1. ¹Division of Psychological Medicie and Psychiatry, Section of Neuroimaging, Institute of Psychiatry, King's College London, London, UK
2. ²The Psychiatric Clinic, Vasant Vihar, New Delhi, India
3. ³Department of Molecular Neurobiochemistry, International Graduate School of Neuroscience, Ruhr University Bochum, Universitatsstrasse 150, Bochum, Germany
4. ⁴Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India
5. ⁵Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India

Correspondence: Dr S Bhattacharyya, Section of Neuroimaging, Box PO67, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. Tel: (+44) 20 7848 0955, Fax: (+44) 20 7848 0976, E-mail: s.bhattacharyya@iop.kcl.ac.uk

Received 23 February 2009; Revised 24 May 2009; Accepted 26 May 2009; Published online 12 August 2009.

Abstract

Although serum autoantibodies directed against basal ganglia (BG) implicate autoimmunity in the pathogenesis of obsessive–compulsive disorder (OCD), it is unclear whether these antibodies can cross the blood–brain barrier to bind against BG or other components of the OCD circuit. It is also unclear how they might lead to hyperactivity in the OCD circuit. We examined this by investigating the presence of autoantibodies directed against the BG or thalamus in the serum as well as CSF of 23 OCD patients compared with 23 matched psychiatrically normal controls using western blot. We further investigated CSF amino acid (glutamate, GABA, taurine, and glycine) levels and also examined the extent to which these levels were related to the presence of autoantibodies. There was evidence of significantly more binding of CSF autoantibodies to homogenate of BG as well as to homogenate of thalamus among OCD patients compared with controls. There was no significant difference in binding between patient and control sera except for a trend toward more bands to BG and thalamic protein corresponding to 43 kD among OCD patients compared with controls. CSF glutamate and glycine levels were also significantly higher in OCD patients compared with controls, and further multivariate analysis of variance showed that CSF glycine levels were higher in those OCD patients who had autoantibodies compared with those without. The results of our study implicate autoimmune mechanisms in the pathogenesis of OCD and also provide preliminary evidence that autoantibodies against BG and thalamus may cause OCD by modulating excitatory neurotransmission.