Anti-glutamic acid decarboxylase antibody screening in first-episode psychosis

The Royal Australian and New Zealand College of Psychiatrists recommends screening for a range of antibodies in first-episode psychosis, including anti-glutamic acid decarboxylase antibodies. Glutamic acid decarboxylase antibody-associated encephalitis occurs with high antibody titres and may cause cognitive dysfunction, seizures and psychiatric symptoms. However, glutamic acid decarboxylase antibodies are more frequently found in lower titre in association with other autoimmune disorders (such as diabetes mellitus type 1) and in healthy individuals. The utility of testing unselected populations of consumers with psychosis is unclear. The psychiatric manifestations of this disorder are also poorly described.

First, systematic review of cohort and case-control studies that tested for IgG glutamic acid decarboxylase antibodies in psychiatric populations was conducted. Random-effects meta-analysis of odds ratio for antibody positivity in cases with psychosis and controls assessed prevalence. Second, literature review of all published cases and case series of glutamic acid decarboxylase antibody-associated limbic encephalitis was assessed for frequency and description of psychotic symptoms.

There were 17 studies, in which 2754 individuals with psychotic disorders were tested for glutamic acid decarboxylase IgG antibodies. Thirty-one consumers with psychosis (0.7%) had positive glutamic acid decarboxylase antibodies compared to 24 controls (1.0%), all at low titre and not fulfilling diagnostic criteria for autoimmune encephalitis. Meta-analysis found no significant difference in rates of glutamic acid decarboxylase antibody positivity (odds ratio = 1.8, 95% confidence interval: [0.90, 3.63]). Literature review found 321 cases of glutamic acid decarboxylase antibody-associated limbic encephalitis, with psychosis in 15 (4.3%) cases. Clinical screening would have identified all cases that presented to psychiatric services.

Glutamic acid decarboxylase antibodies were uncommon in consumers with psychosis, with no significant difference in prevalence from controls and no cases of encephalitis identified. In cases with established glutamic acid decarboxylase antibody-associated limbic encephalitis, psychotic symptoms were uncommon and identifiable by clinical assessment. Targeted antibody testing guidelines should be further considered.