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The clusters were previously identified by deep learning analysis of self\u2010 and parental\u2010report questionnaires from participants in the Tokyo Teen Cohort (TTC) study in Japan.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We extracted genomic DNA from saliva samples of a subset of TTC participants (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009122) at ages 11, 13, and 15. DNA methylation levels at the functional CpG sites within the\n                      <jats:italic>SLC6A4<\/jats:italic>\n                      promoter were measured using bisulfite pyrosequencing. Five psychopathological and behavioral clusters were applied from the previous study: minimal problems, persistent or worsening internalizing problems, subjective problems overlooked by caregivers, persistent externalizing problems, and chronic severe problems across symptoms. Linear mixed\u2010effects models were applied to assess the associations between DNA methylation levels and psycho\u2010behavioral clusters.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Males exhibited significantly lower mean methylation levels compared to females across all time points. Males classified as persistent externalizing problems showed notably lower methylation levels than those classified as minimal problems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      DNA methylation levels in the\n                      <jats:italic>SLC6A4<\/jats:italic>\n                      could potentially serve as epigenetic signatures for male adolescents exhibiting externalizing behavioral problems. To our knowledge, this is the first study to track\n                      <jats:italic>SLC6A4<\/jats:italic>\n                      methylation at three developmental time points across early to mid\u2010adolescence. Further epigenetic research is warranted to understand the role of environmental and genetic factors in the manifestation of adolescent behavioral problems.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/npr2.70081","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T02:55:28Z","timestamp":1764903328000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association Study on Multi\u2010Timepoint\n                    <scp>DNA<\/scp>\n                    Methylation Levels of Serotonin Transporter Gene and Adolescent Psychological\u2010Behavioral Development"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4436-3962","authenticated-orcid":false,"given":"Tempei","family":"Ikegame","sequence":"first","affiliation":[{"name":"Department of Neuropsychiatry, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miki","family":"Bundo","sequence":"additional","affiliation":[{"name":"Department of Molecular Brain Science, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiki","family":"Nagaoka","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaro","family":"Yanagida","sequence":"additional","affiliation":[{"name":"Department of Molecular Brain Science, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Nakachi","sequence":"additional","affiliation":[{"name":"Department of Molecular Brain Science, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emi","family":"Kiyota","sequence":"additional","affiliation":[{"name":"Department of Molecular Brain Science, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naohiro","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Graduate School of Medicine The University of Tokyo  Tokyo Japan"},{"name":"The International Research Center for Neurointelligence (WPI\u2010IRCN) University of Tokyo Institutes for Advanced Study (UTIAS)  Bunkyo\u2010ku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinsuke","family":"Koike","sequence":"additional","affiliation":[{"name":"University of Tokyo Institute for Diversity &amp; 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