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A theory-driven multilocus genetic profile score (MGPS) was calculated to combine the effects of six common polymorphisms within HPA-axis related genes (<jats:italic>CRHR1<\/jats:italic>, <jats:italic>NR3C1<\/jats:italic>, <jats:italic>NR3C2<\/jats:italic>, <jats:italic>FKBP5<\/jats:italic>, <jats:italic>COMT,<\/jats:italic> and <jats:italic>HTR1A<\/jats:italic>) in a sample of Chinese Han adolescents (<jats:italic>N<\/jats:italic> = 827; 50.2% boys; <jats:italic>M<\/jats:italic><jats:sub>age<\/jats:sub> = 16.45 \u00b1 1.36 years). The results showed that the three-way interaction of HPA-axis related MGPS, childhood maltreatment and recent interpersonal, but not noninterpersonal, stress significantly predicted prospective changes in adolescent depressive symptoms. For adolescents with high but not low HPA-axis related MGPS, exposure to severe childhood maltreatment predisposed individuals more vulnerable to recent interpersonal stress, exhibiting greater prospective changes in adolescent depressive symptoms. The findings provide preliminary evidence for the cumulative risk mechanism regarding gene-by-environment-by-environment (G \u00d7 E<jats:sub>1<\/jats:sub> \u00d7 E<jats:sub>2<\/jats:sub>) interactions that underlie the longitudinal development of adolescent depressive symptoms and show effects specific to interpersonal stress.<\/jats:p>","DOI":"10.1017\/s0954579424000269","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T08:31:11Z","timestamp":1708677071000},"page":"543-554","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":5,"title":["The effects of childhood maltreatment, recent interpersonal and noninterpersonal stress, and HPA-axis multilocus genetic variation on prospective changes in adolescent depressive symptoms: A multiwave longitudinal study"],"prefix":"10.1017","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1215-7761","authenticated-orcid":false,"given":"Kexin","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3675-4210","authenticated-orcid":false,"given":"Cong","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"S0954579424000269_ref55","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/bjc.12333","article-title":"Global prevalence of depression and elevated depressive symptoms among adolescents: A systematic review and meta-analysis","volume":"61","author":"Shorey","year":"2022","journal-title":"The British Journal of Clinical Psychology"},{"key":"S0954579424000269_ref57","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1017\/S0954579414000996","article-title":"Sensitizing effect of early adversity on depressive reactions to later proximal stress: Moderation by polymorphisms in serotonin transporter and corticotropin releasing hormone receptor genes in a 20-year longitudinal study","volume":"26","author":"Starr","year":"2014","journal-title":"Development and Psychopathology"},{"key":"S0954579424000269_ref6","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1111\/j.1939-0025.1982.tb01456.x","article-title":"Attachment and loss: Retrospect and prospect","volume":"52","author":"Bowlby","year":"1982","journal-title":"The American Journal of Orthopsychiatry"},{"key":"S0954579424000269_ref1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0149-7634(03)00005-8","article-title":"Trajectories of brain development: Point of vulnerability or window of opportunity?","volume":"27","author":"Andersen","year":"2003","journal-title":"Neuroscience and Biobehavioral Reviews"},{"key":"S0954579424000269_ref70","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1017\/S0954579420000966","article-title":"Three phases of gene \u00d7 environment interaction research: Theoretical assumptions underlying gene selection","volume":"34","author":"Zhang","year":"2022","journal-title":"Development and Psychopathology"},{"key":"S0954579424000269_ref7","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1017\/S0954579405050145","article-title":"Biological sensitivity to context: I. 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