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Biomark Med. 2017 Sep;11(9):769-780. doi: 10.2217/bmm-2017-0002. Epub 2017 Sep 11.

Redefining the endophenotype concept to accommodate transdiagnostic vulnerabilities and etiological complexity.

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Department of Psychology, The Ohio State University, 225 Psychology Building, 1835 Neil Avenue, Columbus, Ohio 43210, USA.
Departments of Psychiatry & Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA.


In psychopathology research, endophenotypes are a subset of biomarkers that indicate genetic vulnerability independent of clinical state. To date, an explicit expectation is that endophenotypes be specific to single disorders. We evaluate this expectation considering recent advances in psychiatric genetics, recognition that transdiagnostic vulnerability traits are often more useful than clinical diagnoses in psychiatric genetics, and appreciation for etiological complexity across genetic, neural, hormonal and environmental levels of analysis. We suggest that the disorder-specificity requirement of endophenotypes be relaxed, that neural functions are preferable to behaviors as starting points in searches for endophenotypes, and that future research should focus on interactive effects of multiple endophenotypes on complex psychiatric disorders, some of which are 'phenocopies' with distinct etiologies.


ADHD; autism; complex; depression; endophenotype; etiology; genetic; neural

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