Impact of Comorbid Affective Disorders on Longitudinal Clinical Outcomes in Individuals at Ultra-high Risk for Psychosis

F. Schirmbeck*, N.C. van der Burg, M. Blankers, J.M. Vermeulen, P. McGuire, L.R. Valmaggia, M.J. Kempton, M. van der Gaag, A. Riecher-Rossler, R.A. Bressan, N. Barrantes-Vidal, B. Nelson, G.P. Amminger, P. McGorry, C. Pantelis, M.O. Krebs, S. Ruhrmann, G. Sachs, B.P.F. Rutten, J. van OsM. Nordentoft, B. Glenthoj, P. Fusar-Poli, L. de Haan, EU-GEI High Risk Study Group Authors

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Introduction: Diagnoses of anxiety and/or depression are common in subjects at Ultra-High Risk for Psychosis (UHR) and associated with extensive functional impairment. Less is known about the impact of affective comorbidities on the prospective course of attenuated psychotic symptoms (APS). Method: Latent class mixed modelling identified APS trajectories in 331 UHR subjects assessed at baseline, 6, 12, and 24 months follow-up. The prognostic value of past, baseline, and one-year DSM-IV depressive or anxiety disorders on trajectories was investigated using logistic regression, controlling for confounders. Cox proportional hazard analyses investigated associations with transition risk. Results: 46.8% of participants fulfilled the criteria for a past depressive disorder, 33.2% at baseline, and 15.1% at one-year follow-up. Any past, baseline, or one-year anxiety disorder was diagnosed in 42.9%, 37.2%, and 27.0%, respectively. Participants were classified into one of three latent APS trajectory groups: (1) persistently low, (2) increasing, and (3) decreasing. Past depression was associated with a higher risk of belonging to the increasing trajectory group, compared to the persistently low (OR = 3.149, [95%CI: 1.298-7.642]) or decreasing group (OR = 3.137, [1.165-8.450]). In contrast, past (OR =.443, [.179-1.094]) or current (OR =.414, [.156-1.094]) anxiety disorders showed a trend-level association with a lower risk of belonging to the increasing group compared to the persistently low group. Past depression was significantly associated with a higher risk of transitioning to psychosis (HR = 2.123, [1.178-3.828]). Conclusion: A past depressive episode might be a particularly relevant risk factor for an unfavorable course of APS in UHR individuals. Early affective disturbances may be used to advance detection, prognostic, and clinical strategies.
Original languageEnglish
Pages (from-to)100-110
Number of pages11
JournalSchizophrenia Bulletin
Issue number1
Publication statusPublished - 1 Jan 2022


  • ultra-high risk
  • comorbid
  • anxiety
  • depression
  • psychosis
  • schizophrenia
  • prediction


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