Irving Gottesman and the Schizophrenia Spectrum

Abstract

Our knowledge of the genetics of schizophrenia and its borderlands is heavily indebted to the research and writings of Irving Gottesman. In a twin study of personality assessment in adolescents with the Minnesota Multiphasic Personality Inventory (MMPI) begun in 1957 he demonstrated that certain traits were under appreciable genetic influences. In a major twin study of schizophrenia with Shields begun in 1962, using audio-taped interviews, including MMPI, and diagnosed by a cross-national panel of blinded judges, he demonstrated a strong genetic factor, suggesting a polygenic contribution to a multifactorial liability to the disorder. In a study on the offspring of discordant twins he demonstrated that the genetic risk was passed on from non-schizophrenic as well as from schizophrenic identical twins. Super-high-risk studies on the offspring of two schizophrenic parents (2010) showed 4 times increased risk of schizophrenia compared to offspring of only one schizophrenic parent and suggested some kind of genetic overlap with bipolar disorder. In molecular genetics his concept of endophenotypes as interforms between the genotype and its phenotypical manifestations, influenced by epigenetic and environmental factors, have inspired a large number of research studies.