Anticipation in multiplex schizophrenia pedigrees.

Anticipation, a phenomenon in which the symptoms of an inherited disease become more severe and age of onset occurs earlier across generations, has become an issue of importance in schizophrenia. If anticipation is found in families manifesting the illness, a possible type of genetic mutation would be implicated for predisposition to schizophrenia, as anticipation is now known to result from expansion of unstable trinucleotide repeat sequences. Two recent studies have tested for evidence of this phenomenon in schizophrenia families and came to differing conclusions; it is possible that anticipation occurs only in a subset of families. Our sample shows significant decreases in age of onset and increases in severity across generations. To investigate possible ascertainment bias, we looked at early onset parents and found no consistent anticipation effects in this group. We did find some increase in anticipation for mother-child vs father-child pairs; this possible imprinting effect may indicate true anticipation, though the evidence is not strong in our small sample, and the most conservative interpretation of our results is that the differences are due to ascertainment bias.