Schizophrenia and glutamatergic transmission

Area of Science:

• Neuroscience
• Psychiatry
• Neurobiology

Background:

• Schizophrenia is a lifelong human brain disease with unclear biological underpinnings.
• Observations suggest glutamatergic abnormalities in schizophrenia's pathophysiology.
• Phencyclidine's psychotomimetic effects link psychosis to NMDA receptor blockade.

Purpose of the Study:

• Review glutamatergic transmission in animal and human brains.
• Examine the role of glutamate in schizophrenia.
• Discuss other glutamate-related brain diseases and mechanisms.

Main Methods:

• Critically review evidence of glutamatergic abnormalities in schizophrenia.
• Incorporate data from postmortem neurochemistry, in vivo brain imaging, clinical pharmacology, and animal models.
• Articulate current theoretical formulations.

Main Results:

• Evidence suggests glutamatergic abnormalities are implicated in schizophrenia.
• A working glutamate hypothesis is proposed.
• This hypothesis points to diminished glutamatergic transmission in specific brain pathways.

Conclusions:

• The proposed glutamate hypothesis suggests reduced glutamatergic transmission in hippocampal pathways.
• Cerebral dysfunction in the hippocampus and anterior cingulate cortex is implicated.
• Further research is needed to fully formulate and test this hypothesis.