Reduced N-acetyl-aspartate levels in schizophrenia patients with a younger onset age: A single-voxel ¹H spectroscopy study

Schizophrenia is widely considered a neurodevelopmental disorder. The timing of psychosis onset may determine the degree of functional and biological deficits. In this study, the association between age of onset of psychosis and in vivo biochemical levels was assessed in first-episode, antipsychotic-naive (FEAN) schizophrenia subjects. We hypothesized greater biochemical deficits in the younger-onset FEAN subjects. In vivo, ¹H spectroscopy measurements of the left dorsolateral prefrontal cortex (DLPFC) were conducted on FEAN subjects (15 schizophrenia and 3 schizoaffective subjects) and healthy comparison subjects of comparable age and gender distribution (N = 61). N-acetyl-aspartate was significantly lower in the left DLPFC of FEAN subjects as compared to healthy comparison subjects. However, there was a significant subject group-by-age interaction for N-acetyl-aspartate. Early-onset FEAN subjects showed lower N-acetyl-aspartate levels compared to the younger healthy comparison subjects, while adult-onset FEAN and older healthy comparison subjects did not differ. The lower N-acetyl-aspartate levels in the DLPFC of early-onset subjects suggest a reduction in functioning neurons or specifically a reduction in the proliferation of dendrites and synaptic connections, which is not apparent in the adult-onset schizophrenia subjects.