Table 1.
Weight of evidence for candidate endophenotypes for alcohol use disorder, organized by category (anatomical, developmental, electrophysiological, metabolic, sensory, psychological/cognitive, and neuroimaging) and criterion.
| Candidate endophenotype | Endophenotype criterion
|
||||
|---|---|---|---|---|---|
| Associated with AUD | Heritable | State-independent | Co-segregates with illness within families | Presents in nonaffected family members > population | |
| Anatomical | |||||
| Structural brain differences | Boutte et al. [89], Agartz et al. [90], Monnig et al. [137] | Baare et al. [138], Posthuma et al. [139] | Fein, Fein [140], Cheetham et al. [141] | Benegal et al. [91] | |
| Developmental | |||||
| Externalizing behavior | Benegal et al. [91] | Young et al. [67] | Englund et al. [142] | Benegal et al. [91] | |
| Electrophysiological | |||||
| Resting and event-related EEG phenotypes | Ehlers, Phillips [143] Carlson et al. [144]; Roopesh et al. [145], Roopesh et al. [146] | van Beijsterveldt et al. [20] Perlman et al. [147] |
Carlson et al. [144] | c.f. Carlson et al. [144]; c.f. Carlson et al. [32] | Rangaswamy et al. [21] |
| Metabolic | |||||
| HPA axis activity | Wand, Dobs [148], Starcke et al. [149] | Bartels et al. [150] | |||
| Sensory | |||||
| Sweet liking | Kampov-Polevoy et al. [81]; c.f. Kranzler et al. [151] | Keskitalo et al. [152] | Mennella et al. [83], Lange et al. [153] | ||
| Psychological/Cognitive | |||||
| Executive functions | Sjoerds et al. [76] | Friedman et al. [75] | Benzerouk et al. [78], Gierski et al. [77] | ||
| Delayed reward discounting | Mitchell et al. [72] | Anokhin et al. [71] | Petry et al. [73] | ||
| Low subjective response to alcohol (LR) | Schuckit et al. [43], Schuckit et al. [42], Schuckit et al. [44] | Schuckit et al. [154] | Schuckit et al. [43] | Schuckit et al. [43] | |
| Functional Neuroimaging | |||||
| Functional brain differences during spatial working memory tasks | Pfefferbaum et al. [155], Vollstadt-Klein et al. [156], Tapert et al. [157] | Spadoni et al. [133], Spadoni et al. [158] | |||
Notes.
*
Does not meet endophenotype definition itself, but other candidate endophenotypes (e.g., executive functions, delayed reward discounting) are likely to contribute to individual differences in externalizing across development.
**
May also be considered a sensory/motor endophenotype. Studies listed should be considered illustrative and not exhaustive.