{
  "abstract": "Attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized as a lifespan neurodevelopmental disorder, yet the mechanisms underlying its changing clinical presentation across development remain poorly understood. Although childhood ADHD is typically characterized by hyperactivity, impulsivity, and inattention, symptom expression frequently evolves during adolescence and adulthood toward greater reward dysregulation, executive dysfunction, motivational impairment, internal restlessness, and changing manifestations of emotional dysregulation. Existing neurobiological models have substantially advanced understanding of ADHD pathophysiology but provide limited explanation for how symptom continuity can coexist with developmental changes in clinical expression. Here, we propose the Developmental Dopamine Trajectory Hypothesis, which posits that DAT related dopaminergic dysregulation may interact with the sequential maturation of frontostriatal, mesolimbic, and mesocortical circuits to contribute to developmental changes in ADHD symptom expression across the lifespan. A central proposition of the framework is that the functional consequences of DAT related dopaminergic dysregulation depend on the developmental state of the neural circuits on which it acts. Within this framework, childhood manifestations may arise primarily from interactions between dopaminergic vulnerability and developing frontostriatal networks, adolescent manifestations from increasing involvement of reward and emotion related circuitry, and adult manifestations from interactions with mature executive control and motivational systems. By integrating evidence from longitudinal clinical studies, neuroimaging, electrophysiology, pharmacology, genetics, and translational DAT models, the proposed framework provides a mechanistic model for how developmental changes in neural circuit state may contribute to changing symptom expression despite continuity of underlying neurobiological vulnerability. The hypothesis generates testable predictions regarding longitudinal symptom trajectories, developmental biomarker changes, potential developmental differences in treatment responsiveness, and adolescence as a proposed critical neurodevelopmental transition period. Reconceptualizing ADHD through a developmental dopaminergic framework places developmental timing and neural circuit maturation at the center of the relationship between dopaminergic vulnerability and clinical phenotype, providing a basis for future longitudinal, mechanistic, and developmentally informed research across the lifespan.",
  "abstract_shown": true,
  "affiliations": [
    "Networking Group Aging, Department of Ergonomics, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund, Germany.",
    "Experimental Ergonomics, Department of Ergonomics, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund, Germany.",
    "Bradford Institute for Health Research, Temple Bank House, Bradford Royal Infirmary, Bradford, United Kingdom.",
    "Department of Pharmacy, St. Scholastica's College Tacloban Inc., Palo, Leyte, Philippines.",
    "College of Medicine, University of the Philippines Manila, Manila, Philippines.",
    "Division of Child and Adolescent Psychiatry, Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Republic of Korea.",
    "Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, Seoul, Republic of Korea.",
    "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.",
    "Institute for New Drug Development, College of Pharmacy, Jeonbuk National University, Jeollabuk-do, Republic of Korea."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Raly James Perez Custodio"
    },
    {
      "affs": [
        0
      ],
      "name": "Stephan Getzmann"
    },
    {
      "affs": [
        1
      ],
      "name": "Edmund Wascher"
    },
    {
      "affs": [
        2
      ],
      "name": "Michael C Pan"
    },
    {
      "affs": [
        3
      ],
      "name": "Florence Ingred Samante"
    },
    {
      "affs": [
        4
      ],
      "name": "Fred Lawrence Samante"
    },
    {
      "affs": [
        5
      ],
      "name": "Bung-Nyun Kim"
    },
    {
      "affs": [
        6
      ],
      "name": "Hee Jin Kim"
    },
    {
      "affs": [
        7
      ],
      "name": "Eugene C Yi"
    },
    {
      "affs": [
        8
      ],
      "name": "Jae Hoon Cheong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/amnmcp9b1xvv3.bib",
  "cited_by": 0,
  "doi": "10.3389/fpsyt.2026.1944446",
  "fulltext_url": "https://europepmc.org/articles/PMC13684815",
  "id": "amnmcp9b1xvv3",
  "issns": [
    "1664-0640"
  ],
  "landing_url": "https://europepmc.org/article/MED/42909938",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2738|Attention Deficit Hyperactivity Disorder"
    ]
  ],
  "openalex": "W7220836120",
  "pdf_url": "https://europepmc.org/articles/PMC13684815?pdf=render",
  "pmcid": "PMC13684815",
  "pmid": "42909938",
  "published": "2026-10-07",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/amnmcp9b1xvv3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "MED:42909938",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42909938"
    },
    {
      "first_seen": "2026-10-30T12:20:18Z",
      "native_id": "10.3389/fpsyt.2026.1944446",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1944446/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Attention Deficit Hyperactivity Disorder",
      "subfield": "psychiatry"
    }
  ],
  "title": "The developmental dopamine trajectory hypothesis of ADHD across the lifespan.",
  "title_text": "The developmental dopamine trajectory hypothesis of ADHD across the lifespan.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:18Z",
  "url": "https://research.draconitic.com/paper/amnmcp9b1xvv3",
  "venue": "Frontiers in psychiatry",
  "versions": []
}