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

TY - JOUR

T1 - An Investigation of Psychosis Subgroups With Prognostic Validation and Exploration of Genetic Underpinnings - The PsyCourse Study

AU - Dwyer, Dominic B

AU - Kalman, Janos L

AU - Budde, Monika

AU - Kambeitz, Joseph

AU - Ruef, Anne

AU - Antonucci, Linda A

AU - Kambeitz-Ilankovic, Lana

AU - Hasan, Alkomiet

AU - Kondofersky, Ivan

AU - Anderson-Schmidt, Heike

AU - Gade, Katrin

AU - Reich-Erkelenz, Daniela

AU - Adorjan, Kristina

AU - Senner, Fanny

AU - Schaupp, Sabrina

AU - Andlauer, Till F M

AU - Comes, Ashley L

AU - Schulte, Eva C

AU - Klöhn-Saghatolislam, Farah

AU - Gryaznova, Anna

AU - Hake, Maria

AU - Bartholdi, Kim

AU - Flatau-Nagel, Laura

AU - Reitt, Markus

AU - Quast, Silke

AU - Stegmaier, Sophia

AU - Meyers, Milena

AU - Emons, Barbara

AU - Haußleiter, Ida Sybille

AU - Juckel, Georg

AU - Nieratschker, Vanessa

AU - Dannlowski, Udo

AU - Yoshida, Tomoya

AU - Schmauß, Max

AU - Zimmermann, Jörg

AU - Reimer, Jens

AU - Wiltfang, Jens

AU - Reininghaus, Eva

AU - Anghelescu, Ion-George

AU - Arolt, Volker

AU - Baune, Bernhard T

AU - Konrad, Carsten

AU - Thiel, Andreas

AU - Fallgatter, Andreas J

AU - Figge, Christian

AU - von Hagen, Martin

AU - Koller, Manfred

AU - Lang, Fabian U

AU - Wigand, Moritz E

AU - Becker, Thomas

AU - Jäger, Markus

AU - Dietrich, Detlef E

AU - Scherk, Harald

AU - Spitzer, Carsten

AU - Folkerts, Here

AU - Witt, Stephanie H

AU - Degenhardt, Franziska

AU - Forstner, Andreas J

AU - Rietschel, Marcella

AU - Nöthen, Markus M

AU - Mueller, Nikola

AU - Papiol, Sergi

AU - Heilbronner, Urs

AU - Falkai, Peter

AU - Schulze, Thomas G

AU - Koutsouleris, Nikolaos

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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.

AB - 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.

U2 - 10.1001/jamapsychiatry.2019.4910

DO - 10.1001/jamapsychiatry.2019.4910

M3 - SCORING: Journal article

C2 - 32049274

VL - 77

SP - 523

EP - 533

JO - JAMA PSYCHIAT

JF - JAMA PSYCHIAT

SN - 2168-622X

IS - 5

ER -