Whole-Brain Mapping of GABA and Glutamate Dysregulation in Patients with Major Depressive Disorder
Presented During:
Friday, June 27, 2025: 11:30 AM - 12:45 PM
Brisbane Convention & Exhibition Centre
Room:
Great Hall
Poster No:
499
Submission Type:
Abstract Submission
Authors:
Xiaochen Zhang1, Danni Wang2,3, Yibo Zhao4, Sirui Wang1, Wenqi Zhang2, Gai Kong1, Wen Jin4,5, Yudu Li4,6,7, Huixiang Zhuang2, Bin Bo2, Yihong Yang3, Zhi-Pei Liang4,5, Yao Li2, Yingying Tang1
Institutions:
1Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 2School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, 3Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, United States, 4Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States, 5Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States, 6Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States, 7National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States
First Author:
Xiaochen Zhang
Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Co-Author(s):
Danni Wang
School of Biomedical Engineering, Shanghai Jiao Tong University|Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health
Shanghai, China|Baltimore, Maryland, United States
School of Biomedical Engineering, Shanghai Jiao Tong University|Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health
Shanghai, China|Baltimore, Maryland, United States
Yibo Zhao
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign
Urbana, Illinois, United States
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign
Urbana, Illinois, United States
Sirui Wang
Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Gai Kong
Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Wen Jin
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign|Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign
Urbana, Illinois, United States|Urbana, Illinois, United States
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign|Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign
Urbana, Illinois, United States|Urbana, Illinois, United States
Yudu Li
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign|Department of Bioengineering, University of Illinois at Urbana-Champaign|National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign
Urbana, Illinois, United States|Urbana, Illinois, United States|Urbana, Illinois, United States
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign|Department of Bioengineering, University of Illinois at Urbana-Champaign|National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign
Urbana, Illinois, United States|Urbana, Illinois, United States|Urbana, Illinois, United States
Yihong Yang
Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health
Baltimore, Maryland, United States
Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health
Baltimore, Maryland, United States
Zhi-Pei Liang
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign|Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign
Urbana, Illinois, United States|Urbana, Illinois, United States
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign|Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign
Urbana, Illinois, United States|Urbana, Illinois, United States
Yingying Tang
Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Introduction:
Major Depressive Disorder (MDD) is a prevalent and debilitating psychiatric condition, yet its neurobiological mechanisms remain insufficiently understood. Increasing evidence points to the involvement of alterations in the principal neurotransmitters, including gamma-aminobutyric acid (GABA) and glutamate, in the pathophysiology of MDD. However, prior studies have often been restricted to specific brain regions (Fries et al., 2023), leading to inconsistent findings. This study aimed to address these gaps by employing whole-brain in vivo mapping of GABA and glutamate concentrations in patients with MDD and healthy controls, thus providing a comprehensive analysis of region-specific alterations in these key neurotransmitters.
Methods:
We collected and analyzed data from 32 patients with MDD and 23 demographically matched healthy controls (HCs) using the SPICE (Spectroscopic Imaging by Exploiting Spatiospectral Correlation) technique (Lam and Liang, 2014; Peng et al., 2018), which allows for high-resolution spectroscopic imaging in the whole brain. Participants with MDD were recruited from the Shanghai Mental Health Centre, with diagnoses confirmed by psychiatrists according to DSM-5 criteria; depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale. HCs were screened to exclude any psychiatric disorders. Neurochemical concentration maps of GABA and glutamate were parcellated using the Desikan-Killany cortical and Aseg subcortical atlases. Separate analyses of variance (ANOVAs) were performed for each neurotransmitter, controlling for age and sex, with p-values corrected using the false discovery rate (FDR) method for cortical and subcortical regions.
Results:
GABA concentrations were significantly higher in multiple brain regions of patients with MDD compared with healthy controls, including the bilateral rostral anterior cingulate, orbitofrontal cortices, the nucleus accumbens, and caudate (Figures 1A, B). Conversely, glutamate concentrations were significantly lower in several brain regions of patients with MDD, most markedly in the bilateral insula, posterior cingulate cortices, putamen, and thalamus. Interestingly, in regions such as the bilateral entorhinal cortices, glutamate concentrations were higher in patients with MDD. In addition, the glutamate-to-GABA concentration ratios were significantly lower in most brain regions in patients with MDD (Figure 1C). Furthermore, the spatial distribution of glutamate concentration alterations (MDD vs. HC) closely mirrored creatine (Spearman's rho: 0.915; Figure 1D), while the spatial pattern of GABA concentration alterations resembled N-acetylaspartate (0.808). The spatial resemblance between the alteration patterns of GABA and glutamate was moderate (0.638). Notably, GABA concentration was negatively correlated with depression severity in most brain regions in MDD, whereas glutamate concentration was positively correlated (Figure 2). Our observations align with prior studies suggesting decreased glutamate levels in MDD (Fries et al., 2023) but challenge those reporting reduced GABA concentrations (Cutler et al., 2023). The opposing directions of GABA and glutamate alterations observed here, together with the disrupted glutamate-to-GABA concentration ratio, may reflect a broader imbalance in excitatory and inhibitory neurotransmission - a hallmark of MDD. Importantly, the distinct spatial patterns of GABA and glutamate alterations observed in this study call for further research into region-specific neurotransmitter dynamics.
·Figure 1
·Figure 2
Conclusions:
This study highlighted distinct and region-specific alterations in GABA and glutamate concentrations in MDD, which may provide novel insights into the neurochemical mechanisms of the disorder. Importantly, our findings offer potential targets for more tailored therapeutic interventions that would restore the balance between excitatory and inhibitory neurotransmission by possibly correcting specific processes associated with each neurotransmitter.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Novel Imaging Acquisition Methods:
MR Spectroscopy 2
Keywords:
Affective Disorders
GABA
Glutamate
MR SPECTROSCOPY
Psychiatric
Psychiatric Disorders
Other - Major Depressive Disorder
1|2Indicates the priority used for review
Abstract Information
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.
Please indicate which methods were used in your research:
For human MRI, what field strength scanner do you use?
Which processing packages did you use for your study?
Provide references using APA citation style.
Lam, F., & Liang, Z.-P. (2014). A subspace approach to high‐resolution spectroscopic imaging. Magnetic Resonance in Medicine, 71(4), 1349-1357.
Peng, X., Lam, F., Li, Y., Clifford, B., & Liang, Z.-P. (2018). Simultaneous QSM and metabolic imaging of the brain using SPICE. Magnetic Resonance in Medicine, 79(1), 13-21.
Cutler, A. J., Mattingly, G. W., & Maletic, V. (2023). Understanding the mechanism of action and clinical effects of neuroactive steroids and GABAergic compounds in major depressive disorder. Translational Psychiatry, 13(1), 228.