The power of mentorship is clear when you first meet Sarah Yip, PhD, and Sarah Lichenstein, PhD, and hear how their complementary interests and collaborative work have grown and thrived.
As a post-doctoral researcher interested in the effects of substance use on brain health, Dr. Lichenstein sought to work in Dr. Yip’s Yale Imaging and Psychopharmacology Lab, established by Yip in 2017.
For more than seven years, they have collaborated first as post-doctoral student and faculty mentor, and now as two faculty members with a shared goal to better understand the sex-specific impact substances have on the way the brain functions. Today, Yip and Lichenstein are each Women’s Health Research at Yale-funded investigators.
Yip, associate professor of psychiatry, uses neuroimaging and advanced computational techniques to identify sex-specific brain-based predictors of treatment outcomes. Lichenstein, assistant professor of psychiatry, currently focuses on understanding the neural basis of mood and substance use disorders, particularly in adolescents and emerging adults.
“Sex differences in the brain during adolescence are particularly relevant for predicting development trajectories that affect the life course,” says Lichenstein. “By determining those differences between female and male adolescents early on, we can identify and track specific aspects of brain functioning that predict later onset disorders. This provides the foundation for how and when to make early therapeutic interventions.”
As Lichenstein reflects on the development of her career in science, she speaks clearly about the value of Yip as her mentor and the many ways in which they continue to collaborate, whether it is in terms of conducting a study together, sponsoring a project, or unlocking additional funding to fuel research on women’s health.
Helpful Definitions
Sex: A biological classification, generally as male or female, according to the reproductive organs and functions that derive from the chromosomal complement, generally XX for female and XY for male.
Gender: Refers to a person's self-representation influenced by social, cultural, and personal experience.
Cannabis: A flowering plant commonly referred to as marijuana.
Cannabinoids: Naturally occurring compounds in the cannabis plant.
Cannabidiol: A cannabis compound, commonly known as CBD.
Connectome: The complete set of functional brain networks for a given individual.
Machine Learning: A data analysis approach in which a predictive model is developed using a training dataset, then the accuracy of the model is tested in a new dataset.
Sex-Specific Modeling: Creating predictive models using data from each sex separately. Model accuracy can be compared to that of models generated using data from both sexes combined.
The Legacy of Mentorship
“Sarah was my first postdoctoral trainee and is now my close collaborator.” says Yip. “You always want a post-doc in your lab to have an easier, more successful time than you did, and that was my focus with Sarah. Now, watching someone I’ve mentored become a mentor themselves has been wonderful to witness. She recently started training and mentoring her first post-doctoral trainee, as well as an undergraduate, so the cycle continues.”
Yip adds, “I think it’s really important to be sure that each person has their own trajectory and space to grow. It’s like we’re on the same highway, driving in the same direction. Sometimes we’re together in the carpool lane, and other times, we’re driving in our own dedicated lanes, where we’re each focused on our independent but related research, waving to each other as we go by.”
Shared Interest In Studying Sex and Gender Differences
In the Yale Imaging and Psychopharmacology Lab, understanding sex and gender differences in the development of disorders is always at the forefront.
A Look at Dr. Lichenstein’s Research
Never before has a researcher examined the way cannabidiol, more commonly known as CBD and found in a wide array of over-the counter remedies, affects brain function in women.
“We’ve been aware for a long time that a major gap in the research literature is understanding the brain responses to cannabis, cannabinoids, and CBD. The pilot funding from Women’s Health Research at Yale provided the opportunity to conduct the first-ever study on CBD’s impact on women’s brain function. In turn, our hope is to pursue larger funding awards for more comprehensive studies examining sex differences with CBD use,” said Lichenstein.
The vast majority of CBD products are not FDA approved and can be purchased without a prescription. Despite the shallow body of research on their use, they are commonly used and primarily by women, often to deal with feelings of anxiety. Since anxiety disorders are twice as prevalent among women and the CBD market continues to expand, Lichenstein is exploring the neural (brain) response to CBD in female study participants.
Lichenstein and her team recruited healthy females to test reactions to either CBD or placebo when participating in a virtual anxiety-inducing game and an emotional response task. By examining how women’s brains respond to these tasks, researchers can measure the neural responses that underlie the experience of anxiety.
Data collection is complete and preliminary results indicate reduced simultaneous action in patterns of brain activity among subcortical regions of the brain in women following CBD versus placebo administration. This includes regions strongly related to emotional processing and anxiety and suggest that CBD may reduce anxiety by reducing connectivity among these regions.
This is the first evidence to suggest a neural mechanism of CBD’s effects in women. It also provides the foundation for external grants to support research on larger samples of women as well as men to confirm findings and propel the work on sex differences in CBD use and its therapeutic potential in treating anxiety.
Dr. Yip’s Examination of Sex Differences
Yip’s focus is on sex differences in the brain that are related to opioid use disorder (OUD) as well as to pain. A major aspect of her innovative work is the examination of the interface of opioid use and chronic pain.
“There are sex differences in the clinical profile of chronic pain,” says Yip. “There are also sex differences with opioid use disorder. My team is interested in understanding the sex-specific relationship of pain and opioid use so that we can develop effective treatments for both conditions.”
Her most recent Women’s Health Research at Yale-funded project aims to explore the interactions among sex, pain, and brain network dynamics in women and men entering medication-assisted treatment for OUD. She uses neuroimaging and advanced computational techniques to identify brain-based predictors of treatment outcomes and focuses on the brain’s complete set of responses rather than one brain network at a time. This approach to what is happening across brain networks is referred to as studying the “connectome.”
“The funding from Women’s Health Research at Yale was fundamental and enabled us to do a first-of-its kind neuroimaging examination of both women and men with and without chronic pain in treatment for opioid use disorder,” said Yip.
“One big part of our work is collecting sufficient data to do what we call sex-specific modeling,” she continued. “We’re building what is called a ‘machine learning model’ to predict clinical outcomes using neuroimaging data. We do this for females and males combined, and we create separate models for females and males, which enables us to test for sex differences in the brain that relate to treatment outcomes.”
The Golden Thread of Mentorship
Essential to successful research is the capacity for us to teach the next generation as well as learn from one another. The golden thread in this story points to others, which as Yip and other faculty note, includes Carolyn Mazure, PhD, as a driving force in their own careers.
Women’s Health Research at Yale’s associate director for medical education in women’s health and assistant professor of medicine (hematology) Kelsey Martin, MD, reflects, “Dr. Mazure is such an inspiring individual and I feel so lucky to have been able to connect with her on a variety of levels and initiatives. I’ve learned so much from her. The hope is to take those pearls of wisdom and guidance to pass along to the next generation who we’re lucky enough to mentor, including incredible students like Aeka, Emily, Kayla, Mahnoor, and Stephanie.”
Mazure, the Norma Weinberg Spungen and Joan Lebson Bilden Professor in Women’s Health Research, is steadfast in her commitment to mentorship. “Mentorship ensures that the next generation can build on what we know and respond to the questions that remain unanswered. It’s a privilege to mentor those who follow us, and it’s exciting and joyful to see them succeed,” says Mazure, Director of Women’s Health Research at Yale.
“Having Dr. Martin as a mentor has been so important. I think medicine can often make you feel like a small fish in a really big sea. There’s this false notion that medicine should be mysterious and intimidating, and I don’t think that’s how it should be,” says Guru. “Dr. Martin has helped make medicine more accessible to me as she’s guided me through conducting research and effectively making change. I’m really grateful to have this opportunity and experience.”
From Yip to Lichenstein, Lichenstein to Anghad, Mazure to Martin, Martin to Guru, the legacy of mentorship is strong.
Here’s to a lot of waving on the women's health research highway.
Mentoring the Next Generation
For the past decade, Women’s Health Research at Yale’s year-long Undergraduate Fellowship teaches Yale students the history of women’s health research as a backdrop for understanding the need to study the disorders women experience. Fellows are matched with Yale faculty mentors who are experts in their fields and dedicated to exploring the health of women and the influence of sex and gender on health.
This year’s Fellows include Emily Anghad ’25, Aeka Guru ’25, Stephanie Montealegre ’25, Mahnoor Sarfraz ’24, and Kayla Yup ’25.
Mentorship is designed to enrich students’ current studies while complementing their career direction. Students learn to investigate new and timely health and clinical care questions all while gaining exposure to the most contemporary approaches in the science of women’s health. Lichenstein, Yip, Martin, and Mazure are among current Fellowship mentors.