Proline Dehydrogenase Gene Alterations Associated with Schizoaffective Disorder: DNA sequence variations within the 22q11 DiGeorge chromosomal region are likely to confer susceptibility to psychotic disorders. Several heterozygous alterations, including a complete deletion, of the proline dehydrogenase (PRODH) gene, are associated with moderate hyperprolinemia in a subset of schizophrenic patients. In a case-control study including 114 controls, 188 patients with schizophrenia, 63 with schizoaffective disorder and 69 with bipolar disorder, taking into account a confounding effect due to valproate treatment, hyperprolinemia is a risk factor for DSM IIIR schizoaffective disorder (P=0.02, Odds ratio=4.6). No 22q11 interstitial deletions associated with the DiGeorge syndrome nor any association between common PRODH polymorphisms and any of the psychotic disorders were found. In contrast, 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. Hyperprolinemia is a risk factor for schizoaffective disorder. Jacquet H, Demily C, et al. Faculte de Medecine, Rouen, France. Mol Psychiatry. 2005 May;10(5):479-85.

Schizoaffective Patients Often Had Bipolars or Schizophrenics in Family: In a study of the 2.4 million persons born in Denmark after 1952, 1925 persons had a schizoaffective disorder, 3721 had a bipolar disorder, and 12 501 had schizophrenia. The relative risk of schizoaffective disorder was 2.76 if a first-degree relative had a history of mental illness compared with a person with no first-degree relatives with such a history. There was an additional risk of 2.57, 3.23, or 1.92 if the first-degree relative had schizophrenia, bipolar disorder, or schizoaffective disorder, respectively, compared with other psychiatric admissions. When bipolar disorder was the outcome, bipolar disorder in first-degree relatives was by far the significantly strongest risk factor. When schizophrenia was the outcome, the significantly strongest risk factor was schizophrenia among first-degree relatives. Schizoaffective disorder is not simply a subgroup of either bipolar disorder or schizophrenia but may be genetically linked to both, with schizoaffective disorder being a subtype of each or a genetic intermediate form. Family history of psychiatric illness as a risk factor for schizoaffective disorder: a Danish register-based cohort study. Laursen TM, et al. University of Aarhus, Denmark. .