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JAMA Psychiatry. 2020 Feb 12. doi: 10.1001/jamapsychiatry.2019.4910. [Epub ahead of print]

An Investigation of Psychosis Subgroups With Prognostic Validation and Exploration of Genetic Underpinnings: The PsyCourse Study.

Author information

1
Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
2
Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
3
International Max Planck Research School (IMPRS-TP), Munich, Germany.
4
Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.
5
Department of Education, Psychology and Communication, University of Bari Aldo Moro, Bari, Italy.
6
Institute of Computational Biology, Helmholtz Zentrum Munich, Oberschleißheim, Germany.
7
Department of Mathematics, Technical University of Munich Garching, Garching, Germany.
8
Department of Psychiatry and Psychotherapy, University Medical Center Gottingen, Gottingen, Germany.
9
Department of Psychiatry and Psychotherapy, Bezirkskrankenhaus Augsburg, Augsburg, Germany.
10
Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
11
Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
12
Department of Psychiatry, Ruhr University Bochum, LWL University Hospital, Bochum, Germany.
13
Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
14
Department of Physiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
15
Psychiatrieverbund Oldenburger Land gGmbH, Karl-Jaspers-Klinik, Bad Zwischenahn, Germany.
16
Department of Psychiatry, Klinikum Bremen-Ost, Bremen, Germany.
17
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
18
German Center for Neurodegenerative Diseases (DZNE), Gottingen, Germany.
19
Institute of BioMedicine (iBiMED), Medical Sciences Department, University of Aveiro, Aveiro, Portugal.
20
Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria.
21
Department of Psychiatry, Dr Fontheim-Mental Health, Liebenburg, Germany.
22
Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia.
23
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
24
Department of Psychiatry and Psychotherapy, Agaplesion Diakonieklinikum, Rotenburg, Germany.
25
Karl-Jaspers Clinic, European Medical School Oldenburg-Groningen, Oldenburg, Germany.
26
Clinic for Psychiatry and Psychotherapy, Clinical Center Werra-Meißner, Eschwege, Germany.
27
Asklepios Specialized Hospital, Göttingen, Germany.
28
Department of Psychiatry II, Ulm University, Bezirkskrankenhaus Günzburg, Günzburg, Germany.
29
AMEOS Clinical Center Hildesheim, Hildesheim, Germany.
30
Center for Systems Neuroscience, Hannover, Germany.
31
Burghof-Klinik Rinteln, Rinteln, Germany.
32
AMEOS Clinical Center Osnabrück, Osnabrück, Germany.
33
Department of Psychosomatics and Psychotherapeutic Medicine, University Medical Center Rostock, Rostock, Germany.
34
Department of Psychiatry, Psychotherapy and Psychosomatics, Clinical Center Wilhelmshaven, Wilhelmshaven, Germany.
35
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
36
Institute of Human Genetics, University Hospital Bonn, Bonn, Germany.
37
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
38
Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
39
Centre for Human Genetics, University of Marburg, Marburg, Germany.
40
International Max-Planck Research School for Translational Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany.

Abstract

Importance:

Identifying psychosis subgroups could improve clinical and research precision. Research has focused on symptom subgroups, but there is a need to consider a broader clinical spectrum, disentangle illness trajectories, and investigate genetic associations.

Objective:

To detect psychosis subgroups using data-driven methods and examine their illness courses over 1.5 years and polygenic scores for schizophrenia, bipolar disorder, major depression disorder, and educational achievement.

Design, Setting, and Participants:

This ongoing multisite, naturalistic, longitudinal (6-month intervals) cohort study began in January 2012 across 18 sites. Data from a referred sample of 1223 individuals (765 in the discovery sample and 458 in the validation sample) with DSM-IV diagnoses of schizophrenia, bipolar affective disorder (I/II), schizoaffective disorder, schizophreniform disorder, and brief psychotic disorder were collected from secondary and tertiary care sites. Discovery data were extracted in September 2016 and analyzed from November 2016 to January 2018, and prospective validation data were extracted in October 2018 and analyzed from January to May 2019.

Main Outcomes and Measures:

A clinical battery of 188 variables measuring demographic characteristics, clinical history, symptoms, functioning, and cognition was decomposed using nonnegative matrix factorization clustering. Subtype-specific illness courses were compared with mixed models and polygenic scores with analysis of covariance. Supervised learning was used to replicate results in validation data with the most reliably discriminative 45 variables.

Results:

Of the 765 individuals in the discovery sample, 341 (44.6%) were women, and the mean (SD) age was 42.7 (12.9) years. Five subgroups were found and labeled as affective psychosis (n = 252), suicidal psychosis (n = 44), depressive psychosis (n = 131), high-functioning psychosis (n = 252), and severe psychosis (n = 86). Illness courses with significant quadratic interaction terms were found for psychosis symptoms (R2 = 0.41; 95% CI, 0.38-0.44), depression symptoms (R2 = 0.28; 95% CI, 0.25-0.32), global functioning (R2 = 0.16; 95% CI, 0.14-0.20), and quality of life (R2 = 0.20; 95% CI, 0.17-0.23). The depressive and severe psychosis subgroups exhibited the lowest functioning and quadratic illness courses with partial recovery followed by reoccurrence of severe illness. Differences were found for educational attainment polygenic scores (mean [SD] partial η2 = 0.014 [0.003]) but not for diagnostic polygenic risk. Results were largely replicated in the validation cohort.

Conclusions and Relevance:

Psychosis subgroups were detected with distinctive clinical signatures and illness courses and specificity for a nondiagnostic genetic marker. New data-driven clinical approaches are important for future psychosis taxonomies. The findings suggest a need to consider short-term to medium-term service provision to restore functioning in patients stratified into the depressive and severe psychosis subgroups.

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