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Psychotic diseases: The Typing Pool

Posted December 16, 2015

Researchers at Harvard Medical School and Beth Israel Deaconess Medical Center have identified three biomarker-based categories that provide a new and more precise way to classify psychotic diseases based on patients’ underlying brain biology. The study appears online in the December issue of the American Journal of Psychiatry.

Color coding illustrates the relationship between biotypes and diagnoses of schizophrenia, schizoaffective, and psychotic bipolar disorder in study participants. Image credit:

Color coding illustrates the relationship between biotypes and diagnoses of schizophrenia, schizoaffective, and psychotic bipolar disorder in study participants. Image credit:

As many as 19 million Americans experience psychotic diseases, which are severe mental illnesses marked by hallucinations and delusions.

“Over the past 100 years, we have diagnosed psychoses based solely on clinical observation of symptoms, and then classified conditions as schizophrenia, bipolar disorder or schizoaffective disorder,” explained co-author Matcheri Keshavan, the HMS Stanley Cobb Professor of Psychiatry and vice-chair of public psychiatry at Beth Israel Deaconess Medical Center. “But these conditions actually have many overlapping symptoms.”

The identification of these new biomarkers may enable clinicians to more precisely differentiate psychotic conditions and provide patients more targeted—and potentially more effective—treatments. “Other areas of medicine have recognized that classifying illnesses based only on external symptoms is ineffective,” said Keshavan. “A patient could have congestive heart failure due to an underlying kidney, cardiac or respiratory problem. Only by examining the biology of the illness can we determine what is actually causing the disease.”

The study is part of the Bipolar and Schizophrenia Network for Intermediate Phenotypes (B-SNIP) Consortium, a long-term project based at several research centers around the U.S.

In this study, B-SNIP participants underwent cognitive tests, eye-tracking tests, movement tests and electroencephalography (EEG) testing. The study subjects also underwent magnetic resonance imaging brain scans.

“By examining these biological measures, we identified three distinct subtypes—or biotypes—of psychotic disease and were able to differentiate conditions much better than we were with the symptom-based clinical diagnoses,” said Keshavan.

The first subtype, biotype 1, was the most impaired and included participants who demonstrated poor cognition and eye-tracking capabilities, as well as the most evidence of brain tissue loss, primarily distributed over frontal, temporal and parietal regions of brain. Although all three psychosis diagnoses appeared in this subgroup, there was a slight predominance of patients with schizophrenia.  They also tended to have more severe psychotic symptoms than the other groups, including hallucinations and delusions.

The biotype 2 group also demonstrated cognitive impairment and poor eye-tracking. These individuals—whose EEG measures also demonstrated high brain wave response—were often overstimulated, hyperactive or hypersensitive and had worse scores on mood scales, such as depression and mania.

The third subgroup—biotype 3—was the least impaired, with near-normal cognition, EEG function and brain structure. This group was also slightly more likely to be diagnosed with bipolar disorder.

“Schizophrenia and bipolar disorders cause a lot of suffering to patients and their families, and they are expensive to our society,” said Keshavan. “There are a lot of misconceptions about psychotic disorders, and these diseases are still often attributed to personal weakness. The identification of these biomarkers will help us better communicate with the public that these are brain diseases and will also enable us to better identify and tailor individual treatments.”

Source: HMS

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