The Future of Endophenotype Research: Best Practices for Accommodating Etiological Complexity and Interactive Influences of Small Effect Size

Endophenotypes are quantifiable traits that mark genetic vulnerability to psychopathology, independent of clinical state. A common expectation is that endophenotypes mark single disorders—a criterion that has proved elusive. We explain why the expectation of disorder specificity should be abandoned, and propose a revised focus on etiologically complex neural vulnerabilities.