A review of selected candidate endophenotypes for depression

Abstract

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.

Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders

“…It has a strong translational flavour (validated measures adaptable for human use), emphasizes the need for improved animal models (see below), puts behavioural, neurobiological and genetic findings on equal footing, and embraces the notion of endophenotypes or intermediate phenotypes. Intermediate refers to the fact that a specific anomaly (like impaired executive function) lies between a genetic aberration and a psychiatric disorder and hence should be more closely linked to the causal gene (Goldstein and Klein, 2014;. RDoc attempts -in a trans-nosological and dimensional manner -to define the pathophysiological substrates of psychiatric disorders for the general domains of neurocognition, affect, social processing, arousal and reward (Cuthbert and Insel 2012;Kas et al, 2007;Markou et al, 2009;Robbins et al, 2011).…”

Stress and depression: old questions, new approaches

“…Nevertheless, there is widespread recognition that diagnosis-based research in depression has obscured enormous heterogeneity, which along with comorbidity, impedes precision and reproducibility of research findings [1,2]. Future research efforts are increasingly being directed toward alternative conceptualizations of the phenotype, including refining intermediate phenotypes [3,4,5 ] and relating processes to transdiagnostic conceptualizations and dimensional measures [6].…”

Breaking down the genetics of depression using brain endophenotypes

“…The concept has known a great popularity [395], however only a few endophenotypes have been identified for affective disorders [394,396,397]. These include: neuroticism [394], personal life events [9] and perceived social support [7,8].…”

“…These include: neuroticism [394], personal life events [9] and perceived social support [7,8]. MRI brain measurements represent promising endophenotypes, being objective (not self reported), reliable [398] and heritable [27,399].…”

“…The remaining criterion from the definition derive from the presence of genetic correlation: that family members of affected individuals also exhibit the endophenotype, having, on average, a higher disease genetic load than relatives of unaffected. Reliability of the endophenotype is sometimes included as part of the definition [394] and is implied by the trait heritability [67].…”