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

Author(s)

Scotti-Muzzi, Estevao ^[1] ; Chile, Thais ^[2] ; Moreno, Ricardo ^[1] ; Pastorello, Bruno Fraccini ^[3] ; Leite, Claudia da Costa ^[3] ; Henning, Anke ^{[4, 5]} ; Garcia Otaduy, Maria Concepcion ^[3] ; Vallada, Homero ^[2] ; Soeiro-de-Souza, Marcio Gerhardt ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Sch Med FMUSP, Mood Disorders Unit GRUDA, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med FMUSP, Genet & Pharmacogenet Unit PROGENE, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med FMUSP, Inst Radiol InRad, Sao Paulo - Brazil

^[4] Swiss Fed Inst Technol, Zurich - Switzerland

^[5] Univ Zurich, Inst Biomed Engn, Zurich - Switzerland

• Document type: Journal article
• Source: EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE; v. 271, n. 3 JAN 2020.
• Web of Science Citations: 1

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 (H-1-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 H-1-MRS in the dACC (2 x 2 x 4.5 cm(3)) 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. (AU)

• FAPESP's process: 12/23796-2 - "Genetic association study between cognitive performance, polymorphisms of GAD1/Reelin and 3T magnetic ressonance spectroscopy of GABA/glutamate in bipolar I disorder and healthy controls"
• Grantee: Márcio Gerhardt Soeiro-de-Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 10/12286-8 - Genetic association study between single nucleotide polymorphism and cognitive performance in young bipolar I patients: Licavalgene
• Grantee: Márcio Gerhardt Soeiro-de-Souza
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)