{
  "abstract": "Monoamine oxidase B (MAO-B) is a high-density protein located mainly in astrocytes that influences mitochondrial function and transition to astrogliosis. MAO-B produces hydrogen peroxide while metabolizing non-serotonergic monoamines. Elevated MAO-B level is implicated in the pathophysiology of several common neuropsychiatric diseases. The aims are to examine the effect of treatment resistant major depressive episodes, sex, and antidepressant treatment on MAO-B total distribution volume ([11C]SL25.1188 VT), index of MAO-B level. [11C]SL25.1188 PET was applied in 95 adults (29 with MDE and no history of treatment-resistance (NTR-MDE), 26 with MDE and history of treatment-resistance (TRD), and 40 healthy control (HC)). A subset of NTR-MDE and TRD (n=13) were scanned before and after treatment with phenelzine, rasagiline, or duloxetine. [11C]SL25.1188 VT was higher in grey matter regions in females (10%, p<.001). [11C]SL25.1188 VT was also higher in prefrontal cortex in TRD compared to HC (23%, p<.001) and TRD compared to NTR-MDE (6%, p=.033). Duloxetine had minimal effect on [11C]SL25.1188 VT, but occupancy of rasagiline and phenelzine was [~]94%. This study discovered sex differences in MAO-B level, which may explain sex differences in prevalence or trajectory of illnesses with greater MAO-B level like Alzheimers disease, traumatic brain injury and major depressive disorder. Given our findings of greater MAO-B level in prefrontal cortex of TRD and its insensitivity to serotonin reuptake inhibition, combined with potential harm of highly elevated MAO-B level, development of MAO-B inhibitors could be considered for a subset of TRD. Rasagiline and phenelzine demonstrate similarly potent occupancy in vivo at clinical dosage.",
  "abstract_shown": true,
  "affiliations": [
    "Centre for Addiction and Mental Health"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "E. J. Kuik"
    },
    {
      "name": "C. Baena-Tan"
    },
    {
      "name": "S. Moriguchi"
    },
    {
      "name": "J. Braga"
    },
    {
      "name": "L. Miler"
    },
    {
      "name": "P. Rusjan"
    },
    {
      "name": "M. Bagby"
    },
    {
      "name": "M. I. Husain"
    },
    {
      "name": "N. Vasdev"
    },
    {
      "name": "T. Tomoda"
    },
    {
      "name": "M. Banasr"
    },
    {
      "name": "S. Kloiber"
    },
    {
      "affs": [
        0
      ],
      "name": "J. H. Meyer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dn84aryhxgry5.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.08.26362462",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.08.26362462v1.full",
  "id": "dn84aryhxgry5",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.08.26362462v1",
  "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",
      "2736|Treatment of Major Depression"
    ]
  ],
  "openalex": "W7212295886",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.08.26362462v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dn84aryhxgry5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:16Z",
      "native_id": "10.64898/2026.09.08.26362462",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.08.26362462v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:psychiatry and clinical psychology",
      "subfield": "psychiatry"
    }
  ],
  "title": "Effects of sex, treatment resistance, and antidepressant treatment on monoamine oxidase B total distribution volume",
  "title_text": "Effects of sex, treatment resistance, and antidepressant treatment on monoamine oxidase B total distribution volume",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:16Z",
  "url": "https://research.draconitic.com/paper/dn84aryhxgry5",
  "venue": "medRxiv",
  "versions": []
}