By Suzanne Leigh
A UCSF psychiatrist is studying brain waves to identify patients most likely to develop the disorder.
Cameras that have been installed in their homes by the CIA, voices that whisper vicious words, and demons that appear in their bedroom at night.
These are the delusions and hallucinations of psychosis, a core symptom of schizophrenia.
Schizophrenia affects 1% of the global population and is caused by a complex interplay between at least 280 genes and environmental factors like childhood trauma and early cannabis use. Patients with good support and treatment can do well. But those suffering from the disease’s most disabling symptoms — psychosis together with cognitive impairment — often experience fractured relationships, joblessness, homelessness, and a revolving door of 72-hour psychiatric holds and incarcerations.
Daniel Mathalon, PhD, MD, believes that burgeoning knowledge about biomarkers — biological measures of a medical condition that also serve as markers of treatment effectiveness — could help intercept schizophrenia. Mathalon directs the UCSF Path Program, serving young patients with psychosis and those with milder symptoms that put them at high risk of developing it. He also plays a leadership role in identifying biomarkers for the Accelerating Medicines Partnership® Schizophrenia (AMP SCZ) program, a collaboration between the National Institutes of Health (NIH) and industry.
How does your research with high-risk patients in the Path Program contribute to your goal of reducing risk for developing schizophrenia?
In our research, we identify biomarkers that tell us which high-risk patients are most likely to develop schizophrenia and which are most likely to improve on their own. Eventually, such biomarkers could be used to tailor treatment to each patient’s level of risk.
How are biomarkers identified?
Biomarkers may come from biological samples like blood or tissue, or from brain imaging like CT, MRI, or EEG. In my research with high-risk patients, one type of imaging we use is EEG, recorded from the scalp, which measures electrical signals from the brain to identify abnormal brain activity associated with greater risk for schizophrenia.
What if biomarkers indicate a patient will likely develop psychosis?
If biomarker-based predictions are close to 100% accurate, we could consider starting treatment with antipsychotics. We know that delays in prescribing antipsychotics after psychosis onset can cause structural and functional changes in the brain that intensify symptoms and make them harder to treat. With better biomarkers and safer medications, early treatment at the high-risk stage may ultimately lessen the symptoms of schizophrenia or even prevent it.
Why don’t you prescribe antipsychotics for all high-risk patients?
These medications can cause weight gain, diabetes, sedation, tremors, and other movement disorders. For most high-risk patients, the risks of antipsychotics outweigh their benefits. Psychotherapy and medications to treat depression and anxiety are considered the best approach.
How do you use biomarkers to identify patients most at risk of developing psychosis?
One test we perform with EEG is called P300. It’s named for the brain wave produced 300 milliseconds after detecting a distinct sound among other sounds while wearing headphones. High-risk patients who will develop psychosis demonstrate less electrical activity when detecting this distinct sound compared to high-risk patients who will not develop psychosis. This indicates that brain functions supporting auditory processing and attention are abnormal.
The P300 test uses EEG to measure the brain wave 300 milliseconds after hearing a distinct sound. High-risk patients who will develop psychosis demonstrate less electrical activity in detecting this distinct sound compared to high-risk patients who will not develop psychosis. The less intense colors on the right-hand scalp map represent patients who will develop psychosis. [Images: Daniel Mathalon, PhD, MD, UCSF]
What’s the most disabling symptom of schizophrenia?
Cognitive impairment can severely limit a patient’s ability to live independently and remain socially connected. It’s also a primary driver of disability — more so than delusions and hallucinations. About 80% of patients with schizophrenia have cognitive deficits, putting them at risk for unemployment, failure to take medications properly, increased hospitalizations, and low quality of life. Importantly, cognitive deficits also occur in high-risk patients and increase their likelihood of developing psychosis.
Are there treatments for cognitive impairment in schizophrenia or high-risk patients?
There are currently no approved treatments, but I’m working with AMP-SCZ to test a medication to improve cognition in patients at high risk of developing psychosis. During the eight-week clinical trial, we will measure P300 and other biomarkers to see if they change with treatment or predict which patients are most likely to respond to treatment. Patient enrollment has just started.
GET information on trial eligibility and enrollment
About UCSF Psychiatry and Behavioral Sciences
The UCSF Department of Psychiatry and Behavioral Sciences and the Langley Porter Psychiatric Institute are among the nation's foremost resources in the fields of child, adolescent, adult, and geriatric mental health. Together they constitute one of the largest departments in the UCSF School of Medicine and the UCSF Weill Institute for Neurosciences, with a focus on providing unparalleled patient care, conducting impactful research, training the next generation of behavioral health leaders, and advancing diversity, health equity, and community across the field.
UCSF Psychiatry and Behavioral Sciences conducts its clinical, educational, and research efforts at a variety of locations in Northern California, including the UCSF Nancy Friend Pritzker Psychiatry Building; UCSF Langley Porter Psychiatric Hospital; UCSF Health medical centers and community hospitals across San Francisco; UCSF Benioff Children’s Hospitals in San Francisco and Oakland; Zuckerberg San Francisco General Hospital and Trauma Center; the San Francisco VA Health Care System; UCSF Fresno; and numerous community-based sites around the San Francisco Bay Area.
About the UCSF Weill Institute for Neurosciences
The UCSF Weill Institute for Neurosciences, established by the extraordinary generosity of Joan and Sanford I. "Sandy" Weill, brings together world-class researchers with top-ranked physicians to solve some of the most complex challenges in the human brain.
The UCSF Weill Institute leverages UCSF’s unrivaled bench-to-bedside excellence in the neurosciences. It unites three UCSF departments—Psychiatry and Behavioral Sciences, Neurology, and Neurological Surgery—that are highly esteemed for both patient care and research, as well as the Neuroscience Graduate Program, a cross-disciplinary alliance of nearly 100 UCSF faculty members from 15 basic-science departments, as well as the UCSF Institute for Neurodegenerative Diseases, a multidisciplinary research center focused on finding effective treatments for Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease, and other neurodegenerative disorders.
About UCSF
The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF’s primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area.
