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

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.

Figure 1

Midsagittal (a) and axial (b) views of the location of the 30 × 30 × 30 mm³ voxel (white square) in the mPFC. (c) Representative MRS spectrum of GABA and Glx fitted by the LCModel from one HC. The blue line is the raw experimental spectrum. The red line is the model-fitting of the experimental spectrum. The black line is the background signal. The peaks of GABA and Glx are shown.

Figure 2

Absolute concentrations of GABA (a) and Glx (b) among FES patients and UHR and HC subjects. Lower GABA and Glx concentrations were observed in FES patients than UHR and HC subjects (∗ for P < 0.05 and ∗∗ for P < 0.01).

Figure 3

Scatter plots with linear regression fit for the relationship between GABA and glutamate+glutamine (Glx) levels among patients with first-episode schizophrenia (FES, r = 0.79, P < 0.001), subjects at ultrahigh risk for psychosis (UHR, r = 0.56, P = 0.008), and healthy controls (HC, r = 0.53, P = 0.009).