Sex differences between serum total bilirubin levels and cognition in patients with schizophrenia

Cognitive deficits are common in patients with schizophrenia (SCZ). Abnormal serum total bilirubin (TBIL) levels have been involved in cognitive deficits associated with neuropsychiatric diseases such as mild cognitive impairment and subcortical ischemic vascular disease. However, this relationship has not yet been fully investigated in patients with SCZ. Therefore, the aim of this study was to investigate the association between the serum TBIL concentration and cognitive deficits in SCZ patients and to determine whether a sex difference exists in the association.

A total of 455 participants were eligible and included in this cross-sectional study. Cognition was evaluated using the Montreal Cognitive Assessment. Serum TBIL concentration was measured with an automatic biochemistry analyzer according to the routine protocol in the hospital medical laboratory.

Serum TBIL levels were lower in the cognition impairment group than in the cognition normal group in male patients. In contrast, serum TBIL levels tended to be increased in the cognition impairment group in female patients, although the difference was not significant. Further stepwise multiple regression analysis stratified by sex showed that serum TBIL was independently and positively associated with cognitive function in male patients but not in female patients. Moreover, the association between serum TBIL level and cognitive function was also identified by the propensity score matching (PSM) method in male patients, but not in female patients.

These findings suggest that lower serum TBIL levels may be associated with cognitive impairment in male SCZ patients.