Signatures of neuroinflammation in the hippocampus and amygdala in individuals with religious or spiritual problem

Abstract

ABSTRACT The term Religious or Spiritual Problem (RSP), as defined in the revised 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR, 2022), refers to the questioning of faith, transcendent values, or changes in the religious belief system. This condition is often accompanied by marked depression and anxiety. However, it has not been explored whether RSP shares biological features with psychiatric disorders, including neuroinflammation in the amygdala and hippocampus. To elucidate this issue, we investigated 50 individuals with RSP and 50 matched control volunteers. Neuroinflammation was indexed by the diffusion-basis spectral imaging-based restricted fraction (DBSI-RF) measure in magnetic resonance imaging (MRI) scans. Plasma C-reactive protein (CRP) and IL-6 levels were also measured. The results revealed significantly elevated inflammatory measures in the amygdala and hippocampus and increased IL-6 concentrations in RSP. Depressive symptoms predicted the inflammatory measures. IL-6 partially mediated the relationship between depression and inflammation in the amygdala. However, the evidence for this mediation was weak, as revealed by Bayesian statistics. These results indicate that RSP is characterized by putative neuroinflammatory changes in brain structures implicated in emotion regulation, learning, and memory.