Childhood abuse, trait anxiety, and neuroticism are associated with depression, and activation of the amygdala has been hypothesized as the biological basis of these predisposing factors. Anxiety disorder often coexists with major depressive disorder, and this comorbidity has been postulated to occur owing to the above predisposing factors. However, this possibility has not yet been fully confirmed in clinical studies. A history of childhood abuse, and anxiety disorder or anxiety symptoms have been reported to coexist in patients with treatment-resistant depression. Therefore, the above hypothesis may also apply to treatment-resistant depression. Large-scale studies are needed to test whether childhood abuse, propensity for trait anxiety/neuroticism, amygdala activation, and the coexistence of anxiety disorder/anxiety symptoms are more pronounced in patients with treatment-resistant depression than those with non-treatment-resistant depression. At present, it is clinically clear that treatment-resistant depression more frequently occurs in patients with comorbid anxiety disorders and a history of childhood abuse. The clinical care of patients with treatment-resistant depression keeping this information in mind may lead to a better understanding of these patients, and may also assist in the development of effective treatment strategies.