A polymorphism of a variable number tandem repeat (VNTR), that was recently found in the promoter region of the monoamine oxidase-A (MAOA) gene, was shown to be associated with its transcriptional activity. This study examined whether this functional polymorphism of the MAOA gene is associated with the risk of developing mood disorders in a Japanese sample of 161 patients with bipolar disorder, 98 with unipolar depression, and 258 controls. There was no significant genotypic or allelic association, suggesting that the functional VNTR polymorphism in the MAOA gene is unlikely to play a major role in the pathogenesis of bipolar disorder or unipolar depression. Furthermore, we found no association between the polymorphism and a history of suicide attempt.

Based on the neurodevelopmental hypothesis in the etiology of schizophrenia, neurotrophic factors may be involved in the pathogenesis of the illness. We searched for polymorphisms in the promoter region of the neurotrophin-3 (NTF3) gene by using denaturing high performance liquid chromatography (DHPLC). Six single nucleotide polymorphisms (SNPs) were found. When these polymorphisms were examined for association with schizophrenia, a weakly significant difference was observed in the genotype distribution of the G/- 3004/A polymorphism between 184 schizophrenics and 185 controls (P < 0.05), although no statistically significant association was detected in a family-based sample of 50 trios (schizophrenics and their parents). With respect to the other polymorphisms, there was no significant association with schizophrenia. The G/- 3004/A polymorphism was in linkage disequilibrium with the CA repeat polymorphism in the first intron of the NTF3 gene. When haplotype-based analysis was performed, an increased frequency of the haplotype containing the G(- 3004) and the "A3" ([CA]23) alleles was observed for the schizophrenics compared to controls. Our results suggest that the G(- 3004)-A3 haplotype has a modest effect of giving susceptibility to schizophrenia.

Keywords: synaptic vesicle monoamine transporter (SVMT); polymorphism; exon/intron boundaries; schizophrenia; association studyThe synaptic vesicular monoamine transporter (SVMT), alternatively vesicular monoamine transporter 2 (VMAT2), pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Altered functions of SVMT have been implicated in the pathogensis of several neuropsychiatric diseases. We determined exon/intron boundaries of the human SVMT gene and performed mutational analysis for the exonic and neighboring intronic regions of the gene. Detected polymorphisms were subject to association analysis with schizophrenia in a familybased design. The human SVMT gene consists, of 16 exons and 15 introns, which is consistent with the murine SVMT gene. When mutational analysis was performed by the single strand conformational polymorphism (SSCP) analysis, we found two and four single nucleotide polymorphisms (SNPs) in exons and neighboring introns, respectively. Neither exonic SNP results in an amino acid change. In family-based association analyses in a sample of 50 Japanese schizophrenics and their parents, no significant association was found for the intronic polymorphisms. Our data suggest that there is no common polymorphism in the SVMT gene affecting the primary structure of the human SVMT protein. Furthermore, we obtained no evidence for the major effect of the novel polymorphisms on susceptibility to schizophrenia. Molecular Psychiatry (2001) 6, 456-460.The synaptic vesicular monoamine transporter (SVMT), alternatively vesicular monoamine transporter 2 (VMAT2), pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles, using the proton gradient maintained across the synaptic vesicular membrane. 1-3 It plays a central role in determining the amount of monoaminergic neurotransmitters packaged in a vesicle to be available for exocytotic release. 4 The transporter is a site of action of important drugs such as reserpine and tetrabenazine, both of which inhibit vesicular amine transport. Reserpine is a useful drug in the treatment of hypertension and schizophrenia; however, high dosages of reserpine frequently produce a syndrome resembling depressive disorder. 5 Several lines of evidence suggest the involvement of the SVMT in the psychostimulant action of amphetamines which induce monoamine efflux from vesicles, 6 resulting in an increased amount of cytoplasmic neurotransmitter, although the mechanism of action remains to be elucidated. The SVMT is also important for sequestering toxins. It modulates susceptibility to N-methyl-4-phenylpyridinium (MPP + ), the active metabolite of the neurotoxin N-methyl-1,2,3,6-tetrahydropyridine (MPTP) that induces Parkinsonism. 7,8 Recent studies on mutant mice lacking the SVMT gene have provided interesting findings. Although homozygotes for the mutated type die shortly after birth, heterozygous mice are viable into adult life and display reduced amphetamine-condition...

No abstract