The neural substrate of achieving remission in major depressive disorder across treatment modality
Poster No:
394
Submission Type:
Abstract Submission
Authors:
Jinichi Hirano1, Miyuki Tajima1, Kei Kamiya1, Takamasa Noda2, Taro Suwa3, Ryo Ueda1, Nariko Katayama1, Akihiro Takamiya1, Fusaka Minami1, Bun Yamagata1, Yuki Kobayashi1, Yoshimi Arai1, Risa Ogata1, Toshiya Murai3, Kazuyuki Nakagome2, Masaru Mimura1
Institutions:
1Keio University School of Medicine, Shinjyuku, Tokyo, 2National Center of Neurology and Psychiatry, Kodaira, Tokyo, 3Kyoto University, Kyoto, Kyoto
First Author:
Co-Author(s):
Introduction:
Major depressive disorder (MDD) is one of the most burdensome illnesses. Patients with MDD are treated with psychopharmacotherapy, cognitive behavioral therapy (CBT), electroconvulsive therapy (ECT), and repetitive transcranial magnetic stimulation (rTMS). Although achieving remission is the goal of treating MDD, remission rate is still limited, with each treatment modality. A change in resting-state functional MRI-based connectivity (rsfMRI-FC) has been observed in patients with MDD, and previous studies have investigated the mechanism of remission specific to each treatment. However, there is no study that has investigated the mechanism of remission common to the four treatments. Therefore, the aim of this study was to elucidate the common therapeutic mechanisms among these four treatments using whole-brain rsfMRI-FC analysis.
Methods:
This study is a part of multicenter study (Keio University, Kyoto University, National Center of Neurology and Psychiatry) based on usual care for MDD, named Longitudinal MRI study Identifying the Neural Substrates of Remission/Recovery in Mood Disorders (L/R study) (UMIN000038758). In this prospective study, we evaluated rsfMRI-FC at three time points (pre- treatment, post-treatment, follow up (six months later)), in individuals with MDD recieving psychopharmacotherapy, CBT, ECT, and rTMS, and in healthy controls (HC) (Figure 1). The Hamilton Depression Rating Scale (HDRS) was used to assess the depression severity, with remission defined as a score of 7 or less. Resting-state functional MRI scan was performed using two protocols: a multiband HARP protocol (https://bicr.atr.jp/rs-fmri-protocol-2/) and a non-multiband SRPB protocol (https://bicr.atr.jp/rs-fmri-protocol-2/), with five different scanners. The HARP and SRPB scans were preprocessed using the HCP pipelines and fMRI prep pipelines, respectively. After completion of image preprocessing, the AAL atlas-based rsfMRI-FC was extracted using in-house code based on the Nilearn. To reduce the scanner effect, we had made another independent traveling subject dataset comprised of five healthy participants and harmonized rsfMRI-FC data in L/R study (Figure 2). Finally, harmonized rsfMRI-FC data was subjected to general liner model based permutation analysis, using Permutation Analysis of Linear Models (PALM). Correction for multiple comparisons was performed by controlling for the family-wise error rate (FWER) (p < 0.025). To elucidate common therapeutic mechanisms among the four treatment modalities, we examined an interaction between remission status (remitted vs. non-remitted) and time (pre-treatment vs. post-treatment) with treatment modality as a covariate in the whole-brain analysis.
·Flow of L/R study
·Flow of traveling subjects and Harmonization of scanners
Results:
276 MDD cases (psychopharmacotherapy 83, CBT 106, ECT 45, rTMS 42) and 181 HC) were included. In the MDD samples, HDRS score showed significant improvement after treatment (Pre vs Post vs 6MA; 16.1 ± 6.2 vs 8.6 ± 6.3 vs 7.4 ± 6.2, F = 488.348, p < 0.001), and 115/241 (47.7 %) cases achieved remission. A significant interaction between remission status and time was observed in the functional connectivity between the left globus pallidus and the right putamen (T=4.1098, p=0.0001, FWEc p=0.0208) after correction for multiple comparisons. Moreover, the change in several rsfMRI-FCs seeded with the basal ganglia, tended to show interaction between remission status and time (without reaching the significance after multiple correction).
Conclusions:
This is the first study to investigate common changes in rsfMRI-FC associated with MDD remission in four treatment modalities. The basal ganglia, which receives input from subcortical structures and projects it to the vast cerebral cortex, is thought to link emotion, cognition and motor function. In light of the diverse functions attributed to the basal ganglia, it is postulated that the basal ganglia play a pivotal role in the attainment of remission in MDD, which is accompanied by the restoration of not only mood but also social functions.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Novel Imaging Acquisition Methods:
BOLD fMRI 2
Keywords:
Affective Disorders
FUNCTIONAL MRI
Psychiatric
Psychiatric Disorders
Therapy
1|2Indicates the priority used for review
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