Jh. Callicott et al., HIPPOCAMPAL N-ACETYL ASPARTATE IN UNAFFECTED SIBLINGS OF PATIENTS WITH SCHIZOPHRENIA - A POSSIBLE INTERMEDIATE NEUROBIOLOGICAL PHENOTYPE, Biological psychiatry, 44(10), 1998, pp. 941-950
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.