Elevated plasma γ-aminobutyrate/glutamate ratio and responses to risperidone antipsychotic treatment in schizophrenia

Backgroundγ-aminobutyrate (GABA) and Glutamate (Glu) are respectively two major inhibitory and excitatory neurotransmitters in the central nervous system and recent theories propose that both of their signaling complexes are compromised in patients with schizophrenia.MethodsThe changes in plasma GABA, Glu and GABA/Glu ratio in schizophrenia have been studied and may be potential clinical markers. Here, we examined if plasma GABA, Glu and GABA/Glu ratio are altered in 32 schizophrenics, including a comprehensive investigation of their involvements with clinical course of a 6-week risperidone antipsychotic treatment.ResultsPlasma levels of GABA and Glu were significantly lower in patients than in controls, while plasma GABA/Glu ratio was significantly elevated. During treatment, a non-significant further decrease of plasma GABA, a significant increase of plasma Glu and a significant reduction of plasma GABA/Glu ratio were observed. The ratio returned to the control level at week 6 even though concentrations of GABA and Glu were still distant from normal. After the Bonferroni correction, partial correlation analyses showed that plasma GABA and GABA/Glu ratio were positively correlated with the dose of risperidone and plasma concentration of 9-hydroxyrisperidone. The reduction of plasma GABA/Glu ratio was positively correlated with the improvement of activation symptom cluster.ConclusionsThe elevated plasma GABA/Glu ratio reinforces the idea of an abnormal GABA-Glu interaction in schizophrenia. The ratio may be a good peripheral state-like marker in schizophrenia research.

Research highlights
► we firstly report a significant elevation of plasma γ-aminobutyrate /glutamate (GABA/Glu) ratio in schizophrenia.
► the results indicate that risperidone can decrease GABA, increase Glu and normalize GABA/Glu ratio in plasma of schizophrenia.
► the results also suggest that plasma GABA/Glu ratio may be a good peripheral state-like marker in schizophrenia research.