MIR124 polygenic risk and functional connectivity of the striatum in patients with bipolar disorder: mediation by childhood trauma.

Background: Both genetic and environmental factors can influence brain function in individuals with bipolar disorder (BD). This study aimed to investigate the aberrant functional connectivity (FC) of the striatum and its relationship with the polygenic risk score (PRS) of MicroRNA-124 (MIR124) and experiences of childhood trauma.

Methods: The study recruited 80 patients with BD and 54 healthy controls (HCs). Resting-state functional magnetic resonance imaging data were collected from all participants. Six pairs of striatal subregions were selected as seeds for the FC analysis. Additionally, MIR124 PRS was calculated, and childhood trauma was assessed. Partial correlation and mediation analyses were conducted to explore these associations.

Results: BD exhibited higher incidence of childhood trauma and increased MIR124 PRS compared to HCs. When compared to HCs, BD showed decreased FC between the left dorsal caudate (dCa) and right thalamus, the right dCa and left medial superior frontal gyrus, and the right dlPu and right median cingulate/paracingulate gyri. Conversely, increased FC was observed between the right dorsolateral putamen (dlPu) and left precentral gyrus, the right globus pallidus (GP) and precentral gyrus. Notably, mediation analyses revealed that scores for emotional neglect (EN) and physical neglect (PN) from the Childhood Trauma Questionnaire (CTQ) mediated the relationship between MIR124 PRS and FC between the right GP and left precentral gyrus.

Conclusions: These findings suggest that an elevated MIR124 PRS and experiences of childhood trauma may be associated with altered FC within corticostriatal circuits in BD, offering potential new insights into the underlying mechanisms of BD.