Detecting synaptic autoantibodies in psychoses: need for more sensitive methods

Schizophrenic psychosis affects near 1% of the population. It typically starts in the first three decades of life, leading most often to chronic disability: antipsychotic treatment is palliative, not curative. The neurobiological abnormalities underlying psychoses are likely to differ across patients, ranging from autosomal dominant genetic disease to substance abuse, but a decreased function of the N-methyl-D-aspartate (NMDA) receptor seems to be a common theme. Emerging evidence suggests that decreased NMDA receptor function may be caused by auto-antibodies against this receptor in some patients currently being diagnosed as having schizophrenia.

Studies searching for antibodies against the NMDA receptor in the sera of patients with schizophrenia have been either negative or found them in a very small minority of patients. Furthermore, similar antibodies have been detected in the general population. From these findings, however, it cannot be concluded that relevant auto-antibodies are not responsible for a subgroup of psychoses. Shortcomings in current antibody detection methodology may be responsible for the negative studies.

Given the high probability that a considerable proportion of patients with psychosis may have auto-antibodies not detectable with current methods and therefore harbour a potentially treatable disease, research to increase antibody detection sensitivity is urgently needed.