Dwyer, Dominic B., Buciuman, Madalina-Octavia, Ruef, Anne, Kambeitz, Joseph, Sen Dong, Mark, Stinson, Caedyn, Kambeitz-Ilankovic, Lana ORCID: 0000-0002-8218-0425, Degenhardt, Franziska, Sanfelici, Rachele, Antonucci, Linda A. ORCID: 0000-0002-7919-7402, Lalousis, Paris Alexandros ORCID: 0000-0001-9642-3080, Wenzel, Julian, Urquijo-Castro, Maria Fernanda, Popovic, David, Oeztuerk, Oemer Faruk, Haas, Shalaila S., Weiske, Johanna, Hauke, Daniel, Neufang, Susanne ORCID: 0000-0002-4927-2969, Schmidt-Kraepelin, Christian, Ruhrmann, Stephan ORCID: 0000-0002-6022-2364, Penzel, Nora, Lichtenstein, Theresa, Rosen, Marlene, Chisholm, Katharine ORCID: 0000-0002-0575-0789, Riecher-Roessler, Anita, Egloff, Laura, Schmidt, Andre, Andreou, Christina, Hietala, Jarmo ORCID: 0000-0002-3179-6780, Schirmer, Timo, Romer, Georg, Michel, Chantal ORCID: 0000-0003-1165-6681, Rossler, Wulf, Maj, Carlo, Borisov, Oleg, Krawitz, Peter M., Falkai, Peter, Pantelis, Christos ORCID: 0000-0002-9565-0238, Lencer, Rebekka, Bertolino, Alessandro, Borgwardt, Stefan, Noethen, Markus, Brambilla, Paolo, Schultze-Lutter, Frauke, Meisenzahl, Eva, Wood, Stephen J., Davatzikos, Christos, Upthegrove, Rachel ORCID: 0000-0001-8204-5103, Salokangas, Raimo K. R. and Koutsouleris, Nikolaos (2022). Clinical, Brain, and Multilevel Clustering in Early Psychosis and Affective Stages. JAMA Psychiatry, 79 (7). S. 677 - 690. CHICAGO: AMER MEDICAL ASSOC. ISSN 2168-6238

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Abstract

IMPORTANCE Approaches are needed to stratify individuals in early psychosis stages beyond positive symptom severity to investigate specificity related to affective and normative variation and to validate solutions with premorbid, longitudinal, and genetic risk measures. OBJECTIVE To use machine learning techniques to cluster, compare, and combine subgroup solutions using clinical and brain structural imaging data from early psychosis and depression stages. DESIGN, SETTING, AND PARTICIPANTS A multisite, naturalistic, longitudinal cohort study (10 sites in 5 European countries; including major follow-up intervals at 9 and 18 months) with a referred patient sample of those with clinical high risk for psychosis (CHR-P), recent-onset psychosis (ROP), recent-onset depression (ROD), and healthy controls were recruited between February 1, 2014, to July 1, 2019. Data were analyzed between January 2020 and January 2022. MAIN OUTCOMES AND MEASURES A nonnegative matrix factorization technique separately decomposed clinical (287 variables) and parcellated brain structural volume (204 gray, white, and cerebrospinal fluid regions) data across CHR-P, ROP, ROD, and healthy controls study groups. Stability criteria determined cluster number using nested cross-validation. Validation targets were compared across subgroup solutions (premorbid, longitudinal, and schizophrenia polygenic risk scores). Multiclass supervised machine learning produced a transferable solution to the validation sample. RESULTS There were a total of 749 individuals in the discovery group and 610 individuals in the validation group. Individuals included those with CHR-P (n = 287), ROP (n = 323), ROD (n = 285), and healthy controls (n = 464), The mean (SD) age was 25.1 (5.9) years, and 702 (51.7%) were female. A clinical 4-dimensional solution separated individuals based on positive symptoms, negative symptoms, depression, and functioning, demonstrating associations with all validation targets. Brain clustering revealed a subgroup with distributed brain volume reductions associated with negative symptoms, reduced performance IQ, and increased schizophrenia polygenic risk scores. Multilevel results distinguished between normative and illness-related brain differences. Subgroup results were largely validated in the external sample. CONCLUSIONS AND RELEVANCE The results of this longitudinal cohort study provide stratifications beyond the expression of positive symptoms that cut across illness stages and diagnoses. Clinical results suggest the importance of negative symptoms, depression, and functioning. Brain results suggest substantial overlap across illness stages and normative variation, which may highlight a vulnerability signature independent from specific presentations. Premorbid, longitudinal, and genetic risk validation suggested clinical importance of the subgroups to preventive treatments.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Dwyer, Dominic B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buciuman, Madalina-OctaviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruef, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kambeitz, JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sen Dong, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stinson, CaedynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kambeitz-Ilankovic, LanaUNSPECIFIEDorcid.org/0000-0002-8218-0425UNSPECIFIED
Degenhardt, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanfelici, RacheleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antonucci, Linda A.UNSPECIFIEDorcid.org/0000-0002-7919-7402UNSPECIFIED
Lalousis, Paris AlexandrosUNSPECIFIEDorcid.org/0000-0001-9642-3080UNSPECIFIED
Wenzel, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Urquijo-Castro, Maria FernandaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Popovic, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oeztuerk, Oemer FarukUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haas, Shalaila S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiske, JohannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauke, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neufang, SusanneUNSPECIFIEDorcid.org/0000-0002-4927-2969UNSPECIFIED
Schmidt-Kraepelin, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruhrmann, StephanUNSPECIFIEDorcid.org/0000-0002-6022-2364UNSPECIFIED
Penzel, NoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lichtenstein, TheresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosen, MarleneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chisholm, KatharineUNSPECIFIEDorcid.org/0000-0002-0575-0789UNSPECIFIED
Riecher-Roessler, AnitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Egloff, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andreou, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hietala, JarmoUNSPECIFIEDorcid.org/0000-0002-3179-6780UNSPECIFIED
Schirmer, TimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Romer, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michel, ChantalUNSPECIFIEDorcid.org/0000-0003-1165-6681UNSPECIFIED
Rossler, WulfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maj, CarloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borisov, OlegUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krawitz, Peter M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Falkai, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pantelis, ChristosUNSPECIFIEDorcid.org/0000-0002-9565-0238UNSPECIFIED
Lencer, RebekkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bertolino, AlessandroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borgwardt, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noethen, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brambilla, PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schultze-Lutter, FraukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meisenzahl, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wood, Stephen J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davatzikos, ChristosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Upthegrove, RachelUNSPECIFIEDorcid.org/0000-0001-8204-5103UNSPECIFIED
Salokangas, Raimo K. R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koutsouleris, NikolaosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-697800
DOI: 10.1001/jamapsychiatry.2022.1163
Journal or Publication Title: JAMA Psychiatry
Volume: 79
Number: 7
Page Range: S. 677 - 690
Date: 2022
Publisher: AMER MEDICAL ASSOC
Place of Publication: CHICAGO
ISSN: 2168-6238
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ULTRA-HIGH RISK; LONG-TERM COURSE; 1ST-EPISODE PSYCHOSIS; NEGATIVE SYMPTOMS; MENTAL STATE; SCHIZOPHRENIA; DISORDERS; PREVENTION; PSYCHIATRY; DEPRESSIONMultiple languages
PsychiatryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69780

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