Psychiatry Investig.  2014 Apr;11(2):179-185. 10.4306/pi.2014.11.2.179.

Association of the PPAR-gamma Gene with Altered Glucose Levels and Psychosis Profile in Schizophrenia Patients Exposed to Antipsychotics

Affiliations
  • 1Office of Research and Development, Taipei Medical University, Taipei, Taiwan.
  • 2Yuli Veterans Hospital, Yuli Township, Hualian County, Taiwan.
  • 3Faculty of Medicine, National Yang Ming University, Taipei, Taiwan.
  • 4Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan.
  • 5Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan.
  • 6Chung Hwa University of Medical Technology, Tainan, Taiwan.
  • 7Department of Psychiatry, Min-Sheng General Hospital, Taoyuan City, Taiwan.
  • 8Institute of Public Health and Department of Public Health, National Yang Ming University, Taipei, Taiwan.
  • 9Department of Health Care and Social Work, Yu Da University of Science and Technology, Chao-chiao Township, Miaoli County, Taiwan.
  • 10Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
  • 11Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
  • 12Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan. lohew@hotmail.com

Abstract


OBJECTIVE
Metabolic abnormalities, e.g., diabetes, are common among schizophrenia patients. Peroxisome proliferator activated receptor-gamma (PPAR-gamma) regulates glucose/lipid metabolisms, and schizophrenia like syndrome may be induced by actions involving retinoid X receptor-alpha/PPAR-gamma heterodimers. We examined a possible role of the PPAR-gamma gene in metabolic traits and psychosis profile in schizophrenia patients exposed to antipsychotics.
METHODS
Single nucleotide polymorphisms (SNPs) of the PPAR-gamma gene and a serial of metabolic traits were determined in 394 schizophrenia patients, among which 372 were rated with Positive and Negative Syndrome Scale (PANSS).
RESULTS
SNP-10, -12, -18, -19, -20 and -26 were associated with glycated hemoglobin (HbA1c) whereas SNP-18, -19, -20 and -26 were associated with fasting plasma glucose (FPG). While SNP-23 was associated with triglycerides, no associations were identified between the other SNPs and lipids. Further haplotype analysis demonstrated an association between the PPAR-gamma gene and psychosis profile.
CONCLUSION
Our study suggests a role of the PPAR-gamma gene in altered glucose levels and psychosis profile in schizophrenia patients exposed to antipsychotics. Although the Pro12Ala at exon B has been concerned an essential variant in the development of obesity, the lack of association of the variant with metabolic traits in this study should not be treated as impossibility or a proof of error because other factors, e.g., genes regulated by PPAR-gamma, may have complicated the development of metabolic abnormalities. Whether the PPAR-gamma gene modifies the risk of metabolic abnormalities or psychosis, or causes metabolic abnormalities that lead to psychosis, remains to be examined.

Keyword

Schizophrenia; Psychosis; Glucose; PPAR-gamma gene

MeSH Terms

Antipsychotic Agents*
Blood Glucose
Exons
Fasting
Glucose*
Haplotypes
Hemoglobin A, Glycosylated
Humans
Obesity
Peroxisomes
Polymorphism, Single Nucleotide
Psychotic Disorders*
Schizophrenia*
Triglycerides
Antipsychotic Agents
Glucose
Triglycerides
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