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A search was conducted in PubMed, Scopus, PsycINFO, SciELO, and LILACS. Study selection, data extraction, and quality assessment were performed independently by two reviewers. Twenty-four studies were included, encompassing 1,119,606 participants. Family structure adversities and sexual and physical abuse were the most frequently examined exposures, although their associations with MDD varied across studies. Emotional abuse, domestic violence, and bullying were less commonly assessed but showed more consistent associations with MDD. Evidence regarding TRD was limited, with childhood neglect as a risk factor for poorer treatment response. Greater cumulative exposure to ACEs was associated with higher risk of MDD and TRD. Overall, the findings support childhood adversity as a clinically relevant determinant of depressive risk and clinical course, although heterogeneity across study designs and high risk of bias limit causal inference.<\/jats:p>","DOI":"10.1007\/s10578-026-01977-w","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T08:26:18Z","timestamp":1771662378000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Role of Adverse Childhood Experiences in the Development of Major Depressive Disorder and Treatment-Resistant Depression"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4748-2330","authenticated-orcid":false,"given":"Mar\u00edlia Aparecida Batista","family":"Dos Santos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2393-3801","authenticated-orcid":false,"given":"Ana Elisa Palha","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3250-400X","authenticated-orcid":false,"given":"Marcella Monteiro Alvarenga","family":"Say\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4183-983X","authenticated-orcid":false,"given":"Ana Luiza","family":"da Silva Selani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7788-4160","authenticated-orcid":false,"given":"Beatriz Cristina","family":"Betarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8967-8983","authenticated-orcid":false,"given":"Izabelle","family":"de Faria Siqueira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2905-8519","authenticated-orcid":false,"given":"Marcela","family":"Forgerini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,21]]},"reference":[{"key":"1977_CR1","doi-asserted-by":"publisher","unstructured":"Afifi TO (2020) Considerations for expanding the definition of ACEs. 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