Selective relationship between prefrontal N-acetylaspartate measures and negative symptoms in schizophrenia

Objective: Certain cognitive, behavioral, and emotional deficits (so-called negative symptoms) in patients with schizophrenia have often been attributed to prefrontal cortical pathology, but direct evidence for a relationship between prefrontal neuronal pathology and negative symptoms has been lacking. The authors hypothesized that an in vivo measure of prefrontal neuronal pathology (N-acetylaspartate [NAA] levels) in patients with schizophrenia would predict negative symptoms. Method: Proton magnetic resonance spectroscopic imaging (H-1-MRSI) and rating scales for negative and positive symptoms were used to study 36 patients with schizophrenia. Magnetic resonance spectra were analyzed as metabolite ratios, and parametric correlations were performed. Results: A regionally selective negative correlation was found between prefrontal NAA-creatine ratio and negative symptom ratings in this group of patients with schizophrenia. Conclusions: Lower prefrontal NAA-and by inference greater neuronal pathology-predicted more severe negative symptoms in patients with schizophrenia. These data demonstrate a relationship between an intraneuronal measure of dorsolateral prefrontal cortex integrity and negative symptoms in vivo and represent further evidence for the involvement of the dorsolateral prefrontal cortex in negative symptoms associated with schizophrenia.