Examining the usefulness of the brain network marker program using fMRI for the diagnosis and stratification of major depressive disorder: a non-randomized study protocol

Go Okada; Yuki Sakai; Maki Shibakawa; Toshinori Yoshioka; Eri Itai; Hotaka Shinzato; Osamu Yamamoto; Kenichi Kurata; Tatsuji Tamura; Hiroaki Jitsuiki; Hidehisa Yamashita; Akio Mantani; Norio Yokota; Mitsuo Kawato; Yasumasa Okamoto

doi:10.1186/s12888-023-04560-y

Examining the usefulness of the brain network marker program using fMRI for the diagnosis and stratification of major depressive disorder: a non-randomized study protocol

BMC Psychiatry. 2023 Jan 24;23(1):63. doi: 10.1186/s12888-023-04560-y.

Authors

Go Okada^#¹, Yuki Sakai^#^{2

3}, Maki Shibakawa³, Toshinori Yoshioka^{2

3}, Eri Itai¹, Hotaka Shinzato¹, Osamu Yamamoto⁴, Kenichi Kurata⁵, Tatsuji Tamura⁶, Hiroaki Jitsuiki⁷, Hidehisa Yamashita⁸, Akio Mantani⁹, Norio Yokota¹⁰, Mitsuo Kawato^{11

12}, Yasumasa Okamoto¹³

Affiliations

¹ Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
² Brain Information Communication Research Laboratory Group, Advanced Telecommunications Research Institute International, Kyoto, Japan.
³ XNef, Inc., Kyoto, Japan.
⁴ Ujina Mental Clinic, Hiroshima, Japan.
⁵ Kabe Mental Health Clinic, Hiroshima, Japan.
⁶ Tamura Mental Clinic, Hiroshima, Japan.
⁷ Jitsuiki Clinic, Hiroshima, Japan.
⁸ Minna No Suimin Stress Care Clinic, Hiroshima, Japan.
⁹ Mantani Mental Clinic, Hiroshima, Japan.
¹⁰ Yokota Mental Clinic, Hiroshima, Japan.
¹¹ Brain Information Communication Research Laboratory Group, Advanced Telecommunications Research Institute International, Kyoto, Japan. kawato@atr.jp.
¹² XNef, Inc., Kyoto, Japan. kawato@atr.jp.
¹³ Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. oy@hiroshima-u.ac.jp.

^# Contributed equally.

Abstract

Background: Although many studies have reported the biological basis of major depressive disorder (MDD), none have been put into practical use. Recently, we developed a generalizable brain network marker for MDD diagnoses (diagnostic marker) across multiple imaging sites using resting-state functional magnetic resonance imaging (rs-fMRI). We have planned this clinical trial to establish evidence for the practical applicability of this diagnostic marker as a medical device. In addition, we have developed generalizable brain network markers for MDD stratification (stratification markers), and the verification of these brain network markers is a secondary endpoint of this study.

Methods: This is a non-randomized, open-label study involving patients with MDD and healthy controls (HCs). We will prospectively acquire rs-fMRI data from 50 patients with MDD and 50 HCs and anterogradely verify whether our diagnostic marker can distinguish between patients with MDD and HCs. Furthermore, we will longitudinally obtain rs-fMRI and clinical data at baseline and 6 weeks later in 80 patients with MDD treated with escitalopram and verify whether it is possible to prospectively distinguish MDD subtypes that are expected to be effectively responsive to escitalopram using our stratification markers.

Discussion: In this study, we will confirm that sufficient accuracy of the diagnostic marker could be reproduced for data from a prospective clinical study. Using longitudinally obtained data, we will also examine whether the "brain network marker for MDD diagnosis" reflects treatment effects in patients with MDD and whether treatment effects can be predicted by "brain network markers for MDD stratification". Data collected in this study will be extremely important for the clinical application of the brain network markers for MDD diagnosis and stratification.

Trial registration: Japan Registry of Clinical Trials ( jRCTs062220063 ). Registered 12/10/2022.

Keywords: Depression & mood disorders; Magnetic resonance imaging; Mental health.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Brain
Brain Mapping / methods
Controlled Clinical Trials as Topic
Depressive Disorder, Major* / diagnostic imaging
Depressive Disorder, Major* / pathology
Escitalopram
Humans
Magnetic Resonance Imaging / methods
Prospective Studies

Substances

Escitalopram