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The influence of 5-HT(2C) and MDR1 genetic polymorphisms on antipsychotic-induced weight gain in female schizophrenic

Martina Rojnic Kuzman1, Vesna Medved, Nada Bozina

  • 1Department of Psychiatry, Zagreb University Hospital Centre, Kispaticeva 12 10000 Zagreb, Croatia. mrojnic@gmail.com

Psychiatry Research
|August 23, 2008
PubMed

Insights

Genetic variants in MDR1, not 5-HT(2C) receptors, influenced weight gain in female schizophrenia patients treated with second-generation antipsychotics. Specific MDR1 variants were linked to risperidone-induced weight gain.

Area of Science:

  • Pharmacogenetics
  • Neuroscience
  • Psychiatry

Background:

  • Second-generation antipsychotics (SGAs) are crucial for schizophrenia treatment but often cause significant weight gain.
  • The 5-HT(2C) receptor and multidrug-resistant protein 1 (MDR1), which encodes P-glycoprotein, are implicated in drug metabolism and response.
  • Understanding genetic predispositions to SGA-induced weight gain is vital for personalized treatment strategies.

Purpose of the Study:

  • To investigate the association between functional genetic variants of the 5-HT(2C) receptor and MDR1 and weight gain in female schizophrenic patients treated with SGAs.
  • To determine if specific genetic variations influence the risk or extent of weight gain induced by olanzapine or risperidone.

Main Methods:

  • A cohort of 108 female schizophrenic patients treated with olanzapine or risperidone was genotyped for 5-HT(2C) receptor (-759C/T) and MDR1 (exon 21 G2677T, exon 26 C3435T) polymorphisms.
  • Patients were categorized based on weight gain (> or = 7% of initial body weight vs. < 7%).
  • Statistical analyses, including haplotype-based analysis, were performed to compare genotype and allele frequencies between weight gain groups.

Main Results:

  • No significant association was found between 5-HT(2C) receptor variants and SGA-induced weight gain.
  • Haplotype analysis of MDR1 revealed a slightly lower representation of the G2677/C3435 haplotype in patients with significant weight gain.
  • In the risperidone subgroup, MDR1 variants 2677T and 3435T, and the 2677T/3435T haplotype were overrepresented in the significant weight gain group, while the G2677/C3435 haplotype was less represented.

Conclusions:

  • The 5-HT(2C) receptor -759C/T polymorphism does not appear to play a significant role in SGA-induced weight gain.
  • MDR1 gene polymorphisms (G2677T and C3435T) show a stronger influence on risperidone-induced weight gain in female schizophrenic patients.
  • MDR1 variants associated with lower P-glycoprotein function may increase risperidone's brain accessibility, potentially leading to enhanced antipsychotic effects and weight gain.

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