Longitudinal grey-matter and glutamatergic losses in first-episode schizophrenia

BACKGROUND: Progressive volumetric changes in the brains of people with schizophrenia have been attributed to a number of factors. AIMS: To determine whether glutamatergic changes in patients with schizophrenia correlated with grey-matter losses during the first years of illness. METHOD: Left anterior cingulate and thalamic glutamatergic metabolite levels and grey-matter volumes were examined in 16 patients with first-episode schizophrenia before and after 10 months and 30 months of antipsychotic treatment and in 16 healthy participants on two occasions 30 months apart. RESULTS: Higher than normal glutamine levels were found in the anterior cingulate and thalamus of never-treated patients. Thalamic levels of glutamine were significantly reduced after 30 months. Limited grey-matter reductions were seen in patients at 10 months followed by widespread grey-matter loss at 30 months. Parietal and temporal lobe grey-matter loss was correlated with thalamic glutamine loss. CONCLUSIONS: Elevated glutamine levels in never-treated patients followed by decreased thalamic glutamine and grey-matter loss in connected regions could indicate either neurodegeneration or a plastic response to reduced subcortical activity.