Zonulin Serum Level in Adolescents with Bipolar I Disorder and Schizophrenia

Abstract

Objective: Evidence on the contribution of intestinal permeability to the pathophysiology of bipolar disorder (BD) and schizophrenia remains limited. Zonulin, a non-invasive biomarker of intestinal permeability, has been suggested as a factor influencing psychiatric outcomes. This study investigated whether adolescents with BD-I or schizophrenia demonstrate altered serum zonulin levels and whether these levels are associated with symptom severity.

Methods: A case-control study was conducted involving 45 adolescents with BD-I, 45 with schizophrenia, and 45 healthy controls. Symptom severity was evaluated using the Young Mania Rating Scale and Beck Depression Inventory in BD patients, and the Positive and Negative Syndrome Scale in schizophrenia patients. The General Health Questionnaire-28 was applied to controls to exclude psychiatric morbidity. All participants also completed the Beck Suicide Inventory, the Suicide Risk–Adolescent Version Modified, and the Snaith–Hamilton Pleasure Scale.

Results: Serum zonulin levels were significantly lower in BD-I patients compared with controls, whereas no significant differences were observed between the schizophrenia and control groups (P = .066) or between the BD-I and schizophrenia groups (P = .297). Mean zonulin levels were highest among controls, intermediate in schizophrenia, and lowest in BD-I. Across both clinical groups, higher serum zonulin concentrations correlated positively with greater symptom severity and suicidal behavior. In schizophrenia, but not in BD-I, zonulin levels were additionally associated with anhedonia.

Conclusion: Serum zonulin does not appear to be a diagnostic biomarker for BD-I or schizophrenia. Nevertheless, it may have clinical relevance given its associations with symptom severity, suicidal behavior, and anhedonia in schizophrenia.

Cite this article as: Mohamed MI, A, Khoweiled AAEH, Khalil MAEF, Baz HA, Ayoub DR. Zonulin serum level in adolescents with bipolar I disorder and schizophrenia. Neuropsychiatr Invest. 2026, 64, 0073, doi: 10.5152/NI.2026.25073.