A New Subtype of Depression Has Been Identified

Researchers have identified a new subtype of depression affecting about one in four patients, which is less responsive to common antidepressants.

Nearly one in five American adults have been diagnosed with depression in their lifetime, according to 2020 data. Although a wide variety of antidepressants is available to people with the condition, about 60% of patients with major depressive disorder (MDD) experience some degree of nonresponse to first-line treatments.

The newly identified subtype of depression — labeled the cognitive biotype — is characterized by slowed thinking, sleeping problems, poor social and occupational function, and a weaker response to commonly prescribed antidepressants. The research team led by Stanford University hopes that the identification will lead to better diagnosis and treatment of the condition.


The study that appeared in JAMA Network Open involved 1,008 adults 37.8 years old on average with previously unmedicated MDD. They were randomly assigned to one of three widely prescribed antidepressants: escitalopram (brand name Lexapro) or sertraline (Zoloft), each of which acts on serotonin, or venlafaxine-XR (Effexor), which acts on both serotonin and norepinephrine. Of all participants, 712 completed the eight-week regimen.

Before and after treatment with medications, the participants’ depressive symptoms were measured using two surveys that included questions related to changes in sleep and eating. The researchers also tracked measures of social and occupational functioning and quality of life.

Additionally, before and after taking antidepressants, participants completed a series of cognitive tests evaluating verbal memory, working memory, and decision speed, among other tasks.

Before treatment, scientists scanned 96 participants using functional magnetic resonance imaging (fMRI) to track their neuronal activity by measuring changes in blood oxygen levels, which showed activity levels in different brain regions. Researchers then compared the participants’ images with those of individuals without depression.

The study found that 27% of the participants had more prominent symptoms of cognitive slowing and insomnia, impaired cognitive function on behavioral tests, as well as reduced activity in certain frontal brain regions, a profile labeled the cognitive biotype of depression.

After treatment, 38.8% of participants with the newly identified biotype and 47.7% of those without it went into remission, defined as the absence of overall depression symptoms. The difference was most pronounced for sertraline, for which the remission rates were 35.9% and 50% for those with the biotype and those without, respectively.

The authors acknowledge the possibility that other behavioral or neurobiological factors that weren’t identified in the study contribute to the cognitive biotype. Moreover, further studies are needed to evaluate if the findings apply to the general population and other antidepressants and treatments.

Researchers say their findings underline the urgent need for treatments specifically targeting cognitive impairment and its mechanisms in depression. Only one antidepressant approved by the US Food and Drug Administration — vortioxetine — has shown promise for improving cognition. However, the mechanisms underlying the drug’s cognitive-enhancing effects are unknown.


The identification of a new subtype of depression defined by slowed thinking and sleeping problems may help to improve the treatment.


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