Characterizing the Clinical Trajectory and Predicting Persistence and Deterioration of Attenuated Psychotic Symptoms in Ultra-High-Risk Individuals

Cassandra Wannan; Isabelle Scott; Dominic Dwyer; Scott R Clark; Simon Hartmann; Rochelle Ruby Ye; G Paul Amminger; Hok Pan Yuen; Suzie Lavoie; Connie Markulev; Miriam R Schaefer; Jessica A Hartmann; Nilufar Mossaheb; Monika Schlögelhofer; Stefan Smesny; Ian B Hickie; Gregor Berger; Eric Y H Chen; Lieuwe de Haan; Dorien H Nieman; Merete Nordentoft; Anita Riecher-Rössler; Swapna Verma; Andrew Thompson; Alison R Yung; Melissa Kerr; Jessica Spark; Nicky Wallis; Andrea Polari; Patrick D McGorry; Barnaby Nelson

doi:10.1093/schbul/sbae204

Characterizing the Clinical Trajectory and Predicting Persistence and Deterioration of Attenuated Psychotic Symptoms in Ultra-High-Risk Individuals

Schizophr Bull. 2024 Dec 20:sbae204. doi: 10.1093/schbul/sbae204. Online ahead of print.

Authors

Cassandra Wannan^{1

2}, Isabelle Scott^{1

2}, Dominic Dwyer^{1

2}, Scott R Clark^{3

4}, Simon Hartmann^{1

2

3}, Rochelle Ruby Ye^{1

2}, G Paul Amminger^{1

2}, Hok Pan Yuen^{1

2}, Suzie Lavoie^{1

2}, Connie Markulev^{1

2}, Miriam R Schaefer^{1

2}, Jessica A Hartmann⁵, Nilufar Mossaheb⁶, Monika Schlögelhofer⁷, Stefan Smesny⁸, Ian B Hickie⁹, Gregor Berger¹⁰, Eric Y H Chen^{11

12}, Lieuwe de Haan¹³, Dorien H Nieman¹³, Merete Nordentoft^{14

15}, Anita Riecher-Rössler¹⁶, Swapna Verma¹⁷, Andrew Thompson^{1

2

18

19}, Alison R Yung²⁰, Melissa Kerr^{1

2}, Jessica Spark^{1

2}, Nicky Wallis^{1

2}, Andrea Polari^{1

2

19}, Patrick D McGorry^{1

2}, Barnaby Nelson^{1

2}

Affiliations

¹ Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia.
² Orygen, Parkville, Victoria 3052, Australia.
³ Discipline of Psychiatry, University of Adelaide, Adelaide, SA 5064, Australia.
⁴ Basil Hetzel Institute, Woodville, SA 5011, Australia.
⁵ Department of Public Mental Health, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, Heidelberg 69117, Germany.
⁶ Department of Psychiatry and Psychotherapy, Clinical Division of Social Psychiatry, Medical University Vienna, 1090 Vienna, Austria.
⁷ Biopsychosocial Corporation, BioPsyC, Non-Profit Association for Research Funding Ltd., 1090 Vienna, Austria.
⁸ Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena 07747, Germany.
⁹ Brain and Mind Centre, The University of Sydney, Sydney, NSW 2006, Australia.
¹⁰ Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich 8057, Switzerland.
¹¹ Department of Psychiatry, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, 2/F New Clinical Building, Queen Mary Hospital, Pok Fu Lam, Hong Kong.
¹² The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pok Fu Lam, Hong Kong.
¹³ Department of Psychiatry, Academic Medical Center, Amsterdam 1105, The Netherlands.
¹⁴ CORE - Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen. Mental Health Services in the Capital Region of Denmark, 2900, Denmark.
¹⁵ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Denmark.
¹⁶ Medical Faculty, University of Basel, 4001, Switzerland.
¹⁷ Institute of Mental Health, 539747, Singapore.
¹⁸ Warwick Medical School, University of Warwick, Coventry, CV4 7AL, United Kingdom.
¹⁹ Orygen Specialist Program, Melbourne Health, Melbourne 3052, Australia.
²⁰ Institute of Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, Victoria 3220, Australia.

PMID: 39707153
DOI: 10.1093/schbul/sbae204

Abstract

Background: Almost 40% of individuals at ultra-high risk (UHR) for psychosis experience persistent attenuated psychotic symptoms (APS) yet it is unclear (1) whether they share overlapping clinical and functional outcomes compared to individuals who transition to psychosis, (2) when symptom and functioning trajectories begin to diverge between UHR individuals with different clinical outcomes, and (3) whether non-remission (persistent APS or transition) can be predicted using baseline and/or longitudinal data.

Study design: Participants were drawn from 2 randomized clinical trials: Neurapro (n = 220; discovery sample) and STEP (n = 180; external validation sample). First, 12-24 month symptoms and functioning were compared between UHR individuals with persistent APS, sustained remission, or transition to psychosis. Next, short-term changes in symptoms and functioning were compared between groups to determine timepoints at which trajectories began to diverge. Finally, we used support vector machines to predict non-remission (persistent APS or transition) vs sustained remission using data from baseline, 6-month follow-up, and combined baseline and 6-month follow-up.

Results: Individuals with persistent APS had substantially poorer outcomes compared to those who remitted, and more closely resembled individuals who later transitioned to psychosis. Despite few baseline differences between groups, clinical and functional trajectories of the persistent APS and transition groups rapidly diverged from those who remitted. Prediction of non-remission was poor using baseline data but improved substantially when using 6-month follow-up or combined baseline-6-month data.

Conclusions: Ultra-high-risk individuals with persistent APS display similar clinical and functional trajectories to transitioned cases, suggesting that more intensive and sustained intervention is required for this subgroup. However, prospective identification of individuals with poor clinical outcomes (ie, persistence or deterioration of attenuated psychotic symptoms) may require longitudinal monitoring of symptom and functioning trajectories for several months.

Keywords: attenuated positive symptoms; longitudinal; prediction; psychosis; ultra high risk.

Abstract

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