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NIMH support bolsters early psychosis research efforts

Aug. 5, 2021, 9:30 AM

The psychosis study team includes, from left, Neil Woodward, PhD, Maureen McHugo, PhD, Stephan Heckers, MD, MSc, Suzanne Avery, PhD, and Kristan Armstrong, PhD.
The psychosis study team includes, from left, Neil Woodward, PhD, Maureen McHugo, PhD, Stephan Heckers, MD, MSc, Suzanne Avery, PhD, and Kristan Armstrong, PhD. (photo by Susan Urmy)

by Emily Stembridge

The Department of Psychiatry and Behavioral Sciences has received an additional $4 million from the National Institute of Mental Health (NIMH) to study the evolution of hippocampal dysfunction in the early stage of psychosis.

Stephan Heckers, MD, MSc, William P. and Henry B. Test Professor of Schizophrenia Research and chair of Psychiatry and Behavioral Sciences, brought the NIMH grant to VUMC when he was recruited in 2006.

“Over the last 15 years, we were able to grow our research into an ambitious project,” Heckers said. “The funding, which has doubled over the years, validates the success we’ve already had and recognizes that we are capable of expanding the study into the future.”

The renewed grant will fund a longitudinal study of the hippocampus in persons experiencing psychosis. Smaller hippocampal volume is one of the most significant brain abnormalities in chronic schizophrenia but is less pronounced in the early stages of psychosis. In contrast, hyperactivity of the hippocampus is already present in early psychosis. Clinical and preclinical studies have identified an imbalance of excitation and inhibition as a plausible mechanism for hippocampal hyperactivity in psychosis.

The study will evaluate two cohorts: a new group of acutely ill patients in the first two years of psychosis and an already established group of psychotic patients who had previously participated in repeated assessments of the hippocampus. Healthy control participants will also be recruited. Participants will be evaluated using high-density, multi-dimensional assessments, including functional imaging of the hippocampus.

“In our previous longitudinal study, few participants dropped out,” Heckers said. “This is only possible because of the clinical team we’ve built at Vanderbilt Psychiatric Hospital. It shows what we, clinicians and researchers, can achieve together here at Vanderbilt.”

Around two-thirds of patients who experience psychosis will progress to schizophrenia, but in one-third of patients symptoms will remit. The hippocampus may be an early indicator of to which group a patient belongs.

“Even with a focus on a small brain region like the hippocampus, examining its size and activity may allow us to predict the progression of psychosis,” Heckers said.

The researchers will combine a clinical trial’s design with functional brain imaging to allow for a greater understanding of the timing and mechanism of hippocampal dysfunction in psychotic disorders. The integration of these approaches aims to establish a staging model of psychotic disorders, with the goal to aid early detection of psychosis and prevention of schizophrenia.

“If we have a way to predict and identify what’s going to happen to a patient in the long run, we can be more thoughtful about allocating the right treatment and helping patients manage their illness,” Heckers said.

The research is embedded into the department’s practice of coordinated specialty care for people experiencing psychosis. This care ensures patients have access to therapists, psychiatrists, social workers, a supportive employment and education specialist (SEES), and a certified peer recovery specialist (a person who has experienced psychosis firsthand and works to help others manage their condition).

“Our patients, most of them young adults, have access to a specialized team,” Heckers said. “We help them go back to school or find a job and manage their psychosis. It’s the definition of personalized care.”

Co-investigators at VUMC working with Heckers include Maureen McHugo, PhD, Kristan Armstrong, PhD, Suzanne Avery, PhD, and Neil Woodward, PhD, in Psychiatry and Behavioral Sciences, Simon Vandekar, PhD, in Biostatistics and Manus Donahue, PhD, from the Vanderbilt University Institute of Imaging Science.

Funding is provided through National Institutes of Health (R01 MH070560).

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