A generalizable normative deep autoencoder for brain morphological anomaly detection: application to the multi-site StratiBip dataset on bipolar disorder in an external validation framework

bioRxiv [Preprint]. 2024 Sep 7:2024.09.04.611239. doi: 10.1101/2024.09.04.611239.

Abstract

The heterogeneity of psychiatric disorders makes researching disorder-specific neurobiological markers an ill-posed problem. Here, we face the need for disease stratification models by presenting a generalizable multivariate normative modelling framework for characterizing brain morphology, applied to bipolar disorder (BD). We employed deep autoencoders in an anomaly detection framework, combined with a confounder removal step integrating training and external validation. The model was trained with healthy control (HC) data from the human connectome project and applied to multi-site external data of HC and BD individuals. We found that brain deviating scores were greater, more heterogeneous, and with increased extreme values in the BD group, with volumes prominently from the basal ganglia, hippocampus and adjacent regions emerging as significantly deviating. Similarly, individual brain deviating maps based on modified z scores expressed higher abnormalities occurrences, but their overall spatial overlap was lower compared to HCs. Our generalizable framework enabled the identification of subject- and group-level brain normative-deviating patterns, a step forward towards the development of more effective and personalized clinical decision support systems and patient stratification in psychiatry.

Publication types

  • Preprint

Grants and funding

I.W.S. was supported by grants from ERAINS-Italy, project funded under the National Recovery and Resilience Plan (NRRP), Mission 4, “Education and Research” - Component 2, “From research to Business” Investiment 3.1 - Call for tender No. 3264 of Dec 28, 2021 of Italian Ministry of University and Research (MUR) funded by the European Union – NextGenerationEU, with award number: Project code IR0000011, Concession Decree No. 117 of June 21,2022 adopted by the Italian Ministry of University and Research, CUP B51E22000150006, Project title “EBRAINS-Italy (European Brain ReseArch INfrastructureS-Italy).