Effects of different stressors are modulated by different neurobiological systems: The role of GABA-A versus CB1 receptor gene variants in anxiety and depression
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Environmental stress and its interaction with genetic variation are key contributors in the development of depression and anxiety, yet there is a failure to identify replicable genetic variants and gene-interaction effects in the background of these psychiatric symptoms. Recently it has been reported that 5-HTTLPR and NOSI interact with financial but not other types of recent stressors in the development of depression. In the present study we investigated the interaction of GABRA6 rs3219151 and CNR1 rs7766029 in interaction with different types of recent life events on the presence of depression and anxiety in a large general population sample. 2191 participants completed the List of Threatening Experiences questionnaire which covers 4 categories of stressful life events (financial problems, illness/personal problems, intimate relationships, social network) experienced over the previous year and the Brief Symptom Inventory for depression and anxiety symptoms. Participants were genotyped for rs3219151 and rs7766029. Data were analysed with linear regression models with age and gender as covariates. Results indicated that CNR1 rs7766029 interacted significantly with financial but not other types of life events both in case of depression and anxiety symptoms. In contrast, GABRA6 rs3219151 showed a significant interaction with social network related life events in case of anxiety and with illness/personal problem-related life events in case of depression. Our results suggest that the psychological impact of different types of recent stress may be differentially modulated by distinct molecular genetic pathways. Furthermore, in case of certain genetic variants, the occurring psychiatric symptom may depend on the type of stress experienced.
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Different types of recent life stressors and negative life events may cause similar anxiety symptoms in humans by different neurobiological pathways.
“Evidence indicates that different types of recent life stressors and negative life events may cause similar anxiety symptoms in humans by different neurobiological pathways [see e.g., (Gonda et al., 2019;Hassell Jr., Nguyen, Gates, & Lowry, 2018)].”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Gonda et al., 2019
Preclinical research for subtype-selective BDZ ligands is still ongoing in parallel with the identification of novel interesting subunit-specific target sites at the GABA-A receptor such as the α6 subunit.
“The preclinical research for such ligands is still ongoing (Prevot et al., 2019) in parallel with the identification of novel interesting subunit-specific target sites at the GABA-A receptor such as the α 6 subunit (Gonda et al., 2019).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Gonda et al., 2019
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Cuttoli, R. D.-D., Martínez-Rivera, F. J., Li, L., Minier-Toribio, A. M., Dong, Z., Cai, D. J., Russo, S. J., Nestler, E. J., & Sweis, B. M. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.12.011 · Cited by 8 · see citing works
CB1 receptor signaling: Linking neuroplasticity, neuronal types, and mental health outcomes
Gao, Q., & Asim, M. (2025) · Neurochemistry International · doi:10.1016/j.neuint.2025.105938 · Cited by 6 · see citing works
Bokor, J., Krause, S., Török, D., Eszlári, N., Sütöri, S., Gál, Z., Petschner, P., Anderson, I. M., Deakin, J. F. W., Bagdy, G., et al. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00567 · Cited by 6 · see citing works
Ramos-Galarza, C., Flores, F., Argoti, T., Díaz‐Guerra, D. D., Hernández-Lugo, M. D. L. C., & Broche‐Pérez, Y. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1580673 · Cited by 5 · see citing works
Grantham, E. K., Tiwari, G. R., Ponomareva, O. Y., Harris, R. A., Lopez, M. F., Becker, H. C., & Mayfield, R. D. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109768 · Cited by 5 · see citing works
Syunyakov, T., Zakharov, A. V., Gayduk, A., Ignatenko, J. S., Kuvshinova, N. Y., Pavlichenko, A. V., Spikina, A., Fedotov, I. A., Yashikhina, A., Gonda, X., et al. (2023) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro202312310188 · Cited by 5 · see citing works
Gál, Z., Török, D., Gonda, X., Eszlári, N., Anderson, I. M., Deakin, J. F. W., Petschner, P., Juhász, G., & Bagdy, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252011332 · Cited by 5 · see citing works
Biological Mechanisms of Psychosomatic Symptoms
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Finasteride, pharmacogenomics, and suicide risk: a public health concern
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Genes, depression, and nuclear DNA
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Variability in Daily Stressors and Depressed Mood in the Context of Chronic HIV Stressors
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- Authors
- Gonda, X., Petschner, P., Eszlari, N., Sutori, S., Gal, Z., Koncz, S., Anderson, I. M., Deakin, B., Juhasz, G., & Bagdy, G.
- Affiliations
- Semmelweis University (HU)
- Manchester Academic Health Science Centre (GB)
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2019-04-09
- Volume
- 13
- Pages
- 138-138
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC6467241
- OpenAlex
- W2937776832
- Cited by
- 37
- References
- 69
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 7 · 2020: 8 · 2019: 3
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, cc-by)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- Funders
- AstraZeneca
- National Institute for Health and Care Research
- University of Manchester
- Semmelweis Egyetem (KTIA_NAP_13–2- 2015-0001, 2017-1.2.1-NKP-2017-00002, ÚNKP-18-4)
- Magyar Tudományos Akadémia (KTIA_NAP_13-1-2013-0001, NKP-18-4, 2017-1.2.1-NKP-2017-00002, 1.2.1-NKP-2017-00002, KTIA_13_NAPA-II/14, KTIA_NAP_13-2- 2015-0001, ÚNKP-17-3)
- Emberi Eroforrások Minisztériuma (ÚNKP‐18‐4, ÚNKP-16, ÚNKP-17-4-I, ÚNKP-17–4, ÚNKP-17-3-III-SE-2, ÚNKP-16-3, ÚNKP-17-3, 2017-1.2.1-NKP-2017-00002, ÚNKP-17-3-III)
- Servier
- H. Lundbeck A/S (P1vital)
- Nemzeti Fejlesztési Ügynökség (2017-1.2.1-NKP-2017-00002, KTIA_13_NAPA-II/14, KTIA_NAP_13-2-2015-0001, KTIA_NAP_13-1-2013-0001)
- Manchester Biomedical Research Centre
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- gene-environment interaction, financial stress, illness-related stress, anxiety symptoms, depressive symptoms, genetic polymorphism
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