Study Report

Reference	Serretti, A.,2001(b) PMID: 11353451
Citation	Serretti, A., R. Lilli, et al. (2001). "DRD4 exon 3 variants associated with delusional symptomatology in major psychoses: a study on 2,011 affected subjects." Am J Med Genet 105(3): 283-290.
Disease Type	Bipolar Disorder & Schizophrenia & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	2,011 inpatients affected by bipolar disorder (n = 811), major depressive disorder (n = 635), schizophrenia (n = 419), delusional disorder (n = 104), psychotic disorder not otherwise specified (n = 42), and 601 healthy controls
SNP/Region/Marker Size	1 variant
Predominant Ethnicity	Caucasian
Population	Italian
Gender	42% males in patients and 44% males in controls
Age Group	Adults : Mean age(SD)(year):45.92(14.44);31.41(12.42) at onset for BD patients and 47.45(14.96) for controls

Sample Diagnosis	DSM
Sample Status	Two thousand and eleven inpatients consecutively admitted to the Department of Psychiatry at the Institute H. San Raffaele were included in this study (811 bipolars, 635 major depressives, 104 delusionals, 419 schizophrenics, 42 psychotic NOS). Six hundreds and ninety-three patients were previously reported [Serretti et al., 1998, 1999a] and 432 subjects were part of the sample collected for the European Collaborative Project on Affective Disorders [Souery et al., 1998].A subsample of 1,264 patients (548 bipolars, 348 major depressives, 272 schizophrenics, 71 delusionals, 27 psychotic NOS) were evaluated using the OPCRIT checklist with a lifetime perspective [McGuffin et al., 1991]. Criteria for inclusion in the study were diagnosis of major psychoses. The presence of concomitant diagnoses of mental retardation or drug dependence, together with somatic or neurological illnesses that impaired psychiatric evaluation, represented exclusion criteria. Six hundred and one control subjects were recruited from both healthy department personnel, people attending the general laboratory, and the surgery department of our hospital. Before drawing blood samples, controls were closely investigated to determine whether they or their first-degree relatives had psychiatric disturbances or previous psychiatric treatment, through interviews with subjects and relatives when possible. Only unaffected subjects with negative family histories were included in the study. It should be noted that those data were not collected through the detailed methodology used in family studies, and that a substantial rate of false negatives is commonly observed [Andreasen et al., 1977]. No further restriction or selection was applied to controls. These were unrelated and of Italian descent, with antecedents from all parts of the country.
Technique	genotyping
Statistical Method	chi-square tests
Result Summary	DRD4 allele and genotype frequencies in bipolars, schizophrenics, delusionals, and psychotic NOS were not significantly different from controls; major depressives showed a trend toward an excess of DRD4*Short and DRD4*Short/Short variants versus controls. The ANOVA on factor scores in the whole subsample of 1,264 subjects showed a significant difference on delusion factor in allele analysis (P = 0.007), and in genotype one (P = 0.018), with DRD4*Long containing variants associated with severe symptomatology. The analysis in the replication subjects only (n = 803) showed a trend in the same direction, though not reaching the significance level. This analysis in an enlarged sample suggests that DRD4*Long alleles exert a small but significant influence on the delusional symptomatology in subjects affected by major psychoses.