Despite rapidly growing knowledge of the clinical high-risk (CHR) state for psychosis, the vast majority of case-control studies have relied on healthy volunteers as a reference point for drawing inferences about the CHR construct. Researchers have long recognized that results generated from this design are limited by significant interpretive concerns, yet little attention has been given to how these concerns affect the growing field of CHR research. We argue that overreliance on healthy controls in CHR research threatens the validity of inferences concerning group differences, hinders advances in understanding the development of psychosis, and limits clinical progress. We suggest that the combined use of healthy and help-seeking (i.e., psychiatric) controls is a necessary step for the next generation of CHR research. We then evaluate methods for help-seeking control studies, identify the available CHR studies that have used such designs, discuss select findings in this literature, and offer recommendations for research.
Keywords: clinical high-risk; etiology; psychosis; research design; transdiagnostic.