Treatment of schizophrenia in the 21st Century: beyond the neurotransmitter hypothesis

Abstract

Over the last six decades, the treatment of schizophrenia has focused primarily on interactions at monoamine neurotransmitter receptor sites, including those for dopamine and serotonin. While first-generation antipsychotics demonstrate antagonism at the dopamine 2 receptor, newer atypical agents involve multiple receptors at various neurotransmitter sites. Despite the advent of these newer agents, the treatment of schizophrenia continues to elude clinicians, perhaps owing to a lack of information about the factors contributing to the development of the disease. While the etiology is complex and not yet fully delineated, we suggest that treating clinicians be willing to look beyond neurotransmitters and entertain other potential factors involved in the pathogenesis of schizophrenia. One such factor that is often overlooked is the possible contribution of autoimmunity to disease development in at least a subset of patients. In this article we make an argument for consideration of immune dysfunction in the development of schizophrenia and suggest future directions for the field.

Keywords::

• autoantibody
• autoimmunity
• etiology
• immunosuppressant
• immunosuppressive therapy
• schizophrenia

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

^*Antibodies directed against nuclear antigens, including anti-DNA and anti-Smith antigens.

^‡Multiple antibodies were assessed, including anti-thyroid microsomal antigen, antinuclear, anti-thyroglobulin, anti-mitochondria, rheumatoid factor and anti-parietal cells.

^§Panel of antibodies against amygdala, frontal cortex, cingulated gyrus, entorhinal cortex, putamen, maxillary bodies and caudate nucleus.

HSP: Heat-shock protein.