A team of UTHealth Houston researchers has been awarded a five-year, $3.8 million grant from the National Institute of Mental Health to create an individualized, biomarker-guided therapy program that aims to mitigate the risk factors of schizophrenia among children who are at a high risk of developing the condition.
Schizophrenia is a serious, lifelong mental health condition defined by hallucinations and delusions. People are typically diagnosed with the condition in their late teens to their early 20s, but research has linked the illness to changes in brain development between childhood and adolescence.
The team has hypothesized that for children who are at a high risk of developing schizophrenia due to a family history of the illness, their genetic predisposition combined with stressful life events may subtly alter the brain in a way that makes the illness more likely to emerge.
“We know that stress, especially stress in the family, can create immune reactivity,” said co-investigator Cesar Soutullo, MD, PhD, who holds the John S. Dunn Professorship and is vice chair and chief of Child and Adolescent Psychiatry in the Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences at McGovern Medical School at UTHealth Houston. “The stress of being under pressure from school, social interactions, or a family situation may trigger an immune reaction, and that affects how the brain develops.”
Roughly 100 families and their children in the Houston area will undergo the four-month therapy program.
“The program starts with a thorough review of the child’s personal, school, and family life, and considers factors such as sleep, relationships with friends and family, school performance, and levels of physical activity,” said co-principal investigator Yizhou “Cherry” Ma, PhD, an instructor in the Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences at McGovern Medical School. “Looking at a child’s exposure to stressors lets us rank them by risk, identify the ones most likely to interfere with brain development, and begin to reduce them.”
The team’s program will be guided by imaging of both children participating in the study and findings from the Adolescent Brain Cognitive Development Study, the largest long-term study of children’s brain development in the United States that is supported by the National Institutes of Health. Drawing on images from the study, the team built a measure called the regional vulnerability index, which scores how closely an individual child’s brain pattern resembles the brain pattern seen in individuals with schizophrenia.
Because that score can shift toward or away from the illness pattern over time, it offers an objective way to gauge whether the therapy is working before the primary onset window of schizophrenia.
“?We can see that children with more life stress and more genetic liability already have higher risk scores, even at age 9,” Ma said. “Our idea is that we can use this objective brain measure to guide our intervention for kids at potential risk of developing schizophrenia.”
Co-principal investigator Peter Kochunov, PhD, professor in the Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences at McGovern Medical School, said the team’s primary goal is to evaluate therapies for preventing schizophrenia rather than treating it after diagnosis.
“What we propose may be innovative in mental health, but it’s common practice in internal medicine. We see our family doctor every six or 12 months for blood tests and a physical exam because we understand the processes behind common metabolic and cardiac illnesses. We’ve developed medications aimed not at treatment, but at prevention—of heart attacks, of ischemic brain events,” said Kochunov, who holds the John S. Dunn Chair. “This is among the first attempts to do the same for schizophrenia.”
Elliot Hong, MD, director of the Houston Psychosis Research Center in the Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences at McGovern Medical School, who holds the Stephen Brannan, MD, Distinguished Professorship in Clinical Methodology, is the principal investigator on the grant.