Reduced γ-Aminobutyric Acid and Glutamate+Glutamine Levels in Drug-Naïve Patients with First-Episode Schizophrenia but Not in Those at Ultrahigh Risk.

Junjie Wang,Yingying Tang,Jijun Wang,Zheng Lu,Gaiying Li,Botao Zeng,Chunbo Li,Jianye Zhang,Tianhong Zhang,Hui Liu,Yu Li,Huiru Cui,Lihua Xu

doi:10.1155/2016/3915703

Abstract

Altered γ-aminobutyric acid (GABA), glutamate (Glu) levels, and an imbalance between GABAergic and glutamatergic neurotransmissions have been involved in the pathophysiology of schizophrenia. However, it remains unclear how these abnormalities impact the onset and course of psychosis. In the present study, 21 drug-naïve subjects at ultrahigh risk for psychosis (UHR), 16 drug-naïve patients with first-episode schizophrenia (FES), and 23 healthy controls (HC) were enrolled. In vivo GABA and glutamate+glutamine (Glx) levels in the medial prefrontal cortex were measured using proton magnetic resonance spectroscopy. Medial prefrontal GABA and Glx levels in FES patients were significantly lower than those in HC and UHR, respectively. GABA and Glx levels in UHR were comparable with those in HC. In each group, there was a positive correlation between GABA and Glx levels. Reduced medial prefrontal GABA and Glx levels thus may play an important role in the early stages of schizophrenia.

Highlights

Schizophrenia is a severe psychiatric disorder that affects 1% of the population worldwide; it is characterized by a complex phenotype, including positive, negative, affective symptoms and cognitive impairments [1, 2]
A recent neurodevelopmental model of schizophrenia has proposed that an imbalance of excitation and inhibition in the prefrontal cortex is involved in the pathophysiology of schizophrenia [4]
We hypothesized that (1) medial prefrontal GABA or Glx levels should change in gradient with illness progression, and these changes would be more prominent in first-episode schizophrenia (FES) patients than in ultrahigh risk for psychosis (UHR) subjects; (2) GABA levels should be correlated with Glx levels in FES and UHR subjects, and the correlations may differ across the three groups

Summary

Introduction

Schizophrenia is a severe psychiatric disorder that affects 1% of the population worldwide; it is characterized by a complex phenotype, including positive, negative, affective symptoms and cognitive impairments [1, 2]. De la Fuente-Sandoval et al suggested significant correlations between these two neurotransmitters in both the mPFC and dorsal caudate across UHR and HC [17] These correlations could differ among various brain regions in the two groups. More attention should be paid to studies combining the GABA and Glu alterations in both drug-naıve FES patients and UHR subjects. This holds great promise for uncovering the impact of GABA and Glu alterations on the onset and course of psychosis. We recruited drug-naıve UHR subjects, drug-naıve FES patients, and HC subjects and measured both GABA and Glx levels in the mPFC. We hypothesized that (1) medial prefrontal GABA or Glx levels should change in gradient with illness progression, and these changes would be more prominent in FES patients than in UHR subjects; (2) GABA levels should be correlated with Glx levels in FES and UHR subjects, and the correlations may differ across the three groups

Subjects

Results

Discussion