Association of Bile Acids with Connectivity of Executive Control and Default Mode Networks in Patients with Major Depression

Dunlop, B.; Cha, J.; Mayberg, H. S.; Choi, K. S.; Craighead, W. E.; Mahmoudiandehkordi, S.; Bhattacharyya, S.; Rush, A. J.; Kaddurah-Daouk, R.

doi:10.1101/2024.12.20.629637

bioRxiv · 10.1101/2024.12.20.629637

Association of Bile Acids with Connectivity of Executive Control and Default Mode Networks in Patients with Major Depression

Dunlop, B.·Cha, J.·Mayberg, H. S.·Choi, K. S.·Craighead, W. E.·Mahmoudiandehkordi, S.·Bhattacharyya, S.·Rush, A. J.·Kaddurah-Daouk, R.

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Abstract

Objective: Bile acids may contribute to pathophysiologic markers of Alzheimers disease, including disruptions of the executive control network (ECN) and the default mode network (DMN). Cognitive dysfunction is common in major depressive disorder (MDD), but whether bile acids impact these networks in MDD patients is unknown. Methods: Resting state functional magnetic resonance imaging (fMRI) scans and blood measures of four bile acids from 74 treatment-naive adults with MDD were analyzed. Dorsolateral prefrontal cortex (DLPFC) seeds were used to examine connectivity of the ECN and posterior cingulate cortex (PCC) seeds were used for the DMN. Using a whole-brain analysis, the functional connectivity of these seeds was correlated with serum levels chenodeoxycholic acid (CDCA) and its bacterially-derived secondary bile acid, lithocholic acid (LCA). Results: CDCA levels were strongly and inversely correlated with connectivity between DLPFC regions of the ECN (R2= .401, p<.001). LCA levels were strongly and positively correlated with connectivity of the DLPFC and left inferior temporal cortex of the ECN (R2=.263, p<.001). The LCA/CDCA ratio was strongly and positively correlated with connectivity of the DLPFC with two components of the ECN: bilateral inferior temporal cortex and the left superior and inferior parietal lobules (all R2>.24, all p<.001). For the DMN, the LCA/CDCA ratio was strongly and negatively correlated with connectivity of the PCC with multiple bilateral insula regions (all R2>0.25, all p<.001). Conclusions: The relationship between LCA and CDCA levels and functional connectivity of the ECN and DMN suggests potential shared pathophysiologic processes between Alzheimers disease and MDD.

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Dunlop, B., Cha, J., Mayberg, H. S., Choi, K. S., Craighead, W. E., Mahmoudiandehkordi, S., Bhattacharyya, S., Rush, A. J., Kaddurah-Daouk, R.. 2024-12-23. Association of Bile Acids with Connectivity of Executive Control and Default Mode Networks in Patients with Major Depression. https://doi.org/10.1101/2024.12.20.629637

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