Erik Anderson, M.D.
2019 Career Development Awardee
Feinstein Institute for Medical Research
Mentor: Meggan Mackay, MD, MS
Study: Tryptophan Pathway Activation by Interferon-alpha: Impact on Mood and Cognition in SLE
About the Researcher
Erik Anderson’s research involvement began as an undergraduate at Johns Hopkins University, where he majored in psychological and brain sciences. His interest in brain and behavior first led him to the lab, where he worked with a mouse model of schizophrenia. This research investigating pathogenic mechanisms and potential drug targets aligned with his interest in medicine.
Dr. Anderson completed medical school and residency at Stony Brook University. His interest in rheumatology was sparked by fascinating cases, and his concern in applying the best practices in the field spurred his initiation of several clinical outcomes and quality improvement projects. He began his rheumatology fellowship at Northwell Health, and his desire to pursue a career as an independent clinician-scientist led him to enter the Ph.D. program in molecular medicine. The department’s current work studying the relationship of cognitive and behavioral disturbances in systemic lupus erythematosus (SLE) to autoantibodies and brain imaging offered Dr. Anderson the unique opportunity to combine his interests in psychology, neuroscience, and SLE while working alongside leaders in the field.
Depression and cognitive dysfunction (CD) are highly prevalent in SLE. IFNα contributes to SLE pathogenesis, associates with these phenotypes independent of SLE, and stimulates the kynurenine/tryptophan (KYN/TRP) pathway, causing an increase in quinolinic acid (QA) relative to kynurenic acid (KA) that predisposes to neurotoxicity. This metabolite imbalance is associated with depression, CD, and changes in brain structure and function. We hypothesize that IFNα contributes to SLE-mediated CD and depression through activation of the KYN/TRP pathway.
This is a prospective, observational one-year study of 74 female SLE subjects and 74 healthy controls (HC) without history of focal neurologic or primary psychiatric disorders. SLE subjects have been recruited with a broad range of disease activity, and follow-up visits occur with a change in disease activity from baseline, or at 6 months. HC subjects are followed at six months. All subjects have neuropsychological testing and phlebotomy for TRP, KYN, QA and KA levels, as well as IFNα gene expression. SLE subjects are assessed for disease activity, disease damage, and medication use. A subset of SLE and HC subjects have brain imaging.
We predict 1) SLE subjects will have higher serum KYN/TRP and QA/KA ratios than HC; 2) IFNα gene expression in SLE will correlate with these ratios, 2a) these ratios and IFNα gene expression will vary longitudinally according to disease activity, 2b) these ratios and IFNα gene expression will correlate with depression and CD, both cross-sectionally and longitudinally; and 3) these ratios and IFNα gene expression in SLE will correlate with regional brain metabolism, volumes, microstructural integrity, and altered binding of CNS5161 (marker of NMDA receptor activation).
Biomarkers for SLE-related depression or CD are unavailable. This study of associations between IFNα and TRP metabolites using neuropsychological tests and neuroimaging will determine their relationship to these phenotypes, identify potential biomarkers, and highlight possible therapeutic targets.
Abstracts and Publications
- Anderson E*, Kello N*, Diamond B. Cognitive Dysfunction in Systemic Lupus Erythematosus: A Case for Initiating Trials. Arthritis Rheumatol. 2019 Sep; 71(9):1413-1425. PMID:31102496.
* co-first authors
- Ploran E, Tang C, Mackay M, Small M, Anderson E, Storbeck J, Bascetta B, Kang S, Aranow C, Sartori C, Watson P, Volpe B, Diamond B, Eidelberg D. Assessing cognitive impairment in SLE: examining relationships between resting glucose metabolism and anti-NMDAR antibodies with navigational performance. Lupus. 2019 Jul 11;6(1): e000327. PMID:31413849.
- Mackay M, Vo A, Tang CC, Small M, Anderson E, Ploran EJ, Storbeck J, Bascetta B, Kang S, Aranow C, Sartori C, Watson P, Volpe BT, Diamond B, Eidelberg D. Metabolic and microstructural alterations in the SLE brain correlate with cognitive impairment. JCI Insight. 2019 Jan 10;4(1). pii:124002. PMID: 30626758.
- Anderson E, Ploran E, Hong J, Diamond B, Volpe B, Aranow C, Mackay M. The Impact of Disease Activity and Related Factors on Cognitive Dysfunction in SLE [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10).
- Anderson E, Vo A, Ploran E, Diamond B, Volpe B, Aranow C, Eidelberg D, Mackay M. Anti-NMDA Receptor Antibodies in Systemic Lupus Erythematosus Associate with Decreased White Matter Integrity and Impaired Spatial Memory [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10).
- Anderson E, Ploran EJ, Diamond B, Volpe B, Aranow C, Mackay M. Spatial Navigation Impairment Associated with Anti-NMDA Receptor Antibodies in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10).
- Anderson E, Ploran E, Fishbein J, Mackay M. Activation of the Kynurenine/Tryptophan Pathway by Interferon-α and its Relation to Depression and Cognitive Dysfunction in SLE. ACR Rheumatology Research Workshop, St. Louis, MO, June 2017.
For more information on Lupus Foundation on America’s granted research, please contact Ashley Marion at [email protected]