Hippocampal abnormalities of glutamate/glutamine, N-acetylaspartate and choline in patients with depression are related to past illness burden

Hippocampal abnormalities of glutamate/glutamine, N-acetylaspartate and choline in patients with depression are related to past illness burden

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J Psychiatry Neurosci 2013; 38(2):107-116

Javier de Diego-Adeliño, MD; Maria J. Portella, PhD; Beatriz Gómez-Ansón, MD, PhD; Olga López-Moruelo, BSc; Maria Serra-Blasco, BSc; Yolanda Vives, PhD; Dolors Puigdemont, MD; Rosario Pérez-Egea, MD; Enric Álvarez, MD, PhD; Víctor Pérez, MD, PhD

de Diego-Adeliño, Portella, Puigdemont, Pérez-Egea, Álvarez, Pérez — 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 Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain; Gómez-Ansón, López-Moruelo — 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; Serra-Blasco, Vives — Port d’Informació Científica (PIC), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

Abstract

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.


Submitted Nov. 30, 2011; Revised Mar. 9, May 8, 2012; Accepted May 14, 2012.

Acknowledgments: This study is funded by 2 grants of the Fondo de Investigación Sanitaria (FIS: PI10/00372 awarded to the Centro de Investigación Biomédica en Red de Salud Mental CIBERSAM, where M.J. Portella was the principal investigator; FIS: 07/00770 awarded to the Institut d’Investigació Biomédica Sant Pau, IIB Sant Paul, where B. Gómez-Ansón was the principal investigator) from the Instituto de Salud Carlos III, by the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) and by the Centro de Investigación Biomédica para Enfermedades Neurodegenerativas (CIBERNED). J. de Diego-Adeliño is funded by the Instituto de Salud Carlos III through a “Rio Hortega” research fellowship. M.J. Portella is funded by the Ministerio de Ciencia e Innovación of the Spanish Government and by the Instituto de Salud Carlos III through a “Miguel Servet” research contract (CP10-00393), cofinanced by the European Regional Development Fund (ERDF; 2007–2013). We thank the staff of the Department of Psychiatry and the Department of Neuroradiology of Hospital de la Santa Creu i Sant Pau who generously provided their time and experience. Finally, we also thank the patients who participated in the study for their cooperation.

Competing interests: As above for V. Pérez declares having received educational honoraria from Sanofi-Aventis, Lundbeck, Pfizer, Astra-Zeneca and Eli Lilly, and research funding from Boehringer-Ingelheim for this work. E. Alvarez has received consulting and educational honoraria from several pharmaceutical companies including Eli Lilly, Sanofi-Aventis, Lundbeck and Pfizer, and he has participated as main local investigator in clinical trials from Eli Lilly, Bristol-Myers and Sanofi-Aventis and also as national coordinator of clinical trials from Servier and Lundbeck. None declared for J. de Diego-Adeliño, M.J. Portella, B. Gómez-Ansón, O. López-Moruelo, M. Serra-Blasco, Y. Vives, D. Puigdemont and R. Pérez-Egea.

Contributors: J. de Diego-Adeliño, M.J. Portella, B. Gómez-Ansón and V. Pérez designed the study and acquired and analyzed the data. O. López-Moruelo, M. Serra-Blasco, Y. Vives, D. Puigdemont, R. Pérez-Egea and E. Alvarez also acquired the data. J. deDiego-Adeliño and M.J. Portella wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.110185

Correspondence to: M.J. Portella, Department of Psychiatry, Hospital de la Santa Creu i Sant Pau (UAB, CIBERSAM), Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), Sant Antoni Ma. Claret, 167, 08025 Barcelona, Spain; mportella@santpau.cat