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Hyperprolinemia is a risk factor for schizoaffective disorder.
Molecular Psychiatry
|October 21, 2004
Summary
Moderate hyperprolinemia is a risk factor for schizoaffective disorder, particularly in individuals with rare proline dehydrogenase (PRODH) gene alterations. This finding highlights hyperprolinemia as an intermediate phenotype for psychosis.
Area of Science:
- Genetics
- Psychiatry
- Biochemistry
Background:
- 22q11 DiGeorge chromosomal region variations are linked to psychotic disorders.
- Previous studies identified proline dehydrogenase (PRODH) gene alterations associated with hyperprolinemia in schizophrenia patients.
Purpose of the Study:
- To investigate the association between hyperprolinemia and susceptibility to schizophrenia, schizoaffective disorder, and bipolar disorder.
- To correlate hyperprolinemia with proline dehydrogenase (PRODH) genotypes.
Main Methods:
- A case-control study involving 114 controls and 320 patients with psychiatric disorders.
- Analysis of PRODH genotypes and proline levels in study participants.
- Statistical analysis accounting for confounding factors like valproate treatment.
Main Results:
- Hyperprolinemia is a significant risk factor for DSM-IV schizoaffective disorder (OR=4.6, P=0.02), independent of valproate treatment.
- No association was found between common PRODH polymorphisms or 22q11 deletions and psychotic disorders.
- Five rare PRODH alterations, including deletions and missense mutations, were associated with hyperprolinemia.
Conclusions:
- Moderate hyperprolinemia serves as an intermediate phenotype for specific forms of psychosis.
- Rare PRODH gene variations are linked to hyperprolinemia and potentially psychosis susceptibility.