Associations between cognitive function and levels of glutamatergic metabolites and GABA in antipsychotic-naïve patients with schizophrenia or psychosis

Abstract Background Abnormal glutamate and gamma-aminobutyric acid (GABA) levels have been found in the early phase of schizophrenia and may underlie cognitive deficits. However, the association between cognitive function and levels of glutamatergic metabolites and GABA has not been investigated in a large group of antipsychotic-naive patients. Methods Fifty-six antipsychotic-naive patients with schizophrenia or psychotic disorder and 51 healthy controls underwent magnetic resonance spectroscopy to measure glutamate, glutamate+glutamine (glx), and GABA levels in dorsal anterior cingulate cortex (ACC) and glutamate and glx levels in left thalamus. The cognitive domains attention, working memory, and IQ were assessed. Results The whole group of antipsychotic-naive patients had lower levels of GABA in dorsal ACC (p=0.03) and the subgroup of patients with a schizophrenia diagnosis had higher glutamate levels in thalamus (p=0.01), but glx levels in dorsal ACC and thalamus did not differ between groups. Glx levels in dorsal ACC were positively associated with working memory (logarithmically transformed: b=-0.016 (higher score indicates worse performance), p=0.005) and attention (b=0.056, p=0.035) in both patients and healthy controls, although the association with attention did not survive adjustment for multiple comparisons. Conclusions The findings suggest a positive association between glutamatergic metabolites and cognitive function that do not differ between patients and healthy controls. Moreover, our data indicate that decreased GABAergic levels in dorsal ACC are involved in schizophrenia and psychotic disorder, whereas increased glutamate levels in thalamus seem implicated in the schizophrenia pathophysiology. The findings imply that first-episode patients with cognitive deficits may gain from glutamate modulating compounds.