A NOS-III haplotype that includes functional polymorphisms is associated with bipolar disorder
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; pglobal=0.021; pt-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 Online June 21 2005)
(Received November 9 2004)
(Reviewed February 9 2005)
(Revised February 28 2005)
(Accepted March 9 2005)
Key Words: Affective disorders; endothelial NOS; haplotype analysis; NO; polymorphism.
c1 Clinical and Molecular Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstr. 15, D-97080 Würzburg, Germany. Tel.: +49 931 201 76000 Fax: +49 931 201 77550 E-mail: email@example.com