Heritability and molecular genetic basis of electrodermal activity: a genome-wide association study.

Beginning with the seminal work of Carl Jung in the early 1900s, electrodermal activity (EDA) has been extensively used for over 100 years to study emotional and cognitive activity (Dawson, Schell, & Filion, 2007). Abnormalities in EDA have been linked to psychiatric conditions such as schizophrenia and psychopathy (Dawson et al., 2007), leading to proposals that it be used as an endophenotype (Iacono, 1985). Endophenotypes are laboratory-measured characteristics present in individuals who are predisposed to a psychiatric disorder—regardless of the presence of overt symptoms of that disorder (Gottesman & Gould, 2003; Iacono, 1998; Iacono & Malone, 2011). Considered more proximal to the effect of genes than the psychiatric phenotypes with which they are associated, they may provide an easier route to the genetic architecture underlying that disorder. Various criteria have been proposed to identify endophenotypes, including that they are stable over time, heritable, present in affected and unaffected relatives, and able to predict the subsequent development of psychopathology in longitudinal research. EDA is particularly suited for investigating the endophenotype concept as it fits these criteria. EDA is typically measured by passing a weak electrical current through electrodes placed on the fingertips and monitoring changes in conductance that occur in the eccrine sweat glands while subjects are at rest or engaged in a task (for a comprehensive review of EDA methods, applications, and findings, see Boucsein, 2012). EDA reflects arousal processes (Holdcraft & Iacono, 2002; Holdcraft, Iacono, & McGue, 1998) and indexes the degree of perceived stimulus significance, for example, when the stimulus has relevance to the subject, as in a conditioning study (e.g., de Geus, 2010) or in a recognition memory protocol such as the concealed information or guilty knowledge test (Iacono & Malone, 2011). EDA includes both tonic and phasic components. Tonic components include skin conductance level (SCL), a baseline measure that changes slowly with altered arousal state, and nonspecific fluctuations consisting of spontaneous responses that arise in the absence of apparent stimulation and that also index arousal. Phasic responses are stimulus elicited, and typically quantified by measuring the change in conductance (the skin conductance response, SCR) that occurs in response to a discrete stimulus. EDA is often measured in classic conditioning experiments, but as a putative endophenotype, it is probably most commonly assessed as part of a habituation task in which subjects listen to a series of intermittently presented tones that initially trigger orienting responses, followed eventually by ceased responding. EDA has also been hypothesized to index a defensive reaction in response to a stimulus that is potentially so aversive that it threatens well-being or survival. In this context, habituation of the response would not be expected, and a “fight or flight” response would ensue. In EDA protocols commonly used in psychopathology research, diminished responding, characterized by low SCL, small SCRs, and rapid habituation (or total lack of responding) has been associated with psychotic (Iacono, 1985) and externalizing (Fowles & Kochanska, 2000; Fung et al., 2005; Isen, Iacono, Malone, & McGue, 2012) psychopathology. Hyperresponding has most commonly been associated with anxiety disorders such as posttraumatic stress disorder (PTSD; Pole, 2007).