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By Christina Hernandez Sherwood
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Iowa Women's Brain Initiative

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UI researchers are leveraging advanced neuroscience techniques to discover treatment targets for affective disorders among girls and women.

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After a harrowing birth experience left Danielle Meyer, now 36, with post-traumatic stress disorder and anxiety, the first-time mom struggled to bond with her newborn son and gave up on her dreams of having more children.

“I wasn’t OK,” she says. “I was numb.”

Meyer’s experience represents a broader problem impacting thousands of women and girls across Iowa and the United States. The risk of developing affective disorders such as anxiety and depression spikes during specific female life stages, including the onset of puberty, phases of the menstrual cycle, pregnancy, and the postpartum period. Affective disorders are a leading cause of disability and can significantly limit the ability of women and girls to take part in daily life.

Mental health conditions are the most common complication of pregnancy and childbirth, and suicide and overdose are the most frequent causes of death in the first postpartum year. The burden is greatest in rural communities, where new mothers have less access to care. More than one-third of Iowa’s counties are considered maternal care deserts.

The challenge is not limited to pregnancy, childbirth, or parenthood. A Centers for Disease Control and Prevention report from 2023 noted that nearly three in five U.S. teen girls felt persistently sad or hopeless — twice the rate of teen boys and a nearly 60% increase over the previous decade.

And for a predominantly rural state like Iowa, where over 70 of its 99 counties have no practicing psychiatrists, access to mental health care for women and girls remains difficult.

A problem this pervasive — and harmful — calls for innovative thinking from a collaborative of experts using advanced scientific techniques in new ways.

To that end, a group of University of Iowa researchers — led by Carver College of Medicine investigators Hanna Stevens, MD, PhD, professor in the Department of Psychiatry, and Banu Gumusoglu (20PhD, 23F), assistant professor in the Department of Obstetrics and Gynecology — have come together on an ambitious, three-year grant project to understand brain circuits and hormone and immune system mechanisms underlying women and girls’ risk for affective disorders.

“Women’s and girls’ health has been neglected, but particularly the brain has been neglected,” Stevens says. “Everyone thinks about hormones when they think about women’s health. But the brain may be one of the major reasons anxiety and depression are problems for women and girls.”

The project, funded by the Iowa Neuroscience Institute, is a unique collaborative that will study the female brain from multiple angles — and during multiple life phases — using high-tech genetic tools like CRISPR, samples from the UI Women’s Health Tissue Repository and the Stead Family Department of Pediatrics Division of Neonatology, and other advanced techniques.

Taken together, the Iowa Women’s Brain Initiative aims to glean new insights into how to prevent and treat affective disorders among girls and women.

Much of the previous work on affective disorders has merely accounted for female biology rather than treating it as the subject of investigation, according to Gumusoglu.

“This program flips that narrative,” she says. “We can take advantage of naturally occurring changes in female biology to reveal new mechanisms of risk. We’re using female biology to understand the roots of anxiety and depression more broadly.”

Women’s and girls’ health has been neglected, but particularly the brain has been neglected. Everyone thinks about hormones when they think about women’s health.”
Hanna Stevens, MD, PhD
Banu Gumusoglu (left) and Hanna Stevens, are leading the Iowa Women’s Brain Initiative.
Banu Gumusoglu (left) and Hanna Stevens, are leading the Iowa Women’s Brain Initiative.

‘A tremendous opportunity’

Stevens, a psychiatrist and neuroscientist, became interested in how pregnancy impacts both mother and child when she was expecting her first baby more than two decades ago. Training as both an adult and child psychiatrist at the time, she wondered about the origin of mental health struggles.

“We have so little understanding of where depression and anxiety come from,” Stevens says. “We need more research on these topics, so patients can get answers.”

Gumusoglu, a mother of three, completed her PhD in neuroscience and postdoctoral training in reproductive biology in the Carver College of Medicine.

“Pregnancy came into focus as such an important window of time for both women and their children,” she says. “When someone is pregnant, they often see a provider upwards of 10 or more times in nine months. It’s a tremendous opportunity with a high degree of patient access, and parents are extraordinarily motivated.”

And yet, while science has made major strides by discovering targeted interventions for certain risks to the brain — think prescribing folic acid during pregnancy to minimize a baby’s spina bifida risk — there are few interventions for brain disorders during early life.

At Iowa, discovering those interventions, and others for different periods of risk for women and girls will take a multidisciplinary team of collaborators, including Avrama Blackwell, VMD, PhD, the Roy J. Carver Professor of Biomedical Engineering in the UI College of Engineering; Jennifer Bermick, MD, associate professor in the Stead Family Department of Pediatrics; Sarah Ferri, PhD, assistant professor in the Stead Family Department of Pediatrics; Rainbo Hultman, PhD, assistant professor in the Department of Molecular Physiology and Biophysics; and Isaac Petersen, PhD, associate professor in the UI College of Liberal Arts and Sciences.

Collaborative research into a common problem

The grant comprises three different, but related, research tracks.

One group of researchers uses mouse models to map brain circuits during periods of vulnerability, including puberty and parenting. This will include the use of brain network-mapping, a specialty of the Hultman, Blackwell, and Ferri labs that involves studying connections between brain regions to see how the brain dictates and responds to behavior. Network-mapping has been shown to predict vulnerability — and resilience — to depression-like behavior.

“That resilience is almost more exciting to us than predicting a deficit,” Gumusoglu says. “Predicting what makes animals resilient is what we’d all love to know as humans seeking good health.”

Another part of the project will use both mouse and human models to identify immune and endocrine markers of pregnancy-related depression. One key question: Does an illness in pregnancy signify a higher risk of developing a postpartum affective disorder? 

“Think of pregnancy like receiving an organ transplant,” Gumusoglu says. “The fetus has foreign genetic and immune material that the mom's body has to accommodate. If that adaptation fails, you can have problems like fetal growth restriction or even pregnancy loss. You might also get risks to the mom’s brain.”

We can take advantage of naturally occurring changes in female biology to reveal new mechanisms of risk. We’re using female biology to understand the roots of anxiety and depression more broadly.”
Banu Gumusoglu, PhD

Finally, Stevens’ lab is leading an effort to understand how signals from the placenta shape a baby’s brain development and how those developmental effects can predict vulnerability to affective disorders differently in girls and boys. In mouse models, researchers will use CRISPR (technology used by scientists to selectively modify the DNA of an organism) to alter the genetics of the placentas in one group. They’ll study the brain development of fetuses with both altered and unaltered placentas, connecting placental changes to long-term brain outcomes. 

“We’re one of only a handful of labs trying to link placental factors to brain development,” Stevens says. “We’re using these high-level genetics tools, which is a strength at the University of Iowa, to understand that basic biology. The placenta accompanies you for less than a year of your life, but if you change its biology, it causes permanent changes in your brain.” 

Hanna Stevens with Michelle Chen, a student in the Carver College of Medicine’s Medical Scientist Training Program.
Hanna Stevens with Michelle Chen, a student in the Carver College of Medicine’s Medical Scientist Training Program.

A proactive approach to affective disorders

The researchers’ goal is not a single prevention or treatment, but a more proactive approach to affective disorders across the lifespan.

“The point of our work is not to blame moms for their mental health or for the mental health of their children,” Gumusoglu says. “It’s to treat maternal health as a common societal good and identify strategies to address the structural and biomedical determinants of health, so families have better options at their disposal.”

They also hope that a better understanding of the circuitry of the brain yields more ways to protect mental health when families are just beginning, Stevens notes.

“How the brain changes in parenthood may tell us if we need to give people more practice with certain information about children,” she says. “For instance, some parents’ brains may support parental care better if they have more experience with hearing baby sounds.”

Or perhaps a targeted hormonal or immune treatment could help the brain become more resilient to affective disorders, for example.

The group is inspired by progress in other fields that have realized the promise of personalized medicine. Gumusoglu says she hopes this new research could uncover similar biomarkers for brain resilience.

“The earlier interventions are leveraged, the better the outcomes are for families,” she says. “Imagine a world where you don’t just know the risk your child might have for mental health, but you can do things proactively during pregnancy that are therapeutic for both mom and baby. That would bring this idea of early and integrated intervention to the earliest point, and that's very exciting.”

The researchers envision the work as a potential boon for Iowa families, who would be among the first to benefit from the prevention strategies and treatment options they discover.

“Any solutions we find,” Stevens says, “we're going to start applying them here.” 

Banu Gumusoglu with Samantha Anema, a student in the Interdisciplinary Graduate Program in Neuroscience.
Banu Gumusoglu with Samantha Anema, a student in the Interdisciplinary Graduate Program in Neuroscience.
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Support for anxiety and depression during pregnancy

If you’re experiencing symptoms of anxiety or depression, talk to your primary care provider or obstetrician-gynecologist. Some patients are referred to UI Health Care’s Women’s Wellness and Counselling Service, a unique resource that provides specialized psychotherapy and medication management to birthing individuals and their partners.