Differences in biochemical metabolism and cognitive function between bipolar I and bipolar II disorder

BACKGROUND: This study aimed to characterise neurometabolic differences between bipolar disorder I (BD-I) and bipolar disorder II (BD-II), and to examine their associations with cognitive function. METHODS: A total of 50 patients diagnosed with BD-I, 80 patients with BD-II, and 50 healthy controls (HCs) were recruited for this study. Metabolite concentrations—specifically N-acetylaspartate (NAA) and choline-containing compounds (Cho)—were measured in the prefrontal white matter (PWM), anterior cingulate cortex (ACC), and thalamus through proton magnetic resonance spectroscopy (¹H-MRS). Cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: When compared to HCs, patients with BD-II showed significantly higher Cho/Cr ratios in the right PWM and left ACC, along with lower NAA/Cr ratios in the right thalamus; compared to BD-II patients, those with BD-I exhibited higher Cho/Cr ratios in the right PWM and lower NAA/Cr ratios in the right thalamus; among BD-I patients, the Cho/Cr ratio in the left ACC was negatively correlated with measures of information processing speed and attentional vigilance. CONCLUSIONS: This study demonstrates that BD-II patients exhibit greater cholinergic dysregulation in the left ACC and the right PWM, whereas BD-I patients show more pronounced neuronal dysfunction in the right thalamus. Furthermore, the left ACC Cho/Cr ratio was specifically associated with cognitive impairments in information processing speed and attentional vigilance, but only among patients with BD-I. This suggests that subtype-specific mechanisms underlie the relationship between neurometabolic abnormalities and cognitive deficits. CLINICAL TRIAL NUMBER: Not applicable.