Biomarkers Delineate 3 Distinct Psychosis Biotypes

February 9, 2016

Brain-based biomarkers identify more biologically homogeneous categories of psychosis than do clinical diagnoses.

Whereas psychiatry relies on clinical phenomenology for diagnosis, biological formulations of disease are transforming diagnosis and treatment in other medical disciplines. Psychotic symptoms may represent the final common pathway of multiple different etiologies, much in the same way that there are many potential underlying causes of fever.

Clementz and colleagues1 evaluated a more neuroscience-based classification of psychotic disorders, with the aim of delineating more biologically homogeneous subgroups of patients with psychosis independent of clinical symptoms. The Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) investigators recruited 711 probands with psychosis (DSM-defined schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features), 811 first-degree relatives of patients with psychosis, and 278 demographically comparable healthy controls. They collected a large panel of biomarkers of known relevance to psychosis and functional brain activity, including neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms.

Using multivariate taxometric analyses, they found a subset of the biomarker panel that differentiated people with psychosis from healthy controls. These biomarkers-including cognitive control and sensorimotor reactivity-were used to create distinct subgroups of patients with psychosis. Three neurobiologically distinct phenotypes, termed biotypes, of patients with psychosis were identified.

The 3 psychosis biotypes did not respect categories based on clinical symptoms (ie, each biotype included patients with schizophrenia, schizoaffective disorder, and psychotic bipolar disorder). External validating measures-including social functioning, structural MRI, family biomarkers, and clinical information-supported the distinctiveness of the 3 psychosis biotypes.

The bottom line
This study illustrates how distinct pathways may lead to clinically similar symptomatology, namely psychosis. The results also help explain heterogeneous findings across studies of a given marker in psychotic disorders when patients are classified based on clinical diagnosis. The investigators concluded that psychosis biotypes may facilitate novel clinical, basic, and molecular research.


1. Clementz BA, Sweeney JA, Hamm JP, et al. Identification of distinct psychosis biotypes using brain-based biomarkers. Am J Psychiatry. 2015 Dec 7. appiajp201514091200.