{
  "abstract": "Introduction: MicroRNAs are candidate regulators and biomarkers of molecular processes relevant to behavior, but their relationships with neuroendocrine signaling in humans remain poorly characterized. Earlier studies in overlapping cohorts identified hypermethylation-associated downregulation of peripheral blood-derived hsa-miR-4456 in men with hypersexual disorder and implicated oxytocin-related pathways through in-silico target prediction; a subsequent study found higher plasma oxytocin in the same clinical context. Whether miR-4456 expression and oxytocin covary within the same individuals had not been examined.\n\nMethods: We performed a secondary cross-sectional analysis of baseline, pretreatment measurements from clinically characterized men with hypersexual disorder and healthy male controls. miR-4456 was measured by RT-qPCR in EDTA blood-derived material and plasma oxytocin by radioimmunoassay. The submitted pooled robust regression included 74 paired measurements; revised group-adjusted and interaction models included 73 complete cases (51 hypersexual disorder and 22 controls). miR-4456, but not oxytocin, was rank-based inverse-normal transformed using Blom's method.\n\nResults: In the submitted pooled model, higher miR-4456 was associated with lower plasma oxytocin (β = −4.039 pmol/L, 95% CI −6.149 to −1.930; p < 0.001). After adjustment for diagnostic group, the estimate remained negative but was attenuated (β = −1.522, 95% CI −3.376 to 0.333; p = 0.106). The control-specific estimate was −0.613 (95% CI −3.693 to 2.467; p = 0.696), the hypersexual-disorder estimate was −2.223 (95% CI −4.514 to 0.069; p = 0.057), and the interaction was not significant ( p = 0.414). Post hoc sensitivity analyses were directionally consistent but imprecise.\n\nConclusions: To our knowledge, this is the first human study to directly examine paired peripheral miR-4456 and plasma oxytocin measurements. Although diagnostic-group differences explained part of the pooled association, the paired observation connects previously separate epigenetic, expression, pathway-prediction, and neuroendocrine findings and identifies a focused hypothesis for independent replication. The cross-sectional peripheral measurements do not establish directionality, causation, or central nervous system regulation. Experimental studies are needed to determine whether miR-4456 has any functional influence on oxytocin-related biology.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet",
    "Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital",
    "Department of Clinical Sciences/Psychiatry, Umeå University",
    "Medical School, University of Cyprus",
    "Department of Clinical Neuroscience/Psychology, Karolinska Institutet",
    "Center for Clinical Research Dalarna, Uppsala University",
    "Department of Medicine, Karolinska Institutet, Karolinska University Hospital",
    "Department of Laboratory Medicine, Clinical Physiology, Karolinska Institutet"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
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        1,
        2
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      "name": "Adrian E. Desai Boström"
    },
    {
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        2,
        3
      ],
      "name": "Andreas Chatzittofis"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Peter Andersson"
    },
    {
      "affs": [
        2,
        6
      ],
      "name": "Josephine Savard"
    },
    {
      "affs": [
        6
      ],
      "name": "Katarina Görts Öberg"
    },
    {
      "affs": [
        6
      ],
      "name": "Stefan Arver"
    },
    {
      "affs": [
        7
      ],
      "name": "John N. Flanagan"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jussi Jokinen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8a3etv9396pje.bib",
  "cited_by": 0,
  "doi": "10.3389/fnins.2026.1946302",
  "fulltext_url": "https://europepmc.org/articles/PMC13713500",
  "id": "8a3etv9396pje",
  "issns": [
    "1662-453X",
    "1662-4548"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fnins.2026.1946302/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
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      "openalex",
      "1306|MicroRNA in disease regulation"
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  "openalex": "W7221785564",
  "pdf_url": "https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2026.1946302/pdf",
  "pmcid": "PMC13713500",
  "pmid": "42952647",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/8a3etv9396pje.ris",
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  "subjects": [
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      "field": "medicine",
      "origin": "openalex:1306|MicroRNA in disease regulation",
      "subfield": "oncology"
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  ],
  "title": "Association between peripheral hsa-miR-4456 expression and plasma oxytocin in men with hypersexual disorder and healthy controls: a secondary cross-sectional analysis",
  "title_text": "Association between peripheral hsa-miR-4456 expression and plasma oxytocin in men with hypersexual disorder and healthy controls: a secondary cross-sectional analysis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:09Z",
  "url": "https://research.draconitic.com/paper/8a3etv9396pje",
  "venue": "Frontiers in Neuroscience",
  "versions": []
}