New Type of Depression Identified by Stanford Medicine Researchers

Introduction

Stanford Medicine researchers have identified a new type of depression, the “cognitive biotype,” accounting for 27% of patients whose symptoms are not effectively managed by typical antidepressants. The cognitive biotype exhibits impaired cognitive functions, such as planning and self-control, and reduced activity in specific brain areas, suggesting the need for more targeted treatments.

Uncovering the Cognitive Biotype

Researchers, utilizing methods such as surveys, cognitive examinations, and brain scans, have uncovered a form of depression impacting approximately one-fourth of patients. The objective is to diagnose and treat the condition more precisely.

• A study carried out by researchers from Stanford Medicine has identified a novel type of depression known as the “cognitive biotype.”
• This newly classified form of depression affects approximately 27% of people suffering from depression and is not effectively treated by commonly prescribed antidepressants.
• These patients, identified by cognitive tasks, demonstrated challenges in planning ahead, exhibiting self-control, maintaining concentration in the presence of distractions, and suppressing inappropriate behavior.
• Brain imaging revealed diminished activity in two brain areas responsible for these tasks.

Targeting Cognitive Dysfunctions

Because depression has traditionally been defined as a mood disorder, doctors commonly prescribe antidepressants that target serotonin (known as selective serotonin reuptake inhibitors or SSRIs), but these are less effective for patients with cognitive dysfunction. Researchers said that targeting these cognitive dysfunctions with less commonly used antidepressants or other treatments may alleviate symptoms and help restore social and occupational abilities.

Study Details

The study, recently published in JAMA Network Open, is part of a broader effort by neuroscientists to find treatments that target depression biotypes, according to the study’s senior author, Leanne Williams, Ph.D., the Vincent V.C. Woo Professor and professor of psychiatry and behavioral sciences.

• In the study, 1,008 adults with previously unmedicated major depressive disorder were randomly given one of three widely prescribed typical antidepressants: escitalopram (brand name Lexapro) or sertraline (Zoloft), which act on serotonin, or venlafaxine-XR (Effexor), which acts on both serotonin and norepinephrine.
• Before and after treatment with the antidepressants, the participants’ depressive symptoms were measured using two surveys — one, clinician-administered, and the other, a self-assessment, which included questions related to changes in sleep and eating.
• The participants also completed a series of cognitive tests, before and after treatment, measuring verbal memory, working memory, decision speed, and sustained attention, among other tasks.
• Pre-treatment fMRI showed those with the cognitive biotype had significantly reduced activity in the dorsolateral prefrontal cortex and dorsal anterior cingulate regions during the GoNoGo task compared with the activity levels in participants who did not have the cognitive biotype.

Implications for Treatment

After treatment, the researchers found that for the three antidepressants administered, the overall remission rates — the absence of overall depression symptoms — were 38.8% for participants with the newly discovered biotype and 47.7% for those without it. This difference was most prominent for sertraline, for which the remission rates were 35.9% and 50% for those with the biotype and those without, respectively.

Williams and Hack propose that behavior measurement and imaging could help diagnose depression biotypes and lead to better treatment. A patient could complete a survey on their own computer or in the doctor’s office, and if they are found to display a certain biotype, they might be referred to imaging for confirmation before undergoing treatment.

Conclusion

Researchers at the Stanford Center for Precision Mental Health and Wellness are studying another medication — guanfacine — that specifically targets the dorsolateral prefrontal cortex region. They believe this treatment could be more effective for patients with the cognitive subtype. Further studies will be conducted to compare different types of medication with treatments such as transcranial magnetic stimulation and cognitive behavioral therapy.

“I regularly witness the suffering, the loss of hope, and the increase in suicidality that occurs when people are going through our trial-and-error process,” Hack said. “And it’s because we start with medications that have the same mechanism of action for everyone with depression, even though depression is quite heterogeneous. I think this study could help change that.”