Autoantibodies against voltage-gated potassium channel (VGKC) and glutamic acid decarboxylase (GAD) in psychosis: A systematic review, meta-analysis and case series.

Rosemary Grain, King's College London
John Lally, Royal College of Surgeons in Ireland
Brendon Stubbs, South London and Maudsley NHS Foundation Trust
Steffi Malik, South London Psychosis Research Team
Anne LeMince, South London and Maudsley NHS Foundation Trust
Timothy R. Nicholson, King's College London
Robin M. Murray, King's College London
Fiona Gaughran, King's College London

This is the peer reviewed version of the following article: Grain R, Lally J, Stubbs B, Malik S, LeMince A, Nicholson TR, Murray RM, Gaughran F. Autoantibodies against voltage-gated potassium channel and glutamic acid decarboxylase in psychosis: A systematic review, meta-analysis, and case series. Psychiatry and Clinical Neurosciences. 2017;71(10):678-689. which has been published in final form at DOI:10.1111/pcn.12543 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Abstract

Antibodies to the voltage-gated potassium channel (VGKC) complex and glutamic acid decarboxylase (GAD) have been reported in some cases of psychosis. We conducted the first systematic review and meta-analysis to investigate their prevalence in people with psychosis and report a case series of VGKC-complex antibodies in refractory psychosis. Only five studies presenting prevalence rates of VGKC seropositivity in psychosis were identified, in addition to our case series, with an overall prevalence of 1.5% (25/1720) compared to 0.7% in healthy controls (12/1753). Meta-analysis established the pooled prevalence of GAD65 autoantibodies was 5.8%(95%CI:2.0-15.6%;I2=91%;9 studies) in psychotic disorders,with a prevalence of 4.6%(95%CI:1.2-15.9%;9 studies;I2=89%%) and 6.2% (95%CI:1.2-27.0%;2 studies;I2=69%) in schizophrenia and bipolar disorder respectively. People with psychosis were more likely to have GAD65 antibodies than controls (OR 2.24;95%CI:1.28- 3.92%;p = 0.005;8 studies;I2=0%).Among 21 participants with treatment-resistant psychosis, none had VGKC antibodies. The prevalence of VGKC antibodies is low in psychosis. Our preliminary meta-analysis suggests GAD autoantibodies are more common in people with psychosis than in controls, although few studies accounted for the possibility of co-existing type 1 diabetes mellitus and the clinical significance of reported GAD titres remains unclear. The paucity of studies reporting thresholds for defining GAD abnormality, and rates of comorbid type 1 DM,preclude interpretations regarding the influence of GAD antibodies on the development of psychotic disorders;and may have led to an overestimate of the prevalence of GAD. Our case series fails to support the hypothesis that VGKC antibodies are linked to treatment resistance in psychosis, but the literature to date is remarkably sparse.