Incidence of anti-brain antibodies in children with obsessive–compulsive disorder
Dale RC, Heyman I, Giovannoni G and Church AW;
Commented by , 23 Oct 2005
Background
Evidence from various sources points towards a neuropsychiatric basis for obsessive-compulsive disorder (OCD). In particular, it has been suggested that the origin of the disorder, or of a subgroup of the disorder, may be linked to autoimmune factors.
Aims of the study
To investigate whether obsessive-compulsive disorder in children may be linked to streptococcal infections via the presence of antibodies that cross-react with basal ganglia.
Method
The blood serum of 50 children with OCD was examined for the presence of anti-basal ganglia antibodies (ABGA) using both enzyme-linked immunosorbant essay (ELISA) and western immunoblotting. The results were compared with 3 paediatric control groups: a neurological control group, a group with uncomplicated streptococcal infections, and a group with auto-immune disorders without neurological involvement.
Results
The mean ABGA ELISA binding in the OCD group was high in comparison with each of the 3 control groups. The presence of ABGA on western immunoblotting was high (42%) in the OCD group, and significantly more common in the OCD group than in each of the control groups.
Professor Pull's comments
OCD is part of a number of neuropsychiatric disorders that have been associated with basal ganglia dysfunction due to an aberrant post-streptococcal autoimmune response against neurones in the basal ganglia.
The disorder most consistently linked to post-streptococcal auto-immune factors is Sydenham’s chorea. Other disorders include Tourette’s syndrome, adult-onset tic disorders, and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).
The proposal that these disorders are mediated by autoimmune mechanisms has remained controversial however. Reasons for conflicting results in the field have been related mainly to issues concerning the detection of ABGA.
In particular, differences in Western immunoblotting methods have been suggested to explain the differences in the reported prevalence rates of ABGA in these disorders.
In the present study, a subgroup of children with OCD had ABGA findings similar to those seen in Sydenham’s chorea. This finding suggests that auto-immunity may indeed play a role in the aetiology and/or maintenance of OCD, or of a subgroup of OCD.
The presence of ABGA in the blood serum of patients with OCD cannot, however, by itself, be considered as a definite proof that anti-neuronal antibodies are involved in the origin of the disorder. As pointed out by the authors themselves, such antibodies could be produced as a non-specific response to streptococcal infection, and, as such, represent a simple epiphenomenon or marker of the infection.
Other limitations of the study are related to the methods used to detect ABGA or to identify specific autoantigens.
In spite of these limitations, this study represents an important contribution to a growing body of knowledge about the aetiology of OCD. If confirmed, the results could have major implications for the prevention of OCD, with in particular a possibility to prevent the occurrence of the disorder by means of a more systematic treatment of streptococcal infections with antibiotics.