Fiona Gaughran1, John Lally2, Katherine Beck2, Ruaidhri McCormack3, Poonam Gardner-Sood2, Ester Coutinho4, Leslie Jacobson4, Bethan Lang4, Ricardo Sainz-Fuertes5, Evangelos Papanastasiou6, Marta Di Forti7, Tim Nicholson8, Angela Vincent9, Robin M Murray1. 1. National Psychosis Service,South London and Maudsley NHS Foundation Trust. 2. Department of Psychosis Studies,Institute of Psychiatry,Psychology and Neuroscience,King's College London,London,UK. 3. Addenbrooke's Hospital,Cambridge,UK. 4. Nuffield Department of Clinical Neurosciences,Oxford University Hospitals, University of Oxford,Oxford,UK. 5. Basic and Clinical Neuroscience at the Institute of Psychiatry,Psychology, & Neuroscience,King's College London,London,UK. 6. Cognition Schizophrenia and Imaging Laboratory (CSI Lab),Department of Psychosis Studies,Institute of Psychiatry Psychology and Neuroscience,King's College London,London,UK. 7. SGDP, Institute of Psychiatry,Psychology and Neuroscience,King's College London, and South London and Maudsley NHS Foundation Trust,London,UK. 8. Section of Cognitive Neuropsychiatry,Department of Psychosis Studies,Institute of Psychiatry,Psychology and Neuroscience,King's College London,London,UK. 9. Nuffield Department of Clinical Neurosciences,University of Oxford,John Radcliffe Hospital,Oxford,UK.
Abstract
BACKGROUND: There has been much recent excitement about the possibility that some cases of psychosis may be wholly due to brain-reactive antibodies, with antibodies to N-methyl-D-aspartate receptor (NMDAR) and the voltage-gated potassium channel (VGKC)-complex reported in a few patients with first-episode psychosis (FEP). METHODS: Participants were recruited from psychiatric services in South London, UK, from 2009 to 2011 as part of the Genetics and Psychosis study. We conducted a case-control study to examine NMDAR and VGKC-complex antibody levels and rates of antibody positivity in 96 patients presenting with FEP and 98 controls matched for age and sex. Leucine-rich glioma inactiviated-1 (LGI1) and contactin-associated protein (CASPR) antibodies were also measured. Notably, patients with suspicion of organic disease were excluded. RESULTS: VGKC-complex antibodies were found in both cases (n = 3) and controls (n = 2). NMDAR antibody positivity was seen in one case and one control. Either LGI1-Abs or CASPR2-Abs were found in three cases and three controls. Neuronal antibody staining, consistent with the above results or indicating potential novel antigens, was overall positive in four patients but also in six controls. Overall, antibody positivity was at low levels only and not higher in cases than in controls. CONCLUSIONS: This case-control study of the prevalence of antibodies in FEP does not provide evidence to support the hypothesis that FEP is associated with an immune-mediated process in a subgroup of patients. Nevertheless, as other bio-clinical factors may influence the effect of such antibodies in a given individual, and patients with organic neurological disease may be misdiagnosed as FEP, the field requires more research to put these findings in context.
BACKGROUND: There has been much recent excitement about the possibility that some cases of psychosis may be wholly due to brain-reactive antibodies, with antibodies to N-methyl-D-aspartate receptor (NMDAR) and the voltage-gated potassium channel (VGKC)-complex reported in a few patients with first-episode psychosis (FEP). METHODS: Participants were recruited from psychiatric services in South London, UK, from 2009 to 2011 as part of the Genetics and Psychosis study. We conducted a case-control study to examine NMDAR and VGKC-complex antibody levels and rates of antibody positivity in 96 patients presenting with FEP and 98 controls matched for age and sex. Leucine-rich glioma inactiviated-1 (LGI1) and contactin-associated protein (CASPR) antibodies were also measured. Notably, patients with suspicion of organic disease were excluded. RESULTS: VGKC-complex antibodies were found in both cases (n = 3) and controls (n = 2). NMDAR antibody positivity was seen in one case and one control. Either LGI1-Abs or CASPR2-Abs were found in three cases and three controls. Neuronal antibody staining, consistent with the above results or indicating potential novel antigens, was overall positive in four patients but also in six controls. Overall, antibody positivity was at low levels only and not higher in cases than in controls. CONCLUSIONS: This case-control study of the prevalence of antibodies in FEP does not provide evidence to support the hypothesis that FEP is associated with an immune-mediated process in a subgroup of patients. Nevertheless, as other bio-clinical factors may influence the effect of such antibodies in a given individual, and patients with organic neurological disease may be misdiagnosed as FEP, the field requires more research to put these findings in context.
Authors: Belinda Lennox; Ksenija Yeeles; Peter B Jones; Michael Zandi; Eileen Joyce; Ly-Mee Yu; Giuliano Tomei; Rebecca Pollard; Sally-Anne Vincent; Mio Shimazaki; Iona Cairns; Francis Dowling; Thomas Kabir; Thomas R E Barnes; Anne Lingford Hughes; Akram A Hosseini; Timothy Harrower; Camilla Buckley; Alasdair Coles Journal: Trials Date: 2019-06-07 Impact factor: 2.279
Authors: Thomas A Pollak; Matthew J Kempton; Conrad Iyegbe; Angela Vincent; Sarosh R Irani; Ester Coutinho; David A Menassa; Leslie Jacobson; Lieuwe de Haan; Stephan Ruhrmann; Gabriele Sachs; Anita Riecher-Rössler; Marie-Odile Krebs; Paul Amminger; Birte Glenthøj; Neus Barrantes-Vidal; Jim van Os; Bart P F Rutten; Rodrigo A Bressan; Mark van der Gaag; Robert Yolken; Matthew Hotopf; Lucia Valmaggia; James Stone; Anthony S David; Philip McGuire Journal: Mol Psychiatry Date: 2020-10-19 Impact factor: 13.437
Authors: Fredrik Piehl; Sarosh R Irani; Jakob Theorell; Melanie Ramberger; Ruby Harrison; Victor Mgbachi; Leslie Jacobson; Patrick Waters; Sophie Erhardt; Carl M Sellgren; Simon Cervenka Journal: Transl Psychiatry Date: 2021-11-05 Impact factor: 6.222
Authors: Graham Blackman; Mao Fong Lim; Thomas Pollak; Adam Al-Diwani; Mkael Symmonds; Asif Mazumder; Ben Carter; Sarosh Irani; Anthony David Journal: J Neurol Date: 2022-07-05 Impact factor: 6.682
Authors: M B Schou; S G Sæther; O K Drange; E Brenner; J Crespi; L Eikenes; M S Mykland; C Pintzka; A K Håberg; T Sand; A Vaaler; D Kondziella Journal: Sci Rep Date: 2019-12-31 Impact factor: 4.379