60.3 GABA Spectroscopy and Cognitive Functioning in Schizophrenia

Abstract

Background: Schizophrenia is characterized by loss of brain volume, which may represent an ongoing pathophysiological process. This loss of brain volume may be explained by reduced neuropil rather than neuronal loss, suggesting abnormal synaptic plasticity and cortical microcircuitry. Schizophrenia is also characterized by cognitive impairments. A possible mechanism in schizophrenia is hypofunction of the NMDA-type of the glutamate receptor in the medial prefrontal cortex, which reduces the excitation of inhibitory GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal neurons. Disinhibition of pyramidal cells may result in excessive stimulation by glutamate, which in turn could cause neuronal damage or death through excitotoxicity. Methods: We measured GABA–creatine ratios, and glutamate, NAA, creatine and choline concentrations in the prefrontal and parieto-occipital cortices using proton magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T (Marsman et al, 2014). In addition, general cognitive functioning was measured using the Wechsler Adult Intelligence Test. Measurements were available in 17 patients with schizophrenia and 23 healthy controls. Results: Significantly lower GABA/Cr ratios were found in patients with schizophrenia in the prefrontal cortex as compared to healthy controls. Moreover, GABA–Cr ratios in the prefrontal cortex were inversely correlated with cognitive functioning in the patients. No significant differences in metabolite concentrations in the parieto-occipital cortex were found between the groups. Conclusion: Our findings support a mechanism involving altered GABA levels distinguished from glutamate levels in the medial prefrontal cortex in schizophrenia, particularly in high functioning patients. In a second study, including siblings of patients with schizophrenia we are currently assessing whether altered GABA levels are related to causes or consequences of the disease.