Schizophrenia and schizophrenic spectrum disorders among the first degree relatives of child and young adult onset schizophrenic patients (original) (raw)

1995, Schizophrenia Research

Serotonin (5-HT) receptors are thought to be involved in a range of behaviours including appetite, sleep, mood and sexual behaviour and are candidates for aetiological involvements in psychosis and affective disorders. Serotonin receptors have been identified by pharmacological and molecular methods (the 5-HT1, 5-HT2, and 5-HT3 families, 5-HT 4 and the recently described 5-HTs, 5-HT6 and 5-HT7). Atypical neuroleptics show high occupancy of serotonin receptors, specially the 5-HT2 receptor (and the structurally similar 5-HTlc). These 5-HT2 receptors are G-protein-coupled, and share a significant number of molecular, pharmacological and biochemical characteristics. Clozapine, a potent atypical neuroleptic, with up to 60% success in patients refractory to other drugs, has high affinity for 5-HT 2 receptors. We wish to test the hypothesis that a mutation in the genes coding for these receptors could potentially be involved in drug response. A sample of clozapine treated patients (n=l16), including responders and nonresponders to clozapine, was typed for a 5-HT 2 polymorphism described by Warren et al. (1993). This polymorphism, a T/C change at position 102 of the 5-HTz gene has two alleles (C1 and C2) at a frequency of 0.42 and 0.58, respectively. A higher number of homozygous C2/C2 than expected was observed in the group of non-responders (significance p<0.05) suggesting a possible relation between this allele and failure to respond to clozapine. We are currently replicating this study in a larger sample.