Does Biology Transcend the Symptom-based Boundaries of Psychosis?

Abstract

Psychotic disorders, as defined by clinical features alone, overlap considerably in terms of symptoms, familial patterns, risk genes, outcome, and treatment response. As a result, numerous neurobiological measurements fail to distinguish patients with the most prevalent classic psychotic syndromes. Statistical methods applied to such biological measurements in large numbers of patients with psychosis yield novel categories that cut across traditional diagnostic boundaries. Such new classification approaches within psychosis hopefully represent an opportunity to transcend clinical phenomenologically defined syndromes in psychiatry with neurobiologically defined diseases that can advance drug discovery and support precision medicine approaches in psychiatry.

Keywords: Biotype; Bipolar; Neurobiology; Psychosis; Reclassification; Schizoaffective; Schizophrenia.

Figure 1

A possible example of a biomarker-based classification, agnostic to conventional diagnostic categories, illustrating how dimensional or spectrum concepts might plausibly delineate psychotic disorders differently than current, symptom-based categorical classifications. Such a novel taxonomy would be based on multi-domain endophenotype measures as described in the text. In addition to the three major diagnoses examined in BSNIP-1 (schizophrenia, schizoaffective disorder and psychotic bipolar disorder), theoretically allied conditions are incorporated into this schema as illustrated, including psychostimulant-induced psychoses (upper left) and psychotic depression (lower right). Additional conditions portrayed include individuals who can be conceived of as existing on the mild end of a theoretical continuum with psychotic disorders, for example, persons lacking a psychiatric diagnosis but who experience phenomena allied to auditory hallucinations (so-called “voice-hearers”) as well as the cluster-A “personality disorders” listed in DSM-IV (schizotypal, paranoid and schizoid). Courtesy of M. Keshavan, MD, Boston, MA.