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Our present aim was to investigate CTNNA2 gene-wide associations of single-nucleotide polymorphisms (SNPs) with psychiatric and cardiovascular risk factors to test the potential mediating role of rumination, a perseverative negative thinking phenotype in these associations. Linear mixed regression models were run by FaST-LMM within a sample of 795 individuals from the Budakalasz Health Examination Survey. The psychiatric outcome variables were rumination and its subtypes, and ten Brief Symptom Inventory (BSI) scores including, e.g., obsessive-compulsive, depression, anxiety, hostility, phobic anxiety, and paranoid ideation. Cardiovascular outcome variables were BMI and the Framingham risk scores for cardiovascular disease, coronary heart disease, myocardial infarction, and stroke. We found nominally significant CTNNA2 associations for every phenotype. Rumination totally mediated the associations of CTNNA2 rs17019243 with eight out of ten BSI scores, but none with Framingham scores or BMI. Our results suggest that CTNNA2 genetics may serve as biomarkers, and increasing the expression or function of CTNNA2 protein may be a potential new therapeutic approach in psychiatric disorders with perseverative negative thinking including, e.g., depression. Generally, an antiruminative agent could be a transdiagnostic and preventive psychopharmacon.<\/jats:p>","DOI":"10.3390\/ph14090850","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T09:27:57Z","timestamp":1629970077000},"page":"850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Catenin Alpha 2 May Be a Biomarker or Potential Drug Target in Psychiatric Disorders with Perseverative Negative Thinking"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4913-028X","authenticated-orcid":false,"given":"Nora","family":"Eszlari","sequence":"first","affiliation":[{"name":"Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1089 Budapest, Hungary"},{"name":"NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8120-2322","authenticated-orcid":false,"given":"Zsolt","family":"Bagyura","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, V\u00e1rosmajor utca 68, H-1122 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andras","family":"Millinghoffer","sequence":"additional","affiliation":[{"name":"NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1089 Budapest, Hungary"},{"name":"Department of Measurement and Information Systems, Budapest University of Technology and Economics, Magyar Tud\u00f3sok krt. 2, H-1521 Budapest, Hungary"},{"name":"Abiomics Europe Ltd., Z\u00f3lyomi \u00fat 23, H-1118 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0137-4341","authenticated-orcid":false,"given":"Tamas","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Measurement and Information Systems, Budapest University of Technology and Economics, Magyar Tud\u00f3sok krt. 2, H-1521 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5975-4267","authenticated-orcid":false,"given":"Gabriella","family":"Juhasz","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1089 Budapest, Hungary"},{"name":"MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1089 Budapest, Hungary"},{"name":"SE-NAP 2 Genetic Brain Imaging Migraine Research Group, Hungarian Brain Research Program, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Antal","sequence":"additional","affiliation":[{"name":"Department of Measurement and Information Systems, Budapest University of Technology and Economics, Magyar Tud\u00f3sok krt. 2, H-1521 Budapest, Hungary"},{"name":"Abiomics Europe Ltd., Z\u00f3lyomi \u00fat 23, H-1118 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela","family":"Merkely","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, V\u00e1rosmajor utca 68, H-1122 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyorgy","family":"Bagdy","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1089 Budapest, Hungary"},{"name":"NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1089 Budapest, Hungary"},{"name":"MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/s41588-018-0166-0","article-title":"Biallelic loss of human CTNNA2, encoding alphaN-catenin, leads to ARP2\/3 complex overactivity and disordered cortical neuronal migration","volume":"50","author":"Schaffer","year":"2018","journal-title":"Nat. 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