Steroid receptors/co-receptors and schizophrenia: An association study

Objective: Differences between males and females in the phenotypic expression of schizophrenia have been consistently reported. Oestrogen hormone is thought to be involved in this variability. In addition, several pathological conditions involving other transcription factors of the steroid receptor family (androgen, glucocorticoids, thyroid hormones) may present with psychotic manifestations. The purpose of this study is to investigate the relation between allelic variants of two steroid receptors (oestrogen and androgen) or receptor coactivator genes (hSNF2a, the receptor-coactivator 3, and the CREB-binding protein) and schizophrenia or its phenotypic variability. Methods: A CA repeat in the promotor region of the oestrogen receptor gene and CAG allelic variants of the other four genes were compared between two groups of schizophrenic patients, one of excellent neuroleptic responders (n = 44) and one of nonresponders (n = 64), and one group of healthy volunteers screened for major psychiatric disorders (n = 127). Results: There was no association between schizophrenia or neuroleptic responsiveness and the androgen and oestrogen receptor gene repeats. A nonexpanded (+1CAG) rare allele (allele 1) of the hSNF2a was observed in seven schizophrenic patients but not in controls (Yates corrected χ² = 6.37, df = 1, P = 0.01).Rare allelic variants, including allele 1, were more common in schizophrenic patients, irrespective of their neuroleptic responsiveness and gender, than in normal controls (respectively, 5.6% vs. 0.7%; odds ratio = 7.56, [4.2, 13.5]). Conclusion: These results suggest that the rare allelic variants of the SNF2a may increase the genetic susceptibility for schizophrenia. Further investigations are needed to confirm their role.