Biomarkers beat DSM categories for capturing nuances in psychosis




Three biotypes surpass traditional diagnostic categories when it comes to identifying subgroups of psychosis, a study showed.

“Classification and treatment of brain diseases subsumed by psychiatry rely on clinical phenomenology, despite the call for alternatives,” wrote Brett A. Clementz, Ph.D., of the University of Georgia, Athens, and his coinvestigators. “There is overlap in susceptibility genes and phenotypes across bipolar disorder with psychosis and schizophrenia, and considerable similarity between different psychotic disorders on symptoms, illness course, cognition, psychophysiology, and neurobiology [while] drug treatments for these conditions overlap extensively” (Am J Psychiatry. 2015. doi: 10.1176/appi.ajp.2015.14091200).

The researchers recruited 711 people from Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium sites (probands). All subjects had diagnoses of schizophrenia, schizoaffective disorder, or bipolar disorder with psychosis, and underwent interviews and laboratory data collection at the time of enrollment. In addition, 883 first-degree relatives of the 711 initial enrollees also were clinically evaluated, along with a cohort of 278 people deemed “demographically comparable [and] healthy” by investigators.

Biotypes for all individuals enrolled in the study were determined through laboratory tasks designed to “assess brain function at the neurocogntive/perceptual level.” These tasks consisted of the Brief Assessment of Cognition in Schizophrenia (BACS), pro- and antisaccade tasks, stop signal tasks, auditory paired stimuli and oddball evoked brain responses, and MRI acquisition and voxel-based morphometry.

The Structured Clinical Interview for DSM-IV and the Structured Interview for DSM-IV Personality Disorders were used for interviewing enrollees. Data compiled from these tests underwent multivariate taxometric analyses to compare biomarker variance across the three cohorts, in order to determine what, if any, heterogeneity exists in psychosis biotypes.

According to the results, diagnoses made with the clinical DSM guidelines yielded a single-severity continuum showing schizophrenia to be the most severe, followed by schizoaffective disorder and bipolar psychosis. However, biotypes showed significant variation, with investigators noting that “the three biotypes had distinctive patterns of abnormality across biomarkers that were neither entirely nor efficiently captured by a severity continuum.”

Larger separations were seen in biotype cohorts than in the DSM, specifically among probands. Among probands, group separation from healthy subjects was –2.58, –1.94, and –0.35 for biotype 1, 2, and 3 respectively for the BACS. Separation was –0.99, –0.78, and –0.05 for the stop signal task, and 3.32, 1.90, and 1.19 for the antisaccade errors. On the other hand, DSM diagnostics revealed group differences of –1.01, –1.51, and –1.83 for bipolar disorder psychosis, schizoaffective disorders, and schizophrenia, respectively, for the BACS test. Separation was –0.41, –0.61, and –0.55 for the stop signal task, and 1.36, 1.66, and 2.45 for antisaccade errors.

“Each biotype included all DSM psychosis categories, but probands diagnosed with schizophrenia were more numerous in biotype 1 (although 20% had bipolar disorder with psychosis), and probands diagnosed with bipolar disorder with psychosis were more numerous in biotype 3 (although 32% had schizophrenia), respectively,” the investigators noted.

The authors added that “when considered across proband and relative data, the biotype subgroups were superior to DSM diagnostic classes in between-group separations on external validating measures, illustrating the former scheme’s superiority for capturing neurobiological distinctiveness.”

Investigators noted that their approach did not use social functioning, brain structure, and characteristics of biological relatives in the creation of biotypes, which could have led to stronger results. Also, trial participants were mostly already on medication, classified as chronically psychotic, and tested at least once previously. The trial also had no replication sample for this sample population.

The study was supported by grants from the National Institute of Mental Health. Dr. Clementz did not report any relevant financial disclosures. Dr. Matcheri S. Keshavan reported receiving a grant from Sunovion and serving as a consultant to Forum Pharmaceuticals. Dr. Carol A. Tamminga also reported potential conflicts.

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