What is the role of the neurotransmitter system in the pathogenesis of schizophrenia?

Updated: Mar 16, 2018
  • Author: Frances R Frankenburg, MD; Chief Editor: Glen L Xiong, MD  more...
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Answer

Abnormalities of the dopaminergic system are thought to exist in schizophrenia. The first clearly effective antipsychotic drugs, chlorpromazine and reserpine, were structurally different from each other, but they shared antidopaminergic properties. Drugs that diminish the firing rates of mesolimbic dopamine D2 neurons are antipsychotic, and drugs that stimulate these neurons (eg, amphetamines) exacerbate psychotic symptoms.

Hypodopaminergic activity in the mesocortical system, leading to negative symptoms, and hyperdopaminergic activity in the mesolimbic system, leading to positive symptoms, may coexist. (Negative and positive symptoms are defined elsewhere; see Presentation.) Moreover, the newer antipsychotic drugs block both dopamine D2 and serotonin (5-hydroxytryptamine [5-HT]) receptors.

Clozapine, perhaps the most effective antipsychotic agent, is a particularly weak dopamine D2 antagonist. Thus, other neurotransmitter systems, such as norepinephrine, serotonin, and gamma-aminobutyric acid (GABA), are undoubtedly involved.

Much research focuses on the N -methyl-D-aspartate (NMDA) subclass of glutamate receptors because NMDA antagonists, such as phencyclidine and ketamine, can lead to psychotic symptoms in healthy subjects. [9, 10] Some researchers consider schizophrenia, in large part, a hypoglutamatergic disorder.


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