Project Summary
This project investigates the role of the immune system in brain function and depression in a nonclinical population. Major depression is the most prevalent and disabling noncommunicable disease worldwide, accounting for 1% GDP in Europe, and increasing risk for other illnesses (e.g., heart disease, dementia, cancer). Traditional drugs are only effective in 33% of cases (with more severe depression). It is therefore important to identify novel strategies to treat milder forms of depression. This requires a fundamental understanding of implicated brain and body mechanisms. Four brain systems, measured using brain scanning methods, have been proposed to underpin depression. These networks underpin symptoms of negative mood (e.g., sadness), rumination (repetitive negative thoughts), inflexibility in thinking and loss of pleasure/motivation. Alterations in these brain networks may be underpinned by changes in brain chemicals that are affected by the immune system and the presence of molecules that cause inflammation. This is because enzymes produced during inflammation affect how an amino acid known as Tryptophan is broken down (or catabolised). However, no study has yet investigated the relationship between tryptophan catabolism and the four brain networks implicated in depression. The student will work within a cross-college, multidisciplinary team with expertise in psychology, immunology, nutrition, aging, oncology, and biochemistry to undertake basic biological investigation of the association between inflammation, tryptophan catabolites and brain function. In the first week, the student will receive induction and training on brain scan methods, specifically a technique known as electroencephalography (EEG). In weeks 2-7, they will work in a team, assisting their supervisor and bench manager in collecting EEG data and blood samples, respectively. Participants will also complete self-reports of depression and associated personality traits. We have other researchers on this project that the student can also learn with. The student would attend our weekly research group meetings and can engage online with our international research networks. Whilst the student’s work would be in the general population, this cohort would act as control in one of three larger studies. Depending on the student’s interest, they could work on prostate cancer, nutrition and healthy aging and/or neurological disorder studies. Thus, there would be opportunities for the student to expand this work in various directions in the context of a PhD. We would anticipate the student’s involvement in data collection taking approximately 16 hours per week. Also, in this time, the student will learn how to perform signal processing of EEG data; and a technique used to measure inflammatory molecules and tryptophan catabolites, known as enzyme-linked immunosorbent assay. In the final weeks, the student would apply these skills to the data they have collected. Finally, also in the ninth week, they would prepare and present a presentation to our international research group on their work.
Full Project Details
This project investigates tryptophan catabolites in brain networks implicated in depression in a nonclinical population. Major depression is the most prevalent and disabling noncommunicable disease worldwide, accounting for 1% GDP in Europe, and increasing risk for other illnesses (e.g., heart disease, dementia, cancer). Traditional antidepressants are only effective in 33% of cases (with more severe depression). It is therefore important to identify novel strategies to treat milder forms of depression. This requires a fundamental understanding of implicated brain and body mechanisms. Four brain networks, measured using neuroimaging methods, have been proposed to underpin depression. These include two networks for negative affectivity (including amygdala) and self-referential thoughts (default mode network) that are hyperactive; and two networks implicated in cognitive control (central executive) and reward (basal ganglia) that are under active. These networks underpin symptom/cognition clusters of dysphoria, rumination, cognitive inflexibility and anhedonia. Alterations in these brain networks may be underpinned by deficiency in monoamine systems and excessive amygdaloid glutamatergic activity. The presence of inflammation drives tryptophan catabolism through induction of indoleamine (2,3)-dioxygenase, preventing the synthesis of serotonin and increasing the presence of tryptophan catabolites, such as kynurenine (an NMDA antagonist) and quinolinic acid (a neurotoxic NMDA agonist). Whilst some studies have explored the relationship between the presence of pro-inflammatory biomarkers and neurocognitive function, no study has yet investigated the relationship between tryptophan catabolites and the four brain networks implicated in depression. The student will work within a cross-college, multidisciplinary team with expertise in psychology, immunology, nutrition, aging, oncology, and biochemistry to undertake basic biological investigation of the association between inflammatory biomarkers (e.g., CRP, IL-6), tryptophan catabolites and brain function (assessed using electroencephalography, EEG). In the first week, the student will receive induction and training on EEG. In weeks 2-7, they will work in a team, assisting their supervisor and bench manager in collecting EEG data and blood samples, respectively. Participants will also complete self-reports of depression and associated personality traits. We have other researchers on this project that the student can also learn with. The student would attend our weekly research group meetings and can engage online with our international research networks. Whilst the student’s work would be in the general population, this cohort would act as control in one of three larger studies. Depending on the student’s interest, they could work on prostate cancer, nutrition and healthy aging and/or functional neurological disorder studies. Thus, there would be opportunities for the student to expand this work in various directions in the context of a PhD. We would anticipate the student’s involvement in data collection taking approximately 16 hours per week. Also, in this time, the student will learn how to perform signal processing of EEG data; and enzyme-linked immunosorbent assay for inflammatory molecules (e.g., C-reactive protein, IL-6) and tryptophan catabolites (kynurenine, quinolinic acid). In the final weeks, the student would apply these skills to the data they have collected. Finally, also in the ninth week, they would prepare and present a presentation to our international research group on their work.