Cognitive Decline as a Primary Concern in Major Depressive Disorder

One-Off 'Low Cost' Intervention Helps Prevent Depression in Teenagers
One-Off ‘Low Cost’ Intervention Helps Prevent Depression in Teenagers
Cognitive impairment in individuals with major depressive disorder should be treated as a primary problem.

Major depressive disorder (MDD) is one of the most common mental disorders in the United States, according to the National Institute of Mental Health. In 2012, an estimated 16 million adults aged 18 years or older in the United States had at least one major depressive episode in the previous year, representing 6.9% of all adults.

According to the World Health Organization, major depressive disorder carries the heaviest burden of disability among mental and behavioral disorders.1 It’s likely that the burden of disease is attributable to multiple factors, including mood disturbances and cognitive dysfunction. The impact from cognitive impairment is likely twofold because it serves as both a primary and secondary factor associated with the condition.

“Cognitive difficulties come secondary to lack of energy, motivation, and lack of interest in MDD. These features likely impair an individual’s ability to be focused and mentally engaged, having a secondary effect,” said Roger McIntyre, MD, Head of the Mood Disorders Psychopharmacology Unit at the University Health Network-Toronto Western Hospital in Canada.

“We also learned that depression is a disturbance in brain function, in which the brain circuits become disrupted, similar to the motherboard on a computer that is comprised of circuits,” McIntyre, a member of Psychiatry Advisor’s editorial board, added. “The circuits in the brain that are responsible for cognitive function are abnormal in structure and function. Individuals with MDD have disturbances in brain circuits relative to performing cognitively, which is a secondary manifestation and core primary problem.”

Morbidity Tied to MDD Linked to Cognitive Dysfunction

More recently, the morbidity associated with MDD has been shown to be associated with cognitive decline, which is very similar to other mental disorders, including bipolar disorder and schizophrenia.

“When we look at morbidity of mental disorders that affect individuals and society at large, there is some component that is attributable to cognitive dysfunction,” McIntyre said. “It is important because cognitive dysfunction can affect how an individual fulfills a role in society, [such as] contributing to the economy, society, and family.”

The goal of treatment is to increase quality of life and functioning by not only improving mood but also addressing cognition.

“It is no secret that outcomes in psychiatry have been disappointing to date, in part because of our lack of ability to modify measures of cognition,” he noted. “The burden of mental illness is largely a statement of cognitive problems. If we could improve and prevent cognitive outcomes, overall outcomes would improve for the individual and the society at large.”

Risk Factors Contributing to MDD and Cognitive Impairment

Risk factors tied to MDD and cognitive dysfunction include sociodemographic, clinical, and treatment factors. In terms of sociodemographic factors, older age and lower educational levels contribute to MDD and cognitive impairment. In terms of clinical factors, people with depression that is especially severe, recurrent, or chronic are more likely to have cognitive difficulties.

In addition, the prescription medications people take for MDD can interfere with cognitive function, because these can make the patient drowsy or sleepy.

Addressing Cognition Separately in Treatment Considered New Approach

The FDA has not yet approved any treatments for cognitive decline associated with MDD.

“Until recently, cognitive function in MDD hasn’t been something physicians have been thinking about. We knew it was part of the condition but didn’t realize it could be an independent factor tied to the condition,” said McIntyre.

The first step in treating MDD and cognitive decline is to treat the depression fully and effectively, according to McIntyre. Unfortunately, ongoing cognitive problems persist, even with improvement in overall depressive symptoms and the use of stimulants to address cognitive dysfunction.2,3

McIntyre and his colleagues looked at the new antidepressant vortioxetine (Brintellix) to evaluate the effects on mood and cognition separately and independently.4

“For the first time ever, we showed that an antidepressant medication improved measures of cognitive dysfunction in younger adults with MDD. This improvement was impactful and clinically relevant. The benefit that was seen was in the domain of cognitive function, independent of depressive symptoms. In addition, the benefits that were seen [were] not only in objective measures of cognition but also in self-rated measures of cognition,” said McIntyre.

Overall, cognitive dysfunction is very common during depressive episodes and is also a criterion item for diagnosis of MDD. In addition, once the depressive symptoms lift, cognitive dysfunction is a residual factor that needs to be addressed.

Beth Gilbert is a freelance writer based in West Palm Beach, Florida. This article has been medically reviewed by Pat F. Bass III, MD, MS, MPH.


    1.   National Institute of Mental Health. “Major Depression Among Adults.” Available at: Accessed: September 29, 2014.

    2.   McIntyre RS. “Major Depressive Disorder and Cognitive Impairment.” J Psychiatry Neurosci. 2014; 39 (5): E36-37.

    3.   McIntyre RS et al. “Cognitive Deficits and Functional Outcomes in Major Depressive Disorder: Determinants, Substrates, and Treatment Interventions.” Depress Anxiety. 2013; 30 (6): 515 -527.

    4.   McIntyre RS, et al. “A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults.” International J  Neuropsychopharmacol. 2014; 17: 1557-1567.

This article originally appeared on Psychiatry Advisor