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Three Distinct Psychosis Biotypes Identified Using Brain-Based Biomarkers; Findings Should Aid Diagnosis & Treatment; Work Reported by B-SNIP Consortium (Yale, Harvard, UT Southwestern, U Chicago, U Georgia)

In a ground-breaking study led by scientist at the University of Texas Southwestern Medical Center (UT Southwestern), a comprehensive set of empirical biomarkers has been established to aid in the diagnosis and treatment of psychosis. To date, the gold standard for diagnosis of psychosis has been clinical observation, classifying patients into schizophrenia, schizoaffective, and bipolar disorders. But in this new study, the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) identified three neurobiologically distinct biotypes that do not always match up with the conventional clinical diagnosis. An estimated 6 percent of the U.S. population experiences schizophrenia, schizoaffective, or bipolar disorders. That’s as many as 19 million Americans. “In a sense, we have totally deconstructed and re-thought the basis for diagnosis in psychosis,” said Carol Tamminga, M.D., Chair of Psychiatry and Professor of Psychiatry at UT Southwestern, who leads the consortium. “Building diagnoses based on biology, not just phenomenology, makes it possible for the biological bases of these brain disorders to stand out as molecular targets for disease definition and novel treatments.” The B-SNIP consortium, which also includes Harvard University, Yale University, the University of Chicago, and the University of Georgia, published its findings online today(December 8, 2015) in the American Journal of Psychiatry. The article is titled “Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers.” “In the end, we found the term ‘psychosis’ might actually describe a number of unique psychiatric disorders, just as the term ‘congestive heart failure’ might describe a range of cardiac, renal, and pulmonary disorders, each having distinctive mechanisms and treated with specific remedies,” said Elena Ivleva, M.D., Ph.D., Assistant Professor of Psychiatry and the study co-leader at UT Southwestern. Considerable evidence has previously shown that a symptom-based diagnosis of psychotic illness incompletely captures biologically meaningful differentiations, often resulting in less-than-satisfactory treatments.

In the newly-reported study, participants submitted to various cognitive, eye-tracking movement, and electroencephalography (EEG) tests, as well as to several modalities of magnetic resonance imaging (MRI).

The group included psychotic individuals, their first-degree relatives, and a control group of subjects. Analysis of the results of the biomarker battery in 1,872 of those tested demonstrated three distinct clusters, or biotypes, of psychoses.


Biotype 1 was the most impaired group, demonstrating poor cognition and eye-tracking capabilities, and the most brain tissue damage, primarily distributed over frontal, temporal, and parietal regions of the brain. Although all of the usual psychosis diagnoses appear in Biotype 1, there was a slight predominance (59 percent) of schizophrenia cases in this most impaired biotype, and this group tended to have more severe psychotic symptoms (hallucinations and delusions) than the other groups.


Biotype 2 demonstrated cognitive impairment and poor eye-tracking, but exhibited high brain wave response as measured by EEG, something neuroscientists often call “noisy brain.” These individuals are often rated as overstimulated, hyperactive, or hypersensitive. Biotype 2 also had gray matter loss in frontal and temporal regions, but less than that found in Biotype 1. Biotype 2 cases also had worse scores on mood scales, such as depression and mania.


Biotype 3 was the least impaired, with near-normal evaluations of cognition, EEG function, and brain structure. Their symptoms were of moderate severity. Subjects in this group were slightly more likely to be diagnosed with bipolar disorder (60 percent).


“What’s puzzling, and fascinating at the same time, is that all three biologically-driven disease constructs, or biotypes, might be clinically diagnosed as having schizophrenia, schizoaffective, or bipolar disorder,” said Dr. Tamminga, who holds the Lou and Ellen McGinley Distinguished Chair in Psychiatric Research, and the Communities Foundation of Texas, Inc. Chair in Brain Science at UT Southwestern.

“There are multiple examples in other fields of medicine where use of biomarkers has led to a distinction of unique diseases that overlap in their symptom presentations,” said Dr. Tamminga.


“Hopefully, this neurobiological examination of severe mental illness will lead to more precise, biologically meaningful diagnoses and novel treatments.”

Dr. John Sweeney, Ph.D., Adjunct Professor of Psychiatry and Pediatrics at UT Southwestern, was a Co-Principal Investigator on this study. Dr. Sweeney holds the Townsend Distinguished Chair in Research on Autism Spectrum Disorders at UT Southwestern.

The photo below shows Dr. Ivleva (left) and Dr. Tamminga.

[UT-Sowuthwestern Medical Center] [American Journal of Pschiatry abstract]