Molecules of the Mind

This month’s column is an example of the perils and the promises of using an animal model to ferret out one of psychiatry’s most intractable problems: the genetic substrates mediating schizophrenia and depression. The subject concerns what some describe as the “schizophrenic mouse,” an animal carrying a disrupted gene called “disrupted in schizophrenia 1” (DISC1), and its utility in illuminating the human molecular machinery behind this most frustrating disorder. It is a hopeful tale that illustrates the great progress of the research community in characterizing this tragic illness. It also represents a cautionary tale in the interpretation of results. The goal of this column is to describe some of the biology of this interesting gene and its potential links to mental health in light of this caution. I will start with some of the general concerns about using animal models to describe anything about human behavior. Then I will move on to the isolation of specific genetic sequences in a famously troubled Scottish family. I will end with a description of some truly remarkable progress associated with laboratory rodents carrying mutated DISC1 genes and add a quick comment about exactly what this animal model may (and may not) reveal about the disorder.