Tag Archive for: personalized treatment

Behind the Science: Identifying Predictive Biomarkers in Bipolar Disorder and Related Suicidality to Improve Disease Outcomes

Interviewee: Dr. Sara Afjeh, Postdoctoral fellow, Centre for Addiction and Mental Health (CAMH) | Authors/Editors: Romina Garcia de leon, Janielle Richards (Blog Co-coordinators)

Can you tell us a little bit about your research?

Genes serve as the blueprint for how our bodies and minds function. My research seeks to decode this genetic blueprint to understand how psychiatric disorders manifest differently in women. The primary goals are to identify predictive genetic markers for mental disorders like bipolar disorder and related suicidality, as well as biomarkers to assess medication responses. I use machine learning to develop predictive models that can anticipate disorder progression and treatment outcomes. These advancements push us closer to personalized mental health care, where each individual’s unique combination of genetics, environmental, and societal factors are considered. By uncovering these genetic markers, we can bring greater precision to mental health care, ultimately improving outcomes for those most affected.

 

How did you get into this field of research? 

I first became interested in genetics because it plays such a critical role in our understanding of health and disease. As I delved deeper into the field, I discovered how genetic research could transform our approach to complex conditions like mental disorders. Over time, I became particularly drawn to studying gender differences in mental health, as emerging research showed that men and women often experience mental disorders in unique ways. Unfortunately, many diagnostic tools and treatments overlook these distinctions. By focusing on the genetics of mental health in women, I hope to bridge this gap and develop more accurate diagnostic and treatment options that account for women’s specific biological and societal factors, especially during life stages where mental health can be most vulnerable.

 

Can you elaborate on the impact of gender differences in mental health research?

Gender differences play a crucial role in how mental health issues manifest, especially for women. Hormonal, biological, and societal factors, such as stigma, unique stressors, and trauma, all contribute to how women experience mental disorders. These influences shift throughout a woman’s life, impacting mental health in complex ways that are often overlooked. Ignoring these factors can lead to misdiagnosis or less effective treatments, underscoring the importance of research that addresses gender-specific needs in mental health care.

 

Are there any findings that you can share with us? 

During my PhD, I identified a genetic variant associated with bipolar disorder, suicidality, and response to lithium treatment in individuals diagnosed with bipolar disorder. When examining gender differences within this population, I discovered that this variant had a stronger effect in women than in men, which inspired me to continue my research with a specific focus on women. Additionally, I found that an ADCY variant was associated with bipolar disorder in women, which was further supported by findings from genome-wide association studies. These insights emphasize the importance of examining genetic markers in a gender-specific context, especially for complex mental health disorders.

 

What are your long term goals for your research?

My long-term goal is to contribute to a future where mental health care is personalized, especially for women. I aim to achieve this by integrating genetic insights into our understanding of mental disorders, which would help create diagnostic tools that identify these conditions earlier and more accurately for women. Early detection could help women avoid years of undiagnosed suffering. I also hope my research will lead to improved pharmacotherapy, addressing the unique needs of women with mental health challenges. Many medications currently have side effects that can lead to treatment discontinuation or relapse. Through my work, I aspire to support the development of treatments that are more effective, come with fewer side effects, and ultimately enhance the quality of life for women facing mental health issues.

 

Where to learn more about Sara’s work?

Linkedin Profile: www.linkedin.com/in/sara-afjeh-365847b8

Publication: Predictive Biomarkers of Bipolar Disorder

More publications: Google scholar

 

Ovarian Cancer Prevention: Within Reach but Unevenly Accessible

Authors: Emily Thorlakson, BSN RN (Vancouver Coastal Health) Alexandra Lukey, PhD(c), MSN, RN (University of British Columbia, Department of Obstetrics and Gynecology)  | Editors: Romina Garcia de leon, Janielle Richards (Blog Co-Coordinators)

Published: October 4, 2024

The current state of ovarian cancer

Ovarian cancer is ranked number five in the leading causes of cancer deaths among females. Screening is a key pillar in cancer prevention, but unfortunately, there are no effective screening options for ovarian cancer. This leads to the majority of cases being diagnosed at late stages which reduces the chance of surviving ovarian cancer. Interestingly, science has shown over the last twenty years that most ovarian cancers start on the fallopian tubes and later spread to the ovaries instead of starting on the ovaries as researchers initially thought. This recent understanding has led to a new primary prevention opportunity called “opportunistic salpingectomy.”

 Can Ovarian Cancer Be Prevented?

Opportunistic salpingectomy involves removing both fallopian tubes while leaving the ovaries intact; this procedure is typically completed during another scheduled surgery. Salpingectomy has gained traction as the latest research has proven that removing the fallopian tubes significantly decreases the risk of getting the most common and deadly type of ovarian cancer, called high-grade serous ovarian cancer. The most promising evidence of this comes from a population-based cohort study of people who received opportunistic salpingectomy for cancer prevention. This study found that individuals who had this particular surgery had no cases of serous ovarian cancer and significantly fewer than expected cases of other types of ovarian cancer. Also, researchers looked at the rates of different types of cancers that we would not expect salpingectomy to impact, and the study found that rates of other cancers, such as breast and colorectal cancers, were within the expected range. Therefore, these results increased the confidence that it was salpingectomy and not other confounding factors causing the lower ovarian cancer rates.

 Is Salpingectomy Accessible to Everyone?

As salpingectomy becomes a more common procedure, we must ensure that everyone has equal access to it. Studies have already shown that geographical location, race, ethnicity, and rurality influence whether or not patients are offered opportunistic salpingectomy. For example, people who live in rural locations have less opportunity to be offered an opportunistic salpingectomy. Lack of equity is evident in research, as a study discovered that Black females were nearly half as likely to receive opportunistic salpingectomy in contrast to tubal ligation when sterilization was being done at the same time as a caesarian section. So, while they received permanent contraception, they did not receive the full preventative benefit of salpingectomy. Barriers to salpingectomy are compounded further by healthcare provider bias, lack of insurance coverage, low awareness or lack of healthcare resources.

Equity regarding salpingectomy is further complicated by the history of injustices and reproductive violence, such as forced and coerced sterilization of immigrants, Black, Latina, and Indigenous people; people with disabilities; and people with chronic medical conditions. For opportunistic salpingectomy to be available and equitably accessible to everyone, we must face the root of the problem by getting researchers, clinicians, and policymakers to address historical injustices while maintaining patient autonomy.

 How Can We Make Opportunistic Salpingectomy More Accessible?
  • Understand Barriers in Rural Areas: Identify and address challenges in rural and remote areas to patients who want opportunistic salpingectomy.
  • Partner with Indigenous Communities: Collaborate with Indigenous leaders to have culturally safe discussions about ovarian cancer prevention.
  • Knowledge Mobilization: Provide education and bias training for healthcare providers to ensure they offer this option fairly to all patients.

Menopause Series Part 3: What Do We Know About Menopause and Hormone Therapy?

Authors: Romina Garcia de leon, PhD Student, University of Toronto, Alana Brown, PhD Student, University of Toronto, Jingmin Zhang, BSc, Human Biology, University of Toronto, Krembil Research Institute, | Editors: Shayda Swann

Published: October 27th, 2023

*Regarding terminology: “HT” is usually used when discussing spontaneous menopause, while “HRT” is usually used when discussing early oophorectomy (surgical menopause), with the idea being that there is a hormone that needs “replacing” after oophorectomy (but this isn’t the case for spontaneous menopause)*

As we learned in Blog 1, “What You Missed Learning About Menopause” – we can now appreciate that menopause is neither a single stage nor a symptom. Strikingly, most women go into menopause with little to no prior knowledge of what that will look like for them. As mentioned, menopause has a long list of symptoms that oftentimes go untreated. Yet, although there are viable treatments, there is often some confusion about which treatment is best for individuals seeking relief from their symptoms. 

Across various menopause types, in addition to visible symptoms, there are ‘invisible’ physiological changes that happen in the brain (less discussed because of brain health stigma) and body with the decrease in levels of estrogens, progesterone and follicle-stimulating hormone (FSH). As covered in Blog 2, “All About Reproductive Hormones” estrogens and progesterone have many actions that contribute to menopausal symptoms and disease risk. For example, reproductive hormones exert their effects on immune, vascular, and cardiovascular systems. Moreover, menopause can be associated with increased risk of some health conditions, such as osteoporosis, cardiovascular disease, and vulva, vagina, and urinary tract issues (more broadly genitourinary syndrome), emphasizing the importance of monitoring women’s health during midlife. Reproductive hormones also influence neuroplasticity, potentially resulting in cognitive changes. For example, many women report increased “brain fog” throughout menopause. Additionally, the early and abrupt loss of reproductive hormones, such as 17β-estradiol (E2–a type of estrogen), associated with oophorectomy (surgical removal of the ovaries) is related to increased dementia risk. Do treatments address these risks?

Common treatment options include:

  1. Hormone therapy (HT) (targets hot flashes and sleep disturbances—also known as vasomotor symptoms—and other symptoms as well…read more to find out)
  2. Vaginal estrogen (to relieve vaginal dryness and urinary symptoms)
  3. Low-dose antidepressants (to help with depressive symptoms), 
  4. Medications to prevent or treat osteoporosis

HT appears to be the most effective treatment for menopause symptoms. For individuals navigating the physiological transitions associated with menopause, HT offers a multifaceted approach to symptom management. HT not only alleviates discomfort associated with hot flashes and sleep disturbances but also has a pivotal role in mitigating bone loss, thus serving as a preventive measure against osteoporosis. Moreover, research indicates that women under 60, or those within a decade of starting menopause without a history of cardiovascular disease, may experience a decreased risk of coronary heart disease with hormone therapy.

It’s worth noting that the implications of HT on mental health and cognitive function are complex. While some studies suggest that hormone therapy may ameliorate depressive symptoms during spontaneous (“natural”)  menopause, perimenopausal and early postmenopausal stages, caution is advised for those considering initiation before the age of 50 due to potential mood destabilization. Notably, this may be different for women with oophorectomy. Additionally, the timing of HT introduction holds significance in relation to cognitive outcomes: early initiation appears to be protective against dementia, whereas late initiation and extended duration of treatment may elevate the risk. This is also seen in rodent studies, finding that hormone replacement therapy (HRT) in rats who have had an oophorectomy is beneficial for reducing Aβ plaques (associated with Alzheimer’s), but not when given at a later time point. This suggests that the timing and duration of HRT should be carefully considered in women’s personalized treatment strategies. This is also true for women taking HT for spontaneous menopause. 

Although HT is a highly effective treatment for symptoms of menopause, research on its effects remains nuanced. Some studies have led practitioners and patients to fear HT due to associations with breast and endometrial cancer risks. However, known risks (as well as benefits) of HT are specifically dependent on the individual receiving HT, their medical history (e.g., genetics, cancer history, and pregnancy history), whether the formulation contains testosterone, estradiol, and/or progesterone, dose, route of administration, age, and type of menopause

Generally, the known benefits outweigh the risks, especially when given the appropriate formulation… 

For instance, estrogens have been related to increased hippocampal volume and improved cognition in cis-and transgender women. However, these effects can be time- and dose-dependent. In rodent studies, for example, a low dose of estradiol was seen as beneficial, but a high dose was detrimental to cognition. In humans, estradiol appears to be beneficial for hippocampal volume and spatial memory, but only for a limited period of time and with estradiol alone. Regardless of the complexities of taking estradiol, reducing “brain fog” for some can drastically improve quality of life. These and multiple other studies showing the benefit of HT for cognition are promising for those considering treatment for these symptoms. 

What about the non-estradiol-alone options? 

There can be several types of formulations (such as estradiol alone, estradiol with multiple types of estrogens (conjugated equine estrogen or CEE), and estrogen(s) with progesterone). The type of formulation matters greatly in HT, and the benefits seen in estradiol alone are not the same for other types of HT. For example, Premarin, a common brand containing multiple estrogen formulations (CEE), was a big reason for the bad press that HT received for years. The bad press (hear more about this controversy through our WHRC Seminar series talk with Carol Tavris) followed after the Women’s Health Initiative (WHI) released a study claiming that HT increased breast cancer risk, stroke, pulmonary embolism, and dementia. However, this study only used Premarin and not estradiol alone. Since then, studies have found additional negative effects of Premarin, as it’s been shown to impair cognition and neuroplasticity in rodents and decrease hippocampal volume in human studies.

So what does this all mean? 

In short, the answer to whether HT addresses menopause symptoms depends on many factors. It simply should not be a one-size-fits-all treatment. Instead, medical practitioners should move towards an individualized approach to hormone therapy, and women (both cis and transgender people) should take their individual health histories into consideration when thinking about HT. Moreover, as outlined briefly here, much research has shown that many HT options are safe and effective for symptom management and should be discussed with one’s medical practitioner for more information. Lastly, further research should investigate HT use in trans women and men to further expand our understanding of its effects. 

Although our Menopause blog series ends here– stay tuned for more on menopause and hormone therapy soon!