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Biomarkers more effectively identified psychosis subgroups vs. traditional diagnoses

Recent findings identified three biomarker-based categories that outperformed traditional diagnoses in categorizing individuals with psychosis into distinct subgroups based on brain biology.

“The biotypes were more biologically homogeneous than categories based on observable symptoms,” Bruce Cuthbert, PhD, acting director of the NIMH, said in a press release. “Just as fever or infection can have many different causes, multiple psychosis-causing disease processes — operating via different biological pathways — can lead to similar symptoms, confounding the search for better care.”

Brett A. Clementz, PhD, of the University of Georgia, Athens, and colleagues collected a large biomarker panel characterizing different aspects of brain function from 711 individuals with schizophrenia, schizoaffective disorder or bipolar disorder with psychosis, their first-degree relatives (n = 883) and healthy controls (n = 278). Biomarker variance across patterns were used to create nine integrated variables to assess neurobiological variance among individuals with psychosis.

Multivariate taxometric analyses identified three neurobiologically distinct psychosis biotypes that did not match clinical diagnosis boundaries. The three biotypes differentiated groupings of individuals with psychosis more than traditional DSM diagnoses, according to researchers.

External measures, including social functioning, brain structure, psychosis-related illness rates and biomarker patterns within first-degree relatives, indicated neurobiological distinctiveness between biotype subgroups more than distinctiveness of symptom-based categories.

Psychosis-related impairments differed between biotypes. Individuals in biotype 1 exhibited the greatest impairment in cognitive control, or the ability to control attention and information processing to meet goals, and were the most socially impaired.

Individuals in biotype 2 exhibited intermediate levels of impaired cognitive control but had normal-to-increased brain responses to sensory inputs and fast visual orienting.

Individuals in biotype 3 exhibited normal cognitive control, modestly impaired sensorimotor reactivity and were the least socially impaired. They also had the lowest positive and negative psychosis symptoms.

Each biotype overlapped with traditional diagnostic categories. Fifty-nine percent of individuals in biotype 1 and 32% of individuals in biotype 3 were diagnosed with schizophrenia. Bipolar disorder with psychosis was diagnosed among 20% of individuals in biotype 1 and 44% of in biotype 3.

“These divergent biomarker patterns across biotypes also illustrate the difficulty with using solely clinical psychosis diagnoses as the ‘gold standard’ for capturing neurobiological distinctiveness. The psychosis probands (as a group) showed at least some degree of cognitive control deviation, but the remarkable difference between diminution and accentuation of sensorimotor reactivity across individuals with psychosis would certainly lead to devaluing this group of measures for understanding psychosis neurobiology in mixed samples,” the researchers concluded. – by Amanda Oldt

Disclosure: Clementz reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.