Beyond the Descriptive: A Comprehensive, Multi-domain Validation of Symptom Trajectories for Individuals at Clinical High Risk for Psychosis.

Background: Although the Clinical High-Risk for Psychosis (CHR-P) criteria are widely used to ascertain individuals at heightened risk for imminent onset of psychosis, it remains controversial whether CHR-P status define a diagnostic construct in its own right. In a prior study, CHR-P non-converters were observed to follow three distinct trajectories in symptoms and functioning: remission, partial remission, and maintenance of symptoms and functional impairments at subthreshold levels of intensity.

Methods: Here, we utilized the North American Prodrome Longitudinal Study Phase 3 (NAPLS3) sample (N = 806) to determine whether: 1) the same trajectory groups can be detected when assessing symptoms at 2-month intervals over an 8-month period and 2) the resulting trajectory groups differ from each other and from healthy controls and converting CHR-P cases in terms of risk factors, comorbidities, and functional outcomes.

Results: Three distinctive subgroups within the CHR non-converters were identified, largely paralleling those previously observed. Importantly, these extracted groups, along with non-CHR controls and CHR converters, differ from each other significantly with respect to putative etiological risk factors (e.g., predicted risk scores, physiological and self-report measures of stress), affective comorbidities, as well as functional outcomes, providing converging evidence supporting the validity of the identified trajectory groups.

Conclusions: This pattern, along with the fact that even the subgroup of CHR-P nonconverters showing a remission trajectory deviated from healthy controls, supports treating the CHR-P syndrome not just as a status that denotes risk for onset of full psychosis, but also as a marker of ongoing distress for a population in need of interventions.