Cognitive Dysfunction in Major Depressive Disorder: Effects on Psychosocial Functioning and Implications for Treatment

Major depressive disorder is a common condition with a high rate of recurrence, chronicity, and staggering economic burden, including disability in the workforce.1 In 2010, MDD was the second leading medical cause of burden globally, with highest estimates of disability in people of working age.2 In Canada, the annual prevalence of MDD is 3% to 4% overall, and 79% of people with MDD report some interference with work functioning, either decreased work productivity and (or) absenteeism.1 In addition to work impairment, the psychosocial impact of MDD often affects a person’s level of functioning in family and social relationships. While there is clearly an association between improvement in depressive symptoms and functioning, symptom improvement can also be dissociated from functional improvement and work loss.3,4 Hence there has been increasing recognition that symptomatic remission is an insufficient goal of treatment for MDD and that return to premorbid psychosocial functioning should be targeted.5 Cognitive dysfunction refers to deficits in attention, verbal and nonverbal learning, short-term and working memory, visual and auditory processing, problem solving, processing speed, and motor functioning. Cognitive dysfunction may be a primary mediator of functional impairment in MDD.6 Cognitive complaints are core symptoms of acute MDEs, and diminished ability to think or concentrate and (or) indecisiveness are criterion items for the diagnosis of MDD. Several other core symptoms of MDD may act as mediators of cognitive dysfunction, including psychomotor retardation, amotivation, fatigue, insomnia, and mood disturbances. Deficits on neuropsychological testing are well demonstrated in people with MDD, compared with healthy subjects, with many studies and meta-analyses showing moderate effect sizes in neurocognitive domains of processing speed, attention, executive function, learning, and memory7,8 as well as in cognitive affective bias. Cognitive affective bias reflects distorted information processing and (or) focus moving away from positive stimuli and toward negative stimuli,7 and abnormal responses to negative feedback and decision making.9 It is also apparent that, while cognitive dysfunction in MDD may improve with treatment and resolution of depressive symptoms, cognitive deficits can still be detected even in periods of symptom remission. In a 3-year, follow-up study of patients with MDD, the proportion of time with cognitive complaints was reported as 94% during acute depressive episodes; this remained at 44% despite full or partial symptom remission during treatment.10 Cognitive performance on tests of immediate memory, attention,11 and processing speed12 was reported to be inferior in patients with MDD who met criteria for remission, compared with healthy subjects. Meta-analyses show that cognitive deficits in executive function are still present in remitted patients,13,14 which may explain persistent psychosocial impairment in remission. While it is beyond the scope of our paper to review the underlying pathophysiology, recent evidence points to neural mechanisms that also support a neurocognitive model of depression.15 Overall, cognitive dysfunction, work, and psychosocial limitations are prevalent in patients with current and remitted depression.10 Therefore, we hypothesize that cognitive dysfunction may be a major mediator of psychosocial limitations in patients with MDD. We aimed to review recent evidence that cognitive dysfunction is a mediator of functional disability in MDD, and that pharmacotherapy and psychotherapy specifically target the cognitive domain. We conducted a PubMed literature search for the period from January 2000 up to January 2014 to identify relevant studies (search strategy available on request) for this review.