Impact of Comorbid Affective Disorders on Longitudinal Clinical Outcomes in Individuals at Ultra-high Risk for Psychosis
Authors: Schirmbeck Frederike , van der Burg Nadine C , Blankers Matthijs , Vermeulen Jentien M , McGuire Philip , Valmaggia Lucia R , Kempton Matthew J , van der Gaag Mark , Riecher-Rössler Anita , Bressan Rodrigo A , Barrantes-Vidal Neus , Nelson Barnaby , Amminger G Paul , McGorry Patrick , Pantelis Christos , Krebs Marie-Odile , Ruhrmann Stephan , Sachs Gabriele , Rutten Bart P F , van Os Jim , Nordentoft Merete , Glenthøj Birte ,   EU-GEI High Risk Study Group Authors, Calem Maria , Tognin Stefania , Modinos Gemma , Pisani Sara , Hedges Emily , Velthorst Eva , Kraan Tamar C , van Dam Daniella S , Burger Nadine , Politis Athena , Goodall Joanne , Borgwardt Stefan , Studerus Erich , Gadelha Ary , Brietzke Elisa , Asevedo Graccielle , Asevedo Elson , Zugman Andre , Domínguez-Martínez Tecelli , Monsonet Manel , Hinojosa Lidia , Racioppi Anna , Kwapil Thomas R , Kazes Mathilde , Daban Claire , Bourgin Julie , Gay Olivier , Mam-Lam-Fook Célia , Nordholm Dorte , Randers Lasse , Krakauer Kristine , Birkedal Glenthøj Louise , Gebhard Dominika , Arnhold Julia , Klosterkötter Joachim , Lasser Iris , Winklbaur Bernadette , Delespaul Philippe A , Fusar-Poli Paolo , de Haan Lieuwe 
Published: July 2021

Abstract

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.