Universität zu Köln

Lennertz, Leonhard, Franke, Petra E., Grabe, Hans Joergen, Rampacher, Friederike, Schulze-Rauschenbach, Svenja, Guttenthaler, Vera, Ruhrmann, Stephan ORCID: 0000-0002-6022-2364, Pukrop, Ralf, Klosterkoetter, Joachim, Falkai, Peter ORCID: 0000-0003-2873-8667, Maier, Wolfgang, Wagner, Michael ORCID: 0000-0003-2589-6440 and Moessner, Rainald (2013). The functional coding variant Asn107Ile of the neuropeptide S receptor gene (NPSR1) influences age at onset of obsessive-compulsive disorder. Int. J. Neuropsychopharmacol., 16 (9). S. 1951 - 1959. NEW YORK: CAMBRIDGE UNIV PRESS. ISSN 1461-1457

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lennertz, Leonhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Franke, Petra E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Grabe, Hans Joergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Rampacher, Friederike UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulze-Rauschenbach, Svenja UNSPECIFIED UNSPECIFIED UNSPECIFIED Guttenthaler, Vera UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruhrmann, Stephan UNSPECIFIED orcid.org/0000-0002-6022-2364 UNSPECIFIED Pukrop, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Klosterkoetter, Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED Falkai, Peter UNSPECIFIED orcid.org/0000-0003-2873-8667 UNSPECIFIED Maier, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, Michael UNSPECIFIED orcid.org/0000-0003-2589-6440 UNSPECIFIED Moessner, Rainald UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-475389
DOI:	10.1017/S1461145713000382
Journal or Publication Title:	Int. J. Neuropsychopharmacol.
Volume:	16
Number:	9
Page Range:	S. 1951 - 1959
Date:	2013
Publisher:	CAMBRIDGE UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1461-1457
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SYSTEM CANDIDATE GENES; ASSOCIATION ANALYSIS; PANIC DISORDER; FAMILY; MICE; SCHIZOPHRENIA; PHARMACOLOGY; METAANALYSIS; RELIABILITY; PHENOTYPES Multiple languages Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47538