SCHIZOPHRENIA - NORMAL SEQUENCE IN THE DOPAMINE-D2 RECEPTOR REGION THAT COUPLES TO G-PROTEINS - DNA POLYMORPHISMS IN D2

Because dopamine (DA) D2 receptors are a target in neuroleptic therapy and have been found to be elevated in schizophrenia, the human DA D2 receptor gene was examined for possible abnormalities in schizophrenia. Moreover, since D2 receptors in psychosis have a reduced coupling to D1 receptors, the cytoplasmic third loop of D2 was chosen for deoxyribonucleic acid (DNA) sequencing, since this region is essential for coupling to G-proteins. This region also contains exon 5, which is expressed in the long form of D2, but not in the short form of D2. In eight schizophrenia cases, this region had normal exon sequences (exons 4, 5 and 6), and normal sequences at its intron-exon junctions. However, exon 6 contained three DNA polymorphic base changes, and introns 4 and 5 revealed three missing bases and two polymorphic base changes, none of which would be expected to alter the D2 receptor protein in schizophrenia.