CLINICAL AND FUNCTIONAL CORRELATES OF A DOPAMINE D3 RECEPTOR POLYMORPHISM

This is a review of our research on dopamine receptor D3 (DRD3) gene p olymorphism in psychiatric patients. We found that heterozygosity at a diallelic Ball polymorphic site in the first exon of the DRD3 gene wa s associated with schizophrenia, as did another group (Mant et al., 19 94). However others did not reproduce our findings and raised doubts a bout a possible role of the DRD3 in schizophrenia. More recently, we f ound that homozygosity for allele 2 at the same site was associated wi th lower cortisol and ACTH responses to apomorphine. We had also previ ously reported lower ACTH and cortisol responses to apomorphine in par anoid schizophrenics compared to controls (Mokrani et al., in press). This suggests that DRD3 polymorphisms might be associated with functio nal differences that could secondarily influence the expression of sch izophrenia, in spite of the lack of clear association with schizophren ia. More generally, classical association studies may be limited in th eir power to prove or disprove minor gene effects in schizophrenia bec ause the disorder is heterogeneous and various genes may have additive effects in different patients. Biological measures that are closer to gene effects may be a better way to test candidate genes than the ass ociation with a complex clinical phenotype.