A review of selected candidate endophenotypes for depression

• Gottesman and Gould's (2003) criteria were used to review depression endophenotypes.
• Neuroticism, morning cortisol, CAR, and EEG frontal asymmetry had the most support.
• Cognitive tasks lacked substantial support or necessary studies for many criteria.
• In particular, heritability and cosegregation studies are lacking.
• Studies of shared genetics among endophenotypes and with depression are needed.

Endophenotypes are proposed to occupy an intermediate position in the pathway between genotype and phenotype in genetically complex disorders such as depression. To be considered an endophenotype, a construct must meet a set of criteria proposed by Gottesman and Gould (2003). In this qualitative review, we summarize evidence for each criterion for several putative endophenotypes for depression: neuroticism, morning cortisol, frontal asymmetry of cortical electrical activity, reward learning, and biases of attention and memory. Our review indicates that while there is strong support for some depression endophenotypes, other putative endophenotypes lack data or have inconsistent findings for core criteria.