Stanley Cobb, the Rockefeller Foundation and the evolution of American psychiatry.

Stanley Cobb founded the Harvard Departments of Neurology (1925) and Psychiatry (1934) with Rockefeller Foundation funding. Cobb was an important transitional figure in both neurology and psychiatry. He and his friend Alan Gregg were the most visible parts of the Rockefeller Foundation psychiatry project, which prepared American psychiatry for the rapid growth of psychiatric research after World War II. Edward Shorter called him the founder of American biological psychiatry, but this misunderstands Cobb and the Hegelian evolution of twentieth-century American psychiatry. I review the major role of the Rockefeller Foundation in the evolution of American academic psychiatry and the disappearance of Cobb's teaching and that of his mentor Adolf Meyer, a founding father of American academic psychiatry.

Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a triplet (CAG) expansion mutation. The length of the triplet repeat is the most important factor in determining age of onset of HD, although substantial variability remains after controlling for repeat length. The Venezuelan HD kindreds encompass 18,149 individuals spanning 10 generations, 15,409 of whom are living. Of the 4,384 immortalized lymphocyte lines collected, 3,989 DNAs were genotyped for their HD alleles, representing a subset of the population at greatest genetic risk. There are 938 heterozygotes, 80 people with variably penetrant alleles, and 18 homozygotes. Analysis of the 83 kindreds that comprise the Venezuelan HD kindreds demonstrates that residual variability in age of onset has both genetic and environmental components. We created a residual age of onset phenotype from a regression analysis of the log of age of onset on repeat length. Familial correlations (correlation +/- SE) were estimated for sibling (0.40 +/- 0.09), parent-offspring (0.10 +/- 0.11), avuncular (0.07 +/- 0.11), and cousin (0.15 +/- 0.10) pairs, suggesting a familial origin for the residual variance in onset. By using a variance-components approach with all available familial relationships, the additive genetic heritability of this residual age of onset trait is 38%. A model, including shared sibling environmental effects, estimated the components of additive genetic (0.37), shared environment (0.22), and nonshared environment (0.41) variances, confirming that approximately 40% of the variance remaining in onset age is attributable to genes other than the HD gene and 60% is environmental.