The functional coding variant Asn107Ile of the neuropeptide S receptor gene (NPSR1) influences age at onset of obsessive-compulsive disorder
| Autor: | Vera Guttenthaler, Leonhard Lennertz, Peter Falkai, Friederike Rampacher, Petra Franke, Joachim Klosterkötter, Stephan Ruhrmann, Rainald Mössner, Wolfgang Maier, Hans J. Grabe, Ralf Pukrop, Svenja Schulze-Rauschenbach, Michael Wagner |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Heterozygote Obsessive-Compulsive Disorder medicine.medical_specialty Late onset Polymorphism Single Nucleotide behavioral disciplines and activities Receptors G-Protein-Coupled Young Adult 03 medical and health sciences 0302 clinical medicine Gene Frequency Risk Factors Germany Internal medicine mental disorders Neuropeptide S Genotype Odds Ratio medicine Humans Genetic Predisposition to Disease Pharmacology (medical) Age of Onset Neuropeptide S receptor Genetic Association Studies Pharmacology Chi-Square Distribution Panic disorder Homozygote Odds ratio Middle Aged medicine.disease 030227 psychiatry Psychiatry and Mental health Phenotype Endocrinology Schizophrenia Case-Control Studies Female Age of onset Psychology 030217 neurology & neurosurgery |
| Zdroj: | The International Journal of Neuropsychopharmacology; Vol 16 |
| ISSN: | 1469-5111 |
| DOI: | 10.1017/S1461145713000382 |
| Popis: | Neuropeptide S (NPS) is a novel central acting neuropeptide that modulates several brain functions. NPS has shown strong anxiolytic-like effects and interactions with other central transmitter systems, including serotonin and glutamate. A coding variation (Asn107Ile) of the NPS receptor gene (NPSR1) was associated with panic disorder and schizophrenia. Based on these encouraging findings, the present study aimed at exploring a potential role of NPSR1 in obsessive–compulsive disorder (OCD). A sample of 232 OCD patients was successfully genotyped for the NPSR1 Asn107Ile variant (rs324981). Age at onset was taken into account to address the heterogeneity of the OCD phenotype. The NPSR1 genotype significantly affected age at onset of the OCD patients, with a mean age at onset approximately 4 yr earlier in homozygous carriers of the low-functioning Asn107 variant compared to patients with at least one Ile107 variant (p = 0.032). Case–control analyses with 308 healthy control subjects reveal a highly significant association of the Asn107 variant with early onset OCD (odds ratio = 2.36, p = 0.0004) while late onset OCD or the OCD group as a whole were unrelated to the NPSR1 genotype. Based on our association finding relating NPSR1 genotype to early onset OCD, we suggest a differential role of the NPS system in OCD. In particular, the early onset OCD subtype seems to be characterized by a genetically driven low NPS tone, which might affect other OCD-related transmitter systems, including the serotonin and glutamate systems. In agreement with preclinical research, we suggest that NPS may be a promising pharmacological candidate with anti-obsessional properties. |
| Databáze: | OpenAIRE |
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