ACID DECARBOXYLASE (GAD) AUTOANTIBODY POSITIVITY IN SCHIZOPHRENIA
Kemether*, William Byne, James Schmeidler, Liesl Jones, Robert
McEvoy, and Kenneth Davis. Mount Sinai School of Medicine, New
Various etiopathogenic mechanisms
for schizophrenia have been proposed, including autoimmune
dysregulation. Accounts of non-specific autoantibody responses, T
cells and interleukin disorders, and intrathecal production of
immunoglobulins have been reported. Glutamic acid decarboxylase
(GAD) catalyzes the decarboxylation of glutamate to form the
inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Antibodies targeting GAD have been implicated in Stiff-Man
Syndrome (SMS) and Insulin-Dependent Diabetes Mellitus (IDDM).
Both disorders are thought to result from autoimmune destruction
of GAD-containing cells. In SMS, the targeted cells are GABAergic
Abnormalities of the GABAergic
system have been described in schizophrenia including the loss of
small interneurons believed to be GABAergic in layer II of the
prefrontal and cingulate cortices and decreased GAD activity in
the frontal cortex. While a loss of GABA neurons could be
accounted for by a variety of mechanisms, the possibility of GAD
autoantigenicity has not been investigated. Because GABAergic
neuronal loss and dysregulation have been implicated in
schizophrenia by empirical evidence as well as theory, and
because GAD autoantigenicity may disrupt GABAergic neurons in
SMS, we conducted the present study to examine the prevalence of
GAD autoantibodies in schizophrenia.
Sera were collected from 186
patients at Mount Sinai Medical Center meeting DSM-IV criteria
for schizophrenia or schizoaffective disorder and from 220
healthy adult controls. Antibodies to recombinant human GAD65
were measured by a commercial immunoprecipitation assay (Kronus).
The proportion of schizophrenics
(5.4%) who tested positive for the antibody did not differ
significantly from controls (3.2%). These data do not support a
role for GAD autoantigenicity in the pathogenesis of
schizophrenia. However, it remains possible that GAD
autoantigenicity plays a role early in the pathogenesis of at
least some cases of schizophrenia and that the prevalence of the
antibody decreases with time after the initial insult. If so, an
increase in the prevalence of GAD autoantibodies might only be
detected shortly after the onset of the illness.