Study Identifies Distinct ‘Biotypes’ Occurring Across Psychosis Diagnoses

Three neurobiologically distinct psychosis “biotypes” have been identified that appear to cross clinical diagnostic boundaries for schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis, according to a report published December 7, 2015, in AJP in Advance.

The study illustrates how multiple pathways may lead to clinically similar psychosis manifestations.

“These data suggest that we have been grouping people in non-biologically homogeneous groups up until now,” said senior author Carol Tamminga, M.D., who is the Lou and Ellen McGinley Distinguished Chair in Psychiatric Research at the University of Texas Southwestern Medical Center. “We anticipate that each of these biotypes will have a distinctive genetic profile; moreover, if these groups differ in their biological substrate, then unique medications ought to be available to treat each biotype,” she told Psychiatric News.

Tamminga and colleagues recruited 800 patients with schizophrenia, schizoaffective disorder, and psychotic bipolar disorder along with 1,000 first-degree relatives of the patients and 250 healthy controls to complete a battery of neurocognitive and perceptual tasks. The researchers then characterized the participants according to biomarkers corresponding to cognition, auditory stimulation, brain electrical function (as measured by electroencephalogram), and oculomotor movements, among other variables. Using statistical analyses, the researchers identified three neurobiologically distinct subgroups of psychosis.

“We found that these biomarkers do not fall onto the conventional diagnoses, even partially,” Tamminga said. “This told us that our conventional diagnoses do not account for biological distinctions between psychosis subtypes.”

Though the distribution of DSM diagnoses across the biotypes was not equal, there was considerable overlap across the biotypes. For instance, in biotype 1, patients with schizophrenia comprised 58.6 percent of the cases; schizoaffective disorder, 21.2 percent, and bipolar disorder, 20.2 percent. For biotype 2, the respective percentages were 46, 26.8, and 27.2. For biotype 3, the respective percentages were 31.7, 24.5, and 43.9. Similarly, there was considerable overlap across the neurobiologically distinct biotypes on global psychosis-related clinical ratings.

“We saw that the biotypes were distinct from each other in highly interesting ways that implicated distinctive biological etiologies,” Tamminga told Psychiatric News. “This is the first time that a taxonomy has been proposed for psychotic illnesses that is based on brain biology and not on clinical phenomenology.”

Much cutting-edge research in schizophrenia is moving toward the identification of biomarkers of disease that may help to individualize treatment. For instance, a 2015 report in Schizophrenia Bulletin demonstrated that levels of cortisol and biological markers of inflammation appear to predict treatment response and could point the way to potential targets for the development of novel therapeutic agents. Similarly, at the 2013 International Congress on Schizophrenia Research, several researchers reported evidence showing that inflammatory blood biomarkers could help distinguish those individuals identified at high risk for psychosis who are likely to convert to active psychosis (Psychiatric News, June 7, 2013).

The work by Tamminga and colleagues goes further by identifying neurobiological phenotypes that underlie the clinical diagnoses. In similar work, the National Institute of Mental Health’s Research Domain Criteria (RDoC) seeks to reconceptualize diagnosis of mental illness according to “domains” of brain function defined by genetics and neurobiology.

The findings of the study “illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard,” Tamminga and colleagues wrote.

The three biotypes identified in the study will aid future studies of pathophysiology and/or etiology of serious mental illness, Tamminga told Psychiatric News. “If these groups differ in their biological substrate, then unique medications ought to be available to treat each biotype,” she said. “We hope to test some new compounds by biotype in the future.” ■

“Identification of Distinct Psychosis Biotypes Using Brain Biomarkers” can be accessed here.