Bile Acids and Functional Connectivity of Executive Control and Default Mode Networks in Patients With Major...

Bile acids may contribute to pathophysiological markers of neuropsychiatric disorders, including disruptions of the executive control network (ECN) and the default mode network (DMN). Cognitive dysfunction is common in major depressive disorder; the authors examined whether bile acids affect these networks among patients with depression.

Resting-state functional MRI scans and blood levels of four bile acids from 74 treatment-naïve adults with major depressive disorder were analyzed. Dorsolateral prefrontal cortex (DLPFC) seeds were used to examine connectivity of the ECN, and posterior cingulate cortex (PCC) seeds were used to examine DMN connectivity. Using a whole-brain analysis, the authors examined correlations between the functional connectivity of these seeds and serum levels of chenodeoxycholic acid (CDCA) and its bacterially derived secondary bile acid, lithocholic acid (LCA).

CDCA levels were strongly and inversely correlated with connectivity among DLPFC regions of the ECN (R²=0.400, p<0.001). CDCA levels were also strongly and inversely correlated with connectivity of the DLPFC and left inferior temporal cortex of the ECN (R²=0.268, p<0.001). The LCA-to-CDCA ratio was strongly and positively correlated with connectivity of the DLPFC with two ECN components: the bilateral inferior temporal cortex and the left superior and inferior parietal lobules (all R²>0.250, p<0.001). For the DMN, the LCA-to-CDCA ratio was strongly and inversely correlated with connectivity of the PCC with multiple bilateral insula regions (all R²>0.250, p<0.001).

The relationship between LCA and CDCA levels and functional connectivity of the ECN and DMN suggests that major depressive disorder shares pathophysiological processes with other neuropsychiatric disorders.