Researchers Study Biological Markers’ Role in Psychosis Onset

Jerome Taylor, MD, and his team are studying the role of oxidative stress in the onset of psychosis symptoms.

By Kate Knab

Although there are several gold-standard treatments for schizophrenia, not all patients respond to medications, and if they do, antipsychotic medications often have adverse effects like weight gain and extrapyramidal symptoms that can cause movement and muscle problems. Even when medications ease distressing symptoms, they are not 100% effective, and residual symptoms often persist.

"Untreated schizophrenia is one of the most disabling health conditions that exists," said Jerome Taylor, MD, a psychiatrist in the Department of Child and Adolescent Psychiatry and Behavioral Services. "Amidst the mental health crisis, if we can catch these kids earlier and improve long-term outcomes, it will hopefully ease this crisis we're seeing."

Dr. Taylor's research focuses on biological factors that may cause the progression of psychosis symptoms in children, and with a new grant awarded by the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program, he plans to delve deeper into the role of oxidative stress in psychosis.

Psychosis encompasses mental illnesses such as schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features that make it difficult for people to tell what is real and what is not. Symptoms typically occur between the ages of 15 to 30 and manifest in the form of delusions and hallucinations that require treatment. By studying the cause of symptom progression in pediatric patients, Dr. Taylor hopes to better diagnose and treat patients before the condition develops further in late adolescence.

"If we are thinking about interventions, we need to ensure that the same mechanisms that drive psychosis in the pediatric population are those that are active in the adult population," Dr. Taylor said. "Oxidative stress levels are elevated in the adult population, but we don't know if they're elevated in the child population."

Our brain requires about 20% of our total energy to function, and this process creates a lot of reactive oxygen species that could cause damage to cells, which is why we have an antioxidant system to counterbalance any unpaired electrons or free radicals. Oxidative stress occurs when antioxidant levels are low, resulting in excess free radicals in cells and tissue.

Oxidative stress levels are typically measured in blood samples, but this method presents the challenge of unreliable measurement because oxidative stress reactions happen when blood is taken from the body. To address this, Dr. Taylor and his colleagues plan to study F2-isoprostanes, biomarkers that correlate with oxidative stress, in both blood and urine samples.

Support from the Robert Wood Johnson Foundation will allow Dr. Taylor and his colleagues to study 12-year outcomes focused on oxidative stress to understand its role in psychosis symptom progression, in addition to medical morbidity and childhood adversity. Data was collected from more than 300 youth enrolled in the CHOP-Penn Philadelphia Neurodevelopmental Cohort (PNC) between 2009 to 2011 who were, on average, about 14 years old upon enrollment. The grant will investigate different biomarkers and exposures to traumatic, stressful events in the PNC that may spur psychosis onset.

The second aim of Dr. Taylor's project is to evaluate adolescents enrolled in the CHOP First Episode Psychosis Program, a program developed by Dr. Taylor and Alexander Moxam, MD, offering uniquely valuable resources and support in the form of psychotherapy, educational support, and medication. The results of this program are studied at baseline, at two months, and at one year to determine how oxidative stress and immune activation change over the course of treatment.

"While we work on scientific breakthroughs for next steps in pediatric psychosis care, it's important to remember that psychosis is partly genetic, and partly environment-mediated," Dr. Taylor said. "There are treatment programs and specialty care options currently available that do work for many youths."