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Brain Wave May Help Predict Psychosis

August 14, 2019

By Marilynn Larkin

NEW YORK—Deficits in amplitude of the auditory P300 event-related potential, a measure that can be detected by EEG, may be a prognostic biomarker of outcomes in patients with psychosis risk syndrome (PRS), researchers say.

"Clinical outcomes vary among young people exhibiting attenuated psychotic symptoms as part of the PRS," said Dr. Daniel Mathalon of the University of California, San Francisco and Dr. Holly Hamilton, who was his post-doc at the time of the study and is now on the UCSF faculty.

"About 20% progress to full-blown psychosis - most often schizophrenia - over a 2- to 3-year follow-up period, and about 30% improve and achieve remission," they told Reuters Health by email. "Current research efforts are focused on identifying biomarkers that can be used to predict the likelihood of progression to psychosis versus remission from the risk syndrome."

"In our study from a large sample of at-risk youth," they said, "we show that a scalp-recorded EEG brain wave known as the P300, which is elicited in response to target sounds presented during a simple auditory task, provides prognostic information about these clinical outcomes."

"Individuals with smaller P300s were more likely to progress to psychosis, while those with larger P300s were more likely to achieve clinical remission," they add.

Drs. Mathalon, Hamilton and colleagues analyzed auditory P300 data collected as part of a multisite, case-control longitudinal study at eight university-based outpatient programs. Participants included 552 individuals meeting PRS criteria and 236 non-PRS controls.

Baseline electroencephalography was recorded during an auditory task. Two P300 subcomponents were measured: P3b, elicited by infrequent target stimuli, and P3a, elicited by infrequent non-target novel stimuli.

As reported online August 7 in JAMA Psychiatry, the PRS group included 552 patients (mean age, 19.2; 42.8% women); the control group consisted of 236 patients (mean age, 20.4; 47% women).

Auditory P300 data of 73 participants at risk for PRS who converted to psychosis were compared with data from 135 nonconverters who continued to be symptomatic during follow-up and 90 who remitted from the PRS.

Overall, target P3b and novelty P3a amplitudes were reduced in at-risk individuals versus controls. However, target P3b, but not novelty P3a, was significantly reduced in psychosis converters versus nonconverters.

Further, smaller target P3b amplitude was associated with a shorter time to psychosis onset in at-risk individuals (hazard ratio, 1.45).

In addition, participants with PRS who remitted had baseline target P3b amplitudes that were similar to those of controls and greater than those of converters and at-risk individuals who remained symptomatic.

Summing up, the authors state, "In this study, deficits in P300 amplitude appeared to precede psychosis onset. Target P3b amplitudes, in particular, may be sensitive to clinical outcomes in the PRS, including both conversion to psychosis and clinical remission. Auditory target P3b amplitude shows promise as a putative prognostic biomarker of clinical outcome in the PRS."

Drs. Mathalon and Hamilton said, "Follow-up studies are planned to determine whether this simple EEG-based measure, when combined with other clinical and biological measures, can be implemented in clinical settings to help match treatments to a patient's level of risk."

Dr. Joshua Kantrowitz, Associate Professor of Clinical Psychiatry at Columbia University in New York City, commented in an email to Reuters Health, "I think is a useful study by a well-respected group. The measure requires a level of expertise to interpret, which limits its clinical relevance. It adds to a growing literature of using electrophysiological outcomes, including mismatch negativity as predictive biomarkers."


JAMA Psychiatry 2019.

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