While studies have not explored the direct role of CRF signaling within the insula in mediating negative affect in nicotine addiction, CRF signaling within the insula is known to mediate other types of addiction (Goudriaan et al. 2010; Rotge et al. 2017; Sánchez et al. 1999; Martin-Fardon et al. 2010; Cottone et al. 2009). The gene discussed is CRH; the disease is nicotine dependence.