Knowns and unknowns for psychophysiological endophenotypes: integration and response to commentaries

Area of Science:

• Psychophysiology
• Molecular Genetics
• Psychiatric Genetics

Background:

• Endophenotypes are measurable biological traits linked to psychiatric disorders.
• Seven molecular genetic studies on 17 psychophysiological endophenotypes are reviewed.
• Criticisms and future research directions are addressed.

Purpose of the Study:

• To summarize current molecular genetic findings on psychophysiological endophenotypes.
• To evaluate the utility of endophenotypes in psychiatric disorder gene discovery.
• To propose future research strategies for endophenotype genetics.

Main Methods:

• Review and synthesis of seven molecular genetic studies.
• Analysis of 17 psychophysiological endophenotypes.
• Consideration of criticisms from accompanying commentary pieces.

Main Results:

• Endophenotypes are polygenic and may be influenced by rare genetic variants.
• Endophenotypes are not genetically simpler than clinical phenotypes for direct gene discovery.
• Associated endophenotypes can illuminate psychological and neural mechanisms of disorder pathology.

Conclusions:

• Endophenotypes are unlikely to directly facilitate psychiatric disorder gene discovery.
• Endophenotypes are valuable for understanding the mechanisms of psychiatric disorders.
• Large consortia are needed to identify genetic variants influencing psychophysiological measures.