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Background:  Aquaporin 4 (AQP4) polymorphism may influence the required dosage of antipsychotic drugs. However, the roles of AQP4 polymorphisms in the blood—brain barrier (BBB) and different neuroprotective effects need further exploration. This study aims to investigate whether the gene polymorphisms and haplotype of AQP4 are associated with serum S100 calcium-binding protein B (S100B) level and clinical symptoms in patients with schizophrenia (SCZ).   Methods:  We recruited 190 patients with SCZ. They provided demographic data, completed relevant questionnaires, and submitted samples to test for four AQP4 tag single nucleotide polymorphisms (SNPs) and eight haplotypes. The rating scales of Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP), the Global Assessment of Functioning (GAF), Clinical Global Impression (CGI) were assessed and serum S100B level were measured repeatedly during antipsychotic treatment at weeks 0 (baseline), 3, 6, and 9. Using generalized estimating equation (GEE) analyses, log-transformed S100B (logS100B) level was tested for associations with haplotype and other dependent variables.   Results:  Discretization via the median split procedure showed that logS100B level >1.78 or ≤ 1.78 had the best discriminant validity to stratify the patients into two groups. After 9 weeks of treatment, the serum S100B level was decreased. The TAA haplotype of AQP4 SNPs was associated with increased serum S100B level ( p  = 0.006). The PANSS negative subscale (PANSS-N) ( p  = 0.001) and Clinical Global Impression–Improvement (CGI-I) ( p  = 0.003) scores had a positive association with S100B level.   Conclusion:  Patients with the TAA haplotype of the AQP4 polymorphism are likely to have increased serum S100B level, negative symptoms and poor control of neuroinflammation. A logS100B level >1.78 may be sufficiently specific to predict a higher severity of negative symptoms. Further study including healthy controls and patients with first and recurrent episodes under selective AQP4 modulators will be necessary to explore the profound effects on the treatment of patients with SCZ and may positively influence their overall outcome.

frontiers in psychiatry

Human Aquaporin 4 Gene Polymorphisms and Haplotypes Are Associated With Serum S100B Level and Negative Symptoms of Schizophrenia in a Southern Chinese Han Population