{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T14:40:04Z","timestamp":1779374404785,"version":"3.53.1"},"reference-count":28,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Sports, Science and Culture, Japan, Grant-in-Aid for Scientific Research","award":["18K19709"],"award-info":[{"award-number":["18K19709"]}]},{"name":"Ministry of Education, Sports, Science and Culture, Japan, Grant-in-Aid for Scientific Research","award":["24K13471"],"award-info":[{"award-number":["24K13471"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>We previously reported that the fathers of the Bien Hoa birth cohort in Vietnam showed altered brain regional gray matter volumes, as measured by magnetic resonance imaging, and social anxiety traits associated with perinatal dioxin exposure. In the present study, we aimed to compare gray matter volumes and social anxiety scale scores between dioxin-exposed fathers in Bien Hoa and unexposed controls in an unsprayed area. Fat-based bioassay-toxic equivalency levels in serum were used to indicate dioxin exposure in adulthood. Results indicated that the longer Bien Hoa residency group (\u226530 years) exposed to dioxins during the perinatal period and early childhood showed higher gray matter volumes in the right and left temporal lobes than controls. However, no significant differences in temporal lobe gray matter volumes were found between the shorter Bien Hoa residency group (&lt;30 years) and controls. Furthermore, the longer, but not shorter, Bien Hoa residency group showed higher social\u2013emotional subscale scores than controls. Additionally, fat-based bioassay-toxic equivalency levels were inversely correlated with gray matter volumes in several right temporal gyri. These findings suggest biphasic life stage-dependent adverse effects of dioxin exposure: perinatal dioxin exposure increases gray matter volumes, especially in the temporal lobe, which leads to neurodevelopmental disorders with socio-emotional disturbances, whereas dioxin exposure after brain development decreases cortical gray matter volumes, possibly leading to cognitive dysfunction.<\/jats:p>","DOI":"10.3390\/toxics13090710","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:09:53Z","timestamp":1756080593000},"page":"710","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Dioxin Exposure on Brain Regional Volumes of Fathers from Birth Cohorts in Herbicide-Sprayed and Unsprayed Areas in Vietnam"],"prefix":"10.3390","volume":"13","author":[{"given":"Hai Minh","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Diagnostic Imaging, Military Hospital 103, Vietnam Military Medical University, Hanoi 12108, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4863-0653","authenticated-orcid":false,"given":"Hoa Thi","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Military Hygiene, Vietnam Military Medical University, Hanoi 12108, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thao Ngoc","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Functional Diagnosis, Military Hospital 103, Vietnam Military Medical University, Hanoi 12108, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5878-7307","authenticated-orcid":false,"given":"Tai","family":"Pham-The","sequence":"additional","affiliation":[{"name":"Biomedical and Pharmaceutical Research Centre, Vietnamese Military Medical University, Hanoi 12108, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yokawa","sequence":"additional","affiliation":[{"name":"Kobe Imaging Center, Bio View Co., Kobe 650-0047, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Hiyoshi Corporation, Omihachiman 523-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Hiyoshi Corporation, Omihachiman 523-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneko","family":"Nishijo","sequence":"additional","affiliation":[{"name":"Epidemiology and Public Health, Kanazawa Medical University, Uchinada 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8726-0661","authenticated-orcid":false,"given":"Yutaro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Epidemiology and Public Health, Kanazawa Medical University, Uchinada 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Nishino","sequence":"additional","affiliation":[{"name":"Epidemiology and Public Health, Kanazawa Medical University, Uchinada 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nghi Tran","family":"Ngoc","sequence":"additional","affiliation":[{"name":"Faculty of Clinical Medicine, Hanoi University of Public Health, Hanoi 12108, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4786-4610","authenticated-orcid":false,"given":"Hisao","family":"Nishijo","sequence":"additional","affiliation":[{"name":"Department of Sport and Health Sciences, Faculty of Human Sciences, University of East Asia, Shimonoseki 751-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1097\/00043764-200105000-00002","article-title":"Recent dioxin contamination from Agent Orange in residents of a southern Vietnam city","volume":"43","author":"Schecter","year":"2001","journal-title":"J. Occup. Environ. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"516","DOI":"10.2105\/AJPH.85.4.516","article-title":"Agent Orange and the Vietnamese: The persistence of elevated dioxin levels in human tissues","volume":"85","author":"Schecter","year":"1995","journal-title":"Am. J. Public Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.chemosphere.2005.01.052","article-title":"Dioxin hot spots in Vietnam","volume":"60","author":"Dwernychuk","year":"2005","journal-title":"Chemosphere"},{"key":"ref_4","first-page":"484","article-title":"Association of dioxin exposure and reproductive hormone levels in men living near the Bien Hoa airbase, Vietnam","volume":"628\u2013629","author":"Tai","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5732","DOI":"10.1021\/es506211p","article-title":"Dioxins and Nonortho PCBs in Breast Milk of Vietnamese Mothers Living in the Largest Hot Spot of Dioxin Contamination","volume":"49","author":"Nghi","year":"2015","journal-title":"Environ. Sci. Technol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.scitotenv.2019.02.395","article-title":"Adverse effects of maternal dioxin exposure on fetal brain development before birth assessed by neonatal electroencephalography (EEG) leading to poor neurodevelopment; a 2-year follow-up study","volume":"667","author":"Nghiem","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"113661","DOI":"10.1016\/j.ijheh.2020.113661","article-title":"Effects of perinatal dioxin exposure on neonatal electroencephalography (EEG) activity of the quiet sleep stage in the most contaminated area from Agent Orange in Vietnam","volume":"232","author":"Pham","year":"2021","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Vu, H.T., Pham, T.N., Yokawa, T., Nishijo, M., The, T.P., Do, Q., Nishino, Y., and Nishijo, H. (2021). Alterations in regional brain regional volume associated with dioxin exposure in men living in the most dioxin-contaminated area in Vietnam: Magnetic Resonance Imaging (MRI) analysis using Voxel-Based Morphometry (VBM). Toxics, 9.","DOI":"10.3390\/toxics9120353"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jpsychires.2023.09.002","article-title":"Impact of dioxin exposure on brain morphometry and social anxiety in men living in the most dioxin-contaminated area in Vietnam","volume":"166","author":"Vu","year":"2023","journal-title":"J. Psychiatr. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Nakamura, M., Matsuda, R., Vu, H.T., Pham-The, T., Pham, T.N., Takiguchi, T., Nishino, Y., Nishijo, H., and Nishijo, M. (2025). Bioassay using the DR-EcoScreen system to measure diox-in-related compounds in serum samples from individuals ex-posed to dioxins originating from Agent Orange in Vietnam. Toxics, 13.","DOI":"10.3390\/toxics13060513"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.neuroimage.2005.02.018","article-title":"Unified segmentation","volume":"26","author":"Ashburner","year":"2005","journal-title":"NeuroImage"},{"key":"ref_12","unstructured":"Fix, J.D. (1995). Neuroanatomy, Williams & Wilkins, a Waverly Company. [2nd ed.]."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ribas, G.C. (2010). The cerebral sulci and gyri. Neurosurg. Focus, 28.","DOI":"10.3171\/2009.11.FOCUS09245"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.chemosphere.2008.08.015","article-title":"In vitro screening for aryl hydrocarbon receptor agonistic activity in 200 pesticides using a highly sensitive reporter cell line, DR-EcoScreen cells, and in vivo mouse liver cytochrome P450-1A induction by propanil, diuron and linuron","volume":"74","author":"Takeuchi","year":"2008","journal-title":"Chemosphere"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [5th ed.].","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_16","first-page":"5","article-title":"Validation of the Social Anxiety Questionnaire for Adults (SAQ-A30) with Spanish university students: Similarities and differences among degree subjects and regions","volume":"18","author":"Caballo","year":"2010","journal-title":"Behav. Psychol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.beth.2011.07.001","article-title":"The multidimensional nature and multicultural validity of a new measure of social anxiety: The Social Anxiety Questionnaire for Adults","volume":"43","author":"Caballo","year":"2012","journal-title":"Behav. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6430","DOI":"10.1073\/pnas.0607061104","article-title":"Social concepts are represented in the superior anterior temporal cortex","volume":"104","author":"Zahn","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Grecucci, A., Rubicondo, D., Siugzdaite, R., Surian, L., and Job, R. (2016). Uncovering the Social Deficits in the Autistic Brain. A Source-Based Morphometric Study. Front. Neurosci., 10.","DOI":"10.3389\/fnins.2016.00388"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1661617","DOI":"10.1155\/2021\/1661617","article-title":"Neurodevelopmental disorder traits in taijin-kyofu-sho and social anxiety disorder: A cross-sectional study among university students","volume":"2021","author":"Kajitani","year":"2021","journal-title":"Psychiatry J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.neuro.2022.07.002","article-title":"Long-term effects of defoliant exposure on brain atrophy progression in humans","volume":"92","author":"Lee","year":"2022","journal-title":"NeuroToxicology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.14283\/jpad.2024.84","article-title":"Risk of dementia in Korean Vietnam War veterans","volume":"11","author":"Lee","year":"2024","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1001\/jamaneurol.2020.5011","article-title":"Agent Orange Exposure and Dementia Diagnosis in US Veterans of the Vietnam Era","volume":"78","author":"Martinez","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ramos-Garc\u00eda, N.A., Orozco-Ibarra, M., Estudillo, E., Elizondo, G., G\u00f3mez Apo, E., Ch\u00e1vez Mac\u00edas, L.G., Sosa-Ortiz, A.L., and Torres-Ramos, M.A. (2020). Aryl Hydrocarbon Receptor in Post-Mortem Hippocampus and in Serum from Young, Elder, and Alzheimer\u2019s Patients. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21061983"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ojo, E.S., and Tischkau, S.A. (2021). The Role of AhR in the Hallmarks of Brain Aging: Friend and Foe. Cells, 10.","DOI":"10.3390\/cells10102729"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ntt.2015.10.005","article-title":"Developmental origin of abnormal dendritic growth in the mouse brain induced by in utero disruption of aryl hydrocarbon receptor signaling","volume":"52","author":"Kimura","year":"2015","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1002\/dneu.22825","article-title":"Persistent organic pollutants at the synapse: Shared phenotypes and converging mechanisms of developmental neurotoxicity","volume":"81","author":"Latchney","year":"2021","journal-title":"Dev. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00018-022-04520-x","article-title":"Aryl hydrocarbon receptor (AhR) reveals evidence of antagonistic pleiotropy in the regulation of the aging process","volume":"79","author":"Salminen","year":"2022","journal-title":"Cell. Mol. Life Sci."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/13\/9\/710\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:34:53Z","timestamp":1760034893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/13\/9\/710"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,23]]},"references-count":28,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["toxics13090710"],"URL":"https:\/\/doi.org\/10.3390\/toxics13090710","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,23]]}}}