{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:46:02Z","timestamp":1789487162545,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,10]]},"group-title":"Psychiatry and Clinical Psychology","reference-count":52,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["1R01MH115014-01"],"award-info":[{"award-number":["1R01MH115014-01"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/03a63f080","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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 ([\n                  <jats:sup>11<\/jats:sup>\n                  C]SL25.1188 V\n                  <jats:sub>T<\/jats:sub>\n                  ), index of MAO-B level. [\n                  <jats:sup>11<\/jats:sup>\n                  C]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. [\n                  <jats:sup>11<\/jats:sup>\n                  C]SL25.1188 V\n                  <jats:sub>T<\/jats:sub>\n                  was higher in grey matter regions in females (10%,\n                  <jats:italic>p<\/jats:italic>\n                  &lt;.001). [\n                  <jats:sup>11<\/jats:sup>\n                  C]SL25.1188 V\n                  <jats:sub>T<\/jats:sub>\n                  was also higher in prefrontal cortex in TRD compared to HC (23%, p&lt;.001) and TRD compared to NTR-MDE (6%,\n                  <jats:italic>p<\/jats:italic>\n                  =.033). Duloxetine had minimal effect on [\n                  <jats:sup>11<\/jats:sup>\n                  C]SL25.1188 V\n                  <jats:sub>T<\/jats:sub>\n                  , but occupancy of rasagiline and phenelzine was \u223c94%. 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 Alzheimer\u2019s 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.\n                <\/jats:p>","DOI":"10.64898\/2026.09.08.26362462","type":"posted-content","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:10:13Z","timestamp":1789143013000},"source":"Crossref","is-referenced-by-count":0,"title":["Effects of sex, treatment resistance, and antidepressant treatment on monoamine oxidase B total distribution volume"],"prefix":"10.64898","author":[{"given":"Emily JY","family":"Kuik","sequence":"first","affiliation":[{"name":"Brain Health Imaging Centre and Azrieli Centre for Neuro-Radiochemistry, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada"},{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Baena-Tan","sequence":"additional","affiliation":[{"name":"Brain Health Imaging Centre and Azrieli Centre for Neuro-Radiochemistry, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-9708","authenticated-orcid":false,"given":"Sho","family":"Moriguchi","sequence":"additional","affiliation":[{"name":"Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan"},{"name":"Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joeffre","family":"Braga","sequence":"additional","affiliation":[{"name":"Brain Health Imaging Centre and Azrieli Centre for Neuro-Radiochemistry, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada"},{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Miler","sequence":"additional","affiliation":[{"name":"Brain Health Imaging Centre and Azrieli Centre for Neuro-Radiochemistry, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0075-2918","authenticated-orcid":false,"given":"Pablo","family":"Rusjan","sequence":"additional","affiliation":[{"name":"Douglas Research Centre and Department of Psychiatry, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bagby","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Toronto, Toronto, ON, Canada"},{"name":"Department of Psychology, University of Toronto, Toronto, ON, Canada"},{"name":"Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5771-5750","authenticated-orcid":false,"given":"M Ishrat","family":"Husain","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Toronto, Toronto, ON, Canada"},{"name":"Clinical Trials Unit, Centre for Addiction and Mental Health, Toronto, ON, Canada"},{"name":"Krembil Brain Institute, University Health Network, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2087-5125","authenticated-orcid":false,"given":"Neil","family":"Vasdev","sequence":"additional","affiliation":[{"name":"Brain Health Imaging Centre and Azrieli Centre for Neuro-Radiochemistry, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3587-0914","authenticated-orcid":false,"given":"Toshifumi","family":"Tomoda","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON, Canada"},{"name":"Neurobiology of Depression and Aging, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mounira","family":"Banasr","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON, Canada"},{"name":"Neurobiology of Depression and Aging, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6838-4114","authenticated-orcid":false,"given":"Stefan","family":"Kloiber","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Toronto, Toronto, ON, Canada"},{"name":"General Adult Psychiatry and Health Systems Division, Centre for Addiction and Mental Health, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4684-5052","authenticated-orcid":false,"given":"Jeffrey H","family":"Meyer","sequence":"additional","affiliation":[{"name":"Brain Health Imaging Centre and Azrieli Centre for Neuro-Radiochemistry, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada"},{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON, Canada"},{"name":"General Adult Psychiatry and Health Systems Division, Centre for Addiction and Mental Health, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091506451371000_2026.09.08.26362462v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(97)00113-9"},{"issue":"6","key":"2026091506451371000_2026.09.08.26362462v1.2","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/jcbfm.2013.19","article-title":"Distribution of monoamine oxidase proteins in human brain: implications for brain imaging studies","volume":"33","year":"2013","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"2026091506451371000_2026.09.08.26362462v1.3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-05-01977.1992"},{"key":"2026091506451371000_2026.09.08.26362462v1.4","doi-asserted-by":"publisher","DOI":"10.3390\/molecules31010186"},{"key":"2026091506451371000_2026.09.08.26362462v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-021-01097-4"},{"issue":"6","key":"2026091506451371000_2026.09.08.26362462v1.6","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1001\/jamapsychiatry.2019.0044","article-title":"Monoamine oxidase B total distribution volume in the prefrontal cortex of major depressive disorder: an [11C] SL25. 1188 positron emission tomography study","volume":"76","year":"2019","journal-title":"JAMA psychiatry"},{"key":"2026091506451371000_2026.09.08.26362462v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90311-5"},{"issue":"8","key":"2026091506451371000_2026.09.08.26362462v1.8","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.biopsych.2024.09.027","article-title":"Astrogliosis marker [11C] SL25. 1188 after COVID-19 with ongoing depressive and cognitive symptoms","volume":"97","year":"2025","journal-title":"Biological Psychiatry"},{"issue":"11","key":"2026091506451371000_2026.09.08.26362462v1.9","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1093\/brain\/awad279","article-title":"Astrogliosis marker 11C-SL25. 1188 PET in traumatic brain injury with persistent symptoms","volume":"146","year":"2023","journal-title":"Brain"},{"issue":"9","key":"2026091506451371000_2026.09.08.26362462v1.10","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1093\/brain\/awx172","article-title":"Brain monoamine oxidase B and A in human parkinsonian dopamine deficiency disorders","volume":"140","year":"2017","journal-title":"Brain"},{"key":"2026091506451371000_2026.09.08.26362462v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1883"},{"key":"2026091506451371000_2026.09.08.26362462v1.12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001616"},{"key":"2026091506451371000_2026.09.08.26362462v1.13","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24110"},{"key":"2026091506451371000_2026.09.08.26362462v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-024-02712-2"},{"key":"2026091506451371000_2026.09.08.26362462v1.15","first-page":"253","article-title":"Reactive gliosis and monoamine oxidase B","volume":"41","year":"1994","journal-title":"J Neural Transm Suppl"},{"key":"2026091506451371000_2026.09.08.26362462v1.16","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12229"},{"key":"2026091506451371000_2026.09.08.26362462v1.17","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.067439"},{"key":"2026091506451371000_2026.09.08.26362462v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2017.03.032"},{"issue":"10","key":"2026091506451371000_2026.09.08.26362462v1.19","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1002\/jlcr.1908","article-title":"Radiosynthesis of [11C] SL25. 1188 via [11C] CO2 fixation for imaging monoamine oxidase B","volume":"54","year":"2011","journal-title":"Journal of Labelled Compounds and Radiopharmaceuticals"},{"issue":"5","key":"2026091506451371000_2026.09.08.26362462v1.20","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/jcbfm.2014.34","article-title":"Kinetic modeling of the monoamine oxidase B radioligand [11C] SL25. 1188 in human brain with high-resolution positron emission tomography","volume":"34","year":"2014","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"2026091506451371000_2026.09.08.26362462v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)37161-7"},{"key":"2026091506451371000_2026.09.08.26362462v1.22","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.23.3125"},{"key":"2026091506451371000_2026.09.08.26362462v1.23","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12020470"},{"key":"2026091506451371000_2026.09.08.26362462v1.24","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12040942"},{"key":"2026091506451371000_2026.09.08.26362462v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2010.05.011"},{"issue":"6","key":"2026091506451371000_2026.09.08.26362462v1.26","first-page":"429","article-title":"Psychiatric Comorbidity in 36 Adults with Mitochondrial Cytopathies","volume":"12","year":"2014","journal-title":"CNS Spectrums"},{"key":"2026091506451371000_2026.09.08.26362462v1.27","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0252"},{"key":"2026091506451371000_2026.09.08.26362462v1.28","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-001-0959-0"},{"issue":"1","key":"2026091506451371000_2026.09.08.26362462v1.29","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/jcbfm.2009.190","article-title":"Measuring drug occupancy in the absence of a reference region: the Lassen plot re-visited","volume":"30","year":"2010","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"2026091506451371000_2026.09.08.26362462v1.30","doi-asserted-by":"crossref","unstructured":"Finberg JP . Pharmacology of rasagiline, a new MAO-B inhibitor drug for the treatment of Parkinson\u2019s disease with neuroprotective potential. Rambam Maimonides Medical Journal. 2010;1(1)","DOI":"10.5041\/RMMJ.10003"},{"key":"2026091506451371000_2026.09.08.26362462v1.31","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-021-01078-3"},{"key":"2026091506451371000_2026.09.08.26362462v1.32","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.150.1.118"},{"key":"2026091506451371000_2026.09.08.26362462v1.33","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyv078"},{"key":"2026091506451371000_2026.09.08.26362462v1.34","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.9.1531"},{"issue":"10","key":"2026091506451371000_2026.09.08.26362462v1.35","first-page":"1618","article-title":"In vivo measurement of brain monoamine oxidase B occupancy by rasagiline, using 11C-L-deprenyl and PET","volume":"46","year":"2005","journal-title":"Journal of Nuclear Medicine"},{"key":"2026091506451371000_2026.09.08.26362462v1.36","doi-asserted-by":"crossref","unstructured":"First MB . Structured clinical interview for the DSM (SCID). The Encyclopedia of Clinical Psychology. 2014:1\u20136.","DOI":"10.1002\/9781118625392.wbecp351"},{"key":"2026091506451371000_2026.09.08.26362462v1.37","unstructured":"First MB . Structured clinical interview for DSM-IV axis II personality disorders,(SCID-II). (No Title). 1997;"},{"key":"2026091506451371000_2026.09.08.26362462v1.38","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"},{"issue":"1","key":"2026091506451371000_2026.09.08.26362462v1.39","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41398-019-0492-8","article-title":"Postmortem transcriptional profiling reveals widespread increase in inflammation in schizophrenia: a comparison of prefrontal cortex, striatum, and hippocampus among matched tetrads of controls with subjects diagnosed with schizophrenia, bipolar or major depressive disorder","volume":"9","year":"2019","journal-title":"Translational Psychiatry"},{"key":"2026091506451371000_2026.09.08.26362462v1.40","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00041.2013"},{"key":"2026091506451371000_2026.09.08.26362462v1.41","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020420"},{"key":"2026091506451371000_2026.09.08.26362462v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2023.01.001"},{"key":"2026091506451371000_2026.09.08.26362462v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01136-X"},{"key":"2026091506451371000_2026.09.08.26362462v1.44","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci16010077"},{"key":"2026091506451371000_2026.09.08.26362462v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2021.111516"},{"key":"2026091506451371000_2026.09.08.26362462v1.46","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2010.32"},{"issue":"8","key":"2026091506451371000_2026.09.08.26362462v1.47","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1001\/jamapsychiatry.2014.250","article-title":"Greater monoamine oxidase A binding in perimenopausal age as measured with carbon 11\u2013labeled harmine positron emission tomography","volume":"71","year":"2014","journal-title":"JAMA Psychiatry"},{"key":"2026091506451371000_2026.09.08.26362462v1.48","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2009.156"},{"issue":"8","key":"2026091506451371000_2026.09.08.26362462v1.49","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.euroneuro.2017.04.003","article-title":"Tranylcypromine in mind (Part II): review of clinical pharmacology and meta-analysis of controlled studies in depression","volume":"27","year":"2017","journal-title":"European Neuropsychopharmacology"},{"key":"2026091506451371000_2026.09.08.26362462v1.50","doi-asserted-by":"publisher","DOI":"10.1097\/WNF.0b013e31823b1da8"},{"key":"2026091506451371000_2026.09.08.26362462v1.51","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12724"},{"key":"2026091506451371000_2026.09.08.26362462v1.52","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbu151"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.08.26362462","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:45:20Z","timestamp":1789479920000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.09.08.26362462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":52,"URL":"https:\/\/doi.org\/10.64898\/2026.09.08.26362462","relation":{},"subject":[],"published":{"date-parts":[[2026,9,10]]},"subtype":"preprint"}}