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Influence of 5-HT_2C receptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia

Division of Psychiatry and Neuroscience, Queen's University Belfast

Ryan O'Neill

Department of Psychiatry, Causeway Hospital, Coleraine

Jennifer K. Doherty

Division of Psychiatry and Neuroscience, Queen's University, Belfast

Jayne V. Woodside

Nutrition and Metabolism Research Group, Queen's University Belfast

Gavin P. Reynolds

Division of Psychiatry and Neuroscience, Queen's University Belfast, UK

Correspondence: Professor Gavin P. Reynolds, Division of Psychiatry and Neuroscience, Queen's University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, UK. Email: g.reynolds{at}qub.ac.uk

Declaration of interest

This study was supported in part by Janssen-Cilag Pharmaceuticals. S.C. has received honoraria as a speaker or advisor panel member for Astellas, Bristol-Myers Squibb, Lilly, Organon and Servier. R.O'N. has received honoraria from AstraZeneca. G.R. has received honoraria as a speaker or advisor panel member for Lilly, AstraZeneca, Organon and Janssen.

Background

Obesity and metabolic syndrome are significant problems for patients taking antipsychotic drugs. Evidence is emerging of genetic risk factors.

Aims

To investigate the influence of two candidate genes, smoking and drug treatment on obesity and metabolic syndrome in patients with schizophrenia.

Method

Patients (n=134) were assessed for measures of obesity, other factors contributing to metabolic syndrome, and two genetic polymorphisms (5-HT_2C receptor –759C/T and leptin –2548A/G).

Results

Neither genotype nor smoking was significantly associated with measures of obesity. However, both leptin genotype and smoking were significantly associated with metabolic syndrome. Significant interaction occurred between the genetic polymorphisms for effects on obesity, whereby a genotype combination increased risk. Drug treatment showed significant effects on measures of obesity and triglyceride concentrations; risperidone was associated with lower values than olanzapine or clozapine.

Conclusions

The findings suggest interacting genetic risk factors and smoking influence development of metabolic syndrome in patients on antipsychotic drugs.

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Highlights of this issue

Kimberlie Dean
BJP 2008 192: A22. [Full Text]