Autoimmunity in Tourette Syndrome and Tic Disorders

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of California
Investigators Name
Hoffman, Kurt, PhD

Tourette Syndrome (TS), tic disorders, and obsessive-compulsive disorder (OCD) have cooccurring symptoms such as tics, obsessive and intrusive thoughts, attentional deficits, and compulsive and repetitive behaviors. These disorders have a strong genetic basis for vulnerability, most often begin in childhood, and are linked to dysfunction in a group of brain structures called the basal ganglia. Many interacting genetic, environmental, and developmental factors could contribute to basal ganglia dysfunction, and therefore result in the symptoms of TS and OCD. During childhood, developing neural circuitry of the basal ganglia may be particularly vulnerable to environmental insults, including infection or abnormal immune responses to infectious agents. Such insults may perturb normal brain development or function and result in neurological and behavioral symptoms. Abnormal immune function associated with group A ß-hemolytic streptococcal (“strep throat”) infection has been proposed to be a factor in the pathogenesis of a subset of TS, chorea, tic disorders, and OCD. Dr. Susan Swedo and colleagues at the National Institutes of Health defined a subgroup of childhood-onset OCD that has an episodic course, marked exacerbation of symptoms associated with streptococcal infection, and other neurobehavioral abnormalities, including hyperactivity and tics. This diagnostic subtype is called PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection), and is believed to be caused by an abnormal immune response to the streptococcal infection that targets the basal ganglia and interrupts their function. I will test the hypothesis that basal ganglia autoimmunity is responsible for the tics and obsessive-compulsive symptoms seen in those who fit the criteria for PANDAS. One prediction is that antibodies directed against the basal ganglia may be present in the serum of these individuals. Using blood samples provided by Dr. Swedo, I will test for the presence of anti-basal ganglia antibodies and attempt to identify the cellular and molecular targets of these antibodies. These experiments may shed light on how abnormal antibody production in response to this common childhood infection causes psychiatric illness and movement disorders in a small group of children. A second prediction of this hypothesis is that experimentally-induced autoimmunity targeting the basal ganglia in an animal model system may result in behavioral abnormalities analogous to those seen in PANDAS. In mice, as in humans, the basal ganglia are responsible for the control of movement, and behavioral symptoms of basal ganglia dysfunction in mice are similar to those in humans. Using mice at several stages in early development, I will experimentally induce autoimmunity toward the basal ganglia, and perform behavioral tests for repetitive and tic-like behaviors. In addition to testing the autoimmune hypothesis of PANDAS, these experiments should define periods of developmental vulnerability of basal ganglia circuits to autoimmune or infectious insults. A long-term goal of these experiments is to establish a mouse model system in which to study the role of central nervous and immune system interactions in the development of neuropsychiatric symptoms. These studies may provide insights into the mechanisms of immune system dysfunction in TS and OCD, and lead to new strategies for prevention and treatment of these disabling neuropsychiatric disorders. Kurt L. Hoffman, Ph.D. University of California, Irvine, Irvine, CA $27,500 Tourette Association of America Inc. – Research Grant Award 2000-2001