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
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
UR - http://www.scopus.com/inward/record.url?scp=77955635778&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2010.05.039
DO - 10.1016/j.biopsych.2010.05.039
M3 - Article
C2 - 20705147
AN - SCOPUS:77955635778
VL - 68
SP - 474
EP - 483
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 5
ER -