CREB1 and dysthymic disorder: Symptoms such as anhedonia, irritability, amotivational status, and dysthymia are consistent with changes in the late-time mesolimbic dopaminergic, with the activation of the CREB/dynorphin pathway and the dumping of the dopaminergic tone (16, 90–92), and may help to explain the presence of “Worthlessness-Being trapped” features (93).