20-year trajectories of positive and negative symptoms after the first psychotic episode in patients with schizophrenia spectrum disorder: results from the OPUS study

Marie Starzer, Helene Gjervig Hansen, Carsten Hjorthøj, Nikolai Albert, Merete Nordentoft, Trine Madsen

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Abstract

This study aimed to identify the 20-year trajectories of positive and negative symptoms after the first psychotic episode in a sample of patients with an ICD-10 diagnosis of schizophrenia spectrum disorder, and to investigate the baseline characteristics and long-term outcomes associated with these trajectories. A total of 373 participants in the OPUS trial were included in the study. Symptoms were assessed at baseline and after 1, 2, 5, 10 and 20 years using the Scales for the Assessment of Positive and Negative Symptoms. We used latent class growth mixture modelling to identify trajectories, and multinominal regression analyses to investigate predictors of membership to identified trajectories. Five trajectories of positive symptoms were identified: early continuous remission (50.9% of the sample), stable improvement (18.0%), intermittent symptoms (10.2%), relapse with moderate symptoms (11.9%), and continuous severe symptoms (9.1%). Substance use disorder (odds ratio, OR: 2.83, 95% CI: 1.09-7.38, p=0.033), longer duration of untreated psychosis (OR: 1.02, 95% CI: 1.00-1.03, p=0.007) and higher level of negative symptoms (OR: 1.60, 95% CI: 1.07-2.39, p=0.021) were predictors of the relapse with moderate symptoms trajectory, while only longer duration of untreated psychosis (OR: 1.01, 95% CI: 1.00-1.02, p=0.030) predicted membership to the continuous severe symptoms trajectory. Two trajectories of negative symptoms were identified: symptom remission (51.0%) and continuous symptoms (49.0%). Predictors of the continuous symptoms trajectory were male sex (OR: 3.03, 95% CI: 1.48-6.02, p=0.002) and longer duration of untreated psychosis (OR: 1.01, 95% CI: 1.00-1.02, p=0.034). Trajectories displaying continuous positive and negative symptoms were linked to lower neurocognition, as measured by the Brief Assessment of Cognition in Schizophrenia (BACS) (z-score: –0.78, CI: –1.39 to –0.17, for continuous positive symptoms; z-score: –0.33, CI: –0.53 to –0.13, for continuous negative symptoms). The same trajectories were also linked to higher use of antipsychotic medication at 20-year follow-up (continuous positive symptoms: 78%; continuous negative symptoms: 67%). These findings suggest that the majority of patients with first-episode schizophrenia spectrum disorder have a trajectory with early stable remission of positive symptoms. Long duration of untreated psychosis and comorbid substance abuse are modifiable predictors of poor trajectories for positive symptoms in these patients. In about half of patients, negative symptoms do not improve over time. These symptoms, in addition to being associated with poor social and neurocognitive functioning, may prevent patients from seeking help.
OriginalsprogEngelsk
TidsskriftWorld Psychiatry
Vol/bind22
Udgave nummer3
Sider (fra-til)424-432
Antal sider9
ISSN1723-8617
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The authors would like to thank L. Mariegaard, M. Birk and H.D. Jensen, who conducted a large number of clinical interviews in the 20‐year follow‐up. Moreover, they are grateful to the trial participants, who took time to share their stories and provided the clinical data for this study. The OPUS trial has been approved by the Regional Ethical Scientific Committee (protocol no. 17023873) and by the Danish data protection agency (RHP‐2017‐047, I‐Suite no. 05855), and registered at ClinicalTrials.gov (NCT00157313). The project was funded by unrestricted grants from the Lundbeck Foundation, Tryg Foundation and Helse Foundation. M. Starzer and H.G. Hansen are joint first authors of this paper. Supplementary information on the study can be found at https://drive.google.com/file/d/19s5TDJ0fQZ9O7I6ez6pau7m3EhRtqI7E/view .

Funding Information:
The authors would like to thank L. Mariegaard, M. Birk and H.D. Jensen, who conducted a large number of clinical interviews in the 20-year follow-up. Moreover, they are grateful to the trial participants, who took time to share their stories and provided the clinical data for this study. The OPUS trial has been approved by the Regional Ethical Scientific Committee (protocol no. 17023873) and by the Danish data protection agency (RHP-2017-047, I-Suite no. 05855), and registered at ClinicalTrials.gov (NCT00157313). The project was funded by unrestricted grants from the Lundbeck Foundation, Tryg Foundation and Helse Foundation. M. Starzer and H.G. Hansen are joint first authors of this paper. Supplementary information on the study can be found at https://drive.google.com/file/d/19s5TDJ0fQZ9O7I6ez6pau7m3EhRtqI7E/view.

Publisher Copyright:
© 2023 World Psychiatric Association.

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