KL2 Scholar Studies Inflammation's Effects on Weakened Reward Circuits in Depression

In those with depression, about one-third have high levels of C-reactive protein (CRP), a marker of inflammation, in their blood. Inflammation is the immune system’s natural response to infection or disease, and the body uses this to protect itself – in typical scenarios, one might see this with a sprained ankle, but the same concept also applies to the brain. Too much inflammation, however, can have adverse effects.

Emory researchers have found that patients with major depressive disorder (MDD) and high levels of inflammation (CRP) exhibited a lack of communication between two parts of their brain: the ventral striatum (associated with decision making and reward behaviors) and the ventromedial prefrontal cortex (associated with processing risk and fear, emotional responses, and decision making), which together regulate motivation and reward. Patients with high inflammation and these changes in reward circuitry also had higher levels of anhedonia, a core symptom of MDD that reflects a loss of capacity to feel pleasure. Anhedonia is also associated with a lack of motivation, and is a difficult symptom to treat in patients with MDD and other psychiatric illnesses.

Jennifer Felger, PhD, MSc, Assistant Professor of Psychiatry and Behavioral Sciences, Emory University School of Medicine and Winship Cancer Institute, former Atlanta Clinical & Translational Science Institute (ACTSI) KL2-Mentored Clinical and Translational Research Scholar, and ACTSI Master of Science in Clinical Research (MSCR) graduate, studies the effects of inflammatory cytokines on neurotransmitters and neural circuits as they relate to behavioral change. Her latest research, recently published in Molecular Psychiatry, supports the idea that the high-inflammation form of depression is distinct.

Felger’s previous research involving nonhuman primates suggested that cytokines, which mediate the inflammatory response, reduce the brain chemical dopamine to lead to anhedonic and depressive behavior. By blocking inflammation or its effects on neurotransmitters in the brain, like dopamine, there is a possibility of reversing anhedonia and helping individuals who fail to respond to antidepressants.

She is planning to test whether L-DOPA, a medicine that increases dopamine, can improve connectivity in reward-related brain regions in patients with high-inflammation depression, a study supported by the Emory University Research Committee/ACTSI Pilot Grants program and by the Dana Foundation. While depression is a complex illness, these investigations will hopefully lead to new innovative therapies for treating this specific high-inflammation depression.

“The ACTSI KL2 program has provided me with resources to collect clinical neuroimaging data that has resulted in important publications and funding from the Dana Foundation, Brain and Behavioral Research Foundation, and the American Cancer Society. Through the MSCR program, I have received mentorship and didactic training in biostatistics, clinical trial design, and ethics, which have provided a foundation for my clinical research,” said Felger. “Importantly, the ACTSI KL2 and MSCR programs have allowed me to develop relationships with a network of clinical and translational researchers in Atlanta. Together these resources have broadened my horizons with translational research and contributed greatly to my developing career at Emory.”

The goal of the ACTSI KL2-Mentored Clinical and Translational Research Scholars (MCTRS) program is to support career development for junior faculty (MD, PhD, or MD/PhD) from a wide variety of disciplines at Emory University, Morehouse School of Medicine, and Georgia Institute of Technology (Georgia Tech) to become independent, established, and ethical clinical and/or translational research investigators. KL2 scholars receive salary support, a budget for their research, and tuition for the MSCR degree. 

The Emory Master of Science in Clinical Research (MSCR) degree program, from the Laney Graduate School at Emory University, provides didactic and mentored clinical and translational research training. The degree is designed for participants at Emory and Georgia Tech who hold a doctorate or equivalent degree (such as physicians and PhD-level scientists) or predoctoral trainees enrolled in a dual degree program (MD/MSCR and PhD/MSCR tracks) and have demonstrated a commitment to a career in clinical investigation. MSM also has an MSCR program for MSM applicants supported through a Research Centers in Minority Institutions (RCMI) grant.

ACTSI is a city-wide partnership between Emory, Morehouse School of Medicine, and Georgia Tech and is one of over 60 in a national consortium striving to improve the way biomedical research is conducted across the country. The consortium, funded through the National Center for Advancing Translational Sciences (NCATS) and the National Institutes of Health’s Clinical and Translational Science Awards, shares a common vision to translate laboratory discoveries into treatments for patients, engage communities in clinical research efforts, and train the next generation of clinical investigators.

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