The dopamine, glutamate, and GABA hypotheses of schizophrenia: Glutamate may be the key

Abstract

This essay explores hypotheses postulating that the neurotransmitters dopamine, glutamate, and gamma-aminobutyric acid (GABA) cause schizophrenia, and reaches the conclusion that a joint model where glutamate affects dopamine and GABA is the most plausible explanatory mechanism. The dopamine hypothesis is supported by evidence that patients with schizophrenia have marked dopamine receptor and neurotransmitter increases and decreases in specific brain areas. Furthermore, drugs targeting dopamine receptors have been successful in reducing schizophrenic symptoms. The glutamate hypothesis proposes that the neurotransmitter glutamate is the basis of the disorder, as affecting NMDA (glutamate) receptors has been shown to cause positive and negative schizophrenic symptoms, including visual and auditory symptoms only ever seen in schizophrenia. Further, there are genetic associations with several genes associated with NMDA receptors and schizophrenia. The GABA model is also explored, as tampering with cells related to GABA has been shown to induce schizophrenic symptoms, though this can be explained as being in conjunction, not opposition, with the glutamate model. The hypotheses are flawed when considered in isolation. The dopamine model cannot explain negative schizophrenic symptoms, and drugs targeting dopamine receptors are still unable to completely reduce self-reported symptoms. Similarly, the glutamate model could be caused by irregular amounts of GABA, and the glutamate hypothesis may also explain the positive effects of treatments targeting dopamine. Evidence shows that drugs causing reduced functioning of NMDA receptors cause dopamine dysfunction. Pairing this with strong evidence of both dopamine and glutamate involvement, the most plausible model is one where NMDA dysfunction causes GABA and dopamine receptor issues