Through multivariate taxometric analyses, the researchers identified 3 neurobiologically-distinct psychosis biotypes that did not align with clinical diagnoses. The existence of the biotypes suggest“more distinct functional brain correlates of psychosis manifestation than were captured by clinical phenomenological diagnostic definitions,” the researchers wrote. While all 3 biotypes featured characteristics of DSM diagnoses and global psychosis clinical ratings, biotype 1 featured more characteristics of schizophrenia (59% of cases) and biotype 3 featured more characteristics of bipolar disorder with psychosis (44% of cases).

There were notable differences across all 3 biotypes in regards to social functioning measures, with biotype 3 having the least impairment and biotype 1 having the most. The biotypes also demonstrated brain structural differences, with biotype 1 having the most extensive reductions in grey matter volume, biotype 2 with fewer reductions but overlapping biotype 1, and biotype 3 with modest reduction in the anterior limbic areas. Biotype 1 and 2 demonstrated evidence for familial psychosis and had similar clinical severity, whereas biotype 3 demonstrated almost normal cognition and less severe clinical psychosis.

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“The outcome of this study provides proof of concept that by considering alternatives to using clinical diagnoses for defining psychosis disease entities, we may be able to capture neurobiological uniqueness,” Dr. Clementz said. “Using such an approach may help to identify specific etiological mechanisms leading to psychosis, and reinvigorate drug discovery. Identifying treatments based on specific mechanisms, rather than serendipity, would provide a revolution in psychiatry.”


  1. Clementz BA, Sweeney JA, Hamm JP. Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers. Am J Psychiatry. 2015; 00:1–12; doi: 10.1176/appi.ajp.2015.14091200.
  2. NIH Press Releases