Cognitive biotypes: new depression subcategories identified that upend conventional treatments

summary: Researchers have discovered a new subtype of depression, the ‘cognitive biotype,’ that affects 27% of patients who respond poorly to commonly prescribed antidepressants. These patients struggle with planning, self-control, staying focused, and inhibiting inappropriate behavior, and brain scans reveal decreased activity in areas responsible for these tasks.

The study suggests the potential benefits of less commonly used antidepressants and other treatments for cognitive impairment in reducing symptoms and restoring performance. The study is part of a larger effort to tailor treatments to specific depression biotypes, leading to more accurate and effective treatments.

Important facts:

1. The study included 1,008 previously medication-naive adults with major depressive disorder who were randomized to one of three commonly prescribed antidepressant medications. administered for 8 weeks.
2. Researchers found that patients with the cognitive biotype had more significant symptoms of cognitive decline and insomnia, cognitive decline on behavioral tests, and reduced activity in specific frontal brain areas. bottom.
3. The overall remission rate after treatment in patients with the cognitive biotype was significantly lower than in patients without this biotype, especially with the use of the antidepressant sertraline.

sauce: Stanford

Scientists at Stanford Medicine conducted a study describing a new category of depression called cognitive biotypes. This category accounts for 27% of patients with depression and cannot be effectively treated with commonly prescribed antidepressants.

Cognitive task results indicated that these patients had difficulty planning ahead, exercising self-control, staying focused despite distractions, and inhibiting inappropriate behavior. Imaging studies showed decreased activity in two of her brain regions responsible for these tasks.

Depression has traditionally been defined as a mood disorder, so doctors commonly prescribe antidepressants that target serotonin (known as selective serotonin reuptake inhibitors or SSRIs), but these also impair cognitive function. It is less effective in patients with

Researchers found that targeting these cognitive impairments with less commonly used antidepressants and other treatments may reduce symptoms and help restore social and occupational abilities. says that there is

The study was published June 15. JAMA network openAccording to Leanne Williams, PhD, lead author of the study and Vincent V.C. It is said that it is part of the efforts.

“One of the big challenges is finding new ways to address the currently trial-and-error process so more people can recover faster,” Williams said.

“By introducing objective cognitive measures like image processing, we can ensure that we are not applying the same treatment to every patient.”

find a biotype

In this study, 1,008 previously medication-naive adults with major depressive disorder were randomly given one of three typical antidepressant drugs that are widely prescribed. escitalopram (trade name Lexapro) or sertraline (Zoloft), which act on serotonin, or venlafaxine-XR (an effector), which acts on serotonin. For both serotonin and noradrenaline.

Of the participants, 712 completed the 8-week dosing regimen.

Participants’ depressive symptoms were measured using two surveys before and after antidepressant treatment. One was a clinician-administered survey and the other was a self-assessment that included questions about changes in sleep and diet. Measures of social and occupational functioning and quality of life were tracked as well.

Participants also completed a battery of cognitive tests measuring verbal memory, working memory, decision-making speed, and sustained attention before and after treatment.

Before treatment, scientists scanned 96 of the participants with functional magnetic resonance imaging and performed a task called “GoNoGo.” In this task, participants are asked to press the button as soon as possible when the green “Go” appears, and not to press the button once it appears. See red “NoGo”.

fMRI tracked neuronal activity by measuring changes in blood oxygen levels and showed activity levels in different brain regions corresponding to Go or NoGo responses. The researchers then compared the images of the participants with those of people without depression.

Researchers found that 27% of participants had more pronounced symptoms of cognitive decline and insomnia, cognitive decline on behavioral tests, and reduced activity in specific frontal brain areas. bottom. This profile was termed the cognitive biotype.

“This study is very important because psychiatrists have few tools to measure depression to help them make treatment decisions,” said Laura Hack, lead author of the study and assistant professor of psychiatry and behavioral sciences. said the doctor of medicine.

“Mainly observational and self-reported measurements. Imaging while performing cognitive tasks is fairly new in depression treatment research.”

On pretreatment fMRI examination, participants with a cognitive biotype had significantly greater dorsolateral prefrontal and dorsal anterior cingulate activity during the GoNoGo task compared to activity levels in participants without a cognitive biotype. was shown to decrease to

Together the two areas form a cognitive control circuit that is responsible for limiting unwanted or irrelevant thoughts and reactions and improving goal selection, among other tasks.

After treatment, the researchers found that the overall remission rate (absence of overall depression symptoms) for the three antidepressants administered was 38.8% among participants with the newly discovered biotype. , 47.7% of participants who did not.

This difference was most pronounced with sertraline, with remission rates of 35.9% and 50% in patients with and without biotype, respectively.

“Even though depression can vary from person to person, finding commonalities, such as similar profiles of brain function, can help medical professionals effectively treat participants by individualizing care.” It helps,” Williams said.

Depression is not a panacea

Williams and Huck propose that behavioral measurements and imaging may help diagnose depression biotypes, leading to better treatments. Patients can complete the survey on their own computer or in the clinic, and if found to exhibit a particular biotype, they can undergo imaging studies for confirmation before undergoing treatment.

Researchers at Williams’ Stanford Precision Mental Health and Wellness Center, in partnership with Huck’s Stanford Translational Precision Mental Health Clinic, support Stanford University In response, he is investigating another drug, guanfacine, which specifically targets the dorsolateral prefrontal cortex region. University Innovative Medicines Accelerator.

They think this treatment may be more effective for patients with the cognitive subtype.

Williams and Huck hope to conduct studies comparing different types of medication with treatments such as transcranial magnetic stimulation and cognitive-behavioral therapy in participants with cognitive biotypes.

In transcranial magnetic stimulation, commonly called TMS, a magnetic field stimulates nerve cells. In cognitive-behavioral therapy, patients are taught to use problem-solving strategies to combat negative thoughts that cause emotional dysregulation and loss of social and occupational abilities.

“I regularly witness the suffering, the loss of hope and the increased suicide rate that occurs when people are going through a process of trial and error,” Huck said. “And that’s because we start with drugs that have the same mechanism of action for all depressed people, even though there are so many different types of depression. I think this study can help change that.” ”

Researcher at the Sierra Pacific Psychiatric Research, Education and Clinical Center. Veterans Administration Palo Alto Medical System. The Brain Dynamics Center, Westmead Institute of Medicine; The University of Sydney, Westmead contributed to this study.

This study was funded through the Brain Resource Company Operations Pty Ltd. and the Clinical Translational Sciences Award Program at Stanford University overseen by the National Center for the Advancement of Translational Sciences at the National Institutes of Health (grant UL1TR003142-01). .

About this Depression Research News

author: Emily Moscow
sauce: Stanford
contact: Emily Moscal – Stanford
image: Image credited to Neuroscience News

Original research: open access.
“Cognitive biotypes and symptoms of depression, behavioral measures, neural circuits, and different treatment outcomes” By Rian Williams et al. JAMA network open

overview

Cognitive biotypes and symptoms of depression, behavioral measures, neural circuits, and different treatment outcomes

Importance

Cognitive impairment in depression is associated with decreased functional capacity, dysfunction of frontal neural circuits, and worsened response to conventional antidepressants. However, whether these disorders combine to identify specific cognitive subgroups (or ‘biotypes’) in patients with major depressive disorder (MDD), and to what extent these disorders influence antidepressant efficacy. It is unknown whether

the purpose

To undertake systematic testing of the validity of proposed cognitive-biological types of MDD across neural circuits, symptoms, social-occupational functioning, and treatment outcome modalities.

Design/Settings/Participants

In this secondary analysis of randomized clinical trials, we implemented data-driven clustering of the results of international studies for predicting optimal treatment in depression. This is an actionable biomarker trial randomizing MDD patients to antidepressant treatment with escitalopram in a 1:1:1 ratio. , sertraline, or venlafaxine, and were evaluated from December 1, 2008 to September 30, 2013 for multimodal outcomes at baseline and 8 weeks. Eligible patients were non-pharmacological outpatients with at least moderate-range nonpsychotic MDD and were recruited. From 17 clinical and academic practices. Some of these patients underwent functional magnetic resonance imaging. This prespecified secondary analysis was performed between 10 June 2022 and 21 April 2023.

Main achievements and measures

Pre- and post-treatment behavioral measures of cognitive performance across nine domains, depressive symptoms assessed using two standard depression scales, and social and occupational functioning rating scales and World Health Organization life Psychosocial functioning, which was assessed using the Quality Scale, was analyzed. Neural circuit functions involved during cognitive control tasks were measured using functional magnetic resonance imaging.

result

A total of 1,008 patients (571) [56.6%] female; average [SD] Age, 37.8 years old [12.6] years) participated in the entire trial and 96 patients participated in the imaging substudy (45) [46.7%] female; average [SD] Age, 34.5 years old [13.5] Year). Cluster analysis identified what she termed a cognitive biotype in 27% of depressed patients with marked behavioral deficits in response-inhibition domains of executive function and cognitive control. This biotype was characterized by a specific profile of pretreatment depressive symptoms, worsening psychosocial functioning (d= -0.25; 95% CI, -0.39 to -0.11. P.< .001), with decreased activation of cognitive control circuits (right dorsolateral prefrontal cortex: d= -0.78; 95% CI, -1.28 to -0.27; P.= .003). Remission was lower in the cognitive biotype-positive subgroup (73 of 188) [38.8%] vs 250/524 [47.7%]; P.= .04), and cognitive deficits persisted regardless of symptom changes (executive function: of_p²= 0.241;P.  <.001; reaction inhibition: of_p²= 0.750;P.< .001). The degree of symptoms and functional changes were mediated specifically by cognitive changes, but not vice versa.

Conclusion and relevance

Our findings support the existence of a cognitive biotype of depression with distinct neural correlates and poor response to standard antidepressants, instead benefiting from treatments specifically targeting cognitive impairment. suggesting the existence of a possible functional clinical profile.

Trial registration

ClinicalTrials.gov Identifier: NCT00693849