HIPPOCAMPAL N-ACETYL ASPARTATE IN UNAFFECTED SIBLINGS OF PATIENTS WITH SCHIZOPHRENIA - A POSSIBLE INTERMEDIATE NEUROBIOLOGICAL PHENOTYPE

Background: Shared neurobiological characteristics of patients with sc hizophrenia and their siblings may represent ''intermediate phenotypes '' that may more closely reflect the genetic susceptibility underlying this illness. We sought evidence of such phenotypes wing magnetic res onance spectroscopy based on previously described regional abnormaliti es in levels of the neuronal marker N-acetyl-aspartate (NAA) in the hi ppocampal area and dorsolateral prefrontal cortex of patients with sch izophrenia. Methods: We studied 47 schizophrenics, 60 unaffected sibli ngs, and 66 healthy control subjects with long echo time multislice pr oton magnetic resonance spectroscopic imaging, primarily measuring NAA , creatine plus phosphocreatine (CRE), and choline-containing compound s. Results: Both patients and their unaffected siblings had significan t reductions in hippocampal area NAA/CRE as compared with control subj ects. As exploratory analyses, estimates of heritability were performe d. Although quantitative correlation of hippocampal NAA between patien ts and sibs was low (likely reflecting measurement noise), qualitative ly defined ''low hippocampal NAA/CRE phenotypes'' yielded relative ris k estimates (lambda(S)) of between 3.8 and 8.8, suggesting this charac teristic is heritable. Conclusions: Our finding adds to the evidence t hat hippocampal abnormalities are associated with schizophrenia and ma y represent a novel biological phenotype for genetic studies of schizo phrenia. Published by Society of Biological Psychiatry.