In a groundbreaking study led by UT Southwestern Medical Center, scientists established a comprehensive set of empirical biomarkers to aid in the diagnosis and treatment of psychosis, including schizophrenia and bipolar disorders. The study, recently published in the American Journal of Psychiatry, is titled “Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers.”
Disease classifications in medicine can be adapted according to the increased knowledge on molecular foundations, especially in conditions where clinical manifestations are diverse and illness trajectories are multifarious. However, clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations.
In the new research, the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) team collected a large biomarker panel characterizing diverse aspects of brain function in individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). All patients underwent cognitive, eye-tracking movement, electroencephalography (EEG) tests, and several modalities of magnetic resonance imaging (MRI). Researchers created nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, structural magnetic resonance imaging, family biomarkers, and clinical information) were also collected.
Statistical analyses identified three neurobiological distinct psychosis biotypes that did not respect clinical diagnosis boundaries:
- Biotype 1 was found to be the most impaired cohort, with patients showing reduced cognition and eye-tracking abilities. This group also had the most damage in brain tissue, mainly disseminated over frontal, temporal, and parietal brain regions. Compared with the other biotypes, biotype 1 was found to have a slightly higher proportion of patients with schizophrenia (59%), and patients with more severe psychotic symptoms (delusions and hallucinations).
- Biotype 2 was found to have poor eye-tracking and cognitive impairment; however, this group exhibited high brain wave response (measured by EEG). These individuals are frequently regarded as hyperactive, over-stimulated, or hypersensitive. These patients also had worse scores on mood scales, such as mania and depression. Biotype 2 patients were also found to have loss of gray matter in frontal and temporal regions of the brain, but less than that found in biotype 1.
- Patients in biotype 3 were found to be less impaired. They had near-normal evaluations of cognition, EEG function, and brain structure. Their symptoms were of moderate severity. Patients in this group were slightly more likely to be diagnosed with bipolar disorder (60%).
“In a sense, we have totally deconstructed and rethought the basis for diagnosis in psychosis,” said Dr. Carol Tamminga, chair of Psychiatry at UT Southwestern and leader of the consortium, in a news release. “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.”
“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,” added Dr. Elena Ivleva, assistant professor of Psychiatry and the study co-leader at UT Southwestern.
“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,” concluded Dr. Tamminga. “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 … Hopefully, this neurobiological examination of severe mental illness will lead to more precise, biologically meaningful diagnoses and novel treatments.”
The B-SNIP consortium also includes Yale University, Harvard University, the University of Georgia, and the University of Chicago.