Neurobiological aspects of functional recovery in major depressive disorder

Major depressive disorder (MDD) is associated with significant psychosocial impairment at individual, family, and societal levels. Despite the importance of functional recovery for patients and clinicians, treatment studies in MDD have only recently begun to focus on functional outcomes rather than symptom outcomes. Among the varied symptoms of MDD, fatigue and cognitive dysfunction are key mediators of functional impairment. Both are also common residual symptoms that impede full functional recovery, even when other symptoms of MDD are remitted. Hence, it is important to carefully consider these symptom complexes to optimize functional recovery in patients with MDD. In this chapter, we review the importance of functional recovery in MDD and summarize some of the neurobiological findings and the effects of antidepressants on fatigue and cognitive dysfunction as key mediators of functional recovery.