LINKED POLYMORPHISMS UPSTREAM OF EXON-1 AND EXON-2 OF THE HUMAN CHOLECYSTOKININ GENE ARE NOT ASSOCIATED WITH SCHIZOPHRENIA OR BIPOLAR DISORDER

The evidence for a significant genetic contribution to the functional psychoses (schizophrenia and bipolar disorder) is now well established . However, in both cases, the non-mendelian mode of inheritance has ma de the identification of susceptibility loci particularly challenging. (1-3) The neuropeptide cholecystokinin (CCK) is present both in the gu t and the CNS. Studies of CCK-like immunoreactivity and CCK mRNA level s in human brains have revealed high concentrations in numerous loci a nd shown colocalisation of CCK with, for example, dopamine and tyrosin e hydroxylase.(4) Furthermore, antagonists of CCK-B receptors, which a re found most frequently in the brain, inhibit the activity of brain d opamine neurons.(5) Such findings suggest that, with respect to neurop sychiatric disorders, CCK is a suitable candidate for analysis using m ethods to detect gene variations which have the potential to affect pr otein structure or expression,(6) In the present study, mutation analy ses were carried out on the human CCK gene, Linked polymorphisms were found in the promoter region and in intron 1 close to the 3' mRNA spli ce acceptor site, However, the allele frequencies of these polymorphis ms in samples of individuals affected with either schizophrenia (n=117 ) or bipolar disorder (n=124) did not differ from those of control sub jects (n=234), suggesting that these variations do not confer a predis position to either of the functional psychoses.