{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T17:10:26Z","timestamp":1767978626285,"version":"3.49.0"},"reference-count":68,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AstraZeneca Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to investigate the influence of genetic variants in neuroplasticity-related genes on antidepressant treatment phenotypes. The BDNF-TrkB signaling pathway, as well as the downstream kinases Akt and ERK and the mTOR pathway, have been implicated in depression and neuroplasticity. However, clinicians still struggle with the unpredictability of antidepressant responses in depressed patients. We genotyped 26 polymorphisms in BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 in 80 patients with major depressive disorder treated according to the Texas Medical Algorithm for 27 months at Hospital Magalh\u00e3es Lemos, Porto, Portugal. Our results showed that BDNF rs6265, PTEN rs12569998, and SYN1 rs1142636 SNP were associated with treatment-resistant depression (TRD). Additionally, MAPK1\u00a0rs6928 and GSK3B rs6438552 gene polymorphisms were associated with relapse. Moreover, we found a link between the rs6928 MAPK1 polymorphism and time to relapse. These findings suggest that the BDNF, PTEN, and SYN1 genes may play a role in the development of TRD, while MAPK1 and GSK3B may be associated with relapse. GO analysis revealed enrichment in synaptic and trans-synaptic transmission pathways and glutamate receptor activity with TRD-associated genes. Genetic variants in these genes could potentially be incorporated into predictive models of antidepressant response.<\/jats:p>","DOI":"10.3390\/ijms24076758","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T02:11:41Z","timestamp":1680660701000},"page":"6758","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Impact of BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes"],"prefix":"10.3390","volume":"24","author":[{"given":"Marlene","family":"Santos","sequence":"first","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade e Ambiente (CISA), Escola Superior de Sa\u00fade, Instituto Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"},{"name":"Molecular Oncology & Viral Pathology, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology, 4200-072 Porto, Portugal"}]},{"given":"Luis","family":"Lima","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6181-0096","authenticated-orcid":false,"given":"Serafim","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Hospital de Magalh\u00e3es Lemos, 4149-003 Porto, Portugal"},{"name":"Instituto Universit\u00e1rio de Ci\u00eancias da Sa\u00fade, 4585-116 Gandra, Portugal"}]},{"given":"Jorge","family":"Mota-Pereira","sequence":"additional","affiliation":[{"name":"Cl\u00ednica M\u00e9dico-Psiqui\u00e1trica da Ordem, 4000-270 Porto, Portugal"}]},{"given":"Paulo","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Tr\u00e1s-os-Montes e Alto Douro Hospital Centre, 5000-508 Vila Real, Portugal"}]},{"given":"Dulce","family":"Maia","sequence":"additional","affiliation":[{"name":"Tr\u00e1s-os-Montes e Alto Douro Hospital Centre, 5000-508 Vila Real, Portugal"}]},{"given":"Diana","family":"Correia","sequence":"additional","affiliation":[{"name":"Hospital de Magalh\u00e3es Lemos, 4149-003 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9011-5992","authenticated-orcid":false,"given":"M. F\u00e1tima","family":"Barroso","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Instituto Superior de Engenharia do Instituto Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"}]},{"given":"Sofia","family":"Gomes","sequence":"additional","affiliation":[{"name":"Hospital de Magalh\u00e3es Lemos, 4149-003 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1157-8196","authenticated-orcid":false,"given":"Agostinho","family":"Cruz","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade e Ambiente (CISA), Escola Superior de Sa\u00fade, Instituto Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Molecular Oncology & Viral Pathology, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology, 4200-072 Porto, Portugal"},{"name":"Research Department, Portuguese League Against Cancer (Norte), 4200-172 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.coph.2006.08.009","article-title":"Role of neurotrophic factors in depression","volume":"7","year":"2007","journal-title":"Curr. 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