Different impacts of aquaporin 4 and MAOA allele variation among olanzapine, risperidone, and paliperidone in schizophrenia.

Apoptosis has been considered to be involved in schizophrenia. Water channels are modulated just before apoptosis. In the aquaporin family, aquaporin 4 (AQP-4) is most highly expressed in the brain and is supposed to play an important role in a neuronal environment. In this clinical study, we investigated the relationship between the AQP-4 polymorphism and drug response in schizophrenia under the control of the MAOA (monoamine oxidase A) promoter gene. We recruited 91 patients with schizophrenia, and they were randomized to receive olanzapine (n = 44), risperidone (n = 23), or paliperidone (n = 24). Genotyping of AQP-4 and MAOA polymorphisms was done in all patients. Patients with the AQP-4 non-C polymorphism needed a higher dosage of olanzapine for treatment (z = 4.163, P = 0.041), and patients with a short form of the MAOA polymorphism needed a higher dosage of risperidone for treatment (z = 5.124, P = 0.024). Patients who smoked cigarettes needed a higher dosage of olanzapine for treatment (z = 4.905, P = 0.027), but cigarette smoking did not affect the dosage of paliperidone. The AQP-4 polymorphism may have an effect in influencing the dosage of olanzapine. However, the roles of AQP-4 polymorphisms in the blood-brain barrier and different neuroprotective effects need further exploration in future studies.
AuthorsTing-Sheng Chung, For-Wey Lung
JournalJournal of clinical psychopharmacology (J Clin Psychopharmacol) Vol. 32 Issue 3 Pg. 394-7 (Jun 2012) ISSN: 1533-712X [Electronic] United States
PMID22544010 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)
Chemical References
  • AQP4 protein, human
  • Antipsychotic Agents
  • Aquaporin 4
  • Isoxazoles
  • Pyrimidines
  • Benzodiazepines
  • olanzapine
  • Monoamine Oxidase
  • Risperidone
  • Paliperidone Palmitate
  • Adult
  • Antipsychotic Agents (administration & dosage, therapeutic use)
  • Aquaporin 4 (genetics, metabolism)
  • Benzodiazepines (administration & dosage, therapeutic use)
  • Diagnostic and Statistical Manual of Mental Disorders
  • Drug Monitoring
  • Female
  • Genetic Association Studies
  • Humans
  • Isoxazoles (administration & dosage, therapeutic use)
  • Male
  • Middle Aged
  • Monoamine Oxidase (genetics, metabolism)
  • Paliperidone Palmitate
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Psychiatric Status Rating Scales
  • Pyrimidines (administration & dosage, therapeutic use)
  • Risperidone (administration & dosage, therapeutic use)
  • Schizophrenia (drug therapy, genetics, metabolism)
  • Smoking (metabolism)
  • Young Adult

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