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Bradley S. Peterson, MD; James F. Leckman, MD; Daniel Tucker, MD; Lawrence Scahill, MSN, PhD; Lawrence Staib, PhD; Heping Zhang, PhD; Robert King, MD; Donald J. Cohen, MD; John C. Gore, PhD; Paul Lombroso, MD

Arch Gen Psychiatry. 2000;57:364-372.

Background  Previous studies have provided preliminary serological evidence supporting the theory that symptoms of tic disorders or obsessive-compulsive disorder (OCD) may be sequelae of prior streptococcal infection. It is unclear, however, whether previously reported associations with streptococcal infection were obscured by the presence of diagnostic comorbidities. It is also unknown whether streptococcal infection is associated in vivo with anatomical alterations of the brain structures that have been implicated in the pathophysiology of these disorders.

Methods  Antistreptococcal antibody titers were measured in 105 people diagnosed as having CTD, OCD, or attention-deficit/hyperactivity disorder (ADHD) and in 37 community controls without a disorder. Subjects were unselected with regard to their history of streptococcal exposure. Basal ganglia volumes were measured in 113 of these subjects (79 patients and 34 controls).

Results  A DSM-IV diagnosis of ADHD was associated significantly with titers of 2 distinct antistreptococcal antibodies, antistreptolysin O and anti–deoxyribonuclease B. These associations remained significant after controlling for the effects of CTD and OCD comorbidity. No significant association was seen between antibody titers and a diagnosis of either CTD or OCD. When basal ganglia volumes were included in these analyses, the relationships between antibody titers and basal ganglia volumes were significantly different in OCD and ADHD subjects compared with other diagnostic groups. Higher antibody titers in these subjects were associated with larger volumes of the putamen and globus pallidus nuclei.

Conclusions  These findings suggest that the prior reports of an association between antistreptococcal antibodies and either CTD or OCD may have been confounded by the presence of ADHD. They also support the hypothesis that in susceptible persons who have ADHD or OCD, chronic or recurrent streptococcal infections are associated with structural alterations in basal ganglia nuclei.

From the Yale Child Study Center (Drs Peterson, Leckman, Tucker, Scahill, King, and Cohen), and the Departments of Diagnostic Radiology (Drs Peterson, Staib, and Gore) and Epidemiology and Public Health (Dr Zhang), Yale School of Medicine, New Haven, Conn.

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