Universität zu Köln

Lennertz, Leonhard, Quednow, Boris B. ORCID: 0000-0001-7933-2865, Schuhmacher, Anna, Petrovsky, Nadine, Frommann, Ingo, Schulze-Rauschenbach, Svenja, Landsberg, Martin W., Steinbrecher, Anja, Hoefels, Susanne, Pukrop, Ralf, Klosterkoetter, Joachim, Franke, Petra E., Woelwer, Wolfgang, Gaebel, Wolfgang, Haefner, Heinz, Maier, Wolfgang, Wagner, Michael ORCID: 0000-0003-2589-6440 and Moessner, Rainald (2012). The functional coding variant Asn(107)Ile of the neuropeptide S receptor gene (NPSR1) is associated with schizophrenia and modulates verbal memory and the acoustic startle response. Int. J. Neuropsychopharmacol., 15 (9). S. 1205 - 1216. OXFORD: OXFORD UNIV PRESS. ISSN 1469-5111

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Abstract

Recently, the neuropeptide S (NPS) neurotransmitter system has been identified as a promising psychopharmacological drug target given that NPS has shown anxiolytic-like and stress-reducing properties and memory-enhancing effects in rodent models. NIPS binds to the G-protein-coupled receptor encoded by the neuropeptide S receptor gene (NPSR1). A functional variant within this gene leads to an amino-acid exchange (rs324981, Asn(107)Ile) resulting in a gain-of-function in the Ile(107) variant which was recently associated with panic disorder in two independent studies. A potential psychopharmacological effect of NPS on schizophrenia psychopathology was demonstrated by showing that NPS can block NMDA antagonist-induced deficits in prepulse inhibition. We therefore explored a potential role of the NPSR1 Asn(107)Ile variation in schizophrenia. A case-control sample of 778 schizophrenia patients and 713 healthy control subjects was successfully genotyped for NPSR1 Asn(107)Ile. Verbal declarative memory and acoustic startle response were measured in subsamples of the schizophrenia patients. The case-control comparison revealed that the low-functioning NPSR1 Asn(107) variant was significantly associated with schizophrenia (OR 1.19, p = 0.017). Moreover, specifically decreased verbal memory consolidation was found in homozygous Asn(107) carriers while memory acquisition was unaffected by NPSR1 genotype. The schizophrenia patients carrying the Ile(107) variant demonstrated significantly reduced startle amplitudes but unaffected prepulse inhibition and habituation. The present study confirms findings from rodent models demonstrating an effect of NIPS on memory consolidation and startle response in schizophrenia patients. Based on these findings, we consider NPS as a promising target for antipsychotic drug development.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lennertz, Leonhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Quednow, Boris B. UNSPECIFIED orcid.org/0000-0001-7933-2865 UNSPECIFIED Schuhmacher, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Petrovsky, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Frommann, Ingo UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulze-Rauschenbach, Svenja UNSPECIFIED UNSPECIFIED UNSPECIFIED Landsberg, Martin W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Steinbrecher, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoefels, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Pukrop, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Klosterkoetter, Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED Franke, Petra E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Woelwer, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaebel, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Haefner, Heinz UNSPECIFIED UNSPECIFIED 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:38-481933
DOI:	10.1017/S1461145711001623
Journal or Publication Title:	Int. J. Neuropsychopharmacol.
Volume:	15
Number:	9
Page Range:	S. 1205 - 1216
Date:	2012
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1469-5111
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PANIC DISORDER; PREPULSE INHIBITION; HABITUATION; REFLEX; PHARMACOLOGY; AROUSAL Multiple languages Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48193