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Topic: Neurovascular and neuroinflammation mechanisms

associated with bipolar disorder

The role of anti‑glutamic acid decarboxylase

autoantibodies in mood disorders

Marco Liguori , Mirko Manchia , Leonardo Tondo 4,5,6
1
2,3
Laboratory of Microbiology and Immunology, G. Brotzu Hospital, 09121 Cagliari, Italy.
1
2 Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
3 Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, 09124 Cagliari, Italy.
4 Mood Disorder Lucio Bini Center, 09128 Cagliari, Italy.
5 Mood Disorder Lucio Bini Center, 00193 Rome, Italy.
6 McLean Hospital, Harvard Medical School, Boston 02115, MA, USA.

ABSTRA CT
Gamma‑aminobutyric acid (GABA) possibly plays a causative role in mood disorders. This hypothesis originated with studies on the
beneficial effect of valproate in mania and as a mood stabilizer. Since valproate is known for its action in increasing the level of GABA, it
was indirectly suggested that decreasing levels of GABA were responsible for mood alterations. To identify factors causing the decreased
levels of GABA, studies have concentrated on the activity of the enzyme L‑glutamic acid decarboxylase (GAD), which catalyzes the
transformation of glutamate to GABA, as a decreasing function of this enzyme induces lower levels of the neurotransmitter. Moreover,
a very limited amount of research investigated the possible role of glutamic acid decarboxylase antibodies (GADA) in determining
a decreased enzymatic function of GAD. If these findings are confirmed, it will be possible to improve diagnosis and treatment of
mood disorders. In addition, if the presence of GADA is associated with a genetic trait, this would allow and facilitate early diagnoses.

Key words: Autoantibodies, bipolar disorder, gamma‑aminobutyric acid, glutamate, L‑glutamic‑acid decarboxylase antibodies,
mood disorders

INTRODUCTION Despite the recent substantial progress in unraveling the
[4]
complex biological underpinnings of MDs, in which
Mood disorders (MDs) are a relatively heterogeneous several biological pathways have been implicated, [5‑7]
spectrum of psychiatric conditions. Differences in the pathophysiological mechanisms underlying
clinical course (single or recurrent episodes), severity these conditions are still unclear. Among these, it
and frequency of mood episodes, and population has been hypothesized that the gamma‑aminobutyric
prevalence may characterize each syndrome [major acid (GABA) pathway takes the major role. Specifically,
[8]
depressive disorder (MDD), bipolar disorder (BD), a low GABAergic function might be associated with the
cyclothymic disorder, dysthymia] within this broad biological disruption leading to clinical symptomatology.
nosological definition. These disorders generally have Furthermore, specific alterations of the GABAergic
a substantial burden on the life of patients as well as molecular pathway might be present in patients
on the public health systems. [1,2] In fact, they have manifesting distinct symptoms. One of these possible
been increasingly recognized as leading causes of the alterations may involve the role of autoantibodies for
worldwide burden of disease and disability. [3] the L‑glutamic acid decarboxylase (GAD), a key enzyme
responsible of the synthesis of GABA.

Corresponding Author: Dr. Leonardo Tondo, We reviewed the limited research on the mechanisms
Mood Disorder Lucio Bini Center, Via Cavalcanti 28,
09128 Cagliari, Italy. responsible for the decreased GABAergic function in
E‑mail: ltondo@mclean.harvard.edu
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Cite this article as: Liguori M, Manchia M, Tondo L. The role of anti-glutamic
DOI: acid decarboxylase autoantibodies in mood disorders. Neuroimmunol
10.4103/2347-8659.167300 Neuroinflammation 2015;2:237-43.
Received: 12-03-2015; Accepted: 26-05-2015

© 2015 Neuroimmunology and Neuroinflammation | Published by Hongkong Partner Publishing Co. Limited 237