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


METHODS
The 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.


RESULTS
Plasma 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.


CONCLUSIONS
The 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.
Cai
Hua-Lin
HL
Clinical Pharmacy and Pharmacology Research Institute, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Zhu
Rong-Hua
RH
Li
Huan-De
HD
Zhang
Xiang-Hui
XH
Hu
Li
L
Yang
Wen
W
Ye
Hai-Sen
HS
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D018698:Glutamic Acid / Q000097:blood*; D006801:Humans; D008297:Male; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D013223:Statistics as Topic; D053719:Tandem Mass Spectrometry / Q000379:methods; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000097:blood*
D014150:Antipsychotic Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D018967:Risperidone