Magnetic resonance spectroscopy of limbic structures displays metabolite differences in young unaffected relatives of schizophrenia probands

Imaging studies of schizophrenia patients showed fronto-temporal brain volume deficits, while magnetic resonance spectroscopy (MRS) studies of patients and unaffected biological relatives have found a decrement of the neuronal marker N-acetyl-aspartate (NAA) in the hippocampus and frontal lobes, and increased choline-containing phospholipids. Using a 3 T MR scanner, we determined the metabolite profile within limbic regions (anterior cingulate cortex (ACC) and left hippocampus) of 36 unaffected, adolescent/young adult relatives of schizophrenia probands (first-degree = 16, second-degree = 20) and 25 healthy controls with no family history of schizophrenia. Significant main effects of group were found on NAA/Cho ratios for both the left hippocampus (F = 6.11, p ≤ 0.02) and ACC (F = 4.89, p ≤ 0.03) as well as for the left hippocampus Cho/Cr ratio (F = 5.55, p ≤ 0.02). Compared to age and sex matched healthy controls without a family history of schizophrenia, first-degree relatives of probands had greater MRS metabolite deviations than second-degree relatives. Greater familial proximity to the schizophrenia proband (or higher schizophrenia susceptibility) among biological relatives was associated with stepwise lowering of NAA/Cho and elevations in Cho/Cr ratios. The observed limbic metabolite changes among young, nonpsychotic biological relatives are likely related to shared genetic vulnerability factors, and may assist in the early identification of schizophrenia for primary and secondary prevention.