Executive and Attention Functioning Among Children in the PANDAS Subgroup

Abstract

Evidence from past studies indicates that adults and children with Obsessive-Compulsive Disorder (OCD) and Tourette syndrome (TS) experience subtle neuropsychological deficits. Less is known about neuropsychological functioning of children and adolescents with a symptom course consistent with the PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection) subgroup of OCD and tics. To provide such information, we administered three tests of attention control and two of executive function to 67 children and adolescents (ages 5-16) diagnosed with OCD and/or tics and a symptom course consistent with the PANDAS subgroup and 98 healthy volunteers (HV) matched by age, sex, and IQ. In a paired comparison of the two groups, the PANDAS subjects were less accurate than HV in a test of response suppression. Further, in a two-step linear regression analysis of the PANDAS group in which clinical variables were added stepwise into the model and in the second step matching variables (age, sex, and IQ) were added, IQ emerged as a predictor of performance on this task. In the same analysis, ADHD diagnosis and age emerged as predictors of response time in a continuous performance task. Subdividing the PANDAS group by primary psychiatric diagnosis revealed that subjects with TS or OCD with tics exhibited a longer response time compared to controls than subjects with OCD only, replicating previous findings within TS and OCD. This study demonstrates that children with PANDAS exhibit neuropsychological profiles similar to those of their primary psychiatric diagnosis.

Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection

“…9,11 The association of this heterogeneous set of neuropsychiatric findings with PANDAS, and the familial overlap reported for OCD, TS and ASD, [56][57][58] raises the possibility of common immune pathways in their pathogenesis. 2,59,60 Features of GABHS donor mice and their passive serum transfer recipients are consistent both with the original PANDAS diagnostic criteria 9 -primarily focused on obsessive-compulsive and tic behaviors-as well as with the broader concept of PANDAS arising from subsequent reports.…”

“…A wide range of neuropsychiatric comorbidities are acknowledged as common; 9,11,17 comorbid diagnoses most frequently identified in PANDAS populations include AD/HD and major depression. 9,17 Clinical disturbances observed most often during PANDAS exacerbations include emotional lability, anxiety, impulsivity, attentional problems and deterioration Figure 5 Superior spatial and reversal learning and memory performance in male group A b-hemolytic streptococcus (GABHS) donor mice.…”

“…6,7 The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) is used to describe a subset of children with OCD or chronic tic disorder after GABHS infection. 8,9 PANDAS diagnostic criteria require presence of a lifetime diagnosis of OCD or a tic disorder; 10 in addition, other clinical features are suggested as part of a broader PANDAS classification, including cognitive, 9 attentional, 11 social, 12 eating 13 and mood disturbances. 3,9 A role for GABHS-induced autoimmunity has also been proposed in AD/HD, 11,14 anorexia nervosa, 15,16 major depression 17 and ASD; 18,19 these conditions are also frequently noted in PANDAS populations as comorbid neuropsychiatric disorders.…”

“…8,9 PANDAS diagnostic criteria require presence of a lifetime diagnosis of OCD or a tic disorder; 10 in addition, other clinical features are suggested as part of a broader PANDAS classification, including cognitive, 9 attentional, 11 social, 12 eating 13 and mood disturbances. 3,9 A role for GABHS-induced autoimmunity has also been proposed in AD/HD, 11,14 anorexia nervosa, 15,16 major depression 17 and ASD; 18,19 these conditions are also frequently noted in PANDAS populations as comorbid neuropsychiatric disorders. 9 Antibodies to basal ganglia are found in SC and PANDAS 4,[20][21][22][23] and may extend beyond the basal ganglia to include cerebellum and cerebral cortex.…”

The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated withStreptococcus, and Related Disorders: A Way Forward

“…The presence of neurological soft signs, such as choreiform movements and pronator sign/drift, are a frequently observed comorbidity among childhood onset OCD, tics, and ADHD; the significance of neurological soft signs in relationship to GAS infections has never been prospectively examined until recently (Murphy et al 2007). In addition to choreiform movements, other subtle signs of neurological impairment have been reported to be associated with PANDAS (Swedo et al 1998); however, neuropsychological dysfunction is commonly reported with OCD/tics (Kuelz et al 2004;Bloch et al 2006) and those with PANDAS may not have differentiating neuropsychological profile when compared with youth with typical (non-PANDAS) OCD and TD (Hirschtritt et al 2009). …”