The characteristic of cognitive impairments in patients with bipolar II depression and its association with N-acetyl aspartate of the prefrontal white matter

BACKGROUND: Cognitive deficit is acknowledged as a core feature of clinical manifestations of bipolar disorder (BD). However, the underlying mechanism of cognitive impairment in bipolar II depression has remained uncertain. We aim to determine the association of cognitive impairments with biochemical metabolism using proton magnetic resonance spectroscopy ((1)H-MRS) and a battery of neuropsychological testing. METHODS: The current study was designed to assess four cognitive domains in a sample of 110 patients with bipolar II depression and 110 healthy controls, using a battery of 6 cognitive tests, including the Digit Symbol Substitution Test (DSST), Wisconsin Cart Sorting Test (WCST), Trail Making Test Part B (TMT-B), Digit Span Test (DST), TMT-part A (TMT-A) and Verbal Fluency Test (VFT). Metabolite levels were obtained in the following brain regions of interest: bilateral prefrontal white matter (PWM), bilateral anterior cingulate cortex (ACC), bilateral lenticular nucleus (LN), and bilateral thalamus. N-acetyl aspartate (NAA)/creatine (Cr) and choline-containing compounds (Cho)/Cr ratios are analyzed. RESULTS: Patients with bipolar II depression performed significantly worse on DSST (score), TMT (completion time), DSB (score), and VFT (valid word number) when compared with healthy controls. In the bilateral PWM, NAA/Cr ratios in the PWM were significantly reduced (bilaterally) than those in healthy controls. Correlation analysis was conducted with data from patients with bipolar II depression, we found that the NAA/Cr ratio of the left PWM was positively correlated with the score of DS and DSB, and the NAA/Cr ratio of the right PWM was negatively correlated with the completion time of TMT-B. CONCLUSIONS: Our findings suggested that psychomotor speed, executive function, working memory, and verbal fluency are impaired in patients with BD II depression. Hypoactivity NAA/Cr in bilateral PWM may be associated with BD II depression's pathophysiology and results in cognitive dysfunction.