Developmental genetics and psychopathology: some new feathers for a fine old hat.

Without even knowing of their existence, Mendel discovered how genes operate when they are completely penetrant, although they rarely are, at least with respect to human personality and psychopathology; yet quantitative genetics results have conclusively demonstrated their substantial macrolevel influence. Now we need to understand just how incompletely penetrant genes make their contributions to psychopathology. Exciting new developments in molecular genetics and epigenetics provide new insight into gene action in principle but have been of limited value so far in understanding the emergence of psychopathology. Some of the most helpful postulates might come from evolutionary and developmental biology and agricultural breeding experiments. I describe the all but forgotten evolutionary mechanisms articulated by Schmalhausen, a Russian evolutionary biologist whose work was suppressed by Stalin in the 1940s. I focus on Schmalhausen's law, the observation that organisms living in conditions at the boundary of their tolerance in any one aspect of existence will be vulnerable to expression of genetic liabilities related to all other aspects of existence. I show how Schmalhausen's ideas are relevant to the results of a century-long corn-breeding experiment and the current concepts of facilitated variation and cryptic genetic variation. I then discuss the relevance of all of these to understanding genetic influences on personality and psychopathology.