{
  "abstract": "Circadian disruption is a transdiagnostic feature of psychiatric illness, particularly in bipolar disorder (BD), where evening chronotype is linked to greater symptom severity. The suprachiasmatic nucleus (SCN) times pineal gland (PG) melatonin synthesis through a well-described feedforward pathway. Moreover, melatonin can also phase-shift the SCN-pacemaker, consistent with a functional feedback limb. Directed effective connectivity between the SCN-containing hypothalamus and the PG has not been estimated in human neuroimaging, and it is unknown whether that directed coupling varies by psychiatric diagnosis or chronotype. We applied cross-spectral dynamic causal modeling (DCM) to resting-state fMRI data in 431 UK Biobank (healthy controls [HC, N=136], BD [N=78], major depressive disorder [MDD, N=154] and psychotic disorders [PY, N=63]). Random-effects Bayesian model selection compared a fully connected model with reduced archiature and, separately, feedforward-only (SCN[->]PG) vs feedback-only (PG[->]SCN) models. A per-subject log Bayes factor difference (dF) indexed directionality preference and was tested against diagnosis, chronotype and their interaction using ANCOVA. The fully connected model was strongly preferred (posterior probability=97.8%, protected exceedance probability [PXP]=1.00). Feedforward architecture dominated overall (70% vs 30%, PXP=1.00). Diagnosis did not predict dF (p=.403), but chronotype did (p=.036), and there was a significant diagnosis-by-chronotype interaction (p<.001). Feedforward dominance was strongest in evening chronotypes (p<.001). Model evidence favored a fully connected architecture with overall feedforward dominance. That preference varied by chronotype and, qualified by the interaction, was strongest in BD evening chronotypes. The pattern supports BD-evening chronotype as a high-risk subgroup and argues for routine chronotype assessment in BD care.",
  "abstract_shown": true,
  "affiliations": [
    "University Hospital of Psychiatry Zurich"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "I. Mehrdadi"
    },
    {
      "name": "S. Kuster"
    },
    {
      "name": "J. Rohrer"
    },
    {
      "name": "E. Seifritz"
    },
    {
      "name": "C. Chatelain"
    },
    {
      "name": "G. Chan"
    },
    {
      "name": "P. Homan"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Tahedl"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4wytw38zg6xr2.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.26363889",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.24.26363889v1.full",
  "id": "4wytw38zg6xr2",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.24.26363889v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "psychiatry and clinical psychology"
    ],
    [
      "openalex",
      "2807|Circadian rhythm and melatonin"
    ]
  ],
  "openalex": "W7214442659",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.24.26363889v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4wytw38zg6xr2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:29Z",
      "native_id": "10.64898/2026.09.24.26363889",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.24.26363889v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:psychiatry and clinical psychology",
      "subfield": "psychiatry"
    }
  ],
  "title": "Directed effective connectivity between the SCN-containing hypothalamus and pineal gland varies by chronotype in bipolar disorder",
  "title_text": "Directed effective connectivity between the SCN-containing hypothalamus and pineal gland varies by chronotype in bipolar disorder",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:29Z",
  "url": "https://research.draconitic.com/paper/4wytw38zg6xr2",
  "venue": "medRxiv",
  "versions": []
}