Assessment of the neuropeptide S system in anxiety disorders

Jonas Donner; Rita Haapakoski; Sini Ezer; Erik Meln; Sami Pirkola; Mnica Gratacs; Marco Zucchelli; Francesca Anedda; Lovisa E. Johansson; Cilla Sderhll; Christina Orsmark-Pietras; Jaana Suvisaari; Roco Martn-Santos; Marta Torrens; Kaisa Silander; Joseph D. Terwilliger; Magnus Wickman; Gran Pershagen; Jouko Lnnqvist; Leena Peltonen; Xavier Estivill; Mauro D'Amato; Juha Kere; Harri Alenius; Iiris Hovatta

doi:10.1016/j.biopsych.2010.05.039

Assessment of the neuropeptide S system in anxiety disorders

Jonas Donner
, Rita Haapakoski
, Sini Ezer
, Erik Meln
, Sami Pirkola
, Mnica Gratacs
, Marco Zucchelli
, Francesca Anedda
, Lovisa E. Johansson
, Cilla Sderhll
, Christina Orsmark-Pietras
, Jaana Suvisaari
, Roco Martn-Santos
, Marta Torrens
, Kaisa Silander
, Joseph D. Terwilliger
, Magnus Wickman
, Gran Pershagen
, Jouko Lnnqvist
, Leena Peltonen

Xavier Estivill, Mauro D'Amato, Juha Kere^*, Harri Alenius, Iiris Hovatta

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

92 Citations (Scopus)

Abstract

Background: The G protein-coupled receptor neuropeptide S receptor 1 (NPSR1) and its ligand neuropeptide S (NPS) form a signaling system mainly implicated in susceptibility to asthma and inflammatory disorders in humans and regulation of anxiety and arousal in rodents. We addressed here the role of NPS and NPSR1 as susceptibility genes for human anxiety disorders. Methods: We performed comprehensive association analysis of genetic variants in NPS and NPSR1 in three independent study samples. We first studied a population-based sample (Health 2000, Finland) of 321 anxiety disorder patients and 1317 control subjects and subsequently a Spanish clinical panic disorder sample consisting of 188 cases and 315 control subjects. In addition, we examined a birth cohort of 2020 children (Barn Allergi Milj Stockholm Epidemiologi [BAMSE], Sweden). We then tested whether alleles of the most significantly associated single nucleotide polymorphisms alter DNA-protein complex formation in electrophoretic mobility shift assays. Finally, we compared acute stress responses on the gene expression level in wild-type and Npsr1^-/- mice. Results: We confirmed previously observed epidemiological association between anxiety and asthma in two population-based cohorts. Single nucleotide polymorphisms within NPS and NPSR1 associated with panic disorder diagnosis in the Finnish and Spanish samples and with parent-reported anxiety/depression in the BAMSE sample. Moreover, some of the implicated single nucleotide polymorphisms potentially affect transcription factor binding. Expression of neurotrophin-3, a neurotrophic factor connected to stress and panic reaction, was significantly downregulated in brain regions of stressed Npsr1^-/- mice, whereas interleukin-1 beta, an active stress-related immunotransmitter, was upregulated. Conclusions: Our results suggest that NPS-NPSR1 signaling is likely involved in anxiety.

Original language	English
Pages (from-to)	474-483
Number of pages	10
Journal	Biological Psychiatry
Volume	68
Issue number	5
DOIs	https://doi.org/10.1016/j.biopsych.2010.05.039
Publication status	Published - 1 Sept 2010
Publication type	A1 Journal article-refereed

Funding

This work was supported by The Academy of Finland (to RH and JK); The Academy of Finland NEURO Research program and academy research fellow funding (to IH); Sigrid Jusélius Foundation (to JK and IH); Yrjö Jahnsson Foundation (to IH); Yrjö and Tuulikki Ilvonen Foundation (to IH); Biocentrum Helsinki Foundation (to IH); L'Oréal Finland and United Nations Educational, Cultural, and Scientific Organization women in science fellowship (to IH); University of Helsinki (to IH); Nylands Nation vid Helsingfors universitet (to JD); H. Lundbeck A/S (to JD); Finnish Foundation for Psychiatric Research (to JD); The Helsinki Biomedical Graduate School (to JD); Fondo de Investigaciones Sanitarias de la Seguridad Social ( P1052565 to RM-S; PI040632 , PI040619 , and CIBER-CB06/02/0058 to XE); Spanish Ministry of Education and Science (to the Spanish National Genotyping Center, and SAF2005-01005 , SAF2007-60827 , GEN2003-20651-C06-03 to XE); The Instituto Carlos III ( GO3/184 to XE and RM-S); The Fundació la Marató-TV3 ( 014331 to RM-S); the Department of Universities, Research and Information Society ( 2005SGR00008 ; 2005SGR 00322 to XE); Genoma España (to the Spanish National Genotyping Center); Swedish Research Council (to Barn Allergi Miljö Stockholm Epidemiologi [BAMSE] study and JK); Stockholm County Council (to BAMSE study); The Swedish Asthma and Allergy Association (to BAMSE study); The Swedish Foundation for Health Care Science and Allergy Research (to BAMSE study); The Swedish Heart and Lung Foundation (to BAMSE study and JK); Chronic Inflammation - Diagnosis and Therapy/Verket för innovationssystem , Sweden (to JK); Centre for Allergy Research, Karolinska Institutet (to BAMSE study); The Bernard Osher Initiative for Research on Severe Asthma at Karolinska Institutet (to LJ); The Swedish Society for Medical Research (to CS); Professor Nanna Svartz Fund (to MD); and The Ruth and Richard Julin Foundation (to MD).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Anxiety disorders
asthma
genetic association
lexicon
neuropeptide S
SNP

ASJC Scopus subject areas

Biological Psychiatry

Access to Document

10.1016/j.biopsych.2010.05.039

Cite this

Donner, J., Haapakoski, R., Ezer, S., Meln, E., Pirkola, S., Gratacs, M., Zucchelli, M., Anedda, F., Johansson, L. E., Sderhll, C., Orsmark-Pietras, C., Suvisaari, J., Martn-Santos, R., Torrens, M., Silander, K., Terwilliger, J. D., Wickman, M., Pershagen, G., Lnnqvist, J., ... Hovatta, I. (2010). Assessment of the neuropeptide S system in anxiety disorders. Biological Psychiatry, 68(5), 474-483. https://doi.org/10.1016/j.biopsych.2010.05.039

@article{f94cb473bbf74326bae335d5859b4d79,

title = "Assessment of the neuropeptide S system in anxiety disorders",

abstract = "Background: The G protein-coupled receptor neuropeptide S receptor 1 (NPSR1) and its ligand neuropeptide S (NPS) form a signaling system mainly implicated in susceptibility to asthma and inflammatory disorders in humans and regulation of anxiety and arousal in rodents. We addressed here the role of NPS and NPSR1 as susceptibility genes for human anxiety disorders. Methods: We performed comprehensive association analysis of genetic variants in NPS and NPSR1 in three independent study samples. We first studied a population-based sample (Health 2000, Finland) of 321 anxiety disorder patients and 1317 control subjects and subsequently a Spanish clinical panic disorder sample consisting of 188 cases and 315 control subjects. In addition, we examined a birth cohort of 2020 children (Barn Allergi Milj Stockholm Epidemiologi [BAMSE], Sweden). We then tested whether alleles of the most significantly associated single nucleotide polymorphisms alter DNA-protein complex formation in electrophoretic mobility shift assays. Finally, we compared acute stress responses on the gene expression level in wild-type and Npsr1-/- mice. Results: We confirmed previously observed epidemiological association between anxiety and asthma in two population-based cohorts. Single nucleotide polymorphisms within NPS and NPSR1 associated with panic disorder diagnosis in the Finnish and Spanish samples and with parent-reported anxiety/depression in the BAMSE sample. Moreover, some of the implicated single nucleotide polymorphisms potentially affect transcription factor binding. Expression of neurotrophin-3, a neurotrophic factor connected to stress and panic reaction, was significantly downregulated in brain regions of stressed Npsr1-/- mice, whereas interleukin-1 beta, an active stress-related immunotransmitter, was upregulated. Conclusions: Our results suggest that NPS-NPSR1 signaling is likely involved in anxiety.",

keywords = "Anxiety disorders, asthma, genetic association, lexicon, neuropeptide S, SNP",

author = "Jonas Donner and Rita Haapakoski and Sini Ezer and Erik Meln and Sami Pirkola and Mnica Gratacs and Marco Zucchelli and Francesca Anedda and Johansson, \{Lovisa E.\} and Cilla Sderhll and Christina Orsmark-Pietras and Jaana Suvisaari and Roco Martn-Santos and Marta Torrens and Kaisa Silander and Terwilliger, \{Joseph D.\} and Magnus Wickman and Gran Pershagen and Jouko Lnnqvist and Leena Peltonen and Xavier Estivill and Mauro D'Amato and Juha Kere and Harri Alenius and Iiris Hovatta",

note = "Funding Information: This work was supported by The Academy of Finland (to RH and JK); The Academy of Finland NEURO Research program and academy research fellow funding (to IH); Sigrid Jus{\'e}lius Foundation (to JK and IH); Yrj{\"o} Jahnsson Foundation (to IH); Yrj{\"o} and Tuulikki Ilvonen Foundation (to IH); Biocentrum Helsinki Foundation (to IH); L'Or{\'e}al Finland and United Nations Educational, Cultural, and Scientific Organization women in science fellowship (to IH); University of Helsinki (to IH); Nylands Nation vid Helsingfors universitet (to JD); H. Lundbeck A/S (to JD); Finnish Foundation for Psychiatric Research (to JD); The Helsinki Biomedical Graduate School (to JD); Fondo de Investigaciones Sanitarias de la Seguridad Social ( P1052565 to RM-S; PI040632 , PI040619 , and CIBER-CB06/02/0058 to XE); Spanish Ministry of Education and Science (to the Spanish National Genotyping Center, and SAF2005-01005 , SAF2007-60827 , GEN2003-20651-C06-03 to XE); The Instituto Carlos III ( GO3/184 to XE and RM-S); The Fundaci{\'o} la Marat{\'o}-TV3 ( 014331 to RM-S); the Department of Universities, Research and Information Society ( 2005SGR00008 ; 2005SGR 00322 to XE); Genoma Espa{\~n}a (to the Spanish National Genotyping Center); Swedish Research Council (to Barn Allergi Milj{\"o} Stockholm Epidemiologi [BAMSE] study and JK); Stockholm County Council (to BAMSE study); The Swedish Asthma and Allergy Association (to BAMSE study); The Swedish Foundation for Health Care Science and Allergy Research (to BAMSE study); The Swedish Heart and Lung Foundation (to BAMSE study and JK); Chronic Inflammation - Diagnosis and Therapy/Verket f{\"o}r innovationssystem , Sweden (to JK); Centre for Allergy Research, Karolinska Institutet (to BAMSE study); The Bernard Osher Initiative for Research on Severe Asthma at Karolinska Institutet (to LJ); The Swedish Society for Medical Research (to CS); Professor Nanna Svartz Fund (to MD); and The Ruth and Richard Julin Foundation (to MD). ",

year = "2010",

month = sep,

day = "1",

doi = "10.1016/j.biopsych.2010.05.039",

language = "English",

volume = "68",

pages = "474--483",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier",

number = "5",

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Donner, J, Haapakoski, R, Ezer, S, Meln, E, Pirkola, S, Gratacs, M, Zucchelli, M, Anedda, F, Johansson, LE, Sderhll, C, Orsmark-Pietras, C, Suvisaari, J, Martn-Santos, R, Torrens, M, Silander, K, Terwilliger, JD, Wickman, M, Pershagen, G, Lnnqvist, J, Peltonen, L, Estivill, X, D'Amato, M, Kere, J, Alenius, H & Hovatta, I 2010, 'Assessment of the neuropeptide S system in anxiety disorders', Biological Psychiatry, vol. 68, no. 5, pp. 474-483. https://doi.org/10.1016/j.biopsych.2010.05.039

TY - JOUR

T1 - Assessment of the neuropeptide S system in anxiety disorders

AU - Donner, Jonas

AU - Haapakoski, Rita

AU - Ezer, Sini

AU - Meln, Erik

AU - Pirkola, Sami

AU - Gratacs, Mnica

AU - Zucchelli, Marco

AU - Anedda, Francesca

AU - Johansson, Lovisa E.

AU - Sderhll, Cilla

AU - Orsmark-Pietras, Christina

AU - Suvisaari, Jaana

AU - Martn-Santos, Roco

AU - Torrens, Marta

AU - Silander, Kaisa

AU - Terwilliger, Joseph D.

AU - Wickman, Magnus

AU - Pershagen, Gran

AU - Lnnqvist, Jouko

AU - Peltonen, Leena

AU - Estivill, Xavier

AU - D'Amato, Mauro

AU - Kere, Juha

AU - Alenius, Harri

AU - Hovatta, Iiris

N1 - Funding Information: This work was supported by The Academy of Finland (to RH and JK); The Academy of Finland NEURO Research program and academy research fellow funding (to IH); Sigrid Jusélius Foundation (to JK and IH); Yrjö Jahnsson Foundation (to IH); Yrjö and Tuulikki Ilvonen Foundation (to IH); Biocentrum Helsinki Foundation (to IH); L'Oréal Finland and United Nations Educational, Cultural, and Scientific Organization women in science fellowship (to IH); University of Helsinki (to IH); Nylands Nation vid Helsingfors universitet (to JD); H. Lundbeck A/S (to JD); Finnish Foundation for Psychiatric Research (to JD); The Helsinki Biomedical Graduate School (to JD); Fondo de Investigaciones Sanitarias de la Seguridad Social ( P1052565 to RM-S; PI040632 , PI040619 , and CIBER-CB06/02/0058 to XE); Spanish Ministry of Education and Science (to the Spanish National Genotyping Center, and SAF2005-01005 , SAF2007-60827 , GEN2003-20651-C06-03 to XE); The Instituto Carlos III ( GO3/184 to XE and RM-S); The Fundació la Marató-TV3 ( 014331 to RM-S); the Department of Universities, Research and Information Society ( 2005SGR00008 ; 2005SGR 00322 to XE); Genoma España (to the Spanish National Genotyping Center); Swedish Research Council (to Barn Allergi Miljö Stockholm Epidemiologi [BAMSE] study and JK); Stockholm County Council (to BAMSE study); The Swedish Asthma and Allergy Association (to BAMSE study); The Swedish Foundation for Health Care Science and Allergy Research (to BAMSE study); The Swedish Heart and Lung Foundation (to BAMSE study and JK); Chronic Inflammation - Diagnosis and Therapy/Verket för innovationssystem , Sweden (to JK); Centre for Allergy Research, Karolinska Institutet (to BAMSE study); The Bernard Osher Initiative for Research on Severe Asthma at Karolinska Institutet (to LJ); The Swedish Society for Medical Research (to CS); Professor Nanna Svartz Fund (to MD); and The Ruth and Richard Julin Foundation (to MD).

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Background: The G protein-coupled receptor neuropeptide S receptor 1 (NPSR1) and its ligand neuropeptide S (NPS) form a signaling system mainly implicated in susceptibility to asthma and inflammatory disorders in humans and regulation of anxiety and arousal in rodents. We addressed here the role of NPS and NPSR1 as susceptibility genes for human anxiety disorders. Methods: We performed comprehensive association analysis of genetic variants in NPS and NPSR1 in three independent study samples. We first studied a population-based sample (Health 2000, Finland) of 321 anxiety disorder patients and 1317 control subjects and subsequently a Spanish clinical panic disorder sample consisting of 188 cases and 315 control subjects. In addition, we examined a birth cohort of 2020 children (Barn Allergi Milj Stockholm Epidemiologi [BAMSE], Sweden). We then tested whether alleles of the most significantly associated single nucleotide polymorphisms alter DNA-protein complex formation in electrophoretic mobility shift assays. Finally, we compared acute stress responses on the gene expression level in wild-type and Npsr1-/- mice. Results: We confirmed previously observed epidemiological association between anxiety and asthma in two population-based cohorts. Single nucleotide polymorphisms within NPS and NPSR1 associated with panic disorder diagnosis in the Finnish and Spanish samples and with parent-reported anxiety/depression in the BAMSE sample. Moreover, some of the implicated single nucleotide polymorphisms potentially affect transcription factor binding. Expression of neurotrophin-3, a neurotrophic factor connected to stress and panic reaction, was significantly downregulated in brain regions of stressed Npsr1-/- mice, whereas interleukin-1 beta, an active stress-related immunotransmitter, was upregulated. Conclusions: Our results suggest that NPS-NPSR1 signaling is likely involved in anxiety.

AB - Background: The G protein-coupled receptor neuropeptide S receptor 1 (NPSR1) and its ligand neuropeptide S (NPS) form a signaling system mainly implicated in susceptibility to asthma and inflammatory disorders in humans and regulation of anxiety and arousal in rodents. We addressed here the role of NPS and NPSR1 as susceptibility genes for human anxiety disorders. Methods: We performed comprehensive association analysis of genetic variants in NPS and NPSR1 in three independent study samples. We first studied a population-based sample (Health 2000, Finland) of 321 anxiety disorder patients and 1317 control subjects and subsequently a Spanish clinical panic disorder sample consisting of 188 cases and 315 control subjects. In addition, we examined a birth cohort of 2020 children (Barn Allergi Milj Stockholm Epidemiologi [BAMSE], Sweden). We then tested whether alleles of the most significantly associated single nucleotide polymorphisms alter DNA-protein complex formation in electrophoretic mobility shift assays. Finally, we compared acute stress responses on the gene expression level in wild-type and Npsr1-/- mice. Results: We confirmed previously observed epidemiological association between anxiety and asthma in two population-based cohorts. Single nucleotide polymorphisms within NPS and NPSR1 associated with panic disorder diagnosis in the Finnish and Spanish samples and with parent-reported anxiety/depression in the BAMSE sample. Moreover, some of the implicated single nucleotide polymorphisms potentially affect transcription factor binding. Expression of neurotrophin-3, a neurotrophic factor connected to stress and panic reaction, was significantly downregulated in brain regions of stressed Npsr1-/- mice, whereas interleukin-1 beta, an active stress-related immunotransmitter, was upregulated. Conclusions: Our results suggest that NPS-NPSR1 signaling is likely involved in anxiety.

KW - Anxiety disorders

KW - asthma

KW - genetic association

KW - lexicon

KW - neuropeptide S

KW - SNP

U2 - 10.1016/j.biopsych.2010.05.039

DO - 10.1016/j.biopsych.2010.05.039

M3 - Article

C2 - 20705147

AN - SCOPUS:77955635778

SN - 0006-3223

VL - 68

SP - 474

EP - 483

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 5

ER -

Assessment of the neuropeptide S system in anxiety disorders

Abstract

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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