Altered biochemical metabolism and its lateralization in the cortico-striato-cerebellar circuit of unmedicated bipolar II depression

Abstract Objectives Evidence of the relationship between neurometabolic changes in the cortico-striato-cerebellar (CSC) circuit and bipolar disorder (BD) is still limited. To elucidate the pathogenesis of BD, we investigated the underlying neurometabolic changes and their effect on CSC lateralization circuits in unmedicated patients with bipolar II depression. Methods Forty unmedicated participants with bipolar II depression and forty healthy controls underwent proton magnetic resonance spectroscopy ( 1 H-MRS). We obtained bilateral metabolic ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in the prefrontal white matter (PWM), anterior cingulate cortex (ACC), basal ganglia (BG) and the cerebellum. Metabolic ratios were characterized using a laterality index (LI) for left-right asymmetry. Results Overall, aberrant lateralization in the CSC circuit was characteristic in patients with bipolar II depression. Patients with bipolar II depression showed significantly lower NAA/Cr ratios in the left PWM, right ACC, left BG and left cerebellum when compared with the healthy controls. For bipolar II depression, we found lower NAA/Cr LI in the PWM, ACC, BG, and cerebellum and higher Cho/Cr LI in the BG and cerebellum when compared to the standard value (1.0). For healthy controls, we found lower NAA/Cr LI only in the BG and higher Cho/Cr LI in the cerebellum when compared to 1.0. Limitations As a cross-sectional study with a small sample size, progressive changes and complex metabolic interactions with treatment were not observed. Conclusions Our findings suggest that abnormal biochemical metabolism with aberrant lateralization in the CSC circuit may be an underlying pathophysiology of bipolar II depression.