Cognitive dysfunction in major depressive disorder: a state-of-the-art clinical review

Major depressive disorder (MDD) is a prevalent and recurring mental disorder often associated with high rates of non-recovery and substantial consequences on psychosocial outcome. Cognitive impairment is one of the most frequent residual symptoms of MDD. The persistence of cognitive impairment even in remitted phases of the disorder, notably in the domains of executive function and attention, suggests that it may serve as a mediational nexus between MDD and poor functional outcome, accounting for occupational and relational difficulties regardless of clinical improvement on depressive symptoms. The critical impact of cognitive deficits on psychosocial dysfunction invites clinicians to regularly screen and assess cognition across multiple domains, taking into account also clinical correlates of cognitive dysfunction in MDD. Despite the availability of several instruments for the screening and assessment of cognitive dysfunction, the lack of consensus guiding the choice of appropriate instruments increases the likelihood to underestimate cognitive dysfunction in MDD in clinical settings. On the other hand, the unsatisfactory effect of most antidepressant treatments on cognitive deficits for many individuals with MDD calls for the development of genuinely novel therapeutic agents with potential to target cognitive dysfunction. Notwithstanding the necessity of further investigations, this review indicates that neuropsychological deficits (e.g., impaired executive functions) are stable markers of MDD and underscores the need for the development of integrative and multi-modal strategies for the prevention and treatment of neuropsychological impairments in MDD.