Bilirubin Concentration Correlates With Positive Symptoms in Patients With Schizophrenia

Objective: Besides its toxic effects, bilirubin has been demonstrated to have antioxidant properties to counteract oxidative stress, which has been suggested to play a role in the pathophysiology of schizophrenia.

Methods: This study investigated the potential association between changes in psychopathology measured by the Lindenmayer model of the Positive and Negative Syndrome Scale (PANSS) and changes in total plasma bilirubin concentrations. Data of patients with schizophrenia (ICD-10) starting monotherapy with a new-generation antipsychotic were analyzed at baseline (N = 52) and 2 (n = 40), 4 (n = 46), and 12 weeks (n = 30) after the initiation of treatment. Data were collected between December 1997 and October 2007 and analyzed retrospectively.

Results: The PANSS total score decreased significantly from baseline to weeks 2, 4, and 12 of treatment (all P values .001). Total plasma bilirubin concentration also dropped significantly from baseline to week 2 (P = .015) and decreased further until week 4 (P = .013); no significant decrease was observed between baseline and week 12. Spearman rank correlation revealed a significant association of bilirubin concentration with the PANSS positive (r = 0.371, P = .007) and excitement (r = 0.322, P = .020) components at baseline. No further correlations were found. From baseline to weeks 2, 4, and 12, changes in the PANSS positive component correlated significantly with changes in plasma bilirubin concentration (all P values < .05), whereas correlations between changes in the remaining PANSS components and bilirubin were less consistent.

Conclusions: Assuming that positive symptoms are associated with the subjective experience of psychological distress, our findings indirectly expand the evidence on potential antioxidant properties of bilirubin in patients with schizophrenia.

J Clin Psychiatry 2016;77(4):512–516