Hyperprolinemia is a risk factor for schizoaffective disorder
| Autor: | Caroline Demily, A Tillaux, Thierry Frebourg, Michel Petit, Sonia Dollfus, Dominique Campion, Jean-François Ménard, J Lerond, G Raux, C Bellegou, Hélène Jacquet, Gabrielle Allio, Florence Thibaut, Emmanuelle Houy, Pascal Delamillieure, Sadeq Haouzir, Gaël Fouldrin, Jacqueline Bou, Thierry d'Amato, Bernadette Hecketsweiler |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Oncology medicine.medical_specialty Psychosis Bipolar Disorder Proline Chromosomes Human Pair 22 Schizoaffective disorder Statistics Nonparametric Cellular and Molecular Neuroscience Sex Factors Antimanic Agents Reference Values Risk Factors Internal medicine DiGeorge syndrome Proline Oxidase medicine Humans Genetic Predisposition to Disease Bipolar disorder Risk factor Psychiatry Molecular Biology Analysis of Variance Valproic Acid medicine.disease Psychiatry and Mental health Phenotype Psychotic Disorders Schizophrenia Case-Control Studies Chromosomal region Hyperprolinemia Female Psychology Gene Deletion |
| Zdroj: | Molecular Psychiatry. 10:479-485 |
| ISSN: | 1476-5578 1359-4184 |
| DOI: | 10.1038/sj.mp.4001597 |
| Popis: | DNA sequence variations within the 22q11 DiGeorge chromosomal region are likely to confer susceptibility to psychotic disorders. In a previous report, we identified several heterozygous alterations, including a complete deletion, of the proline dehydrogenase (PRODH) gene, which were associated with moderate hyperprolinemia in a subset of DSM III schizophrenic patients. Our objective was (i) to determine whether hyperprolinemia is associated with increased susceptibility for any of three psychiatric conditions (schizophrenia, schizoaffective disorder and bipolar disorder) and (ii) to establish a correlation between hyperprolinemia and PRODH genotypes. We have conducted a case-control study including 114 control subjects, 188 patients with schizophrenia, 63 with schizoaffective disorder and 69 with bipolar disorder. We report that, 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, 95% confidence interval 1.3-16.3). We did not detect 22q11 interstitial deletions associated with the DiGeorge syndrome among the 320 patients of our sample and 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. |
| Databáze: | OpenAIRE |
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