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A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function
A Reif1, S Herterich, A Strobel
1Department of Psychiatry and Psychotherapy (Section for Clinical and Molecular Psychobiology and Laboratory for Psychophysiology and Functional Imaging), Julius-Maximilians-University Würzburg, Würzburg, Germany. a.reif@gmx.net
Molecular Psychiatry
|January 4, 2006
Summary
Regulatory polymorphisms in the NOS1 gene are linked to schizophrenia (SCZ) and bipolar disorder, influencing prefrontal brain function. These genetic variations may increase psychosis risk.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Nitric oxide (NO) acts as a neurotransmitter and interacts with dopamine and serotonin systems.
- The NOS-I gene (NOS1) is located on chromosome 12q24.2, a region linked to schizophrenia and bipolar disorder.
Purpose of the Study:
- To investigate if NOS1 gene polymorphisms contribute to the genetic risk of schizophrenia and bipolar disorder.
- To examine the association between NOS1 polymorphisms and psychopathology and prefrontal functioning.
Main Methods:
- Genotyping of five NOS1 polymorphisms and a NOS1 mini-haplotype in 195 schizophrenic patients, 72 bipolar patients, and 286 controls.
- Analysis of associations between polymorphisms, disease status, psychopathology, and prefrontal function (neuropsychological tests, Go-Nogo paradigm).
Main Results:
- The exon 1c promoter polymorphism of NOS1 was associated with schizophrenia (SCZ).
- Long promoter alleles of a repeat polymorphism correlated with less severe psychopathology.
- A NOS1 mini-haplotype showed a significant association with SCZ.
- Regulatory NOS1 polymorphisms, not coding variants, appear to confer genetic risk for psychosis.
- Promoter polymorphisms affected prefrontal functioning in patients.
Conclusions:
- Regulatory polymorphisms in the NOS1 gene contribute to the genetic risk for schizophrenia.
- These NOS1 variants modulate prefrontal brain function, impacting cognitive and electrophysiological parameters.