Detecting synaptic autoantibodies in psychoses: need for more sensitive methods

PURPOSE OF REVIEW: 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.

RECENT FINDINGS: 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.

SUMMARY: 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.