Abstract
Introduction Schizophrenia (SCZ) is a complex, heterogeneous, psychotic disorder with variable phenotypic expressions, variable course patterns and a complex etiology. It affects individuals, families, and the society at large, with most of the affected population having severe symptomatic and functional outcome.
Aims The objectives of this systematic review were to summarize the number of clusters and trajectories of schizophrenia symptoms course patterns discovered until now, to identify predictors of clusters and trajectories, to highlight knowledge gaps and to point out a way forward to optimize future cluster- and trajectory-based studies.
Methods PsycINFO, PubMed, PsycTESTS, PsycARTICLES, SCOPUS, EMBASE, and Web of Science databases were searched using a comprehensive search strategy adapted to each database. Cross-sectional and longitudinal studies published from 2008 to 2018, that reported at least two clusters or trajectory groups of patients, siblings and controls using a statistical method across positive, negative, and cognitive impairment symptom dimensions or combination of symptom dimensions were included. Two reviewers independently screened and extracted the data from included studies. A narrative synthesis was performed, and data were summarized using tables.
Results Of 2,282 studies identified, 47 fulfilled the inclusion criteria and were included in the qualitative synthesis. These studies were conducted globally in more than 17 countries (15 studies in the USA) and published from 2009 to 2019. Sixteen of the included studies had a longitudinal design, involving 11,475 patients with schizophrenia-spectrum disorders, 1,059 siblings and 653 controls, whereas 31 studies had a cross-sectional design involving 5,271 patients with schizophrenia-spectrum disorders, 7,423 siblings, and 2,346 controls. The longitudinal studies discovered two to five patient trajectory groups based on positive and negative symptoms, and four to five patient and sibling trajectory groups identified based on cognitive deficits. Regarding cross-sectional studies, three clusters of patients were found based on positive and negative symptoms while four clusters of siblings were identified based on positive and negative schizotypy. Regarding cognitive deficits, three to five clusters were reported in patients and their unaffected siblings. Age, gender, ethnicity, educational status, age of illness onset, diagnosis of schizophrenia, depressive symptoms, general psychopathology, severity of positive and negative symptoms, cognitive performance, premorbid functioning, quality of life and global functioning were important predictors among patients and their unaffected siblings.
Conclusions The evidence from cluster- and trajectory-based studies in the past decade showed that clinical symptoms of schizophrenia are clearly heterogeneous across patients, siblings and controls. Despite this fact, the extent of heterogeneity is yet to be investigated. To fully understand the heterogeneity, further work is expected from psychiatric researchers targeting longitudinal study design, unaffected siblings and utilizing genetic markers as a predictor.