Congratulations to Dr Sibille and collaborators (Drs Meyer, Banasr, Tomoda, Seney (UPitt)) for the new grant obtained from the Womenmind 2022 Seed Funding Competition of CAMH.

womenmind™ is a community of philanthropists and thought leaders tackling the unique gender issues that underrepresented people face when it comes to their mental health. Inspired and empowered by their support of CAMH, members of the womenmind community connect with and learn from each other while driving change for women’s mental health and women in science.

At CAMH, our definition of women includes cisgender, transgender, and non-binary women.

Lay Abstract of the project:

Periods of hormonal transition are risk factors for major depressive episodes (MDE) in females, with 13% prevalence postpartum and 17% during perimenopause. However, pharmacotherapy and nutraceutical interventions targeting neurobiological changes during perimenopause and postpartum are limited, and conventional antidepressants (ADs) acting via increasing monoamines are slow-acting and only effective in 50% of patients, highlighting critical unmet needs for treatment of women during and after periods of high-risk for MDEs.

Using brain imaging, Dr. Meyer (co-investigator) discovered that monoamine oxidase A (MAOA) levels are elevated throughout the brain during MDE (~35%) and during postpartum and perimenopause (35-45%). These findings correlated with depressive symptom severity and recurrence despite previous AD treatment. MAOA is the enzyme responsible for metabolizing monoamines, such as serotonin. MAOA is also regulated by estrogen. The collective data suggests that MAOA-related pathology is highly relevant to mental health of females.

Using a novel system to manipulate MAOA levels in the rodent brain, this study will model for the first time the MAOA-related MDE pathology for female-oriented drug discovery. Over a series of experiments, we will establish if elevated MAOA reduces serotonin, contributes to depressive-like symptoms and opposes the effects of conventional ADs, and determine the extent to which sex factors contribute to and moderate these outcomes. The newly-developed humanized rodent model will provide an experimental model for subsequent studies to investigate novel therapeutic modalities and biological mechanisms for mental health of females.