Depression Studies

Repeated head impacts from playing contact sports can lead to inflammation in the brain that impacts mood, memory and concentration. This study is being done to learn more about the role of inflammation in depressive and cognitive symptoms in individuals who have played at least 11 years of contact football and may be at risk for chronic traumatic encephalopathy (CTE). This will be tested using a medication called baricitinib that reduces inflammation by inhibiting Janus kinase (JAK) signaling. The study is enrolling men aged 30 to 55 years who have played 11+ years of tackle football and are currently experiencing depressive and cognitive symptoms. Qualifying participants will also have high inflammation as determined by a blood test, and be asked to complete psychiatric and medical assessments, MRI scans of the brain, and to take study medication over a period of eight weeks. At least six in-person visits will occur at Emory University in Atlanta, GA, including screening. If you are interested in participating, please fill out this survey.

Many people with depression also have high inflammation, which may be a cause of some of their depression symptoms. This study is being done to learn how inflammation affects the brain to cause symptoms of depression like anhedonia, low motivation and motor slowing. This will be tested using a medication called baricitinib that blocks one aspect of inflammation involving Janus Kinase (JAK) signaling. The study will enroll individuals with depression and symptoms of anhedonia who have high inflammation as determined by a blood test. Qualified participants will be assessed for markers of inflammation in the blood and symptoms of depression over at least eight visits including screening. In addition, brain scans and computerized testing will be done to measure brain function and levels of motivation and motor speed. Understanding a roll for JAK signaling could lead to new treatments for depression symptoms linked to higher inflammation. If you are interested in participating, please fill out this survey.

Depression is a widespread disorder that affects over 20 million adults in the United States. Current antidepressant medications are effective for some patients; however, many patients fail to respond or continue to experience symptoms of anhedonia like reduced motivation or the inability to experience pleasure. Our previous studies show that inflammation is one biological pathway that can impact the brain to drive symptoms of depression like anhedonia. We have also found that inflammation-related changes in brain reward circuits are reversed by increasing the neurotransmitter dopamine. This study will determine whether an FDA approved medication that increases dopamine could serve as a potential new therapy for depressed patients with anhedonia and higher levels of inflammation. For more information on this study please click here or if you are interested in participating in this study, please fill out this survey.

The risk of depression is substantially higher in people with HIV (PWH) than the general population, and depression in PWH confers worse outcomes regarding treatment adherence, morbidity, and mortality. Risk for depression is further increased in PWH with elevated biomarkers of inflammation, e.g., the acute phase reactant C-reactive protein (CRP), that contributes to resistance to antidepressant therapies. Moreover, increased inflammation in the context of chronic depression in PWH is characterized by worsened cognitive function including impaired processing speed and motor activity. Our recent neuroimaging studies in HIV-negative patients with major depression (MD) demonstrate that endogenous elevations in inflammation (as reflected by increased plasma CRP) are associated with decreased functional connectivity (FC) within corticostriatal reward and motor circuits involving the ventral and dorsal striatum and frontal cortical regions in relation to symptoms of anhedonia and psychomotor retardation. Anhedonia and psychomotor slowing represent fundamental aspects of research domain criteria (RDoC) of Positive and Negative Valence systems and are closely aligned with a symptom cluster overrepresented in PWH referred to as apathy, which is thought to be driven by similar medial prefrontal and subcortical circuitry. Previous work from our group also suggests that reducing inflammation with a traditional cytokine antagonist improves symptoms of anhedonia and psychomotor retardation in HIV-negative patients with MD, but only in patients with higher levels of CRP. These data suggest the hypothesis that inflammation plays a role in anhedonia and motor slowing through effects on corticostriatal reward and motor circuits in PWH.

Members of our study team have performed extensive pre-clinical and clinical work on the Janus Kinase (JAK 1/2) inhibitor drug class for disorders associated with immune dysregulation including inflammation. Baricitinib is one of these compounds and is an FDA-approved, orally bioavailable agent for treatment of rheumatoid arthritis (RA) with recent FDA-approval for treatment of acute COVID-19. The JAKs are members of the cytoplasmic tyrosine kinase group that act to phosphorylate various signal transducers and activators of transcription (STATs) that then translocate to the nucleus and bind to specific transcription sites. This binding promotes the production of a variety of inflammatory mediators including interleukin (IL)-6, tumor necrosis factor (TNF), CRP and others. Thus, the key hallmark of the efficacy of baricitinib in human studies across disease states is its ability to significantly reduce plasma IL-6, TNF, and CRP and ultimately inflammation.

This study will use a biomarker-driven approach to test the hypotheses that inhibition of inflammation through specific inhibition of JAK 1/2 inflammatory signaling pathways will increase FC in corticostriatal reward and motor circuits and improve anhedonia and psychomotor slowing in association with reduced plasma inflammatory markers, as well as additional CSF, neuroimaging, peripheral blood immune cell, and markers of inflammation and the HIV reservoir in PWH with MD and high inflammation. Click here if you wish to participate

Inflammation can increase kynurenine, a molecule that may affect brain function. This study tests whether the amino-acid leucine can block kynurenine from entering the brain through a gateway, potentially improving depression, pleasure (anhedonia), and clarity of thinking.Participants are randomly assigned to take leucine or a comparison amino acid (lysine) daily for 6 weeks. The study includes brain scans and assessments of mood and motivation at the start and end. Both amino-acids are purified part of dietary protein. Eligible participants are ages 30-65 with current symptoms of low motivation or difficulty experiencing pleasure. Contact the study team for more information.

Many people with depression experience low energy, reduced motivation and difficulty experiencing pleasure. Research suggests that inflammation and metabolic health, including how the body processes glucose, may affect brain circuits involved in reward and motivation. The AIM study examines these relationships using an oral glucose tolerance test, a standard glucose drink that allows us to measure the body's metabolic response. We measure brain function, motivation and blood-based markers of inflammation and metabolism before and after the glucose drink. Qualified participants will complete medical and psychiatric assessments, blood draws, MRI brain scans and a computerized motivation task during two visits at Emory University. If you are interested in participating, please complete this survey.

GLP-1-based medications improve metabolic health by helping regulate blood glucose and appetite and may also reduce inflammation. However, how these changes relate to mood, energy, motivation and brain function in people with depression is not yet well understood. This observational study follows people with depression who are planning to begin a GLP-1 medication or have recently started one as part of their regular medical care. The study does not provide, prescribe or manage GLP-1 treatment; medication decisions remain under the supervision of each participant's healthcare provider. Participation lasts approximately eight weeks and includes an initial screening, brief weekly surveys, and in-person visits at baseline and week eight. Study procedures include questionnaires, blood draws and computerized testing of motivation; eligible participants may also complete MRI brain scans. If you are interested in participating, please complete this survey.