Effects of dopamine-based genetic risk score on dynamic low-frequency fluctuations in patients with first-episode drug-naïve schizophrenia

Abstract

Alterations in dynamic intrinsic brain activity and neurotransmitter signaling, such as dopamine, have been independently detected in schizophrenia patients. Yet, it remains unclear whether the dopamine genetic risk variants have additive effects on brain intrinsic activity. We aimed to investigate the schizophrenia-specific dynamic amplitude of low frequency fluctuation (dALFF) altered pattern, and its association with dopamine genetic risk score in first-episode drug-naïve schizophrenia (FES). Fifty-five FES and 53 healthy controls were included. A sliding-window method based on the dALFF was adopted to estimate the dynamic alterations in intrinsic brain activity. Subjects were genotyped, and a genetic risk score (GRS), which combined the additive effects of ten risk genotypes from five dopamine-related genes, was calculated. We used the voxel-wised correlation analysis to assess the effects of dopamine- GRS on dALFF. FES showed significantly increased dALFF left medial prefrontal cortex and significantly decreased dALFF in the right posterior cingulate cortex compared with healthy controls. Greater dopamine GRS in FES was associated with higher dALFF in the left middle frontal gyrus and left inferior parietal gyrus. Our findings indicate that cumulative dopamine genetic risk is associated with a known imaging phenotype for schizophrenia.