title: The functional coding variant Asn107Ile of the neuropeptide S receptor gene (NPSR1) influences age at onset of obsessive-compulsive disorder.
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Lennertz
authors.forename: Petra E
authors.initials: PE
authors.lastname: Franke
authors.forename: Hans Jörgen
authors.initials: HJ
authors.lastname: Grabe
authors.forename: Friederike
authors.initials: F
authors.lastname: Rampacher
authors.forename: Svenja
authors.initials: S
authors.lastname: Schulze-Rauschenbach
authors.forename: Vera
authors.initials: V
authors.lastname: Guttenthaler
authors.forename: Stephan
authors.initials: S
authors.lastname: Ruhrmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Pukrop
authors.forename: Joachim
authors.initials: J
authors.lastname: Klosterkötter
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.forename: Rainald
authors.initials: R
authors.lastname: Mössner
mesh_terms: D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005858:Germany; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled