Journal
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 9, Issue 1, Pages 13-20Publisher
OXFORD UNIV PRESS
DOI: 10.1017/S1461145705005560
Keywords
affective disorders; endothelial NOS; haplotype analysis; NO; polymorphism
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The pleiotropic messenger molecule nitric oxide (NO) has been implicated in a variety of higher CNS functions, including learning, memory, and emotionality. In the human brain, NO is predominantly formed by neuronal NO synthase (NOS-1), while the so-called 'endothelial' isoform NOS-III also contributes to NO generation. We recently reported that NOS-III knockout mice display decreased adult neurogenesis and reduced responsiveness in a learned helplessness paradigm. To examine whether NOS-III plays a role in affective disorders as well, we tested a NOS-III gene haplotype, consisting of three functional polymorphisms, for an association with bipolar disorder and major depression. A significant global haplotype association with bipolar disorder (n = 284 controls; n = 91 patients; p(global) =0.021; p(t-a-g) < 0.001), but not unipolar depression (n = 45) was detected. Our results thus suggest that the NOS-III genotype may convey a modest genetic risk to develop bipolar disorder. This finding should be further clarified by the use of within-family designs and in samples of other ethnicity.
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