title: A NOS-III haplotype that includes functional polymorphisms is associated with bipolar disorder.
abstract: 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.
authors.affiliation: Clinical and Molecular Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany. a.reif@gmx.net
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.forename: Alexander
authors.initials: A
authors.lastname: Strobel
authors.forename: Christian P
authors.initials: CP
authors.lastname: Jacob
authors.forename: Sabine
authors.initials: S
authors.lastname: Herterich
authors.forename: Christine M
authors.initials: CM
authors.lastname: Freitag
authors.forename: Theresia
authors.initials: T
authors.lastname: Töpner
authors.forename: Rainald
authors.initials: R
authors.lastname: Mössner
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fritzen
authors.forename: Angelika
authors.initials: A
authors.lastname: Schmitt
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000209:etiology / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III