High prevalence of obsessive-compulsive symptoms in patients with Sydenham's chorea

Swedo, Susan E.; Rapoport, Judith L.; Cheslow, Deborah L.; Leonard, Henrietta L.; Ayoub, Elía M.; Hosier, Don M.; Wald, Ellen R.

doi:10.1176/ajp.146.2.246

Cited by 350 publications

(25 citation statements)

References 11 publications

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“…We propose that the basal ganglia set the threshold for activation of SECs, and if this threshold is lowered, SECs can be overactivated, resulting in excessive motor activity (e.g., tics) and/or the excessive activation of SECs. Thus damage to the basal ganglia that results in a reduction of its net inhibitory output to the OFC (such as occurs with caudate damage) can result in symptoms of OCD, as observed in cases of autoimmune basal ganglia damage 106. The role of the basal ganglia in our model has some of the properties proposed in the “release” models of OCD 92,97…”

Section: The “Structured Event Complex” Model Of Ocdmentioning

confidence: 88%

A Psychological and Neuroanatomical Model of Obsessive-Compulsive Disorder

Huey¹,

Zahn²,

Moll³

et al. 2008

Journal of Neuropsychiatry

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Imaging, surgical, and lesion studies suggest that the prefrontal cortex (orbitofrontal and anterior cingulate cortexes), basal ganglia, and thalamus are involved in the pathogenesis of obsessive-compulsive disorder (OCD). On the basis of these findings several models of OCD have been developed, but have had difficulty fully integrating the psychological and neuroanatomical findings of OCD. Recent research in the field of cognitive neuroscience on the normal function of these brain areas demonstrates the role of the orbitofrontal cortex in reward, the anterior cingulate cortex in error detection, the basal ganglia in affecting the threshold for activation of motor and behavioral programs, and the prefrontal cortex in storing memories of behavioral sequences (called “structured event complexes” or SECs). The authors propose that the initiation of these SECs can be accompanied by anxiety that is relieved with completion of the SEC, and that a deficit in this process could be responsible for many of the symptoms of OCD. Specifically, the anxiety can form the basis of an obsession, and a compulsion can be an attempt to receive relief from the anxiety by repeating parts of, or an entire, SEC. The authors discuss empiric support for, and specific experimental predictions of, this model. The authors believe that this model explains the specific symptoms, and integrates the psychology and neuroanatomy of OCD better than previous models.

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Section: The “Structured Event Complex” Model Of Ocdmentioning

confidence: 88%

A Psychological and Neuroanatomical Model of Obsessive-Compulsive Disorder

Huey¹,

Zahn²,

Moll³

et al. 2008

Journal of Neuropsychiatry

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“…SC was diagnosed using criteria established by the Jones Criteria. PANDAS was diagnosed using the published NIMH criteria (22), and included patients displaying fine piano playing movements of the fingers and toes in addition to obsessive compulsive symptoms (24). ADHD was diagnosed on the basis of a structured psychiatric interview (K-SADS or DICA) and the Connors Parent and Teacher Rating Scales (34).…”

Section: Methodsmentioning

confidence: 99%

Brain Human Monoclonal Autoantibody from Sydenham Chorea Targets Dopaminergic Neurons in Transgenic Mice and Signals Dopamine D2 Receptor: Implications in Human Disease

Cox

Sharma

Leckman

et al. 2013

The Journal of Immunology

118

139

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How autoantibodies target the brain and lead to disease in disorders such as Sydenham chorea (SC) is not known. SC is characterized by autoantibodies against the brain and is the main neurologic manifestation of streptococcal-induced rheumatic fever. Previously, our novel SC-derived mAb 24.3.1 was found to recognize streptococcal and brain antigens. To investigate in vivo targets of human mAb 24.3.1, VH/VL genes were expressed in B cells of transgenic (Tg) mice as functional chimeric human VH 24.3.1 - mouse constant region IgG1a autoantibody. Chimeric human-mouse IgG1a autoantibody co-localized with tyrosine hydroxylase in the basal ganglia within dopaminergic neurons in vivo in VH 24.3.1 Tg mice. Both human mAb 24.3.1 and IgG1a in Tg sera were found to react with human dopamine D2 receptor (D2R). Reactivity of chorea-derived mAb 24.3.1 or SC IgG with D2R was confirmed by 1) dose dependent inhibitory signaling of D2R as a potential consequence of targeting dopaminergic neurons, 2) reaction with surface-exposed FLAG epitope-tagged D2R, and 3) blocking of Ab reactivity by an extracellular D2R peptide. IgG from SC and a related subset of streptococcal associated behavioral disorders called pediatric autoimmune neuropsychiatric disorder associated with streptococci (PANDAS) with small choreiform movements reacted in ELISA with D2R. Reaction with FLAG-tagged D2R distinguished SC from PANDAS while sera from both SC and PANDAS induced inhibitory signaling of D2R on transfected cells comparable to dopamine. Here we define a mechanism by which the brain may be altered by antibody in movement and behavioral disorders.

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“…In the late 1980's, Swedo et al [14] at the National Institute of Mental Health (NIMH, Bethesda, Md., USA) reported increased frequency of obsessive-compulsive symptoms in children and adolescents with SC. SC is a delayed neurological complication of group A β-hemolytic streptococcal (GABHS) pharyngitis and constitutes one of the major criteria of acute rheumatic fever (RF), an inflammatory autoimmune disease affecting mainly the heart valves.…”

Section: Rheumatic Fever: a Model For Autoimmune Ocdmentioning

confidence: 99%

“…Swedo et al [14] argued that a subset of childhood tic disorders and OCDs could be causally related to streptococcal infection outside the context of RF, the so-called PANDAS, an acronym for ‘pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection'.…”

Section: Rheumatic Fever: a Model For Autoimmune Ocdmentioning

confidence: 99%

Searching for the Immune Basis of Obsessive-Compulsive Disorder

Teixeira¹,

Rodrigues²,

Marques

et al. 2014

Neuroimmunomodulation

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The etiopathogenesis of obsessive-compulsive disorder (OCD) remains elusive. Clinical observation of the elevated frequency of obsessive-compulsive symptoms in patients with rheumatic fever, a post-streptococcal autoimmune disease, prompted the study of immune parameters in OCD. Anti-basal ganglia antibodies have been described in a subset of OCD patients. The assessment of circulating cytokines and immune cells confirmed unequivocal changes in at least some patients, although it is difficult to establish a particular immune profile in OCD. Several factors, including the use of psychotropic drugs and the presence of comorbid conditions, seem to influence these immune parameters.

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High prevalence of obsessive-compulsive symptoms in patients with Sydenham's chorea

Cited by 350 publications

References 11 publications

A Psychological and Neuroanatomical Model of Obsessive-Compulsive Disorder

A Psychological and Neuroanatomical Model of Obsessive-Compulsive Disorder

Brain Human Monoclonal Autoantibody from Sydenham Chorea Targets Dopaminergic Neurons in Transgenic Mice and Signals Dopamine D2 Receptor: Implications in Human Disease

Searching for the Immune Basis of Obsessive-Compulsive Disorder

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