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28.01.2020 | Original Paper

ACC Glu/GABA ratio is decreased in euthymic bipolar disorder I patients: possible in vivo neurometabolite explanation for mood stabilization

Zeitschrift:: European Archives of Psychiatry and Clinical Neuroscience

Autoren:: Estêvão Scotti-Muzzi, Thais Chile, Ricardo Moreno, Bruno Fraccini Pastorello, Cláudia da Costa Leite, Anke Henning, Maria Concepcion Garcia Otaduy, Homero Vallada, Márcio Gerhardt Soeiro-de-Souza

Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://doi.org/10.1007/s00406-020-01096-0) contains supplementary material, which is available to authorized users.

Abstract

Bipolar disorder (BD) is characterized by unstable mood states ranging from mania to depression. Although there is some evidence that mood instability may result from an imbalance between excitatory glutamatergic and inhibitory GABA-ergic neurotransmission, few proton magnetic resonance spectroscopy (¹H-MRS) studies have measured these two neurometabolites simultaneously in BD. The enzyme glutamic acid decarboxylase (GAD1) catalyzes the decarboxylation of glutamate (Glu) to GABA, and its single nucleotide polymorphisms (SNPs) might influence Glu/GABA ratio. Thus, we investigated Glu/GABA ratio in the dorsal anterior cingulate cortex (dACC) of euthymic BD type I patients and healthy controls (HC), and assessed the influence of both mood stabilizers and GAD1 SNPs on this ratio. Eighty-eight subjects (50 euthymic BD type I patients and 38 HC) underwent 3T ¹H-MRS in the dACC (2 × 2 × 4.5 cm³) using a two-dimensional JPRESS sequence and all subjects were genotyped for 4 SNPs in the GAD1 gene. BD patients had lower dACC Glu/GABA ratio compared to HC, where this was influenced by anticonvulsant and antipsychotic medications, but not lithium. The presence of GAD1 rs1978340 allele A was associated with higher Glu/GABA ratio in BD, while patients without this allele taking mood stabilizers had a lower Glu/GABA ratio. The lowering of dACC Glu/GABA could be one explanation for the mood stabilizing action of anticonvulsants and antipsychotics in BD type I euthymia. Therefore, this putative role of Glu/GABA ratio and the influence of GAD1 genotype interacting with mood stabilization medication should be confirmed by further studies involving larger samples and other mood states.

ClincalTrials.gov registration: NCT01237158.

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Titel: ACC Glu/GABA ratio is decreased in euthymic bipolar disorder I patients: possible in vivo neurometabolite explanation for mood stabilization
Autoren:: Estêvão Scotti-Muzzi
Thais Chile
Ricardo Moreno
Bruno Fraccini Pastorello
Cláudia da Costa Leite
Anke Henning
Maria Concepcion Garcia Otaduy
Homero Vallada
Márcio Gerhardt Soeiro-de-Souza
Publikationsdatum: 28.01.2020
DOI: https://doi.org/10.1007/s00406-020-01096-0
Verlag: Springer Berlin Heidelberg
Zeitschrift: European Archives of Psychiatry and Clinical Neuroscience
Print ISSN: 0940-1334
Elektronische ISSN: 1433-8491

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ACC Glu/GABA ratio is decreased in euthymic bipolar disorder I patients: possible in vivo neurometabolite explanation for mood stabilization

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