Emotional processing, motivational processing, and cognitive processing each require interactions within and among specific brain networks. Common psychiatric illnesses involve varying degrees of dysregulation in these three domains. Although major depressive disorder may be considered primarily an illness of emotional dysregulation, it also involves significant cognitive changes. What do we mean by cognitive changes? Cognition is defined in the Psychiatric Glossary of the American Psychiatric Association as “… the mental process of comprehension, judgment, memory, and reasoning as contrasted with emotional and volitional processes.” The Merriam-Webster Dictionary defines cognition as “the activities of thinking, understanding, learning, and remembering.” Depressive disorders are associated with problems in multiple cognitive domains including attention (concentration), memory (learning), and decision making (judgment).

The cognitive changes associated with depression likely contribute to the disabilities experienced by persons with this disorder. As reported by the World Health Organization, major depression is one of the world’s most disabling illnesses.

Many individuals with major depressive disorder respond to treatment. A variety of antidepressants and evidenced-based psychotherapies can be effective in diminishing the non-cognitive symptoms of depression. However, the scales used to measure improvement in depressive symptoms do not contain objective assessments of cognitive deficits, and clinical examinations use relatively crude tools to assess changes in cognition.

In a recent study published in Lancet Psychiatry, Carrie Shilyansky and colleagues describe the influence of antidepressant treatment on the cognitive deficits associated with major depression.

Over 1,000 adults between the ages 18 and 65 (mean age of 37.8 years) who suffered from major depressive disorder were enrolled into this study. None was taking antidepressant medication at the start of the study. In order to measure various aspects of cognition, the investigators administered a variety of neuropsychological tests to individuals before and after treatment with one of three antidepressants. This same 40-minute test battery was administered to a group of age- and education-matched healthy persons in order to control for the possibility of improved performance related to a practice effect of taking the test battery twice.

Over the eight weeks of the study, approximately 45% of individuals experienced remission of clinical symptoms after treatment with an antidepressant. (Remission was defined as improvement below a specified cut-off score on a depression rating scale, reflecting a low level of residual symptoms.) The investigators wanted to know whether performance on cognitive tests also improved in this group of people who responded to treatment.

Prior to treatment, these individuals demonstrated diminished abilities in seven cognitive domains: attention, response inhibition, verbal memory, executive function, cognitive flexibility, decision speed, and information processing. Following treatment and remission of clinical symptoms, these individuals still demonstrated impairment in five of these seven areas. The two cognitive areas that showed improvement were executive function and cognitive flexibility.

For the purposes of this discussion, the exact nature of each of these cognitive areas is less important than the fact that five of the seven cognitive domains remained compromised after the non-cognitive symptoms of depression improved. This suggests that persons with a history of depression may still be handicapped by the cognitive deficits of this illness after other depressive symptoms improve. This pattern occurred independent of which of the three antidepressants was utilized.

In this study, only executive function and cognitive flexibility responded to antidepressant treatment. These findings strongly suggest that different components of the cognitive dysfunction associated with depression may be differentially responsive to antidepressant treatment.  

Psychotherapies, such as cognitive behavioral therapy, can lead to improvement in the clinical symptoms of depression. Do effective psychotherapies also lead to improvement in some or all of the associated cognitive deficits associated with depression? This remains unknown. It is certainly possible that various psychotherapies and pharmacotherapies could differentially influence the cognitive deficits of depression. This possibility makes it imperative to understand the magnitude and time course of cognitive dysfunction in the context of depression. Individuals who have resolution of mood symptoms but not cognitive symptoms could be at high risk for relapse, particularly when they are trying to function in complex work and social environments where their cognitive defects could impact performance.

It is important to recognize that major depression is associated with cognitive impairment, which may persist after other symptoms of the illness remit. As more research is done to elucidate the nature of these deficits and develop better ways to treat them, hopefully we will be able to say that depression is a fully treatable illness sometime in the future. In the meantime, it is important to recognize that some people with depression may not be equipped to function in complex environments, even when their mood symptoms are under control.

This column was written by Eugene Rubin MD, PhD and Charles Zorumski MD.

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