A University of Texas at Dallas researcher is investigating the role estrogen plays in delaying the onset of psychotic disorders that often affect men earlier in life than women.
Dr. Katherine Damme , an assistant professor of psychology in the School of Behavioral and Brain Sciences , has received a two-year grant for more than $500,000 from the National Institute of Mental Health to examine how estrogen levels in late childhood through early adulthood affect brain development and the risk of developing psychosis.
“At the typical age of onset of symptoms for men, it’s just not happening to women,” Damme said. “By determining how estrogen may be protective, our ongoing work could provide an entirely new understanding of how psychosis forms and possibly lead to improved treatment or ways to reduce the risk of psychosis in men.”
Psychosis is characterized primarily by delusions and hallucinations, but it also can involve disorganized behaviors or cognitive impairment. Symptoms are often more severe in men and emerge earlier, in their late teens to early 20s.
“People suffering from psychosis form associations that shouldn’t be formed,” Damme said. “Their brains assign importance to things that they shouldn’t, then try to build meaning around why those things are important, resulting in delusions.”
Damme and her colleagues are analyzing long-term data from the National Institutes of Health’s (NIH) Adolescent Brain Cognitive Development Study, the largest long-term study of brain development and child health ever conducted in the United States.
Research suggests that estrogen might help protect against psychosis by supporting brain flexibility, serotonin activity and the function of regions such as the hippocampus and cerebellum.
“It’s believed that high estrogen levels impede mechanisms that trigger psychosis, but that assertion hasn’t been examined longitudinally in the transition to adolescence,” Damme said.
The biological mechanisms underlying psychosis are not well understood, Damme said, noting that there is no trademark structure of a psychotic brain.
“Brain organization in psychosis varies severely from typical development, but not in any single way,” she said.
Studies have shown that rising estrogen levels in adolescent females affect the growth of the hippocampus, which researchers believe reduces the risk of psychosis and its severity.
“The hippocampus is among the densest receptor sites of estrogen in the brain,” Damme said. “Hippocampal volume, connectivity and shape can be used to predict symptom onset and brain function.”
Psychosis onset in women tends to peak during periods associated with declining estrogen levels, including menopause, postpartum recovery and early adulthood.
“The shared trait of these three time frames is a sudden drop after periods of sustained elevated estrogen levels,” Damme said. “This seems to increase risk for psychosis onset. For instance, in the menopausal age range, women make up 80% of new psychosis diagnoses.”
Earlier mouse models have found that higher estrogen levels promote the growth of nerve cells and improve neural connections that support learning and memory.
“Not only are they making new synapses and dendrites, but those dendrites get fatter in the presence of estrogen, and that improves connectivity,” she said.
Further study of how estrogen provides these safeguards against psychosis could help scientists learn how to treat potential patients.
“Understanding these mechanisms will provide insights into how, when, where and for whom interventions to reduce or delay the transition to psychosis would be most effective,” Damme said.
Dr. Vijay Mittal, chair of psychology at Northwestern University, is co-principal investigator on the NIH grant.