Association of Neuropeptide S Receptor 1 and Glutamate Decarboxylase 1 Gene Polymorphisms with Posttraumatic Stress Disorder
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BACKGROUND: Posttraumatic stress disorder (PTSD) is an anxiety disorder caused by highly traumatic experiences. The aim of this study was to investigate the influence of single nucleotide polymorphisms (SNPs) in the neuropeptide S receptor 1 (NPSR1) and the glutamate decarboxylase 1(GAD1) gene on PTSD and its psychopathological aspects among individuals affected by the Balkan wars during the 90s. SUBJECTS AND METHODS: This study was conducted as part of the South Eastern Europe (SEE) study on molecular mechanisms of PTSD. It comprised 719 participants (539 males), including those with current PTSD, remitted PTSD and healthy volunteers. Psychometric evaluation was performed using the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) andthe Brief Symptom Inventory (BSI). We examined NPSR1 single nucleotide polymorphism (SNP) rs324981 and GAD1 variant rs3749034 genotypes. Case-control analyses were carried out using logistical regression to determine genotype differences between all patients that had either current or remitted PTSD and control individuals. To analyse the influence of the analysed SNPs on PTSD severity, we performed linear regression analyses with CAPS and BSI within each of the two patient groups separately. All of the calculations were performed for additive allelic, recessive, dominant and genotypic models. RESULTS: We observed a nominally significant association for the major allele (G) of GAD1 rs3749034 with an increased risk to develop PTSD in a case control analysis in the recessive model (P=0.0315, odds ratio=0.47, SE=0.35). In contrast, a nominally significant association of the minor allele (A) with higher CAPS scores was identified within the patient group with lifetime PTSD in the dominant model (P=0.0372, β=6.29, SE=2.99). None of these results did withstand correction for multiple tests. No nominal significant results of GAD1 rs3749034 were found with regard to the intensity of psychological BSI symptoms. Case-control analyses of NPSR1 rs324981 revealed a nominally significant higher risk for homozygous T allele carriers to develop PTSD (P=0.0452) in the recessive model. On the other hand, the T allele showed a nominally significant association with higher BSI scores in patients suffering from lifetime PTSD in the recessive model (P=0.0434). Again, these results were not significant anymore after correction for multiple tests. No associations of NPSR1 rs324981 and CAPS score was identified. CONCLUSION: The findings of this study provide some evidence that the NPSR1 and GAD1 polymorphisms might play a role in the development of war-related PTSD and its related psychological expressions. Further research is needed to elucidate the interactions of specific gene variants and environmental factors in the development of PTSD.
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Studies using rat models of PTSD have identified significant temporal differences in gene expression patterns, highlighting pathways such as EIF2, NRF2-mediated oxidative stress response and sirtuin signaling.
“Studies using rat models of PTSD have identified significant temporal differences in gene expression patterns, highlighting pathways such as EIF2, NRF2-mediated oxidative stress response and sirtuin signaling [32,35,73].”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [35]
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- Authors
- Institute of Kosovo Forensic Psychiatry, U. C. C. O. K., Haxhibeqiri, S., Haxhibeqiri, V., Department of Clinical Biochemistry, U. C. C. O. K., Agani, F., Faculty of Medicine, U. H. P., Goci Uka, A., Hoxha, B., Department of Psychiatry, U. C. C. O. K., Dzubur Kulenovic, A., Kucukalic, A., Department of Psychiatric, C. C. U. O. S., Avdibegovic, E., Sinanovic, O., Department of Psychiatry, U. C. C. T., Babic, D., Department of Psychiatry, U. C. C. O. M., Jakovljevic, M., Department of Psychiatry, U. H. C. Z., Kucukalic, S., Bravo Mehmedbasic, A., Department of Psychiatric, C. C. U. O. S., Kravic, N., Muminovic Umihanic, M., Department of Psychiatry, U. C. C. T., Babic, R., Pavlovic, M., Department of Psychiatry, U. C. C. O. M., Jaksic, N., Department of Psychiatry, U. H. C. Z., Aukst Margetic, B., Department of Psychiatry, U. H. C. S. M., Rudan, D., Department of Psychiatry, U. H. C. Z., Feric Bojic, E., Marjanovic, D., Department of Genetics and Bioengineering International Burch University, S., Ziegler, C., Department of Psychiatry and Psychotherapy, M. C. U. O. F., Wolf, C., Warrings, B., Department of Psychiatry, P. A. P., Domschke, K., Department of Psychiatry and Psychotherapy, M. C. U. O. F., Deckert, J., & Department of Psychiatry, P. A. P.
- Affiliations
- University Clinical Center of Kosovo (XK)
- University of Prishtina (XK)
- University Hospital Centre Zagreb (HR)
- University of Freiburg (DE)
- Universitätsklinikum Würzburg (DE)
- Venue
- Psychiatria Danubina
- Publisher
- Medicinska Naklada d.o.o.
- Published
- 2019-07-08
- Volume
- 31
- Issue
- 2
- Pages
- 249-255
- ISSN
- 0353-5053 (ISSN-L)
- OpenAlex
- W2958168555
- Cited by
- 8
- References
- 49
- Citations by year
- 2025: 3 · 2024: 2 · 2022: 1 · 2021: 2
- FWCI
- 0.88
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Psychiatria Danubina (publishedVersion)
- PubMed (publishedVersion)
- University of Zagreb University Computing Centre (SRCE) (submittedVersion, other-oa)
- AAB College Repository (AAB College) (submittedVersion)
- Funders
- Deutscher Akademischer Austauschdienst
- Deutsche Forschungsgemeinschaft (CRC-TRR58, TRR‐58, RTG1253)
- NIH Clinical Center
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- post-traumatic stress disorder, NPSR1, GAD1, single nucleotide polymorphisms, genetic susceptibility, Balkan Wars, PTSD symptom severity, psychological symptoms, gene-environment interaction
- MeSH terms
- Armed Conflicts, Alleles, Europe, Eastern, Female, Glutamate Decarboxylase, Humans, Male, Middle Aged, Stress Disorders, Post-Traumatic, Polymorphism, Single Nucleotide, Receptors, G-Protein-Coupled
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