Deep Clinical Phenotyping of Schizophrenia Spectrum Disorders Using Data-Driven Methods: Marching towards Precision Psychiatry

Heterogeneity is the main challenge in the traditional classification of mental disorders, including schizophrenia spectrum disorders (SSD). This can be partly attributed to the absence of objective diagnostic criteria and the multidimensional nature of symptoms and their associated factors. This article provides an overview of findings from the Genetic Risk and Outcome of Psychosis (GROUP) cohort study on the deep clinical phenotyping of schizophrenia spectrum disorders targeting positive and negative symptoms, cognitive impairments and psychosocial functioning. Three to four latent subtypes of positive and negative symptoms were identified in patients, siblings and controls, whereas four to six latent cognitive subtypes were identified. Five latent subtypes of psychosocial function-multidimensional social inclusion and premorbid adjustment-were also identified in patients. We discovered that the identified subtypes had mixed profiles and exhibited stable, deteriorating, relapsing and ameliorating longitudinal courses over time. Baseline positive and negative symptoms, premorbid adjustment, psychotic-like experiences, health-related quality of life and PRSSCZ were found to be the strong predictors of the identified subtypes. Our findings are comprehensive, novel and of clinical interest for precisely identifying high-risk population groups, patients with good or poor disease prognosis and the selection of optimal intervention, ultimately fostering precision psychiatry by tackling diagnostic and treatment selection challenges pertaining to heterogeneity.