Hippocampal abnormalities of glutamate/glutamine, N-acetylaspartate and choline in patients with depression are related to past illness burden
Open accessAbstract
Background: Smaller hippocampal volumes in major depressive disorder (MDD) have been linked with earlier onset, previous recurrences and treatment refractoriness. The aim of our study was to investigate metabolite abnormalities in the hippocampus associated with past depressive illness burden. Methods: Glutamate/glutamine (Glx), N-acetylaspartate (NAA) and choline (Cho), potential markers of glial/neuronal integrity and membrane turnover, respectively, were measured in adults with depression and healthy controls using a 3 T magnetic resonance spectroscopy scanner. Voxels were placed in the head of the right and left hippocampus. We controlled for systematic differences resulting from volume-of-interest (VOI) tissue composition and total hippocampal volume. Results: Our final sample comprised a total of 16 healthy controls and 52 adult patients with depression in different stages of the illness (20 treatment-resistant/chronic, 18 remitted-recurrent and 14 first-episode), comparable for age and sex distribution. Patients with treatment-resistant/chronic and remitted-recurrent depression had significantly lower levels of Glx and NAA than controls, especially in the right hippocampal region ( p ≤ 0.025). Diminished levels of Glx were correlated with longer illness duration (left VOI r = −0.34, p = 0.01). By contrast, Cho levels were significantly higher in patients with treatment-resistant/chronic depression than those with first-episode depression or controls in the right and left hippocampus (up to 19% higher; all p ≤ 0.025) and were consistently related to longer illness duration (right VOI r = 0.30, p = 0.028; left VOI r = 0.38, p = 0.004) and more previous episodes (right VOI r = 0.46, p = 0.001; left VOI r = 0.44, p = 0.001). Limitations: The cross-sectional design and the inclusion of treated patients are the main limitations of the study. Conclusion: Our results support that metabolite alterations within the hippocampus are more pronounced in patients with a clinical evolution characterized by recurrences and/or chronicity and add further evidence to the potential deleterious effects of stress and depression on this region.
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Generally, studies find lower Glx or glutamate levels in the medial prefrontal cortex and hippocampus in major depressive disorder, with greater reductions in more chronic cases than in first-episode cases.
“Generally, studies have found reduced Glx/glutamate levels in the mPFC and hippocampus in MDD, with those having a more chronic course showing greater declines compared to individuals experiencing a first episode (127,128).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [127]
Human magnetic resonance spectroscopy studies provide evidence of glutamate dysfunction in major depressive disorder.
“magnetic resonance spectroscopy (MRS) studies have provided evidence of glutamate dysfunction in MDD (e.g., 127,128).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [127]
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- Authors
- de Diego-Adeliño, J., Portella, M. J., Gómez-Ansón, B., López-Moruelo, O., Serra-Blasco, M., Vives, Y., Puigdemont, D., Pérez-Egea, R., Álvarez, E., & Pérez, V.
- Affiliations
- Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de In-vestigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
- Department of Neuroradiology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain
- Universitat Autònoma de Barcelona (ES)
- Port d’Informació Científica (PIC), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
- Venue
- Journal of Psychiatry and Neuroscience
- Publisher
- Canadian Science Publishing
- Published
- 2013-03
- Volume
- 38
- Issue
- 2
- Pages
- 107-116
- ISSN
- 1180-4882 (ISSN-L)
- 1488-2434
- PMC
- PMC3581591
- OpenAlex
- W2023025832
- Cited by
- 86
- References
- 34
- Citations by year
- 2026: 3 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 27 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 8 · 2014: 6 · 2013: 4
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Psychiatry and Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministerio de Ciencia e Innovación
- Centro de Investigación Biomédica en Red de Salud Mental
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- Instituto de Salud Carlos III (CP10-00393)
- European Regional Development Fund (2007 – 2013)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- major depressive disorder, hippocampus, glutamate/glutamine, N-acetylaspartate, choline, hippocampal metabolites, disease duration, treatment-resistant depression, chronic depression, recurrent depression, first-episode depression, hippocampal volume, neuroimaging biomarkers
- MeSH terms
- Adult, Aspartic Acid, Choline, Cross-Sectional Studies, Major Depressive Disorder, Female, Glutamine, Hippocampus, Humans, Male, Middle Aged, Magnetic Resonance Spectroscopy, Case-Control Studies, Cost of Illness, Glutamic Acid
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