Faculty Collaboration Database

Neurobiologically Based Stratification of Recent-Onset Depression and Psychosis: Identification of Two Distinct Transdiagnostic Phenotypes. Biol Psychiatry 2022 Oct 01;92(7):552-562

Date

06/19/2022

Pubmed ID

35717212

Pubmed Central ID

PMC10128104

DOI

10.1016/j.biopsych.2022.03.021

Scopus ID

2-s2.0-85132873503 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

BACKGROUND: Identifying neurobiologically based transdiagnostic categories of depression and psychosis may elucidate heterogeneity and provide better candidates for predictive modeling. We aimed to identify clusters across patients with recent-onset depression (ROD) and recent-onset psychosis (ROP) based on structural neuroimaging data. We hypothesized that these transdiagnostic clusters would identify patients with poor outcome and allow more accurate prediction of symptomatic remission than traditional diagnostic structures.

METHODS: HYDRA (Heterogeneity through Discriminant Analysis) was trained on whole-brain volumetric measures from 577 participants from the discovery sample of the multisite PRONIA study to identify neurobiologically driven clusters, which were then externally validated in the PRONIA replication sample (n = 404) and three datasets of chronic samples (Centre for Biomedical Research Excellence, n = 146; Mind Clinical Imaging Consortium, n = 202; Munich, n = 470).

RESULTS: The optimal clustering solution was two transdiagnostic clusters (cluster 1: n = 153, 67 ROP, 86 ROD; cluster 2: n = 149, 88 ROP, 61 ROD; adjusted Rand index = 0.618). The two clusters contained both patients with ROP and patients with ROD. One cluster had widespread gray matter volume deficits and more positive, negative, and functional deficits (impaired cluster), and one cluster revealed a more preserved neuroanatomical signature and more core depressive symptomatology (preserved cluster). The clustering solution was internally and externally validated and assessed for clinical utility in predicting 9-month symptomatic remission, outperforming traditional diagnostic structures.

CONCLUSIONS: We identified two transdiagnostic neuroanatomically informed clusters that are clinically and biologically distinct, challenging current diagnostic boundaries in recent-onset mental health disorders. These results may aid understanding of the etiology of poor outcome patients transdiagnostically and improve development of stratified treatments.

Author List

Lalousis PA, Schmaal L, Wood SJ, Reniers RLEP, Barnes NM, Chisholm K, Griffiths SL, Stainton A, Wen J, Hwang G, Davatzikos C, Wenzel J, Kambeitz-Ilankovic L, Andreou C, Bonivento C, Dannlowski U, Ferro A, Lichtenstein T, Riecher-Rössler A, Romer G, Rosen M, Bertolino A, Borgwardt S, Brambilla P, Kambeitz J, Lencer R, Pantelis C, Ruhrmann S, Salokangas RKR, Schultze-Lutter F, Schmidt A, Meisenzahl E, Koutsouleris N, Dwyer D, Upthegrove R, PRONIA Consortium

Author

Gyujoon Hwang PhD Assistant Professor in the Psychiatry and Behavioral Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Depression
Gray Matter
Humans
Neuroimaging
Phenotype
Psychotic Disorders