Monday, October 31, 2011

Genetics of Neuropeptide S in human panic disorder: from mice to men, and back

Rainer Reinscheid
Rainer K. Reinscheid
Dept. of Pharmaceutical Sciences
University of California Irvine

Monday, October 31st
12:00-1:30 pm
SBSG 1517

For abstract, click 'read more':

Neuropeptide S (NPS) has been shown to promote arousal and wakefulness, produce anxiolytic-like effects and facilitate fear extinction in rodents. In addition, NPS was found to reinstate drug-seeking behavior and attenuate neurochemical effects and psychotic-like behavioral changes produced by NMDA-receptor antagonists. Its effects on anxiety behaviors and fear memories appear to be mediated by NPS receptors in the amygdala where it modulates glutamatergic neurotransmission. While all these recent findings were made in preclinical animal models, much less is known about the physiological functions of the NPS system in humans. 
A coding polymorphism in the human NPS receptor (NPSR) gene was discovered to occur with high frequency in the human gene pool. The single nucleotide polymorphism encodes an Asn to Ile exchange at position 107 of the receptor protein. The two variants of human NPSR differ substantially in their sensitivity to the natural agonist, with NPSR Ile107 being 5-10 fold more sensitive to NPS than NPSR Asn107. It is reasonable to assume that such a significant difference in agonist efficacy might produce phenotypical consequences. Indeed, several genetic association studies recently found evidence that NPSR genotypes might be associated with normal human behavior or psychiatric illness, in particular panic disorder. Neuroimaging studies also suggest NPSR genotype-specific activation of critical brain areas during processing of emotional stimuli or fear conditioning. These results indicate that the NPS system may be involved in modulation of anxiety as well as arousal states in humans and could play a critical role in cognitive processes underlying the psychophathology of panic disorder.