Scientists at Stanford Medicine indicated that they have identified a novel subtype of depression referred to as the cognitive biotype that appears to affect an estimated 27% of patients with major depressive disorder (MDD). The depression subtype is not effectively managed with the use of commonly prescribed antidepressants.

The researchers noted, “Cognitive tasks showed that these patients have difficulty with the ability to plan ahead, display self-control, sustain focus despite distractions, and suppress inappropriate behavior; imaging showed decreased activity in two brain regions responsible for those tasks.”

They also stated that since depression has conventionally been defined as a mood disorder, commonly prescribed antidepressants that target serotonin are used, but these are less effective for patients with cognitive dysfunction.

The researchers also noted that targeting these cognitive dysfunctions with less commonly prescribed antidepressants or other treatments may improve symptoms and help repair social and occupational abilities.

The findings from the study were recently published in the Journal of the American Medical Association Network Open and are a component of a more significant effort by neuroscientists to discover treatments that target depression biotypes. The study’s senior author, Leanne Williams, PhD, the Vincent V.C. Woo professor of psychiatry and behavioral science, stated, “One of the big challenges is to find a new way to address what is currently a trial-and-error process so that more people can get better sooner. Bringing in these objective cognitive measures like imaging will make sure we’re not using the same treatment on every patient.”

The study included 1,008 adults with previously unmedicated MDD who were randomly administered one of three selected commonly prescribed typical antidepressants. Seven hundred and twelve of the participants completed the 8-week regimen.

Before and after treatment with the antidepressants, the participants’ depressive symptoms were measured utilizing two surveys: one that was clinician-administered and one that was a self-assessment comprised of questions related to changes in sleep, eating, and measures on social and occupational functioning; quality of life was documented as well.

Before and after treatment, the participants also completed a series of cognitive tests that evaluated verbal memory, working memory, decision speed, and sustained attention, among other tasks.

The researchers found that 27% of the participants had more prominent symptoms of cognitive slowing and insomnia, impaired cognitive function on behavioral tests, and diminished activity in certain frontal brain regions—a profile they labeled the cognitive biotype.

Based on their findings, the authors concluded, “Our findings suggest the presence of a cognitive biotype of depression with distinct neural correlates and a functional clinical profile that responds poorly to standard antidepressants and instead may benefit from therapies specifically targeting cognitive dysfunction.”

They also noted, “These results suggest that consideration of treatments targeting cognitive dysfunction in a subset of patients with depression is warranted to attain symptomatic and psychosocial improvement.”

Laura Hack, MD, PhD, the study’s lead author and an assistant professor of psychiatry and behavioral sciences, stated, “This study is crucial because psychiatrists have few measurement tools for depression to help make treatment decisions. It’s mostly making observations and self-report measures. Imaging while performing cognitive tasks is rather novel in depression treatment studies.”

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