Multicenter Study

. 2022 Jan 21;48(1):100-110.

doi: 10.1093/schbul/sbab088.

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

Frederike Schirmbeck^{1

2}, Nadine C van der Burg^{1

3}, Matthijs Blankers^{1

2

4}, Jentien M Vermeulen¹, Philip McGuire⁵, Lucia R Valmaggia⁶, Matthew J Kempton⁵, Mark van der Gaag^{7

8}, Anita Riecher-Rössler⁹, Rodrigo A Bressan¹⁰, Neus Barrantes-Vidal^{11

12}, Barnaby Nelson^{13

14}, G Paul Amminger¹³, Patrick McGorry^{13

14}, Christos Pantelis¹⁵, Marie-Odile Krebs¹⁶, Stephan Ruhrmann¹⁷, Gabriele Sachs¹⁸, Bart P F Rutten¹⁹, Jim van Os^{5

19

20}, Merete Nordentoft²¹, Birte Glenthøj²²; EU-GEI High Risk Study Group Authors; Paolo Fusar-Poli^{23

24

25}, Lieuwe de Haan^{1

2}

Collaborators, Affiliations

Collaborators

EU-GEI High Risk Study Group Authors:
Maria Calem, Stefania Tognin, Gemma Modinos, Sara Pisani, Emily Hedges, Eva Velthorst, Tamar C Kraan, Daniella S van Dam, Nadine Burger, Athena Politis, Joanne Goodall, Stefan Borgwardt, Erich Studerus, Ary Gadelha, Elisa Brietzke, Graccielle Asevedo, Elson Asevedo, Andre Zugman, Tecelli Domínguez-Martínez, Manel Monsonet, Lidia Hinojosa, Anna Racioppi, Thomas R Kwapil, Mathilde Kazes, Claire Daban, Julie Bourgin, Olivier Gay, Célia Mam-Lam-Fook, Dorte Nordholm, Lasse Randers, Kristine Krakauer, Louise Birkedal Glenthøj, Dominika Gebhard, Julia Arnhold, Joachim Klosterkötter, Iris Lasser, Bernadette Winklbaur, Philippe A Delespaul

Affiliations

¹ Department of Psychiatry, Amsterdam University Medical Center, Meibergdreef, University of Amsterdam, Amsterdam, the Netherlands.
² Arkin Institute for Mental Health, Amsterdam, the Netherlands.
³ GGZ Centraal, Amersfoort, the Netherlands.
⁴ Trimbos Institute, Institute of Mental Health and Addiction, Utrecht, the Netherlands.
⁵ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁶ Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁷ Department of Clinical Psychology, Faculty of Behavioural and Movement Sciences, Amsterdam Public Mental Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
⁸ Psychosis Research Institute, Parnassia Group, The Hague, the Netherlands.
⁹ Medical Faculty, University of Basel, Basel, Switzerland.
¹⁰ Depto Psiquiatria, Escola Paulista de Medicina, LiNC-Lab Interdisciplinar Neurociências Clínicas, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
¹¹ Departament de Psicologia Clínica i de la Salut, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹² Fundació Sanitària Sant Pere Claver, Spanish Mental Health Research Network (CIBERSAM), Spain.
¹³ Orygen, Parkville, Victoria, Australia.
¹⁴ Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
¹⁵ Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne & Melbourne Health, Carlton South, Victoria, Australia.
¹⁶ University of Paris, GHU-Paris, Sainte-Anne, C'JAAD, Inserm U1266, Institut de Psychiatrie (CNRS 3557), Paris, France.
¹⁷ Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.
¹⁸ Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
¹⁹ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands.
²⁰ Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
²¹ Mental Health Center Copenhagen and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Center Glostrup, Mental Health Services in the Capital Region of Copenhagen, University of Copenhagen, Copenhagen, Denmark.
²² Centre for Neuropsychiatric Schizophrenia Research (CNSR) & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
²³ OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK.
²⁴ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
²⁵ Department of Psychosis Studies, Early Psychosis: Intervention and Clinical-detection (EPIC) Lab, Institute of Psychiatry Psychology & Neuroscience, King's College London, London, UK.

PMID: 34417795
PMCID: PMC8781381
DOI: 10.1093/schbul/sbab088

Multicenter Study

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

Frederike Schirmbeck et al. Schizophr Bull. 2022.

. 2022 Jan 21;48(1):100-110.

doi: 10.1093/schbul/sbab088.

Authors

Collaborators

EU-GEI High Risk Study Group Authors:
Maria Calem, Stefania Tognin, Gemma Modinos, Sara Pisani, Emily Hedges, Eva Velthorst, Tamar C Kraan, Daniella S van Dam, Nadine Burger, Athena Politis, Joanne Goodall, Stefan Borgwardt, Erich Studerus, Ary Gadelha, Elisa Brietzke, Graccielle Asevedo, Elson Asevedo, Andre Zugman, Tecelli Domínguez-Martínez, Manel Monsonet, Lidia Hinojosa, Anna Racioppi, Thomas R Kwapil, Mathilde Kazes, Claire Daban, Julie Bourgin, Olivier Gay, Célia Mam-Lam-Fook, Dorte Nordholm, Lasse Randers, Kristine Krakauer, Louise Birkedal Glenthøj, Dominika Gebhard, Julia Arnhold, Joachim Klosterkötter, Iris Lasser, Bernadette Winklbaur, Philippe A Delespaul

Affiliations

¹ Department of Psychiatry, Amsterdam University Medical Center, Meibergdreef, University of Amsterdam, Amsterdam, the Netherlands.
² Arkin Institute for Mental Health, Amsterdam, the Netherlands.
³ GGZ Centraal, Amersfoort, the Netherlands.
⁴ Trimbos Institute, Institute of Mental Health and Addiction, Utrecht, the Netherlands.
⁵ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁶ Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁷ Department of Clinical Psychology, Faculty of Behavioural and Movement Sciences, Amsterdam Public Mental Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
⁸ Psychosis Research Institute, Parnassia Group, The Hague, the Netherlands.
⁹ Medical Faculty, University of Basel, Basel, Switzerland.
¹⁰ Depto Psiquiatria, Escola Paulista de Medicina, LiNC-Lab Interdisciplinar Neurociências Clínicas, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
¹¹ Departament de Psicologia Clínica i de la Salut, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹² Fundació Sanitària Sant Pere Claver, Spanish Mental Health Research Network (CIBERSAM), Spain.
¹³ Orygen, Parkville, Victoria, Australia.
¹⁴ Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
¹⁵ Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne & Melbourne Health, Carlton South, Victoria, Australia.
¹⁶ University of Paris, GHU-Paris, Sainte-Anne, C'JAAD, Inserm U1266, Institut de Psychiatrie (CNRS 3557), Paris, France.
¹⁷ Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.
¹⁸ Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
¹⁹ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands.
²⁰ Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
²¹ Mental Health Center Copenhagen and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Center Glostrup, Mental Health Services in the Capital Region of Copenhagen, University of Copenhagen, Copenhagen, Denmark.
²² Centre for Neuropsychiatric Schizophrenia Research (CNSR) & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
²³ OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK.
²⁴ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
²⁵ Department of Psychosis Studies, Early Psychosis: Intervention and Clinical-detection (EPIC) Lab, Institute of Psychiatry Psychology & Neuroscience, King's College London, London, UK.

PMID: 34417795
PMCID: PMC8781381
DOI: 10.1093/schbul/sbab088

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.

Keywords: anxiety; comorbid; depression; prediction; psychosis; schizophrenia; ultra-high risk.

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Figures

**Fig. 1.**
Flowchart of included participants. *Abbreviation:* CAARMS: the Comprehensive Assessment of At-Risk Mental States; SCID: Structured Clinical Interview for DSM-IV-TR Axis I Disorders, UHR: ultra-high risk.

**Fig. 2.**
Model estimated class-specific mean predicted trajectories of attenuated psychotic symptoms with 95% confidence intervals. Trajectories were classified as “persistently low” (n = 238; 71.9%), “increasing” (n = 28; 8.5%), and “decreasing” (n = 65; 19.6%) symptom severity.

**Fig. 3.**
Cumulative event Kaplan–Meier function for risk of development of psychotic disorders with 95% Confidence Intervals in 328 ultra-high risk (UHR) individuals stratified for past depression.

See this image and copyright information in PMC

References

1. Fusar-Poli P, Salazar de Pablo G, Correll CU, et al. . Prevention of psychosis: advances in detection, prognosis, and intervention. JAMA Psychiatry 2020;77(7):755–765. - PubMed
1. Catalan A, Salazar de Pablo G, Vaquerizo Serrano J, et al. . Annual research review: prevention of psychosis in adolescents - systematic review and meta-analysis of advances in detection, prognosis and intervention. J Child Psychol Psychiatry. 2021;62(5):657–673. - PubMed
1. Fusar-Poli P, Cappucciati M, Bonoldi I, et al. . Prognosis of brief psychotic episodes: a meta-analysis. JAMA Psychiatry. 2016;73(3):211–220. - PubMed
1. Fusar-Poli P, Rocchetti M, Sardella A, et al. . Disorder, not just state of risk: meta-analysis of functioning and quality of life in people at high risk of psychosis. Br J Psychiatry. 2015;207(3):198–206. - PubMed
1. Addington J, Piskulic D, Liu L, et al. . Comorbid diagnoses for youth at clinical high risk of psychosis. Schizophr Res. 2017;190:90–95. - PMC - PubMed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous