• Science Update
A likely mechanism by which a bacterial infection triggers obsessive compulsive disorder (OCD) in some children has been demonstrated by scientists at the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) and collaborators at California State University (CSU) and the University of Oklahoma (UO). Their research suggests that an antibody against strep throat bacteria sometimes mistakenly acts on a brain enzyme, disrupting communications between neurons and causing a form of obsessive compulsive and related tic disorder in children — pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS).
When added to cultured neurons, three fourths of blood samples from acute, symptomatic PANDAS cases boosted the brain enzyme to significantly higher levels than samples from recovering, non-symptomatic patients. Similarly, nearly three-fourths of the blood samples from symptomatic cases contained antibodies for strep, compared to only 23 percent of samples from recovering, non-symptomatic patients. PANDAS patients' cerebrospinal fluid (CSF), which bathes the brain and directly reflects its activity, contained highly elevated levels of the suspect strep-triggered enzyme, while CSF of non-PANDAS subjects contained little or none. NIMH's Drs. Susan Swedo and Lisa Snider, Christine Kirvan (CSU) and Madeleine Cunningham (UO) report on their discovery in the July 26, 2006 online edition of the Journal of Neuroimmunology.
Although Swedo and her team had long hypothesized such a strep-triggered process in which antibodies gone awry disrupt brain activity, the specific players involved were unclear. To identify them, the researchers followed up clues from their studies of Sydenham chorea , which is marked by involuntary movements and speech impediments, and is thought to be the neurological counterpart of rheumatic fever, which is known to result from a strep-triggered autoimmune process in which the body attacks itself.
All patients with the movement disorder had high levels of the strep antibody that induced activity of the enzyme, thought to play a role in making and releasing neurotransmitters, most notably glutamate, which is implicated in OCD. In addition to the above findings, the researchers showed that PANDAS blood samples cleansed of the antibody failed to activate the enzyme.
Swedo and colleagues propose that in PANDAS somewhat lower levels of enzyme activity than seen in chorea may contribute to OCD symptoms. Although how the antibodies cross the blood-brain barrier remains a mystery, the researchers say the new findings provide insights into how antibodies against strep may disrupt neuronal communications and cell function.
Kirvan CA, Swedo SE, Snider LA, Cunningham MW. Antibody-mediated neuronal cell signaling in behavior and movement disorders . J Neuroimmunol. 2006 Jul 26; [Epub ahead of print]