Striatal metabolic alterations in non-psychotic adolescent offspring at risk for schizophrenia: A 1H spectroscopy study

In vivo proton (1H) Magnetic Resonance spectroscopy (1H MRS) has shown abnormalities in young first-episode patients with schizophrenia. It is unclear whether these abnormalities reflect trait related vs. state related alterations in schizophrenia. We compared young first-degree relatives of schizophrenia patients and healthy controls using 1H MRS. We hypothesized alterations in the 1H MRS metabolites N-acetyl aspartate (NAA) and glutamate in corticostriatal and thalamic brain regions. We obtained multi-voxel, short-TE 1H MRS measurements at 1.5 Tesla in 40 consenting adolescent offspring at risk for schizophrenia (HR), and 48 age matched healthy controls (HC). Absolute levels of NAA, phosphocreatine plus creatine (PCr + Cr), choline-containing compounds (GPC + PC), myo-inositol and glutamate plus glutamine (Glu + Gln) were obtained from the seven different anatomical brain areas (nominal voxel size of 4.5 cm3 each) and corrected for tissue voxel composition. HR subjects showed NAA (p = .0049), PCr + Cr (p = 0.028) and GPC + PC (p = 0.0086) reductions in the caudate compared with HC subjects. Male HR subjects had significant Glu + Gln reductions compared to male HC subjects (p = .0022). HR subjects had increased NAA in prefrontal white matter. NAA levels in the prefrontal white matter and Glu + Gln levels in the inferior parietal/occipital region were both increased in HR without psychopathology compared with HC subjects. Lower NAA, PCr + Cr and GPC + PC levels may reflect an overall reduction in cellular processes in the caudate of HC subjects, perhaps related to decreases in cell density, or synaptic overpruning. Further studies are needed to examine the pathophysiologic significance of these observations, and their potential predictive value for schizophrenia related psychopathology that may emerge in these at risk relatives during adolescence and early adulthood.