Immune-Mediated Neuropsychiatric Disorders

Organizers: Mady Hornig, Columbia University; Betty Diamond, Columbia University

Speakers: Susan Swedo, National Institutes of Mental Health, NIH; Andy Miller, Emory University; Betty Diamond, Columbia University

The Neuroimmunology Discussion Group focuses on the interface between the immune system and the nervous system both in the brain and in the periphery, in normal and pathological conditions. This highly interdisciplinary group seeks to bring together immunologists and neuroscientists interested in exploring the intersection of these two fields in periodic meetings that will include discussions of basic, clinical, and translational aspects of this emerging field.

Abstracts

Childhood-onset Obsessive Compulsive Disorder and the PANDAS Subgroup: Are Contamination Fears Justified?: Susan Swedo

Obsessive-compulsive disorder (OCD) is characterized by the presence of recurrent, intrusive thoughts (obsessions) and/or repetitive, intentional acts or behaviors (compulsions). Although once considered to be the result of psychological trauma, such as punitive toilet training, scientific research and clinical experience has demonstrated that OCD is brain-based and multi-factorial in etiology.

The etiologic heterogeneity made it difficult to elucidate the nature of the obsessive-compulsive symptoms, so researchers sought to identify homogeneous subgroups for study. One such subgroup is known by the acronym PANDAS – Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. The PANDAS subgroup of patients is characterized by five clinical criteria: 1) Presence of OCD and/or tics; 2) Prepubertal symptom onset; 3) Abrupt onset and episodic course; 4) Presence of neurological signs, such as choreiform movements; and 5) Exacerbations triggered by Group A beta-hemolytic streptococcal (GAS) infections.

Sydenham chorea, the neurological variant of rheumatic fever, serves as the medical model for the PANDAS subgroup. In Sydenham chorea, symptoms appear to arise as sequelae of untreated infections with GAS (i.e., "strep throat" infections). The streptococcal bacteria incite the production of antibodies, which cross-react with components of the host's brain, and produce an "autoimmune" reaction.

Since the autoimmune reaction is the result of molecular mimicry, and not an innate loss of tolerance, interventions which modulate the acute immune response can shorten the duration of symptoms, and prophylactic antibiotics are effective in preventing future infection-triggered symptom exacerbations. The process appears to be similar in the PANDAS subgroup, providing new opportunities for treatment of the children's OCD symptoms, and also paving the way towards identifying markers of disease susceptibility and preventing symptom onset.

Cytokines Sing the Blues: Inflammation and the Pathogenesis of Depression: Andy Miller

There is increasing interest in the possibility that the immune system may play a role in the development of psychiatric disorders. Specifically, recent data indicate that activation of the immune system in the form of inflammation may play a role in the pathogenesis of depression.

Indeed, depressed patients have been found to exhibit all of the cardinal features of inflammation, including elevations in proinflammatory cytokines, acute phase reactants, chemokines and cellular adhesion molecules. Moreover, administration of inflammatory cytokines has been found to induce depression-like symptoms in laboratory animals and humans.

Of note, proinflammatory cytokines and their signaling pathways have been shown to interact with virtually every pathophysiologic domain that characterizes depression, including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity and behavior. Interestingly, data suggest that stress, which is a well-known precipitant of depression, is also capable of promoting inflammatory responses; an effect that is exaggerated in depressed patients.