expert roundtables

Exploring the Domains of Cognition in Patients With MDD

by Joseph F. Goldberg, MD, Roger McIntyre, MD, Michael E. Thase, MD

Overview

Major depressive disorder (MDD) often presents with cognitive dysfunction in domains such as attention, executive functions, memory, or psychomotor speed. However, unlike bipolar disorder and schizophrenia, the focus in the field of cognition in MDD is a relatively recent one. Here, expert panelists discuss the conceptual framework for understanding deficits in cognition in patients with MDD.

Q: How do deficits in the various individual domains of cognition impact patients with MDD?

Roger McIntyre, MD

Professor of Psychiatry and Pharmacology
University of Toronto
Head, Mood Disorders Psychopharmacology Unit
University Health Network
Toronto, Ontario

"Clearly, if one is a schoolteacher, or an accountant, or a worker on the assembly line at General Motors, there are potentially going to be very different implications on the effects of a single cognitive deficit."

Roger McIntyre, MD

As relates to cognition and the 4 domains we talk about (ie, executive function, memory, attention, and processing speed), I think that this type of mediational approach may be instructive from the patient-reported outcome or the functional perspective. And much of this is going to be intuitive, since there is not yet that level of refinement in this area.

When one looks at cognition and health outcomes in mood disorders, one knows that the depression is relevant, but taking separate domains and distilling things down based on the individual domains—there has been a bit less work done on that sort of thing. I do recall that when Judith Jaeger, PhD, published her paper, one of the first studies in MDD examining cognition 6 months after discharge from an inpatient visit, that there were select domains of cognition that were more or less correlative of (and some were to be predictive of) functional outcomes.

When considering the cognitive domains and their impact on outcomes, this would also depend on what the individual patient’s level of functioning was to begin with—and what their job is. Clearly, if one is a schoolteacher, or an accountant, or a worker on the assembly line at General Motors, there are potentially going to be very different implications on the effects of a single cognitive deficit. Something else that is interesting is that if a person is higher-functioning but has MDD, he or she may be more likely to achieve remission, all else being equal, when compared with someone who has a lower level of function at baseline. And we see this in STAR*D and other studies.

When we examined the data for vortioxetine, it we saw that performance across these 4 cognitive domains was even greater in people who where higher functioning to begin with. So, in addition to the effect of cognitive deficits on a person’s function, it also seems to be the case that a person’s function may influence the changeability of their cognitive performance; so, it is somewhat bidirectional.

Joseph F. Goldberg, MD

Clinical Professor of Psychiatry
Icahn School of Medicine
Mount Sinai
New York, NY

"When one looks at what we are calling residual symptoms of depression, this might actually be slowed information processing, impaired concentration, anhedonia, and associative fluency."

Joseph F. Goldberg, MD

One of the overarching issues here is that it depends on how you define cognition and what rightfully belongs under that category. Dr McIntyre has spoken eloquently elsewhere about, things that we traditionally think of as “depression symptoms” may more rightfully be subsumed under cognition. Even symptoms such as anhedonia and reward-based behaviors may speak to executive pathways and prefrontal cortical functioning.

When one talks about “responders” to a pharmacological treatment for MDD, the patient may have residual symptoms, as is common, or the patient may even have a rating scale score in the single digits, but not zero; and then, one looks at the functional outcomes that lag behind. When one looks at what we are calling residual symptoms of depression, this might actually be slowed information processing, impaired concentration, anhedonia, and associative fluency.

There is, therefore, something akin to a Venn diagram of overlap between the cognitive symptoms of depression (ie, in the neuropsychological sense) and the things that we conceptualize separately as elements of cognition, irrespective of mood. Those may be the things that lead patients to lag behind (ie, as relates to planning, organization, follow through, motivation, reward-based behaviors, and implementing and executing their plans and intentions) despite the fact that their energy might improve after treatment for other symptoms of depression.

Michael E. Thase, MD

Professor of Psychiatry
Director, Mood and Anxiety Disorders
Treatment and Research Program
University of Pennsylvania
Philadelphia, PA

"If you are not back to your “best self” or your “well self” then you are not able to perceive subtlety, you may not have your same sense of humor, you may not be able to execute problem solving strategies as efficiently, and you certainly may not have the creative capacity to rise above the circumstances to come up with a unique explanation or a unique solution."

Michael E. Thase, MD

In the modern era, we are now seeing patients with MDD who are better, on treatment, but who are having subtle difficulties that do really get in the way of their lives. So, that is how I think of the association of persistent cognitive impairment and psychosocial disability. If you are not back to your “best self” or your “well self” then you are not able to perceive subtlety, you may not have your same sense of humor, you may not be able to execute problem-solving strategies as efficiently, and you certainly may not have the creative capacity to rise above the circumstances to come up with a unique explanation or a unique solution. And if all of those things—or even some of those things—are true, then you are not really yourself. You are a shadow of yourself, and that’s going to affect how you feel, and it’s going to affect your relationships.

References

Jaeger J, Berns S, Uzelac S, et al. Neurocognitive deficits and disability in major depressive disorder. Psychiatry Res. 2006;145(1):39-48.

Mahableshwarkar AR, Zajecka J, Jacobson W, et al. A randomized, placebo-controlled, active-reference, double-blind, flexible-dose study of the efficacy of vortioxetine on cognitive function in major depressive disorder. Neuropsychopharmacology. 2015;40(8):2025-2037.

McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol. 2014;17(10):1557-1567.

McIntyre RS, Harrison J, Loft H, et al. The effects of vortioxetine on cognitive function in patients with major depressive disorder: a meta-analysis of three randomized controlled trials. Int J Neuropsychopharmacol. 2016;19(10):pyw055.

Jaeger J, Berns S, Uzelac S, et al. Neurocognitive deficits and disability in major depressive disorder. Psychiatry Res. 2006;145(1):39-48.

Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-1917.

More in Major Depressive Disorder

Thumb

Major Depressive Disorder

New Insights on Generalized Anxiety and Resiliency at the Workplace

Clinical Study Insights by Roger McIntyre, MD

Clinical Study Title:Efficacy of vortioxetine in working patients with generalized anxiety disorderClinical Study Abstract:Background: Vortioxetine...READ MORE

Thumb

Major Depressive Disorder

Depressive Rumination in Executive Function: Role Still Unclear

Clinical Study Insights by Ira D. Glick, MD

Clinical Study Title:Cognitive Impairments in Unipolar Depression: The Impact of RuminationClinical Study Abstract:There is little scientific under...READ MORE

Thumb

Major Depressive Disorder

Procognitive Effects of Exercise in Depression

Clinical Study Insights by Madhukar Trivedi, MD

Clinical Study Title:Evaluation of the Benefits of Exercise on Cognition in Major Depressive DisorderClinical Study Abstract:Cognition plays an imp...READ MORE

More In Psychiatry

Tardive Dyskinesia

Dopamine Receptor–Blocking Agent Exposure In The Pathophysiology Of Tardive Dyskinesia

Clinical Topic Updates by Andrew J. Cutler, MD

Tardive Dyskinesia

Antipsychotic Switching Strategies In Tardive Dyskinesia

Clinical Topic Updates by Andrew J. Cutler, MD

Tardive Dyskinesia

Clinical Trials, Long Term Follow Up, And Experience With Vmat2 Inhibitors

Clinical Topic Updates by Andrew J. Cutler, MD