The glutamate hypothesis for schizophrenia
Early studies produced mixed results, but new approaches are promising.
Since the 1970s, the "dopamine hypothesis" has been the dominant theory about how schizophrenia develops and causes its devastating symptoms. According to this theory, excessive transmission of the neurotransmitter dopamine produces positive symptoms such as delusions, hallucinations, and disordered thinking, while insufficient transmission may underlie cognitive deficits and negative symptoms such as blunted affect. Both first- and second-generation antipsychotics work primarily by blocking dopamine D2 receptors, thereby affecting dopamine transmission in the brain. But these drugs are relatively ineffective at treating the negative symptoms and cognitive deficits of schizophrenia, leading researchers to investigate whether these symptoms are caused by problems in other neurotransmitter systems.
A theory that first emerged in the 1980s, but which has gained wider support, traces the origins of schizophrenia symptoms to the neurotransmitter glutamate, rather than dopamine.