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. 2025 Sep 8;51(5):1428-1442.
doi: 10.1093/schbul/sbaf045.

Latent Trajectories of Positive, Negative Symptoms and Functioning in Early Intervention Services for First-Episode Psychosis: A 2-Year Follow-Up Study

Olivier Percie du Sert  1   2 , Joshua Unrau  1 , Manish Dama  1 , Lena Palaniyappan  1   2 , Jai Shah  1   2 , Ridha Joober  1   2 , Delphine Raucher-Chéné  1   2 , Ashok Malla  1   2 , Martin Lepage  1   2
Affiliations

Latent Trajectories of Positive, Negative Symptoms and Functioning in Early Intervention Services for First-Episode Psychosis: A 2-Year Follow-Up Study

Olivier Percie du Sert et al. Schizophr Bull. .

Abstract

Background: From the first episode (FEP), the course of psychosis is marked by substantial heterogeneity of clinical and functional outcomes which poses significant challenges in providing prognostic guidance to patients and families. To better understand such heterogeneity within the context of early intervention services (EIS), this study aimed to examine latent trajectories of positive and negative symptoms and functioning among FEP individuals undergoing EIS.

Study design: The Prevention and Early Intervention Program for Psychoses (PEPP-Montreal) is a 2-year EIS for FEP that conducted longitudinal assessments of 689 individuals aged 14-35, including sociodemographics, cognition, psychopathology, and functioning. Latent growth mixture modeling was used to identify distinct patterns of clinical and functional trajectories. The inter-relationship between trajectories, and the association of trajectory membership with baseline characteristics and distal outcomes were investigated using the manual 3-step approach.

Study results: Two positive symptom trajectories (Stable-low-32%, Fluctuating-68%,), 3 negative symptom trajectories (Decreasing-41%, Fluctuating-15%, and Stable-high-44%), and 2 functioning trajectories (Increasing-57%, Stable-moderate-43%) were identified. Early treatment response, particularly on negative symptoms, consistently and strongly predicted better outcome trajectories (OR = [3.4-5.5]). Trajectories of higher symptom severity were associated with trajectory of worse functioning (RR = [1.5-2.2]), which exhibited lower rates of clinical and functional remission.

Conclusion: These findings offer insights into clinically meaningful subgroups of individuals that could inform the prognosis of FEP and the development of individually tailored EIS. Individuals who do not show early improvement in negative symptoms may benefit from earlier psychosocial interventions specifically targeting actionable factors that contribute to secondary negative symptoms.

Keywords: data-driven; growth mixture modeling; heterogeneity; remission; schizophrenia; structural equation modeling.

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Conflict of interest statement

M.L. reports grants from Otsuka Lundbeck Alliance, and Roche, personal fees from Otsuka Canada, Lundbeck Canada, and Boehringer Ingelheim, as well as grants and personal fees from Janssen. A.M. and D.R.C. report no funding from industry in more than 3 years. R.J. reports grants, speaker honoraria, and honoraria from AstraZeneca, Janssen, Otsuka, Lundbeck, Pfizer Canada, BMS, Shire, and Sunovion, and royalties from Henry Stewart Talks. J.S. has received grants and salary awards from the Canadian Institutes of Health Research and Fonds de recherche du Québec–Santé, outside the submitted work. L.P. reports personal fees from Janssen Canada, Otsuka Canada, SPMM Course Limited, UK, Canadian Psychiatric Association; book royalties from Oxford University Press; and investigator-initiated educational grants from Sunovion, Janssen Canada, Otsuka Canada outside the submitted work. These interests had no relation to the present study. Other co-authors have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
Estimated latent trajectories of outcomes over 2-year early intervention servicesNote: Observed individuals’ trajectories are plotted in the background.
Figure 2.
Figure 2.
Cross-Distribution of Individuals between (A) Positive Symptoms and Functioning Trajectories, (B) Negative Symptoms and Functioning Trajectories, and (C) Positive and Negative Symptoms Trajectories Note: Each link represents the number of intersecting individuals between the two trajectories it connects, along with the corresponding proportions it represents in each of these trajectories. For example, 76% of individuals from the Stable-low trajectory of positive symptoms also belong to the Increasing trajectory of functioning, representing 44% of it.
Figure 3.
Figure 3.
Baseline Predictors of Trajectory Membership Note: (1) All results are statistically significant using a Bonferroni-corrected threshold (P < .001). (2) Reference trajectory. (3) Log transformed. (4) Binary variable, proportion of cases coded as yes. CI: Confidence interval, OR: Odds ratio, PS: Positive symptoms, SANS: Scale for the Assessment of Negative Symptoms, SAPS: Scale for the Assessment of Positive Symptoms, SOFAS: Social Occupational Functioning Scale.
Figure 4.
Figure 4.
Trajectory Differences in Distal Outcomes at the End of the 2-Year Follow-Up Period Note: (1) All results are statistically significant using a Bonferroni-corrected threshold (P < .005). (2) Reference trajectory. CI: Confidence interval, SANS: Scale for the Assessment of Negative Symptoms, SAPS: Scale for the Assessment of Positive Symptoms, SOFAS: Social Occupational Functioning Scale, SMD: Standardized Mean Difference.
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