{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:49:00Z","timestamp":1793303340027,"version":"4.5.0"},"reference-count":40,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"\n Importance<\/jats:title>\n Adverse prenatal exposures (APEs) often co-occur and independently associate with risk for childhood psychopathology. Whether exposure to multiple APEs is associated with persistent clinical effects through adolescence or underlying changes in brain maturation remains uncertain.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate longitudinal associations among cumulative APE burden, risk for psychopathology, and age-related cortical thinning in adolescents.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This cohort study analyzed 4-year follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study, which enrolled 11\u202f868 youth aged 9 to 10 years beginning in 2016. Sibling-comparison analysis was performed on 414 nonadopted sibling pairs with discordant APEs. Statistical analysis occurred from March to September 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Cumulative APE burden was calculated by summing 6 binary prenatal exposures that independently associated with psychopathology at baseline: unplanned pregnancy; early maternal prenatal alcohol, tobacco, or marijuana use; complicated pregnancy; and complicated birth.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Outcomes included annual Child Behavior Checklist (CBCL) scores of dimensional psychopathology, using both continuous and thresholded outcomes and biennial cortical thickness measures from structural magnetic resonance imaging, analyzed using linear mixed-effects models.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 8515 singleton children (mean [SD] baseline age, 9.9 [0.6] years; 4460 male [52.4%]), 6644 (78%) were exposed to at least 1 APE. Multiple APEs persistently and dose-dependently associated with increased odds of clinically significant psychopathology (CBCL total problems: exposure to 1 APE [odds ratio (OR), 2.01; 95% CI, 1.28-3.16; corrected\n P<\/jats:italic>\n \u2009=\u2009.006], 2 APEs [OR, 3.82; 95% CI, 2.39-6.11; corrected\n P<\/jats:italic>\n &amp;lt;.001], and 3 or more APEs [OR, 6.75; 95% CI, 4.14-11.02; corrected\n P<\/jats:italic>\n &amp;lt;.001]). Associations of APEs with attention-deficit\/hyperactivity disorder symptoms attenuated over time (interaction:\n F<\/jats:italic>\n \u2009=\u200913.51; corrected\n P<\/jats:italic>\n \u2009=\u20097.13\u2009\u00d7\u200910\n \u22128<\/jats:sup>\n ), whereas those with depressive symptoms potentiated (interaction:\n F<\/jats:italic>\n \u2009=\u20095.82; corrected\n P<\/jats:italic>\n \u2009=\u2009.002). Greater APE burden associated with accelerated age-related cortical thinning in 36 of 68 cortical regions (interaction for the right middle temporal cortex:\n F<\/jats:italic>\n = 8.89; corrected\n P &amp;lt;<\/jats:italic>\n .001). Siblings with more exposures demonstrated persistently higher CBCL total problems (\n t<\/jats:italic>\n \u2009=\u20092.25;\n P<\/jats:italic>\n \u2009=\u2009.03) and accelerated cortical thinning in 5 of the 36 regions implicated in the larger sample.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Results of this cohort study show that multiple prenatal adversities were associated with altered developmental trajectories of psychopathology and cortical maturation into midadolescence. These findings highlight the importance of fetal programming to mental health across life course and the need for additional study of risk and resiliency-conferring factors in utero.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2025.4080","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T16:31:09Z","timestamp":1767803469000},"page":"269","source":"Crossref","is-referenced-by-count":9,"title":["Prenatal Adversities and Risk of Persistent Youth Psychopathology and Altered Cortical Thinning"],"prefix":"10.1001","volume":"83","author":[{"given":"Dongmei","family":"Zhi","sequence":"first","affiliation":[{"name":"Center for Addiction Medicine, Massachusetts General Hospital, Boston"},{"name":"Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia A.","family":"Perdomo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston"},{"name":"MGH\/HST Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam R.","family":"Arteaga","sequence":"additional","affiliation":[{"name":"Center for Addiction Medicine, Massachusetts General Hospital, Boston"},{"name":"Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan E.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin C.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Department of Sociology, College of Liberal Arts, Purdue University, West Lafayette, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil H.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston"},{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Eden","family":"Evins","sequence":"additional","affiliation":[{"name":"Center for Addiction Medicine, Massachusetts General Hospital, Boston"},{"name":"Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harrison T.","family":"Reeder","sequence":"additional","affiliation":[{"name":"Biostatistics, Massachusetts General Hospital, Boston"},{"name":"Department of Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott E.","family":"Hadland","sequence":"additional","affiliation":[{"name":"Division of Adolescent and Young Adult Medicine, Mass General for Children, Boston, Massachusetts"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alysa E.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston"},{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A.","family":"Clauss","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston"},{"name":"MGH\/HST Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua L.","family":"Roffman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston"},{"name":"MGH\/HST Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi M.","family":"Gilman","sequence":"additional","affiliation":[{"name":"Center for Addiction Medicine, Massachusetts General Hospital, Boston"},{"name":"Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"5","key":"yoi250070r1","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/S2215-0366(20)30057-2","article-title":"Prenatal and perinatal risk and protective factors for psychosis: a systematic review and meta-analysis.","volume":"7","author":"Davies","year":"2020","journal-title":"Lancet Psychiatry"},{"issue":"6","key":"yoi250070r2","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1038\/s41591-018-0021-y","article-title":"Convergence of placenta biology and genetic risk for schizophrenia.","volume":"24","author":"Ursini","year":"2018","journal-title":"Nat Med"},{"issue":"9","key":"yoi250070r3","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1001\/jamapsychiatry.2018.1381","article-title":"Association of prenatal exposure to population-wide folic acid fortification with altered cerebral cortex maturation in youths.","volume":"75","author":"Eryilmaz","year":"2018","journal-title":"JAMA Psychiatry"},{"issue":"9","key":"yoi250070r4","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1001\/jamapediatrics.2020.1622","article-title":"Associations of maternal prenatal drug abuse with measures of newborn brain structure, tissue organization, and metabolite concentrations.","volume":"174","author":"Peterson","year":"2020","journal-title":"JAMA Pediatr"},{"issue":"6","key":"yoi250070r5","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1038\/s41593-023-01321-8","article-title":"Genetic patterning for child psychopathology is distinct from that for adults and implicates fetal cerebellar development.","volume":"26","author":"Hughes","year":"2023","journal-title":"Nat Neurosci"},{"key":"yoi250070r6","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1146\/annurev-clinpsy-050718-095539","article-title":"Prenatal developmental origins of future psychopathology: mechanisms and pathways.","volume":"15","author":"Monk","year":"2019","journal-title":"Annu Rev Clin Psychol"},{"issue":"11","key":"yoi250070r7","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1176\/appi.ajp.2020.20010086","article-title":"Association of prenatal alcohol exposure with psychological, behavioral, and neurodevelopmental outcomes in children from the adolescent brain cognitive development study.","volume":"177","author":"Lees","year":"2020","journal-title":"Am J Psychiatry"},{"issue":"3","key":"yoi250070r8","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.jaac.2010.12.004","article-title":"Prenatal alcohol exposure is associated with conduct disorder in adolescence: findings from a birth cohort.","volume":"50","author":"Larkby","year":"2011","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"8","key":"yoi250070r9","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1001\/archgenpsychiatry.2010.92","article-title":"Prenatal smoking exposure and the risk of psychiatric morbidity into young adulthood.","volume":"67","author":"Ekblad","year":"2010","journal-title":"Arch Gen Psychiatry"},{"issue":"1","key":"yoi250070r10","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1001\/jamapsychiatry.2020.2902","article-title":"Associations between prenatal cannabis exposure and childhood outcomes: results from the ABCD Study.","volume":"78","author":"Paul","year":"2021","journal-title":"JAMA Psychiatry"},{"key":"yoi250070r11","doi-asserted-by":"publisher","DOI":"10.1016\/j.dcn.2023.101209","article-title":"Effects of prenatal cannabis exposure on developmental trajectory of cognitive ability and brain volumes in the Adolescent Brain Cognitive Development (ABCD) study.","volume":"60","author":"Hiraoka","year":"2023","journal-title":"Dev Cogn Neurosci"},{"issue":"4","key":"yoi250070r12","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1080\/09297049.2022.2103105","article-title":"Effect of exposure to maternal diabetes during pregnancy on offspring\u2019s brain cortical thickness and neurocognitive functioning.","volume":"29","author":"Ahmed","year":"2023","journal-title":"Child Neuropsychol"},{"issue":"4","key":"yoi250070r13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0250235","article-title":"Association of adverse prenatal exposure burden with child psychopathology in the Adolescent Brain Cognitive Development (ABCD) study.","volume":"16","author":"Roffman","year":"2021","journal-title":"PLoS One"},{"key":"yoi250070r14","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1186\/s12888-015-0562-2","article-title":"Common or distinct pathways to psychosis: a systematic review of evidence from prospective studies for developmental risk factors and antecedents of the schizophrenia spectrum disorders and affective psychoses.","volume":"15","author":"Laurens","year":"2015","journal-title":"BMC Psychiatry"},{"issue":"7906","key":"yoi250070r15","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/s41586-022-04554-y","article-title":"Brain charts for the human lifespan.","volume":"604","author":"Bethlehem","year":"2022","journal-title":"Nature"},{"issue":"11","key":"yoi250070r16","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1001\/jamapsychiatry.2020.1495","article-title":"Assessment of neurobiological mechanisms of cortical thinning during childhood and adolescence and their implications for psychiatric disorders.","volume":"77","author":"Parker","year":"2020","journal-title":"JAMA Psychiatry"},{"issue":"12","key":"yoi250070r17","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.biopsych.2015.08.024","article-title":"Prenatal cannabis and tobacco exposure in relation to brain morphology: a prospective neuroimaging study in young children.","volume":"79","author":"El Marroun","year":"2016","journal-title":"Biol Psychiatry"},{"issue":"7","key":"yoi250070r18","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1111\/acer.15096","article-title":"Delayed cortical thinning in children and adolescents with prenatal alcohol exposure.","volume":"47","author":"Gimbel","year":"2023","journal-title":"Alcohol Clin Exp Res (Hoboken)"},{"key":"yoi250070r19","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/1471-244X-14-83","article-title":"Cortical thickness in youth with major depressive disorder.","volume":"14","author":"Reynolds","year":"2014","journal-title":"BMC Psychiatry"},{"issue":"8","key":"yoi250070r20","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1001\/jamapsychiatry.2022.1728","article-title":"Associations between pregnancy-related predisposing factors for offspring neurodevelopmental conditions and parental genetic liability to attention-deficit\/hyperactivity disorder, autism, and schizophrenia: the Norwegian Mother, Father and Child Cohort Study (MoBa).","volume":"79","author":"Havdahl","year":"2022","journal-title":"JAMA Psychiatry"},{"issue":"8","key":"yoi250070r21","doi-asserted-by":"publisher","first-page":"3171","DOI":"10.1038\/s41380-023-02202-z","article-title":"Towards a youth mental health paradigm: a perspective and roadmap.","volume":"28","author":"Uhlhaas","year":"2023","journal-title":"Mol Psychiatry"},{"issue":"3","key":"yoi250070r22","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1093\/ije\/dyac049","article-title":"Decline in attention-deficit hyperactivity disorder traits over the life course in the general population: trajectories across 5 population birth cohorts spanning ages 3 to 45 years.","volume":"51","author":"Wootton","year":"2022","journal-title":"Int J Epidemiol"},{"issue":"1","key":"yoi250070r23","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/S2215-0366(24)00361-4","article-title":"Tracking the course of depressive and anxiety symptoms across adolescence (the CATS study): a population-based cohort study in Australia.","volume":"12","author":"Robson","year":"2025","journal-title":"Lancet Psychiatry"},{"key":"yoi250070r24","doi-asserted-by":"publisher","DOI":"10.1016\/j.dcn.2021.101031","article-title":"Demographic and mental health assessments in the adolescent brain and cognitive development study: Updates and age-related trajectories.","volume":"52","author":"Barch","year":"2021","journal-title":"Dev Cogn Neurosci"},{"key":"yoi250070r26","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.dcn.2018.03.001","article-title":"The Adolescent Brain Cognitive Development (ABCD) study: Imaging acquisition across 21 sites.","volume":"32","author":"Casey","year":"2018","journal-title":"Dev Cogn Neurosci"},{"issue":"12","key":"yoi250070r27","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.4236\/psych.2013.412146","article-title":"Prevalence of behavioral and emotional problems among two to five years old Kosovar preschool children\u2014Parent\u2019s.","volume":"4","author":"Shala","year":"2013","journal-title":"Rep Psychol"},{"issue":"8","key":"yoi250070r28","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1038\/s41593-025-01990-7","article-title":"Addressing artifactual bias in large, automated MRI analyses of brain development.","volume":"28","author":"Elyounssi","year":"2025","journal-title":"Nat Neurosci"},{"issue":"20","key":"yoi250070r29","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1002\/bdr2.1176","article-title":"Convergent neurobiological predictors of emergent psychopathology during adolescence.","volume":"109","author":"Jones","year":"2017","journal-title":"Birth Defects Res"},{"issue":"3","key":"yoi250070r30","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1097\/EDE.0b013e31828c7381","article-title":"On sibling designs.","volume":"24","author":"Keyes","year":"2013","journal-title":"Epidemiology"},{"issue":"12","key":"yoi250070r31","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1017\/S0033291717000587","article-title":"Prospective association between tobacco smoking and death by suicide: a competing risks hazard analysis in a large twin cohort with 35-year follow-up.","volume":"47","author":"Evins","year":"2017","journal-title":"Psychol Med"},{"issue":"1","key":"yoi250070r32","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/s41380-021-01161-7","article-title":"Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies.","volume":"27","author":"Solmi","year":"2022","journal-title":"Mol Psychiatry"},{"key":"yoi250070r33","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.dcn.2015.01.010","article-title":"Executive function and cortical thickness in youths prenatally exposed to cocaine, alcohol, and tobacco.","volume":"16","author":"Gautam","year":"2015","journal-title":"Dev Cogn Neurosci"},{"issue":"3","key":"yoi250070r34","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.tics.2008.01.001","article-title":"A dual-networks architecture of top-down control.","volume":"12","author":"Dosenbach","year":"2008","journal-title":"Trends Cogn Sci"},{"issue":"2","key":"yoi250070r35","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/nn.3001","article-title":"Anatomical connectivity patterns predict face selectivity in the fusiform gyrus.","volume":"15","author":"Saygin","year":"2011","journal-title":"Nat Neurosci"},{"issue":"Pt 6","key":"yoi250070r36","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1093\/brain\/awu083","article-title":"Longitudinal changes in cortical thickness in autism and typical development.","volume":"137","author":"Zielinski","year":"2014","journal-title":"Brain"},{"key":"yoi250070r37","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.dcn.2018.04.004","article-title":"Recruiting the ABCD sample: design considerations and procedures.","volume":"32","author":"Garavan","year":"2018","journal-title":"Dev Cogn Neurosci"},{"issue":"2","key":"yoi250070r38","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1111\/acer.13305","article-title":"Prenatal alcohol consumption between conception and recognition of pregnancy.","volume":"41","author":"McCormack","year":"2017","journal-title":"Alcohol Clin Exp Res"},{"issue":"9","key":"yoi250070r39","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1007\/s10995-014-1462-7","article-title":"Revisiting retrospective reporting of first-birth intendedness.","volume":"18","author":"Guzzo","year":"2014","journal-title":"Matern Child Health J"},{"key":"yoi250070r40","doi-asserted-by":"publisher","DOI":"10.1016\/j.dcn.2024.101441","article-title":"An introduction to the Healthy Brain and Child Development Study (HBCD) study.","volume":"69","author":"Nelson","year":"2024","journal-title":"Dev Cogn Neurosci"},{"key":"yoi250070r25","volume-title":"Manual for the ASEBA Preschool Forms and Profiles","author":"Achenbach","year":"2000"}],"container-title":["JAMA Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/articlepdf\/2843423\/jamapsychiatry_zhi_2026_oi_250070_1772546835.94575.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T16:00:24Z","timestamp":1772640024000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/fullarticle\/2843423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,1]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamapsychiatry.2025.4080","relation":{},"ISSN":["2168-622X"],"issn-type":[{"value":"2168-622X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3,1]]}}}