Identification of depression subtypes and relevant brain regions using a data-driven approach

Tomoki Tokuda,Go Okada,Kenji Doya,Masahiro Takamura,Yasumasa Okamoto,Shigeto Yamawaki,Yu Shimizu,Junichiro Yoshimoto

doi:10.1038/s41598-018-32521-z

Abstract

It is well known that depressive disorder is heterogeneous, yet little is known about its neurophysiological subtypes. In the present study, we identified neurophysiological subtypes of depression related to specific neural substrates. We performed cluster analysis for 134 subjects (67 depressive subjects and 67 controls) using a high-dimensional dataset consisting of resting state functional connectivity measured by functional MRI, clinical questionnaire scores, and various biomarkers. Applying a newly developed, multiple co-clustering method to this dataset, we identified three subtypes of depression that are characterized by functional connectivity between the right Angular Gyrus (AG) and other brain areas in default mode networks, and Child Abuse Trauma Scale (CATS) scores. These subtypes are also related to Selective Serotonin-Reuptake Inhibitor (SSRI) treatment outcomes, which implies that we may be able to predict effectiveness of treatment based on AG-related functional connectivity and CATS.

Highlights

Major depressive disorder (MDD) is a common, but serious disorder, characterized by severe symptoms that affect how one feels, thinks, and manages daily activities1
Given binary labels of MDD status (TRD or non-Treatment-resistant depression (TRD)), they identified relevant brain areas in which large differences in resting state functional magnetic resonance imaging (fMRI) images are observed between TRD and non-TRD
It is reported that functional connectivity (FC) increased in the subgenus cingulate and the thalamus17, while it decreased in the cerebellum, the precuneus and the inferior parietal lobule for TRD patients18

Summary

Introduction

Major depressive disorder (MDD) is a common, but serious disorder, characterized by severe symptoms that affect how one feels, thinks, and manages daily activities. The results of these studies either conflict or they identify clusters related to depression severity, which does not provide conclusive evidence for subtypes of depressive symptoms. The results of these studies either conflict or they identify clusters related to depression severity, which does not provide conclusive evidence for subtypes of depressive symptoms8 These studies are based on clinical questionnaires without taking into account biological substrates. Clinically meaningful improvement was not observed following the use of two different antidepressants15 These studies approached the question of MDD subtypes in a supervised manner (systematic review paper). Given binary labels of MDD status (TRD or non-TRD), they identified relevant brain areas in which large differences in resting state fMRI images are observed between TRD and non-TRD. Some of these results may not be consistent: FC in the right angular gyrus is higher for TRD than non-TRD19, while the opposite is reported

Objectives

Methods

Results

Conclusion