Comparison of the density of gamma-aminobutyric acid in the ventromedial prefrontal cortex of patients with first-episode psychosis and healthy controls

Background

Abnormality in the concentration and functioning of gamma-aminobutyric acid (γ-aminobutyricacid, GABA) in the brain is not only an important hypothetical link to the cause of schizophrenia but it mayalso be correlated with the cognitive decline and negative symptoms of schizophrenia. Studies utilizinghigh field magnetic resonance spectroscopy (MRS) report abnormal density of GABA in the ventromedialprefrontal cortex (vmPFC) of patients with chronic schizophrenia, but these results may be confounded bystudy participants’ prior use of antipsychotic medications.

Aim

Compare the density of GABA in the vmPFC of patients with first-episode psychosis to that in healthycontrols and assess the relationship of GABA density in the vmPFC to the severity of psychotic symptoms.

Methods

Single-voxel ¹H-MRS was used to assess the concentration of GABA and other metabolites in thevmPFC of 22 patients with first-episode psychosis (10 with schizophrenia and 12 with schizophreniformdisorder) and 23 healthy controls. Thirteen of the 22 patients were drug-naïve and 9 had used antipsychoticmedication for less than 3 days. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate theseverity of psychotic symptoms in the patient group.

Results

The mean (sd) GABA density in the vmPFC was significantly higher in patients than in controls (2.28[0.54] v. 1.93 [0.32] mM, t=2.62, p=0.012). The densities of other metabolites – including N-acetylasparticacid (NAA), glutamic acid (GLU), and glutamine (GLN) – were not significantly different between patients andcontrols. Among the patients, GABA density in the vmPFC was not significantly correlated with PANSS totalscore or with any of the three PANSS subscale scores for positive symptoms, negative symptoms, and generalpsychopathology. GABA concentration was not associated with the duration of illness, but it was significantlycorrelated with patient age (r=0.47, p=0.026).

Conclusion

Elevation of GABA density in the vmPFC of patients with first-episode psychosis confirms thatthis abnormality is independent of medication use. The failure to find a correlation of GABA density in thevmPFC with the severity of psychotic symptoms needs to be confirmed in larger studies, but it suggests thatthere are several intervening steps between brain pathology and clinical symptoms.