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A NOS-III haplotype that includes functional polymorphisms is associated with bipolar disorder.

Reif A, Strobel A, Jacob CP, Herterich S, Freitag CM, Töpner T, Mössner R, Fritzen S, Schmitt A, Lesch KP

Clinical and Molecular Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany. a.reif@gmx.net

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-I), 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.

Published 5 January 2006 in Int J Neuropsychopharmacol, 9(1): 13-20.
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