The BIG Study for Depression is a cutting-edge, placebo-controlled clinical trial that aims to assess whether treatment with a medication called guanfacine, which is currently FDA-approved for attention deficit disorder and high blood pressure, modifies brain activity, decreases cognitive and depressive symptoms, and improves quality of life in individuals with a putative cognitive subtype of depression.
The Biomarker Guide (BIG) Study for Depression
Overview
Depression is the leading cause of disability worldwide, and delays in achieving remission exacerbate disability. Thus, we urgently need to establish biomarkers that will allow clinicians to define and detect specific subtypes of depression that are not likely to remit on standard therapies, and to guide the choice of novel alternative therapies based on underlying brain circuit dysfunction. A promising candidate for such a circuit biomarker is dysfunction in the dorsolateral prefrontal cortex (DLPFC) accompanied by cognitive impairment. Some depressed patients show DLPFC hypoactivation during cognitive function tasks involving working memory and planning. Cognitive impairment is a leading cause of non-remission to conventional antidepressants and contributes disproportionately to poor outcomes and risk of suicide. Immediate release guanfacine, a highly selective 2A (α2A) receptor agonist with high binding potential in the DLPFC, is a promising alternative therapy for modifying DLPFC-related cognitive impairment in depression. The BIG Study will test whether guanfacine preferentially improves DLPFC activity, symptoms, and quality of life in a putative cognitive subtype of depression as compared to depressed individuals without this subtype. Results will have broad implications for advancing novel target-engagement trials of therapies based on mechanisms selective for specific impairments in subtypes of depression.
Sign Up to Participate
If you are interested in participating in the study, please complete the following online screening survey:
Filling out the online screening survey means you’re putting your name on our waitlist, and we’ll contact you as soon as possible. If we do not contact you right away, it means we may not be currently recruiting participants, but we'll be in touch as soon as possible once the study becomes active again.
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Thank you for your interest in our studies!
Our Methods
Our Goals
We have four aims in the BIG Study for Depression:
Aim 1: To determine whether guanfacine will impact DLPFC dysfunction (hypo-activation) in depressed individuals experiencing cognitive impairment.
Aim 2: To assess whether guanfacine in subjects with a DLPFC dysfunction-defined cognitive biotype improves cognitive impairment as measured by commonly used neurocognitive tasks.
Aim 3: To determine whether guanfacine preferentially improves self-reported cognitive symptoms in subjects with a DLPFC dysfunction-defined cognitive biotype.
Aim 4: To assess whether guanfacine taken by subjects with a DLPFC dysfunction-defined cognitive biotype enhances the impact of a selective therapy on functional capacity and suicidality.
We use a variety of methods to assess the impact of guanfacine on the brain, behavior, symptoms, and quality of life in depressed individuals.
NeuoStudy Arm:
Neuropsychiatric Symptom Assessments
Clinical diagnostic interview & surveys to understand each person’s life experience and assess the severity of depression, anxiety, and other mood disorders
1
Neurocognitive Assessments
Behavioral measurements aimed at quantifying memory, executive functioning, and problem solving
2
Neural Circuit Assessments
Brain scans to map with precision the connections among brain circuits and their relative dysfunction, using the classification of imaging biotypes
3
Infectious Disease Arm:
Immunological Assessments
Neuroinflammatory biomarkers and other physical diagnostic information to be used in association with imaging biotypes
1
Meet the Team
Leyla Boyar
Rachel Hilton
Jenna Jubeir
Shanee Regev
Findings
This study is currently collecting data.
Funding
This study is supported through a generous donation from the Cushman Family Foundation.
Contact Us
If you are interested in learning more about the Biomarker Guided (BIG) Study for Depression, please feel free to:
Phone: 650-600-1609
Send us an email at williams-panlab@stanford.edu​ or pmhw_admin@stanford.edu