Q & A: Defining Endophenotype

Q: I’ve heard the term “endophenotype” used in relation to susceptibility to eating disorders. What is an endophenotype, and what does this have to do with eating disorders?

A: Endophenotypes have recently elicited considerable interest in psychiatric genetics. Basically, endophenotypes are observable characteristics that can be robustly and reliably measured (phenotypes), and are thought to be strongly genetic in origin. Endophenotypes are thought to underlie and contribute to certain disease vulnerabilities but not to be part of the disorder itself. As the term was introduced into human psychiatric genetics by Gottesman and Shields in 1973 (Br. J Psychiatry 122:15-30), endophenotypes were defined as being heritable, and to co-segregate with a psychiatric illness yet be present even when the disease is not (i.e., an enduring trait that is “state independent”), and to be found in nonaffected family members at a higher rate than in the general population. An extensive literature exists on psychological, electrophysiological, anatomic, metabolic and sensory deficits associated with attention deficit hyperactivity disorder (ADHD), alcoholism, anxiety, autism, bipolar disorder, depression and schizophrenia, among other psychiatric conditions (Psychol. Med 2007; 37:163).

With respect to eating disorders, attention has recently been drawn to several psychological characteristics thought to contribute to vulnerability to anorexia nervosa, in particular, that occur more commonly in patients with eating disorders and that persist after recovery (Can J Psychiatry 2007; 2:212). Suggested endophenotypes include perfectionism, tendencies to excessive motor activity and exercise, rigidity of thinking associated with difficulty in shifting mental sets (i.e., to think in a fluid, adaptive manner), and difficulties in achieving proper perspective of the big picture (gestalt), and instead dwelling on small details (not seeing the forest for the trees) (Int J Eat Disord 2006; 39: 454; Am J Psychiatry 2005; 162:22695; Am J Psychiatry 2000; 157:1799). Additional endophenotypes will be most certainly be described. Identifying these features suggests genetic targets to be uncovered, and may ultimately offer new biological and psychological treatment strategies.

— J.Y.