TY - JOUR AU - Eszlári, Nóra AU - Hullám, Gábor István AU - Gál, Zsófia AU - Török, Dóra AU - Nagy, Tamás AU - Millinghoffer, András Dániel AU - Baksa, Dániel AU - Gonda, Xénia AU - Antal, Péter AU - Bagdy, György AU - Juhász, Gabriella TI - Olfactory genes affect major depression in highly educated, emotionally stable, lean women: a bridge between animal models and precision medicine JF - TRANSLATIONAL PSYCHIATRY J2 - TRANSL PSYCHIAT VL - 14 PY - 2024 IS - 1 PG - 10 SN - 2158-3188 DO - 10.1038/s41398-024-02867-2 UR - https://m2.mtmt.hu/api/publication/34779723 ID - 34779723 N1 - Funding Agency and Grant Number: Hungarian National Research, Development, and Innovation Office [K 139330, K 143391, PD 146014, 2019-2.1.7-ERA-NET-2020-00005, ERAPERMED2019-108]; Hungarian Brain Research Program [2017-1.2.1-NKP-2017-00002]; Hungarian Brain Research Program 3.0 [NAP2022-I-4/2022, TKP2021-EGA-25]; Ministry of Innovation and Technology of Hungary National Research, Development and Innovation Fund [TKP2021-EGA-25]; National Research, Development, and Innovation Fund of Hungary [TKP2021-EGA-02]; European Union [RRF-2.3.1-21-2022-00004]; New National Excellence Program of the Ministry for Culture and Innovation National Research, Development and Innovation Fund [UNKP-23-4-II-SE-2]; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences; Semmelweis University; [UNKP-22-4-II-SE-1] Funding text: This study was supported by the Hungarian National Research, Development, and Innovation Office, with grants K 139330, K 143391, and PD 146014, as well as 2019-2.1.7-ERA-NET-2020-00005 under the frame of ERA PerMed (ERAPERMED2019-108); by the Hungarian Brain Research Program (grant: 2017-1.2.1-NKP-2017-00002) and the Hungarian Brain Research Program 3.0 (NAP2022-I-4/2022); and by TKP2021-EGA-25, implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. It was also supported by the National Research, Development, and Innovation Fund of Hungary under Grant TKP2021-EGA-02 and the European Union project RRF-2.3.1-21-2022-00004 within the framework of the Artificial Intelligence National Laboratory. NE was supported by the UNKP-22-4-II-SE-1, and DB by the UNKP-23-4-II-SE-2 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund. NE is supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences. This work uses data provided by patients and collected by the NHS as part of their care and support. Copyright (c) (2019), NHS England. Re-used with the permission of the UK Biobank (Application Number 1602). All rights reserved.Open access funding provided by Semmelweis University. AB - Most current approaches to establish subgroups of depressed patients for precision medicine aim to rely on biomarkers that require highly specialized assessment. Our present aim was to stratify participants of the UK Biobank cohort based on three readily measurable common independent risk factors, and to investigate depression genomics in each group to discover common and separate biological etiology. Two-step cluster analysis was run separately in males ( n = 149,879) and females ( n = 174,572), with neuroticism (a tendency to experience negative emotions), body fat percentage, and years spent in education as input variables. Genome-wide association analyses were implemented within each of the resulting clusters, for the lifetime occurrence of either a depressive episode or recurrent depressive disorder as the outcome. Variant-based, gene-based, gene set-based, and tissue-specific gene expression test were applied. Phenotypically distinct clusters with high genetic intercorrelations in depression genomics were found. A two-cluster solution was the best model in each sex with some differences including the less important role of neuroticism in males. In females, in case of a protective pattern of low neuroticism, low body fat percentage, and high level of education, depression was associated with pathways related to olfactory function. While also in females but in a risk pattern of high neuroticism, high body fat percentage, and less years spent in education, depression showed association with complement system genes. Our results, on one hand, indicate that alteration of olfactory pathways, that can be paralleled to the well-known rodent depression models of olfactory bulbectomy, might be a novel target towards precision psychiatry in females with less other risk factors for depression. On the other hand, our results in multi-risk females may provide a special case of immunometabolic depression. LA - English DB - MTMT ER - TY - JOUR AU - Kristóf, Zsüliet AU - Gál, Zsófia AU - Török, Dóra AU - Eszlári, Nóra AU - Sutori, Sara AU - Sperlágh, Beáta AU - Anderson, Ian M. AU - Deakin, Bill AU - Bagdy, György AU - Juhász, Gabriella AU - Gonda, Xénia TI - Embers of the Past: Early Childhood Traumas Interact with Variation in P2RX7 Gene Implicated in Neuroinflammation on Markers of Current Suicide Risk JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 2 PG - 17 SN - 1661-6596 DO - 10.3390/ijms25020865 UR - https://m2.mtmt.hu/api/publication/34496842 ID - 34496842 N1 - Department of Psychiatry and Psychotherapy, Semmelweis University, Balassa utca 6, Budapest, 1082, Hungary Laboratory of Molecular Pharmacology, HUN-REN Institute of Experimental Medicine, Szigony utca 43, Budapest, 1083, Hungary Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyvarad ter 4, Budapest, 1089, Hungary NAP3.0 Neuropsychopharmacology Research Group, Semmelweis University, Nagyvarad ter 4, Budapest, 1089, Hungary National Centre for Suicide Research and Prevention (NASP), Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Granits väg 4, Solna, 17165, Sweden Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biological, Medical and Human Sciences, The University of Manchester, Manchester Academic Health Sciences Centre, 46 Grafton Street, Manchester, M13 9NT, United Kingdom Export Date: 3 May 2024 Correspondence Address: Gonda, X.; Department of Psychiatry and Psychotherapy, Balassa utca 6, Hungary; email: gonda.xenia@semmelweis.hu Chemicals/CAS: P2RX7 protein, human; Receptors, Purinergic P2X7 AB - Both early childhood traumatic experiences and current stress increase the risk of suicidal behaviour, in which immune activation might play a role. Previous research suggests an association between mood disorders and P2RX7 gene encoding P2X7 receptors, which stimulate neuroinflammation. We investigated the effect of P2RX7 variation in interaction with early childhood adversities and traumas and recent stressors on lifetime suicide attempts and current suicide risk markers. Overall, 1644 participants completed questionnaires assessing childhood adversities, recent negative life events, and provided information about previous suicide attempts and current suicide risk-related markers, including thoughts of ending their life, death, and hopelessness. Subjects were genotyped for 681 SNPs in the P2RX7 gene, 335 of which passed quality control and were entered into logistic and linear regression models, followed by a clumping procedure to identify clumps of SNPs with a significant main and interaction effect. We identified two significant clumps with a main effect on current suicidal ideation with top SNPs rs641940 and rs1653613. In interaction with childhood trauma, we identified a clump with top SNP psy_rs11615992 and another clump on hopelessness containing rs78473339 as index SNP. Our results suggest that P2RX7 variation may mediate the effect of early childhood adversities and traumas on later emergence of suicide risk. LA - English DB - MTMT ER - TY - GEN AU - Erdélyi-Hamza, Berta AU - Török, Dóra AU - Gál, Zsófia AU - Győrik, Dorka AU - Eszlári, Nóra AU - Bagdy, György AU - Juhász, Gabriella AU - Gonda, Xénia TI - Hogyan járul hozzá a genetika az endogén és reaktív típusú depresszióhoz? - SNP-alapú öröklődés és genetikai összefüggések bizonyítékai több GWAS-vizsgálat alapján PY - 2023 UR - https://m2.mtmt.hu/api/publication/34175067 ID - 34175067 N1 - XIX. Magyar Neuropszichofarmakológiai Kongresszus, Balatonfüred, Hotel Annabella, 2023. október 12-14. LA - Hungarian DB - MTMT ER - TY - GEN AU - Nagy, Tamás AU - Gezsi, Andras AU - Hullam, Gabor AU - Eszlári, Nóra AU - Antal, Péter AU - Juhász, Gabriella TI - Pharmacological Characterization of Multimorbidity-Based Clusters in Depression PY - 2023 UR - https://m2.mtmt.hu/api/publication/34091555 ID - 34091555 LA - English DB - MTMT ER - TY - GEN AU - Eszlári, Nóra AU - Hullam, Gabor AU - Gál, Zsófia AU - Török, Dóra AU - Nagy, Tamás AU - Millinghoffer, Andras AU - Baksa, Dániel AU - Antal, Péter AU - Bagdy, György AU - Juhász, Gabriella TI - Olfactory Receptors as a Potential Pathomechanism for Depression When No Classic Risk Factors Are Present in Women? Genomic Results from the UK Biobank Cohort PY - 2023 UR - https://m2.mtmt.hu/api/publication/34091468 ID - 34091468 LA - English DB - MTMT ER - TY - GEN AU - Erdelyi-Hamza, Berta AU - Török, Dóra AU - Gál, Zsófia AU - Gyorik, Dorka AU - Eszlári, Nóra AU - Bagdy, György AU - Juhász, Gabriella AU - Gonda, Xénia TI - CLOCK gene plays role in the genetic background of depression after stressful life events – a GWAS study PY - 2023 UR - https://m2.mtmt.hu/api/publication/34091453 ID - 34091453 LA - English DB - MTMT ER - TY - GEN AU - Baksa, Dániel AU - Eszlári, Nóra AU - Török, Dóra AU - Juhász, Gabriella TI - Chronotype Affects Physical and Mental Health Status of Migraineurs PY - 2023 UR - https://m2.mtmt.hu/api/publication/34091418 ID - 34091418 LA - English DB - MTMT ER - TY - GEN AU - Török, Dóra AU - Gecse, Kinga AU - Hammer, Angela AU - Nemeth, Anna AU - Eszlári, Nóra AU - Gonda, Xénia AU - Bagdy, György AU - Petschner, Péter AU - Juhász, Gabriella TI - Investigating the association between polygenic risk score of depression and functional connectivity of the Nucleus Accumbens in healthy individuals: distinct role of SIRT1 PY - 2023 UR - https://m2.mtmt.hu/api/publication/34001410 ID - 34001410 LA - English DB - MTMT ER - TY - GEN AU - Eszlári, Nóra AU - Hullám, Gábor István AU - Gál, Zsófia AU - Török, Dóra AU - Nagy, Tamas AU - Millinghoffer, András Dániel AU - Baksa, Dániel AU - Gonda, Xénia AU - Antal, Péter AU - Bagdy, György AU - Juhász, Gabriella TI - LncRNA or actin cytoskeleton-related genes in depression, depending on the joint pattern of sex, neuroticism, body fat, education, and stress CY - poster PY - 2023 UR - https://m2.mtmt.hu/api/publication/34001390 ID - 34001390 LA - English DB - MTMT ER - TY - JOUR AU - Kristóf, Zsüliet AU - Gál, Zsófia AU - Török, Dóra AU - Eszlári, Nóra AU - Sütöri, Sára AU - Erdélyi-Hamza, Berta AU - Petschner, Péter AU - Sperlágh, Beáta AU - Anderson, Ian M AU - Deakin, John Francis William AU - Bagdy, György AU - Juhász, Gabriella AU - Gonda, Xénia TI - Variation along P2RX7 interacts with early traumas on severity of anxiety suggesting a role for neuroinflammation JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 PG - 13 SN - 2045-2322 DO - 10.1038/s41598-023-34781-w UR - https://m2.mtmt.hu/api/publication/33841048 ID - 33841048 AB - Emotional stress is a leading risk factor in the development of neuropsychiatric disorders possibly via immune activation. P2X7 receptors promote neuroinflammation, and research suggests a relationship between chromosome region 12q2431, in which the P2X7R gene is located, and development of mood disorders, however, few studies concentrate on its association with anxiety. Our aim was to investigate the effects of P2RX7 variation in interaction with early childhood traumas and recent stressors on anxiety. 1752 participants completed questionnaires assessing childhood adversities and recent negative life events, provided data on anxiety using the Brief Symptom Inventory, and were genotyped for 681 SNPs in the P2RX7 gene, 335 of which passed quality control and were entered into linear regression models followed by a linkage disequilibrium-based clumping procedure to identify clumps of SNPs with a significant main or interaction effect. We identified a significant clump with top SNP rs67881993 and containing a set of 29SNPs that are in high LD, which significantly interacted with early childhood traumas but not with recent stress conveying a protective effect against increased anxiety in those exposed to early adversities. Our study demonstrated that P2RX7 variants interact with distal and more etiological stressors in influencing the severity of anxiety symptoms, supporting previous scarce results and demonstrating its role in moderating the effects of stress. LA - English DB - MTMT ER -