Study Report

Reference	Jacquet, H.,2005 PMID: 15494707
Citation	Jacquet, H., C. Demily, et al. (2005). "Hyperprolinemia is a risk factor for schizoaffective disorder." Mol Psychiatry 10(5): 479-485.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	114 control subjects, 188 patients with schizophrenia, 63 with schizoaffective disorder and 69 with bipolar disorder
SNP/Region/Marker Size	14 variants
Predominant Ethnicity	Caucasian
Population	French
Gender	40% males in control,73% males in the schizophrenic sample,60% males in the schizoaffective sample and 52% males in the bipolar sample
Age Group	Adults : Mean age(SD)(year):38(11) in control,37(10) in the schizophrenic sample,40(12) in the schizoaffective sample and 48(15) in the bipolar sample

Sample Diagnosis	DSM
Sample Status	All subjects were unrelated Caucasian born in France. Subjects with alcohol abuse at the time of the study were excluded from the study. Control subjects (n=114) were mainly staff members. Subjects with a history of psychiatric or metabolic disorder or with first-degree relatives with history of psychiatric disorder were not included. All controls were drug-free (except oral contraceptives in women). Affected subjects were ascertained among in- or outpatients from four psychiatric hospitals. Consensus diagnoses for psychiatric cases were established by two raters according to DSM IIIR criteria from all available information following examination of case notes and in most cases direct interview of patients with the Positive and Negative Schizophrenia Scale (PANSS, Kay et al8) and the appropriate sections of the Schedule for Affective disorder and Schizophrenia.The schizophrenic sample consisted of 188 subjects (clinical subtypes: 35 undifferentiated, 90 paranoid, 47 disorganized, 15 residual and 1 catatonic), while the schizoaffective sample contained 63 subjects and the bipolar sample 69 subjects.
Technique	PCR and sequencing
Statistical Method	Statistical comparisons for categorical variables were performed using X2 test or Fisher's exact test when the cells size was small. All tests reported were two-tailed.
Result Summary	We found no association between common PRODH polymorphisms and any of the psychotic disorders. In contrast, we found that five rare PRODH alterations (including a complete PRODH deletion and four missense substitutions) were associated with hyperprolinemia. In several cases, two variations were present simultaneously, either in cis or trans in the same subject. A total of 11 from 30 hyperprolinemic subjects bore at least one genetic variation associated with hyperprolinemia. This study demonstrates that moderate hyperprolinemia is an intermediate phenotype associated with certain forms of psychosis.