdala (pFDRcorr<0.001), and hippocampus (pFDRcorr<0.01), but negatively correlated with hypothalamus connectivity to the middle frontal gyrus (pFDRcorr<0.001).

Conclusions: These findings provide novel evidence of an association between ghrelin and homeostatic-salience/executive network connectivity which mirrors that of cortisol, highlighting new pathways to target for treatments of stress-related psychiatric conditions.

SoundCloud Transcript

Hello. My name is Hyeonmin Ahn. I am a post-doc researcher in the Brigham and women’s hospital working in Dr. Laura Holsen’s lab. In this presentation, I would like to share with you my work about hypothalamus functional connectivity and how it is associated with ghrelin and cortisol in response to acute psychosocial stress.

 

Psychosocial stress is known to affect not only the cortisol release, but also resting state network changes, especially in salience and executive control network. In addition, recent studies reveal the involvement of ghrelin in the adaptation to stress but the relationship between hormones and brain connectivity under stress has not been well characterized.

So, we are working to investigate the association between hypothalamus functional connectivity and individual differences in cortisol and ghrelin responses to acute psychosocial stress.

 

In this study, there were a total of 39 healthy subjects, and they completed a study visit including the Maastricht Acute Stress Test, or MAST, followed by an MRI scan for assessment of resting state functional connectivity (RSFMRI for short). Cortisol and ghrelin were collected one time before and two times after MAST. And for analysis, areas under the curve, or AUC, were calculated for those two hormones. We analyzed RSFMRI data using CONN toolbox.

 

If you look at the result, there was no significant correlation between cortisol and ghrelin AUC. From the resting state fMRI analysis, as you can see in the brain figure, we found positive and negative correlations between hypothalamus connectivity with cortisol and ghrelin AUC in response to stress. If you see the left scatter plot, cortisol AUC was positively correlated with hypothalamus connectivity to the subcallosal cortex. This region is involved in modulation of emotional response and is sensitive to cortisol.

In contrast, cortisol AUC was negatively correlated with hypothalamic connectivity with the cuneal cortex in the occipital lobe. This result is suggesting that cortisol might be related to decoupling between homeostatic and visual system during adaptive responses to psychosocial stress.

 

Ghrelin AUC, on the right scatter plot, was positively correlated with hypothalamus connectivity to regions in the salience network such as amygdala, which exhibit dense expression of ghrelin receptors. In contrast, ghrelin AUC was negatively correlated with connectivity to posterior parietal cortex in the frontoparietal network. These findings parallel previous literature indicating that acute stress induces opposing effects on connectivity patterns of the salience and executive networks. And it is also suggesting that ghrelin might be involved in modulating large scale network coupling in the aftermath of stress.

 

In this study, we found distinct patterns of associations between hypothalamic connectivity and stress-induced changes in cortisol and ghrelin. These findings provide novel evidence of an association between ghrelin and homeostatic-salience/executive network connectivity, highlighting new pathways to target for treatments of stress-related psychiatric conditions.

 

Thank you for your attention, and please leave any questions in the chat box.  

 

Live Zoom Session – April 21st

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Authors

Hyeonmin Ahn, PhD, Jessica N. Busler, PhD, Julia Hall, BS, Benjamin Ryder, BS, Daniel G. Dillon, PhD, Diego A. Pizzagalli, PhD, Jill M. Goldstein, PhD, Laura M. Holsen, PhD

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