Study Report

Reference	Lerer, B.,2001 PMID: 11526472
Citation	Lerer, B., F. Macciardi, et al. (2001). "Variability of 5-HT2C receptor cys23ser polymorphism among European populations and vulnerability to affective disorder." Mol Psychiatry 6(5): 579-585.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	513 patients with recurrent major depression (MDD-R),649 patients with bipolar (BP) affective disorder and 901 normal controls.
SNP/Region/Marker Size	1 variant
Predominant Ethnicity	Caucasian
Population	European
Gender	Male/female:279/370 for BPD patients,163/350 for MDD patients and 426/475 for controls

Sample Diagnosis	DSM
Sample Status	The patients for this study were consecutively recruited in the nine participating centers. Diagnoses of major depression: recurrent and bipolar disorder were according to DSM-IV criteria9 and were based on semistructured interview using the Schedule for Affective Disorders and Schizophrenia: Lifetime version (SADSL)(New York State Psychiatric Institute, New York,1978) or, for the Bulgarian patients, the Schedules for Clinical Assessment in Neuropsychiatry (SCAN)(World Health Organisation, Geneva, 1992). Control subjects were screened to exclude a personal or family history of major psychiatric disorder. Background data and specific clinical characteristics of the subjects were centralized in Brussels and entered into the ECPAD database.
Technique	PCR and RFLP
Statistical Method	The statistical analyses employed Stata Statistical Software (Release 6, Stata Corporation; 1999). For categorical analyses, maximum likelihood chi-square statistics were employed. For bivariate comparisons of parametric data, the student's t-test was used. To evaluate the relationship of more than one independent variable to genotype, a stepwise logistic regression procedure was implemented. The outcome('response') variable of the logistic regression was the presence of the HT2CR ser23 allele.
Result Summary	There was significant variation in the frequency of the HT2CR ser23 allele among the 10 population groups included in the sample (from 24.6% in Greek control subjects to 9.2% in Scots, chi(2) = 20.9, df 9, P = 0.01). Logistic regression analysis demonstrated that over and above this inter-population variability, there was a significant excess of HT2CR ser23 allele carriers in patients compared to normal controls that was demonstrable for both the MDD (chi(2) = 7.34, df 1, P = 0.006) and BP (chi(2) = 5.45, df 1, P = 0.02) patients. These findings support a possible role for genetically based structural variation in 5-HT2C receptors in the pathogenesis of major affective disorder.