Empirical work on the internalizing and externalizing disorders suggests at least two mechanisms that may underlie their co-occurrence. First, negative emotionality, or general distress, is often linked to internalizing psychopathology (Andrews et al. 1990; Clark & Watson, 1991). For example, neuroticism loads onto an internalizing spectrum factor (Hettema et al. 2006; Eaton et al. 2011), and it has substantial genetic overlap with major depression (rG = 0.49–0.67; Fanous et al. 2002). Further, neuroticism is correlated with substance use disorders (Malouff et al. 2007), and affect regulation models suggest that individuals high in trait neuroticism may use alcohol to regulate emotions (Cooper et al. 1995). In addition to being associated with internalizing and externalizing disorders, negative emotionality explains a substantial proportion of the phenotypic covariation among these disorders (Khan et al. 2005; Ellingson et al. 2015). Notably, this risk factor resembles the negative valence system, highlighted in the RDoC proposal, which includes subconstructs related to anxiety (e.g. potential threat) and sadness (e.g. loss).
