Journal Article

FZJ-2021-05144

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Identification of transdiagnostic psychiatric disorder subtypes using unsupervised learning

Pelin, H. (Corresponding author) ; Ising, M. ; Stein, F. ; Meinert, S. ; Meller, T. ; Brosch, K. ; Winter, N. R. ; Krug, A. ; Leenings, R. ; Lemke, H. ; Nenadić, I. ; Heilmann-Heimbach, S. ; Forstner, A. J.FZJ* ; Nöthen, M. M. ; Opel, N. ; Repple, J. ; Pfarr, J. ; Ringwald, K. ; Schmitt, S. ; Thiel, K. ; Waltemate, L. ; Winter, A. ; Streit, F. ; Witt, S. ; Rietschel, M. ; Dannlowski, U. ; Kircher, T. ; Hahn, T. ; Müller-Myhsok, B. ; Andlauer, T. F. M. (Corresponding author)

2021
Nature Publishing Group Basingstoke

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Please use a persistent id in citations: http://hdl.handle.net/2128/29439  doi:10.1038/s41386-021-01051-0

Abstract: Psychiatric disorders show heterogeneous symptoms and trajectories, with current nosology not accurately reflecting their molecular etiology and the variability and symptomatic overlap within and between diagnostic classes. This heterogeneity impedes timely and targeted treatment. Our study aimed to identify psychiatric patient clusters that share clinical and genetic features and may profit from similar therapies. We used high-dimensional data clustering on deep clinical data to identify transdiagnostic groups in a discovery sample (N = 1250) of healthy controls and patients diagnosed with depression, bipolar disorder, schizophrenia, schizoaffective disorder, and other psychiatric disorders. We observed five diagnostically mixed clusters and ordered them based on severity. The least impaired cluster 0, containing most healthy controls, showed general well-being. Clusters 1–3 differed predominantly regarding levels of maltreatment, depression, daily functioning, and parental bonding. Cluster 4 contained most patients diagnosed with psychotic disorders and exhibited the highest severity in many dimensions, including medication load. Depressed patients were present in all clusters, indicating that we captured different disease stages or subtypes. We replicated all but the smallest cluster 1 in an independent sample (N = 622). Next, we analyzed genetic differences between clusters using polygenic scores (PGS) and the psychiatric family history. These genetic variables differed mainly between clusters 0 and 4 (prediction area under the receiver operating characteristic curve (AUC) = 81%; significant PGS: cross-disorder psychiatric risk, schizophrenia, and educational attainment). Our results confirm that psychiatric disorders consist of heterogeneous subtypes sharing molecular factors and symptoms. The identification of transdiagnostic clusters advances our understanding of the heterogeneity of psychiatric disorders and may support the development of personalized treatments.

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Contributing Institute(s):

1. Strukturelle und funktionelle Organisation des Gehirns (INM-1)

Research Program(s):

1. 5251 - Multilevel Brain Organization and Variability (POF4-525) (POF4-525)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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