Collateral Damage: How the Immune Response Can Cause Neuropsychiatric Illness
Posted May 01, 2007
The highly interdisciplinary field of psychoneuroimmunology addresses the dynamic interface between the immune system and the brain. For quite some time the immune system was regarded as the target of events arising in the brain. Recognition of the fascinating and far more complex reality of bi-directional communication between the brain and immune system—in which elements of the immune response itself are capable of significantly influencing events in the brain—emerged about 25 years ago. This bi-directional perspective now provides a fertile area for surprising and fundamental insights into central nervous system (CNS) pathologies that have, until now, proved highly elusive to understanding and effective treatment.
At a December 13, 2006, Academy meeting on the subject of psychoneuroimmunology researchers presented work on the involvement of specific inflammatory cytokines in the development of depression, research into the underpinnings of neuropsychiatric lupus, and an overview of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections), a patient subset of childhood onset obsessive-compulsive disorder.
Use the tabs above to find a meeting report and multimedia from this event.
Cytokines Sing the Blues: Inflammation and the Pathogenesis of Depression
Banks WA. 2006. The blood-brain barrier in psychoneuroimmunology. Neurol. Clin. 24: 413-419.
Blalock JE, Smith EM. 2007. Conceptual development of the immune system as a sixth sense. Brain Behav. Immun. 21: 23-33.
Capuron L, Hauser P, Hinze-Selch D, et al. 2002. Treatment of cytokine-induced depression. Brain Behav. Immun. 16: 575-580.
Capuron L, Neurauter G, Musselman DL, et al. 2003. Interferon-alpha-induced changes in tryptophan metabolism: relationship to depression and paroxetine treatment. Biol. Psychiatry 54: 906-914.
Miller AH, Raison CL. 2006. Cytokines, p38 MAP kinase and the pathophysiology of depression. Neuropsychopharmacology 31: 2089-2090.
Raison CL, Capuron L, Miller AH. 2006. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 27: 24-31.
Raison CL, Miller AH. 2003. Depression in cancer: new developments regarding diagnosis and treatment. Biol. Psychiatry 54: 283-294.
Raison CL, Miller AH. 2001. The neuroimmunology of stress and depression. Semin. Clin. Neuropsychiatry 6: 277-294.
Antibodies, Cognition and Behavior: Lessons From Lupus
Diamond B, Volpe B. 2003. On the track of neuropsychiatric lupus. Arthritis Rheum. 48: 2710-2712.
Kowal C, Degiorgio LA, Lee JY, et al. 2006. Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proc. Natl. Acad. Sci. USA 103: 19854-19859. FULL TEXT
Kowal C, DeGiorgio LA, Nakaoka T, et al. 2004. Cognition and immunity; antibody impairs memory. Immunity 21: 179-188. FULL TEXT
Rice JS, Kowal C, Volpe BT, et al. 2005. Molecular mimicry: anti-DNA antibodies bind microbial and nonnucleic acid self-antigens. Curr. Top. Microbiol. Immunol. 296: 137-151.
Childhood-onset Obsessive Compulsive Disorder (OCD) and PANDAS: Are Contamination Fears Justified?
Kirvan CA, Swedo SE, Snider LA, Cunningham MW. 2006. Antibody-mediated neuronal cell signaling in behavior and movement disorders. J. Neuroimmunol. 179: 173-179.
Kirvan CA, Swedo SE, Kurahara D, Cunningham MW. 2006. Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham's chorea. Autoimmunity 39: 21-29.
Snider LA, Lougee L, Slattery M, et al. 2005. Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biol. Psychiatry 57: 788-792.
Swedo SE, Grant PJ. 2005. Annotation: PANDAS: a model for human autoimmune disease. J. Child Psychol. Psychiatry 46: 227-234.
Perrin EM, Murphy ML, Casey JR, et al. 2004. Does group A beta-hemolytic streptococcal infection increase risk for behavioral and neuropsychiatric symptoms in children? Arch. Pediatr. Adolesc. Med. 158: 848-856.
Snider LA, Swedo SE. 2004. PANDAS: current status and directions for research. Mol. Psychiatry 9: 900-907.
Swedo SE, Leonard HL, Rapoport JL. 2004. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction. Pediatrics 113: 907-911. FULL TEXT
Snider LA, Swedo SE. 2003. Post-streptococcal autoimmune disorders of the central nervous system. Curr Opin Neurol. 16: 359-365.
Irwin MR, Vedhara K, eds. 2005. Human Psychoneuroimmunology. Oxford University Press, New York.
Andrew H. Miller, MD
Emory University School of Medicine
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Andrew Miller is an investigator in the Mind-Body Program in the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine.
Miller attended medical school at the Medical College of Georgia and graduated with his MD in 1981. He did his residency in psychiatry at the Albert Einstein College of Medicine/Montefiore Medical Center in the Bronx, New York, followed by a fellowship in biological psychiatry and psychopharmacology at Albert Einstein. During his fellowship, Miller began his first studies examining the impact of the neuroendocrine system on the immune system including studies on the effects of tricyclic antidepressants on immune function. While at Albert Einstein, Miller also received a Research Scientist Development Award, which he has held until the present.
Since joining the department at Emory University, Miller's research has focused on the impact of cytokines on glucocorticoid receptor function. He has demonstrated that proinflammatory cytokines, like IL-1, can impair glucocorticoid receptor function. Of note, in contrast to IL-1, he has shown that antidepressants can facilitate glucocorticoid receptor function. Most recently, Miller has returned to the clinical arena to study neuroendocrine-immune interactions in patients undergoing cytokine therapy for cancer or infectious diseases. Many of such patients develop significant clinical depression, and Miller is studying the mechanism and treatment of this depression as a model to understand depression in the medically ill. New data demonstrates that antidepressants may prevent the development of depression in cytokine-treated patients, possibly through direct effects on the glucocorticoid receptor.
Betty A. Diamond, MD
Feinstein Institute of Medical Research
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Betty Diamond is the head of the Center for Autoimmune Diseases at the Feinstein Institute of Medical Research, North Shore–Long Island Jewish Health System, which is part of the Albert Einstein College of Medicine.
Diamond received her MD from Harvard Medical School and completed her residency at Columbia Presbyterian Medical Center in New York. After postdoctoral work in immunology at Albert Einstein College of Medicine, she stayed at that institution for 25 years, holding various positions, including chief of rheumatology, director of the Medical Scientist Training Program, the Mitrani Chair in Cardiovascular Research and the Murray and Evelyne Weinstock Chair in Immunology. In 2004, Diamond joined the Departments of Medicine and Microbiology at Columbia University, College of Physicians and Surgeons, where she was the Dorothy and Daniel Silberberg Professor of Medicine and Microbiology. She was also chief of the Division of Rheumatology at Columbia University Medical Center.
Diamond is the recipient of many awards including the Scientific Leadership Award from the SLE Foundation, the Distinguished Investigator Award from the American College of Rheumatology, and the Howley Award from the Arthritis Foundation.
Susan E. Swedo, MD
U.S. National Institute of Mental Health (NIMH)
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Susan Swedo is associate director for Pediatric Research, and chief of the Pediatric & Developmental Neuropsychiatry Branch at the National Institute of Mental Health (NIMH). As a tenured investigator in the NIMH intramural research program, Swedo leads a clinical research team investigating the causes and treatment of pediatric neuropsychiatric disorders such as obsessive-compulsive disorder (OCD), anxiety disorders, and movement disorders, including Sydenham chorea and Tourette's Syndrome. Swedo and her colleagues were the first to identify a post-infectious subtype of OCD, which is known as PANDAS. This line of research has resulted in several novel treatment and prevention strategies for childhood-onset OCD, as well as a patent for a biological marker that can be used to identify at-risk children.
Swedo received her MD from Southern Illinois University School of Medicine in 1980 and completed her residency at Northwestern University's Children's Memorial Hospital. She began her career as a practicing pediatrician in Chicago, where she served as chief of Adolescent Medicine at the McGaw Medical Center of Northwestern University. Swedo moved to the Washington area in 1986 and joined the staff of Judy Rapoport's Child Psychiatry Branch, where she conducted research on a variety of childhood psychiatric disorders.
The recipient of numerous awards, including the Academy of Child and Adolescent Psychiatry Award for Scientific Achievement and the American College of Neuropsychopharmacology International Award for Clinical Research, Swedo is the author of more than 90 professional books and articles. She is also the co-author with Henrietta Leonard of two trade books: It's Not All in Your Head and Is It Just a Phase?—a parent's guide to childhood behavioral problems.
Sheila Sperber Haas
Sheila Sperber Haas is a freelance science and health care writer living in New York City who writes about issues ranging from molecular biology and immunology to complementary and alternative medicine. Her varied projects include Dermatology Focus, bringing the forefront of molecular investigative dermatology to a clinical readership.