Chronic stress is at once a predisposing factor to, a result of, and a perpetuating factor of anorexia nervosa. It can result from genetic susceptibilities, developmental trauma, emotional abuse, or starvation. The chronic stress profile of treatment-resistant depression mimics that of anorexia nervosa, causing hyperactivity of the hypothalamic pituitary adrenal (HPA) axis, immune system activation, microbiome anomalies, reduction of neurogenesis and brain volume, and reduced hippocampal volume, which is also associated with increased cortisol levels, anxiety, and depression. This stress response impairs resilience and may cause reduced mesolimbic dopamine function, anhedonia, and decreased motivation, causing or worsening depression. 50% of anorexia nervosa patients report at least one mood disorder episode in their lifetime, and depression often persists regardless of fluctuations in eating disorder symptomatology. Depression is common about anorexic patients but they often present with fewer somatic symptoms (low energy, reduced neural activation) and more severe cognitive symptoms (negative self-image). Patients with a history of depression prior to onset of anorexia nervosa have been found to have reduced recovery rates, and those struggling with mood comorbidities likewise show worsened long-term outcomes. Anxiety traits, such as obsessive-compulsive personality traits, OCD, and anxiety disorders, are also common in childhood prior to onset of anorexia nervosa. Polygenic risk correlations with anorexia nervosa are strongest with OCD, followed by half-sized correlations with neuroticism, depression, and anxiety. Patients with severe and enduring forms of anorexia nervosa may thus benefit from treatments originally targeted towards treatment-resistant depression and OCD.