Brain metabolite alterations in young adults at familial high risk for schizophrenia using proton magnetic resonance spectroscopy.

BACKGROUND

Proton magnetic resonance spectroscopy ((1)H MRS) enables in-vivo measurement of several relevant brain metabolites and has provided evidence of a range of neurochemical abnormalities in schizophrenia, especially in glutamate and N-acetyl-aspartate (NAA). While individuals at high familial risk for schizophrenia (HR) exhibit some neurobiological findings observed in the disorder, (1)H MRS findings and their clinical correlates are not well characterized in this population.

METHODS

We compared 23 adolescent and young adult offspring of schizophrenia patients with 24 age- and sex-matched healthy controls using (1)H MRS. We acquired multi-voxel, short TE (1)H MRS measurements at 1.5T and obtained metabolite concentrations of N-acetyl-aspartate (NAA), combined glutamate and glutamine (Glu+Gln) and choline-containing compounds (GPC+PC) for the left and right thalamus, anterior cingulate gyrus, and caudate. We also assessed the relationship between regional metabolite levels, clinical measures and brain volume in a subset of 16 high-risk and 15 control subjects.

RESULTS

Compared to healthy controls, high-risk subjects showed reductions in NAA levels in all three regions (thalamus, caudate, and anterior cingulate cortex), increases in Glu+Gln in the thalamus and caudate, and increases in GPC+PC in the anterior cingulate. In HR, thalamic Glu+Gln concentration was positively correlated and thalamic NAA inversely correlated with measures of schizotypy. Anterior cingulate GPC+PC and caudate Glu+Gln were significantly correlated with attenuated psychotic symptom severity. Anterior cingulate NAA was correlated with executive function.

CONCLUSIONS

Our data suggest the occurrence of metabolic alterations in young relatives of schizophrenia patients similar to those seen in patients with established illness. The observed correlations with cognitive deficits and psychosis-related psychopathology suggest that these metabolic measures may have value as biomarkers of risk for schizophrenia.