Effects of sex, treatment resistance, and antidepressant treatment on monoamine oxidase B total distribution volume
- 1Centre for Addiction and Mental Health
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.
Related
- Design, synthesis, and biological evaluation of naphthalimide derivatives as dual monoamine oxidase-B and amyloid-β aggregation inhibitors for Alzheimer's disease.
- Integrating Genetic Variants and Expression Profiles of Pharmacogenes to Investigate Resistance to Antidepressant Treatment
- Temporal enrichment of bacterial monoamine oxidase gene aboard the international space station and neuromodulator impacts of dopamine-driven ammonium formed by space isolate Leifsonia virtsii on Caenorhabditis elegans
- The Antidepressant Effects of the mGlu2/3 Receptor Antagonist TS-161 in Treatment-Resistant Depression
- Transcriptional profiling of antidepressant ketamine and electroconvulsive therapy treatment.
BibTeX
@misc{kuik2026effects,
title = {{Effects of sex, treatment resistance, and antidepressant treatment on monoamine oxidase B total distribution volume}},
author = {E. J. Kuik and C. Baena-Tan and S. Moriguchi and J. Braga and L. Miler and P. Rusjan and M. Bagby and M. I. Husain and N. Vasdev and T. Tomoda and M. Banasr and S. Kloiber and J. H. Meyer},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.08.26362462},
url = {https://www.medrxiv.org/content/10.64898/2026.09.08.26362462v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Effects of sex, treatment resistance, and antidepressant treatment on monoamine oxidase B total distribution volume
AU - E. J. Kuik
AU - C. Baena-Tan
AU - S. Moriguchi
AU - J. Braga
AU - L. Miler
AU - P. Rusjan
AU - M. Bagby
AU - M. I. Husain
AU - N. Vasdev
AU - T. Tomoda
AU - M. Banasr
AU - S. Kloiber
AU - J. H. Meyer
PY - 2026
DA - 2026/09/08
PB - medRxiv
DO - 10.64898/2026.09.08.26362462
UR - https://www.medrxiv.org/content/10.64898/2026.09.08.26362462v1
AB - 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.
ER -