Fiori et al.
(pages 460–467) identified and functionally characterized a number of variants in the promoter region of the gene coding for spermidine/spermine N1-acetyltransferase, SAT1
, in suicide completers, and found several polymorphisms to be associated with differential gene expression both in the brain and in vitro
. These results provide insight into the mechanisms responsible for variation in SAT1
expression, and provide functional evidence to support previous findings of decreased SAT1
expression in the brains of suicide completers. The SAT1
haplotype would be predicted to influence the level of the polyamines, spermidine and spermine. These polyamines modulate the activity of N-
methyl-D-aspartate (NMDA) glutamate receptors. In light of evidence that NMDA glutamate receptor antagonists may have clinically relevant antidepressant effects, the findings with SAT1
may help to bridge risk genes and novel therapeutics for depression.
Wray et al.
(pages 468–476) report a large scale genotyping effort to study the serotonin transporter length repeat polymorphism (5HTTLPR). By genotyping 13 single nucleotide polymorphisms (SNPs) in a 38kb region around the 5HTTLPR, they identified a two SNP haplotype proxy for 5HTTLPR. These two SNPs are in linkage disequilibrium with the previously reported variable number tandem repeat polymorphism. Association analysis for major depression and/or anxiety disorder in unrelated cases and controls provided evidence for association with SNPs positioned about 15.5kb from 5HTTLPR.
Serotonergic neurotransmission is vital to the etiology and pathophysiology of psychiatric disorders. Henningsson et al.
(pages 477–485) show that, in men but not in women, variation in the gene encoding brain-derived neurotrophic factor (BDNF) influences the availability of the serotonin transporter, one of the major regulators of serotonergic transmission. Carriers of variants associated with increased BDNF secretion displayed higher transporter availability.