In schizophrenia, there is no consensus on the association between changes in CNS metabolites and exacerbation of symptoms, phase of the disease, treatment strategy or analyzed brain region [21,22,23,24]. Decreased concentrations of N-acetylaspartate (NAA), a marker of neuron viability and integrity, are commonly observed [25], and reflect neuronal loss and/or mitochondrial dysfunction [26,27]. However, meta-analyses performed by Steen and Brugger [21,22] found that the NAA concentration in the PFC was similar in patients with a first episode of schizophrenia and in the chronic phase of the disease. It was also not affected by the duration of untreated schizophrenia (DUP) [28] and had already decreased during the pre-psychotic period [29]. Concentrations of NAA, glutamic acid (Glu) and glutamine (Gln) are important in the pathogenesis of schizophrenia, however, many studies have failed to confirm any correlation between metabolite concentration and clinical symptoms [30,31,32,33,34,35,36]. Nevertheless, a few studies have noted an association between negative symptoms and concentration of NAA in the PFC, thalamus and anterior cingulate cortex (ACC) [37,38,39,40].
