Few studies have explicitly tested the common cause, precursor, predisposition, and consequences hypotheses for Cloninger’s model. Farmer et al. (2003) found that the never-depressed siblings of patients with MDD reported significantly greater harm avoidance and less self-directedness than did the never-depressed siblings of healthy controls. In addition, Cloninger et al. (2006) reported that in a large community sample, high harm avoidance and persistence and low self-directedness predicted an increase in self-reported depressive symptoms 12 months later. A larger number of studies have addressed the pathoplasticity hypothesis, albeit with mixed results. Low harm avoidance, self-directedness, and reward dependency have predicted a poorer response to treatment in some, but not all, studies; the other dimensions have generally not been associated with course and treatment outcome (Joyce et al. 2007, Kennedy et al. 2005, Morris et al. 2009).
