Cognitive Enhancement in Major Depressive Disorder

Abstract

Major depressive disorder (MDD) is a chronic and disabling illness often associated with elevated rates of non-recovery and substantial psychosocial burden. Cognitive impairment is a common residual manifestations of MDD. Overactivation of the hypothalamic–pituitary–adrenal axis, along with immune–inflammatory imbalances, a decrease in neurotrophin signaling, and an increase in oxidative and nitrosative stress, leads to neuroprogression and cognitive deterioration in MDD. “Cognitive remission” has been proposed as a novel treatment target for MDD. Cognitive remediation therapy has provided encouraging results for the management of cognitive deficits in MDD. The effects of standard antidepressant drugs on MDD-related cognitive dysfunction are often suboptimal, which calls for the development of novel agents with the potential to target cognitive impairments in MDD. The incorporation of biobehavioral strategies (e.g., exercise) and multimodal treatment approaches (e.g., cognitive training, antidepressant therapy, and neuromodulation) is more likely to generate therapeutic benefit.