Prefrontal and Striatal Gamma-Aminobutyric Acid Levels and the Effect of Antipsychotic Treatment in First-Episode Psychosis Patients

Abstract

Background: Abnormally elevated levels of gamma-aminobutyric acid (GABA) in the medial prefrontal cortex (mPFC) have been reported in antipsychotic-free patients with schizophrenia. Whether such GABA elevations are also present in other brain regions and persist after antipsychotic treatment has not been previously investigated.

Methods: Twenty-eight antipsychotic-naïve patients with first-episode psychosis (FEP) and 18 healthy control subjects completed the study. Following baseline proton magnetic resonance spectroscopy scans targeting the mPFC and a second region, the dorsal caudate, patients with FEP were treated with oral risperidone for 4 weeks at an initial dose of 1 mg/day that was titrated as necessary based on clinical judgment. After the 4-week treatment period, both groups were brought back to undergo outcome magnetic resonance spectroscopy scans, which were identical to the scans conducted at baseline.

Results: At baseline, higher GABA levels were found both in the mPFC and in the dorsal caudate of patients with FEP compared with healthy control subjects. Following 4 weeks of antipsychotic treatment, GABA levels in patients with FEP decreased relative to baseline in the mPFC, but decreased only at the trend level relative to baseline in the dorsal caudate. For either brain region, GABA levels at 4 weeks or posttreatment did not differ between patients with FEP and healthy control subjects.

Conclusions: The results of the present study documented elevations of GABA levels both in the mPFC and, for the first time, in the dorsal caudate of antipsychotic-naïve patients with FEP, which normalized in both regions following 4 weeks of antipsychotic treatment.

Keywords: Antipsychotic treatment; First-episode; GABA; Magnetic resonance spectroscopy; Psychosis; Schizophrenia.

Figure 1

Voxel placement in two regions of interest: (A) the medial prefrontal cortex and (C) the bilateral dorsal caudate. (B) Representative J-editing spectra obtained from the medial prefrontal cortex using volume-selective point-resolved spectroscopy with the editing radiofrequency pulse (a) on and (b) off. The difference of the spectra in (a) and (b), showing (c) the edited γ-aminobutyric acid (GABA) and combined resonance of glutamate and glutamine (Glx) peaks, with (d) best-fit model spectrum of (c), and (e) the residuals of the difference between the edited (c) and best-fit (d) spectra. NAA, N-acetyl-aspartate; tCho, total choline; tCr, total creatine.

Figure 2

Scattergrams depicting γ-aminobutyric acid (GABA) levels in the medial prefrontal cortex (left) and bilateral dorsal caudate (right) for individual first episode-psychosis (FEP) patients and healthy control (HC) subjects at baseline and at 4 weeks. Within- and between-group comparisons are depicted as follows: downward-facing dashed-line brackets represent comparisons between the FEP and HC groups [A] at baseline and [B] at 4 weeks for the two brain regions, whereas upward-facing solid-line brackets represent baseline vs. 4-week comparisons [C] within the FEP group and [D] within the HC group for the two brain regions.

Figure 3

The relationship between A) γ-aminobutyric acid (GABA) levels in the medial prefrontal cortex and the PANSS General Psychopathology subscale at baseline; B) GABA levels in the dorsal caudate and the PANSS General Psychopathology subscale at baseline; C) GABA levels in the dorsal caudate and the PANSS Negative subscale.