Meta-analysis of central and peripheral γ-aminobutyric acid levels in patients with unipolar and bipolar depression

Meta-analysis of central and peripheral γ-aminobutyric acid levels in patients with unipolar and bipolar depression

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J Psychiatry Neurosci 2018;43(1):58-66

Bruno Romeo, MD; Walid Choucha, MD; Philippe Fossati, MD, PhD; Jean-Yves Rotge, MD, PhD

Abstract

Background: Many studies have measured central and peripheral γ-aminobutyric acid (GABA) levels in patients with depression. We performed a meta-analysis to provide an objective overview of GABA changes in those with unipolar or bipolar depression.

Methods: After a systematic database search, original data were extracted with the help of seminal authors to calculate standardized mean differences. We compared GABA levels between patients with current major depressive episodes and controls, between euthymic patients and controls, and in patients before and after treatment. We performed meta-regressions to explore the influence of demographic and clinical variables on GABA significant mean differences.

Results: For unipolar depression, central and peripheral GABA levels were diminished in currently depressed patients, but normal in euthymic patients, compared with the healthy controls. For bipolar disorder, GABA levels were diminished in medication-free patients, but seemed to be normalized in medicated patients, compared with the healthy controls. We found no significant association with demographic or clinical variables.

Limitations: There was a great heterogeneity across studies, probably because of the substantial variation of clinical characteristics in the included samples. Many subanalyses were performed to assess how the diagnosis, medications, or the type of measurements of peripheral or central GABA levels may affect the main results.

Conclusion: The GABA levels evolved differentially in patients with unipolar and bipolar disorders. Our results suggest that GABA levels could represent a biomarker of symptomatic states in patients with unipolar disorder and would be normalized by mood stabilizers in those with bipolar disorder.


Submitted Nov. 26, 2016; Revised May 18, 2017; Accepted July 3, 2017; Online first Oct. 3, 2017

Affiliations: From the AP-HP, Pitié-Salpêtrière Hospital, Department of Psychiatry, Paris, France (Romeo, Choucha, Fossati, Rotge); and the Social and Affective Neuroscience (SAN) Team, Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, APHP, Institut du cerveau et de la moelle (ICM)-Hôpital Pitié-Salpétrière, Paris, France (Fossati, Rotge).

Acknowledgements: The authors acknowledge the kind collaboration of Dr. Chadi G. Abdallah (Department of Psychiatry, Yale University School of Medicine), Prof. Gerard Sanacora (Department of Psychiatry, Yale University School of Medicine), Dr. Matthew Mitchell (Clinical Research and Development, Metabolon Inc.), Dr. Gerald Valentine (Department of Psychiatry, Yale University School of Medicine), Dr. Po W. Wang (Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine), Dr. Beata Godlewska (University Department of Psychiatry, Warneford Hospital), Prof. Phillip J. Cowen (University Department of Psychiatry, Warneford Hospital) and Dr. Xinyan Fu (Department of Neurobiology, Zhejiang University School of Medicine), who provided seminal data from their respective studies.

Competing interests: None declared.

Contributors: All authors designed the study. B. Romeo acquired the data, which all authors analyzed. B. Romeo and J.-Y. Rotge wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/jpn.160228

Correspondence to: J.-Y. Rotge, Service de Psychiatrie Adulte, Hôpital Pitié-Salpêtrière, 47-83 Boulevard de l’Hôpital, 75013 Paris, France; jeanyves.rotge@mac.com