Journal ArticleDOI
Neuropeptide S receptor gene variant and environment: contribution to alcohol use disorders and alcohol consumption
Kariina Laas,Andreas Reif,Kirsti Akkermann,Evelyn Kiive,Katharina Domschke,Klaus-Peter Lesch,Klaus-Peter Lesch,Toomas Veidebaum,Jaanus Harro +8 more
TLDR
In the general population, the NPSR1 Asn107Ile polymorphism is associated with AUD and alcohol consumption, dependent on sex, environment and age, in line with the impulsivity and personality regulating role of the N PSR1.Abstract:
The functional polymorphism Asn(107) Ile (rs324981, A > T) of the neuropeptide S receptor (NPSR1) gene is involved in the modulation of traits that affect alcohol use. Hence, we have examined whether the NPSR1 A/T polymorphism is associated with alcohol use disorders (AUD) and alcohol use in a population-representative sample. Lifetime AUD were assessed by the MINI psychiatric interview (n = 501) in the older cohort of the longitudinal Estonian Children Personality Behaviour and Health Study at age 25. Alcohol use, environmental adversities and personality were reported by both the younger (original n = 583) and the older cohort (original n = 593) in three study waves. NPSR1 associations with AUD and alcohol use differed by sex. In females, both AUD [odds ratio (OR) = 7.20 (0.94-55.0), P = 0.029] and harmful alcohol use were more prevalent in A-allele carriers. In contrast, in males, AUD was more frequent in T-allele carriers [OR = 2.75 (1.19-6.36), P = 0.017], especially if exposed to adverse environments at age 15 [OR = 10 (1.18-84.51), P = 0.019]. Alcohol use was higher in male T-allele carriers at ages 15 and 18 as well. Similarly to females, however, the risk allele for higher alcohol use for males at age 25 was the A-allele. Many of the effects on alcohol use were explained by genotype effects on measures of personality. In the general population, the NPSR1 Asn(107) Ile polymorphism is associated with AUD and alcohol consumption, dependent on sex, environment and age. The results are in line with the impulsivity and personality regulating role of the NPSR1.read more
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Assessment of the Neuropeptide S System in Anxiety Disorders
Jonas Donner,Rita Haapakoski,Sini Ezer,Erik Melén,Erik Melén,Sami Pirkola,Sami Pirkola,Mònica Gratacòs,Marco Zucchelli,Marco Zucchelli,Francesca Anedda,Francesca Anedda,Lovisa E. Johansson,Cilla Söderhäll,Christina Orsmark-Pietras,Christina Orsmark-Pietras,Jaana Suvisaari,Rocío Martín-Santos,Marta Torrens,Kaisa Silander,Joseph D. Terwilliger,Joseph D. Terwilliger,Magnus Wickman,Magnus Wickman,Göran Pershagen,Jouko Lönnqvist,Jouko Lönnqvist,Leena Peltonen,Xavier Estivill,Mauro D'Amato,Mauro D'Amato,Juha Kere,Harri Alenius,Iiris Hovatta,Iiris Hovatta +34 more
TL;DR: The results suggest that NPS-NPSR1 signaling is likely involved in anxiety and confirmed previously observed epidemiological association between anxiety and asthma in two population-based cohorts.
Journal ArticleDOI
The role of MAO in personality and drug use.
Jaanus Harro,Lars Oreland +1 more
TL;DR: The "risk variants" of both MAO-s appear to increase behavioural plasticity, as supportive environments may particularly well enhance the hidden potential of their carriers.
Journal ArticleDOI
Activation of Hypocretin-1/Orexin-A Neurons Projecting to the Bed Nucleus of the Stria Terminalis and Paraventricular Nucleus Is Critical for Reinstatement of Alcohol Seeking by Neuropeptide S.
Massimo Ubaldi,Antonio Giordano,Ilenia Severi,Hongwu Li,Marsida Kallupi,Giordano de Guglielmo,Barbara Ruggeri,Serena Stopponi,Roberto Ciccocioppo,Nazzareno Cannella,Nazzareno Cannella +10 more
TL;DR: Results suggest that the Hcrt-1/Ox-A neurocircuitry mediating the facilitation of cue-induced reinstatement by NPS involves structures critically involved in stress regulation such as the PVN and the BNST.
Journal ArticleDOI
Further evidence for the association of the NPSR1 gene A/T polymorphism (Asn107Ile) with impulsivity and hyperactivity
Kariina Laas,Diva Eensoo,Marika Paaver,Klaus-Peter Lesch,Klaus-Peter Lesch,Andreas Reif,Andreas Reif,Jaanus Harro +7 more
TL;DR: The association of the NPSR1 genotype with impulsivity and attention-deficit/hyperactivity disorder (ADHD)-related symptoms was re-examined in two independent non-clinical cohorts and it was confirmed in two additional population-derived samples that the T-allele of the npsR1 rs324981 polymorphism is associated with increased impulsiveness and ADHD-related traits.
Dissertation
Neuropeptide S and mental health: A functional receptor gene variant and environment shaping traits and contributing to psychiatric disorders
Abstract: Hiljutiavastatud neuropeptiid S (NPS) avaldab narilistel omaparast moju, suurendades aktiivsust ja virgust samaaegselt arevuse alandamisega. Inimesel on NPS retseptori geenis NPSR1 funktsionaalne A>T polumorfism (rs324981), mille T-alleeli kooditud retseptorvalk on signaali vahendamisel tohusam. T-alleeli kandlus on seotud suurema virguse, kuid ka paanikahairega, mistottu on T-alleeli hakatud pidama riskialleeliks. Vaitekirjas kajastatud rahvastikupohiste uuringutega loime tasakaalustatuma pildi NPSR1 toimimisest, leides nii soost kui keskkonnast soltuvaid seoseid. Leidsime, et naistel, kellel on madalaima aktiivsusega NPSR1 genotuup, AA, voib juba teismeeas meeleolu ja arevuse regulatsiooniga raskusi olla. Mitteadaptiivsed jooned ilmnesid neil sagedamini just kehvade peresuhete korral, nagu ka suitsiidikatsed 18-ndaks ning arevus- ning meeleoluhaired 25-ndaks eluaastaks. Sagedamini kujunes A-alleeliga naistel valja ka alkoholisoltuvushaire. Seevastu meestel oli NPSR1 T-alleel, eriti TT genotuup, seotud huperaktiivsuse ja impulsiivsusega, ning stressirikkad elusundmused tostsid neid omadusi veelgi rohkem esile. Seetottu pole ullatav, et T-alleeliga meeste hulgas oli oluliselt rohkem soltuvushaireid. Huvitaval kombel raporteerisid sarnaselt naistega alkoholiga liialdamist taiskasvanuna hoopis AA genotuubiga mehed, mis viitab voimalikule taiendavale hilise algusega soltuvuse tekkimise rajale: AA meestel tousid adaptiivne impulsiivsus ja avatus oluliselt 25-ndaks eluaastaks, ning nad olid ka alkoholi kuritarvitamisele vastuvotlikumad. Kas neil ka hiljem soltuvus kujuneb, jaab tuleviku uuringute selgitada. NPSR on huvipakkuv sihtmark ravimiarenduseks, kuna mojutab virgust, emotsionaalseid reaktsioone ja alkoholi kuritarvitamist. AA ja TThomosugootide erinevaid emotsioonide reguleerimise viise on vaja sugavuti tundma oppida.; In this dissertation, we have focused on the functional rs324981 A>T polymorphism of the gene NPSR1 (Asn107Ile) that encodes for the neuropeptide S (NPS) receptor and is a relatively newly identified research target. We have shown that NPSR1 is associated with the development of personality, hyperactivity, anxiety, depressiveness, self-esteem, suicidality, affective/anxiety disorders, alcohol use and alcohol use disorders, and sleep-related measures. We have also found profound NPSR1 genotype by sex interactions in general population.
In females, the probable lower NPS-ergic activity in the NPSR1 A-allele carriers, and especially in AA-homozygotes, bears a risk for affective and anxiety-related dysregulation already in adolescence. The risk for developing maladaptive traits is significantly higher in case of adverse family environment. As a consequence, females with the AA genotype had reported suicidal behaviour more frequently and had more often developed affective/anxiety disorders by age 25. Emotion dysregulation may also render them vulnerable to alcohol use, as some females carrying the A-allele develop AUD already in young adulthood.
In males, an impulsivity-related early-onset pathway to…
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