Depression: Understanding the Cognitive Biotype and Effective Treatments
Introduction
Stanford Medicine scientists have recently conducted a groundbreaking study that has shed new light on the complexity of depression. Their research has identified a new category of depression known as the cognitive biotype, which affects approximately 27% of depressed patients. Moreover, this specific form of depression has been found to be less responsive to commonly prescribed antidepressant medications. This article delves into the details of the study and explores the implications of this new finding.
The Cognitive Biotype: An Overview
A significant finding of the study conducted by Stanford Medicine scientists is the identification of the cognitive biotype of depression. This biotype is characterized by difficulties in cognitive functioning, including the ability to plan ahead, exhibit self-control, maintain focus, and suppress inappropriate behaviors. These cognitive dysfunctions are accompanied by decreased activity in the brain regions responsible for these tasks, as revealed by functional magnetic resonance imaging (fMRI) scans.
Traditionally, depression has been defined as a mood disorder, leading doctors to primarily prescribe antidepressants that target serotonin, such as selective serotonin reuptake inhibitors (SSRIs). However, these medications are found to be less effective in treating patients with cognitive dysfunction, highlighting the need for alternative treatments for this biotype.
Addressing Cognitive Dysfunctions: Alternative Treatments
To effectively manage depression in patients with the cognitive biotype, researchers recommend exploring alternative treatments beyond commonly prescribed antidepressants. By addressing the cognitive dysfunctions specifically, symptoms can be alleviated, and social and occupational skills can be restored. The study suggests considering less frequently used antidepressants or other treatments to target the cognitive biotype and improve patient outcomes.
One of the challenges in treating depression effectively is the current trial and error approach. Incorporating objective cognitive measures, such as imaging, can help tailor treatments to individual patients, ensuring that the same treatment is not applied universally. This personalized approach has the potential to significantly improve outcomes for those with the cognitive biotype of depression.
The Study and Its Methodology
The study involved 1,008 adults diagnosed with major depressive disorder who had not previously received any medication. These participants were randomly assigned to one of three widely prescribed antidepressants: escitalopram (Lexapro), sertraline (Zoloft), or venlafaxine-XR (Effexor). Prior to and after the eight-week treatment period, participants’ depressive symptoms were measured using surveys administered by physicians and self-assessments. Additionally, cognitive tests were conducted to assess various aspects of cognitive functioning.
To further understand the cognitive biotype, the researchers performed fMRI scans on a subset of participants. The scans were conducted while participants performed a cognitive task called “GoNoGo.” The results of the scans revealed differences in neural activity between individuals with the cognitive biotype and those without it.
Effectiveness of Antidepressants on the Cognitive Biotype
The study also evaluated the effectiveness of the three antidepressants in treating depressive symptoms in patients with the cognitive biotype. Overall, the remission rates (absence of general depressive symptoms) varied among the different medications. While all three medications showed some level of effectiveness, sertraline demonstrated the highest remission rates for participants without the cognitive biotype, while the remission rates were slightly lower for participants with the biotype.
These findings emphasize the importance of personalized treatment approaches for depression. By recognizing and targeting specific biotypes, medical professionals can individualize care, leading to better outcomes for patients.
Looking Towards Personalized Treatment for Depression
The discovery of the cognitive biotype of depression opens up new possibilities for personalized treatment options. In addition to traditional antidepressant medications, researchers are exploring other avenues, such as guanfacine, to specifically target the cognitive dysfunctions associated with this biotype. Guanfacine focuses on the region of the brain responsible for cognitive control, which is impaired in individuals with the cognitive biotype.
Furthermore, researchers are interested in comparing the effectiveness of different types of drugs, such as transcranial magnetic stimulation (TMS), and cognitive behavioral therapy (CBT) in treating the cognitive biotype. TMS involves the use of magnetic fields to stimulate nerve cells, while CBT focuses on teaching patients problem-solving strategies to counter negative thoughts contributing to emotional dysregulation and impaired social and occupational functioning.
By examining and addressing the specific cognitive dysfunctions associated with the cognitive biotype, a more targeted and effective approach to depression treatment is within reach.
Conclusion
The groundbreaking study conducted by Stanford Medicine scientists has unveiled the cognitive biotype of depression, shedding new light on this complex condition. By understanding the cognitive dysfunctions inherent in this biotype, alternative treatment approaches can be explored, potentially improving outcomes for patients who do not respond well to commonly prescribed antidepressants.
With further research and the development of personalized treatment options, the future of depression management looks promising. By moving beyond the one-size-fits-all approach and recognizing the diversity of depression presentations, medical professionals can tailor treatments to individuals, providing them with the best chances for recovery and improved quality of life.
Summary
Stanford Medicine scientists conducted a study that has identified a new form of depression called the cognitive biotype. This biotype affects approximately 27% of depressed patients and is not effectively treated with commonly prescribed antidepressants that target serotonin. The study highlights the importance of addressing cognitive dysfunctions associated with the cognitive biotype using alternative treatments. By personalizing treatment approaches and considering less frequently used antidepressants or other interventions, symptoms can be alleviated, and social and occupational skills can be restored. The study’s findings have significant implications for the field of depression research and treatment, paving the way for more targeted and effective interventions in the future.
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Stanford Medicine scientists conducted a study describing a new category of depression, called the cognitive biotype, which accounts for 27% of depressed patients and is not effectively treated with commonly prescribed antidepressants.
Cognitive tasks showed that these patients have difficulties with the ability to plan ahead, show self-control, maintain focus despite distractions, and suppress inappropriate behavior; the images showed decreased activity in two brain regions responsible for those tasks.
Because depression has traditionally been defined as a mood disorder, doctors often prescribe antidepressants that target serotonin (known as selective serotonin reuptake inhibitors, or SSRIs), but these are less effective for patients with cognitive dysfunction. The researchers said that addressing these cognitive dysfunctions with less frequently used antidepressants or other treatments can alleviate symptoms and help restore social and occupational skills.
The study, published June 15 in JAMA Open Networkit’s part of a larger effort by neuroscientists to find treatments that target biotypes of depression, according to the study’s lead author, Leanne Williams, PhD, the Vincent VC Woo professor and professor of psychiatry and behavioral sciences.
“One of the big challenges is finding a new way to approach what is currently a trial and error process so that more people can improve sooner,” Williams said. “Incorporating these objective cognitive measures, such as imaging, will ensure that we are not using the same treatment on all patients.”
find the biotype
In the study, 1,008 adults with major depressive disorder without prior medication 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 serotonin and norepinephrine. Seven hundred twelve of the participants completed the eight-week regimen.
Before and after treatment with antidepressants, participants’ depressive symptoms were measured using two surveys, one administered by a physician and the other, a self-assessment, which included questions related to changes in sleep and eating. Measures of social and occupational functioning, as well as quality of life, were also tracked.
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.
Before treatment, the scientists scanned 96 of the participants using functional magnetic resonance imaging as they performed a task called “GoNoGo” that requires participants to press a button as quickly as possible when they see green “Go” and not press when they see “Go” in green. see “NoGo” in red. The fMRI tracked neural activity by measuring changes in blood oxygen levels, which showed levels of activity 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.
The researchers 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 regions of the brain, a profile they called a cognitive biotype.
“This study is crucial because psychiatrists have few depression measurement tools to help make treatment decisions,” said Laura Hack, MD, PhD, lead author of the study and assistant professor of psychiatry and behavioral sciences. “It’s mostly about making observations and self-report measures. Imaging while performing cognitive tasks is quite new in depression treatment studies.”
Pretreatment fMRI showed that those with the cognitive biotype had significantly reduced activity in the dorsolateral prefrontal cortex and dorsal anterior cingulate regions during the GoNoGo task compared to activity levels in participants without the cognitive biotype. . Together, the two regions form the cognitive control circuitry, which is responsible for limiting unwanted or irrelevant thoughts and responses and improving target selection, among other tasks.
After treatment, the researchers found that for the three antidepressants administered, overall remission rates (the absence of general depressive symptoms) were 38.8% for participants with the newly discovered biotype and 47.7% for those with the newly discovered biotype. they didn’t have 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.
“Depression presents in different ways in different people, but finding commonalities, such as similar brain function profiles, helps medical professionals effectively treat participants by individualizing care,” Williams said.
Depression Is Not One Size Fits All
Williams and Hack propose that behavioral measurement and imaging could help diagnose depression biotypes and lead to better treatment. A patient can complete a survey on their own computer or in the doctor’s office, and if they are found to display a certain biotype, they can be referred for imaging to confirm this before undergoing treatment.
Researchers at the Stanford Center for Precision Mental Health and Wellness, led by Williams, in collaboration with Stanford’s Precision Translational Mental Health Clinic, led by Hack, are studying another drug, guanfacine, which specifically targets the region of the dorsolateral prefrontal cortex with support from the Innovative Medicines Accelerator at Stanford University. They believe that this treatment could be more effective for patients with the cognitive subtype.
Williams and Hack hope to conduct studies with participants who have the cognitive biotype, comparing different types of drugs with treatments such as transcranial magnetic stimulation and cognitive behavioral therapy. In transcranial magnetic stimulation, commonly known as TMS, magnetic fields stimulate nerve cells; In cognitive behavioral therapy, patients are taught to use problem-solving strategies to counter negative thoughts that contribute to both emotional dysregulation and loss of social and occupational skills.
“I am a regular witness to the suffering, loss of hope, and increased suicidality that occurs when people go through our trial and error process,” Hack said. “And it’s because we started with drugs 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.”
Investigators from the Sierra-Pacific Clinical, Educational and Research Center for Mental Illness; the Palo Alto Veterans Affairs Health Care System; Center for Brain Dynamics, Westmead Institute for Medical Research; and the University of Sydney, Westmead contributed to the work.
The study was funded through Brain Resource Company Operations Pty Ltd. and the Stanford University Translation and Clinical Sciences Awards Program overseen by the National Center for the Advancement of Translation Sciences at the National Institutes of Health. (grant UL1TR003142-01).
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