Mood Disorders

Understanding Gender Differences in Brain Development

Hilary Blumberg, M.D.

Hilary Blumberg, M.D.Associate Professor of Psychiatry and Diagnostic Radiology.

Certain mood disorders are more prevalent in women than in men. Women, for example, are twice as likely to suffer from depression as men. Dr. Blumberg’s work focuses on discovering the brain mechanisms in adolescent boys and girls that influence the development of mood disorders. This work has significant implications for gender-specific prevention and treatment of depression and manic-depression.

Highlighted Study Findings

In this study, supported in part by the Ethel F. Donaghue Women’s Health Investigator Program, Dr. Blumberg examined the brains of both adults and teenagers with and without bipolar disorder, also known as manic-depressive illness. She found that the size of the amygdala, a part of the brain that processes emotions, was smaller in both teenagers and adults with bipolar disorder, compared to those who did not have bipolar disorder. This was one of the first studies to show brain differences in adolescents with mood disorders. And importantly, it demonstrated differences in the amygdala in association with adolescent mood disorders. By understanding such differences in the brain, scientists can tailor interventions to target these differences and improve treatment.

Stress Effects on the Developing Brain and Depression Risk

Hilary Blumberg, M.D.

Hilary Blumberg, M.D., Associate Professor of Psychiatry, Diagnostic Radiology, and the Child Study Center, and Director, Mood Disorders Research Program.

Before puberty, rates of depression for girls and boys are about the same. However, after puberty these rates diverge with depression becoming twice as common in women as in men. This bifurcation in rates is found globally, across countries and cultures. Pervasive stress during childhood and adolescent years is strongly associated with adult onset depression, particularly in women. Dr. Blumberg’s study examined the role of stress in the neurodevelopment of white matter, or the emotional circuitry, in the ventral prefrontal cortex of the brain to determine if adolescents exposed to severe stress were more likely to suffer effects in neurodevelopment that made them more vulnerable to depression.

Highlighted Study Findings

Dr. Blumberg had hypothesized that stress adversely affects development of these emotional circuitry connections in the brain and that these effects are more pronounced in girls than in boys. The findings in this pilot study provided evidence supporting this hypothesis. The imaging analyses found greater structural integrity decreases in white matter in adolescents exposed to childhood maltreatment or neglect than controls, with greater effects in the girls with histories of childhood maltreatment than in the boys. She plans to expand her research to study these findings in larger samples and in greater depth. This line of research has the potential to determine the biological underpinnings for the relationship between early developmental trauma and later adult development of depression, and the greater sensitivity to stress in girls may provide insight into why rates of depression may be higher in females than males.

Understanding the Effect of Anti-Depressant Treatment on Cardiac Function in Women

C. Neill Epperson, M.D.Associate Professor of Psychiatry (Collaborator: Christopher J. Howes, MD)

Cardiovascular disease (CVD) and depression are among the most important health concerns for women. CVD is the leading cause of mortality among women, and women are twice as likely as men to experience depression. Furthermore, nearly half of women suffer from depressive symptoms after a heart attack. Pharmacological agents known as Selective Serotonin Reuptake Inhibitors (SSRIs), the most frequently prescribed antidepressants in the United States, can be effective in treating depression and are commonly used in post heart attack depression. However, there have been concerns that SSRIs can have negative effects on protective vascular mechanisms, making them potentially of concern, particularly in those who have diagnosed CVD. Dr. Epperson’s study was designed to compare the effect of three SSRIs (sertraline, citalopram and fluoxetine) on a marker of endothelial function, the workings of the inner linings of blood vessels, which is an early indicator of the development of cardiovascular disease in women with depression.

Highlighted Study Findings

In this Ethel F. Donaghue Women’s Health Investigator Program-funded study, Dr. Epperson conducted a prospective blinded study in 29 women with depressive symptoms. Although all three of the SSRIs were effective in relieving depressive and anxious symptoms, treatment with sertraline was associated with a modest improvement in endothelial function, as compared with a modest decrease in function with the use of the other two SSRIs. This observation may make sertraline a more attractive antidepressant agent in women at risk for vascular dysfunction, such as that found in coronary artery disease.


Pamela Ventola, PhD

Pamela Ventola, PhD, will test the efficacy — for the first time — of an autism therapy for girls that has been demonstrated to be effective with boys with autism.

Boys are diagnosed with autism almost four times as often as girls, a discrepancy that is poorly understood. Researchers have historically excluded girls from studies of children with autism spectrum disorder because of their low numbers or misdiagnoses, or they have included so few as to make it impossible to draw meaningful conclusions.

Now for the first time, investigators at the Yale Child Study Center seek to understand how girls with autism respond to a treatment that has been demonstrated to be effective with boys with autism.

“Girls with developmental disabilities have been largely ignored in terms of the research in the field,” Ventola said. “Right now we are assuming girls are the same as boys.”

Ventola said that recent research has shown girls can have high-functioning autism and subtle social symptoms that doctors might miss.

Dr. Ventola’s study also represents the first attempt to examine the malfunctioning brain circuitry underlying autism by manipulating brain activity related to behavioral change such as social reward and emotion regulation.

“Researchers have not focused on girls when studying autism’s causes and treatments,” Mazure said. “It’s time for clinicians to understand the differences in how girls and boys present on the autism spectrum and how to tailor different approaches toward their treatment.”

In addition, the study aims to investigate an even more overlooked group: parents. The researchers plan to better understand how mothers and fathers react to their children’s treatment to better understand how to support them in their stressful roles.

The study will be the first to explore the impact of treatment for autism on maternal wellbeing.

“Parenting a child with autism is tremendously difficult, and there’s been very little focus on mothers,” Ventola said. “If they are not the primary caregiver, they are the primary worrier. We need to learn how to support these children in a family context.”

About the Investigator

Dr. Pamela Ventola earned her Ph.D. from the University of Connecticut and her B.A. from Hamilton College. Since 2013, she has been an Assistant Professor and the Clinical Director of the Center for Translational Developmental Neuroscience at the Yale Child Study Center.

Since her undergraduate studies, Dr. Ventola has worked with individuals with developmental disabilities. She treats children and adults with autism and collects data on the treatment response of preschool-age girls with autism.