The International Journal of Neuropsychopharmacology

Table of Contents - 2006 - Volume 9, Issue 01  


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

Andreas Reif a1c1, Alexander Strobel a2, Christian P. Jacob a1, Sabine Herterich a3, Christine M. Freitag a4, Theresia Töpner a1, Rainald Mössner a1, Sabrina Fritzen a1, Angelika Schmitt a1 and Klaus-Peter Lesch a1
a1 Clinical and Molecular Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany
a2 Institute of Psychology II, Dresden University of Technology, Dresden, Germany
a3 Department of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany
a4 Department of Child and Adolescent Psychiatry, University Hospital Saarland, Homburg, Germany

Article author query
reif a   [PubMed][Google Scholar] 
strobel a   [PubMed][Google Scholar] 
jacob cp   [PubMed][Google Scholar] 
herterich s   [PubMed][Google Scholar] 
freitag cm   [PubMed][Google Scholar] 
topner t   [PubMed][Google Scholar] 
mossner r   [PubMed][Google Scholar] 
fritzen s   [PubMed][Google Scholar] 
schmitt a   [PubMed][Google Scholar] 
lesch kp   [PubMed][Google Scholar] 

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; 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.

Correspondence:
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: a.reif@gmx.net

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