Glutamatergic Dysfunction and Glutamatergic Compounds for Major Psychiatric Disorders: Evidence From Clinical Neuroimaging Studies

Summary & key facts

This paper reviews recent human studies about glutamate, a brain chemical that excites nerve cells, and how problems with glutamate signaling appear in several major psychiatric illnesses. The authors summarize brain scans and magnetic tests that measure glutamate activity, and they describe new medications that target the glutamate system. They note that ketamine — a drug that blocks one type of glutamate receptor — has shown rapid antidepressant effects for people whose depression did not respond to usual treatments, but the evidence is still developing and more research is needed.

Key facts:

• Glutamate is a brain chemical that helps nerve cells communicate, and releasing too much glutamate has been linked to stress and to some brain diseases.
• Researchers find abnormal glutamate signaling in several major psychiatric disorders, including schizophrenia, bipolar disorder, and major depressive disorder, suggesting glutamate problems are involved in these illnesses.
• Ketamine, which blocks a specific glutamate receptor called NMDA, has shown rapid antidepressant effects in people with depression that did not respond to other treatments.
• The review looked at recent human studies that measured glutamate using methods such as magnetic resonance spectroscopy (a brain scan that measures chemicals), PET or SPECT scans (imaging that tracks tracer molecules), and paired-pulse transcranial magnetic stimulation (a noninvasive magnetic test of brain circuits).
• Several new drugs that act on the glutamate system are being developed and tested for major psychiatric disorders, but the evidence so far is promising rather than definitive and more research is needed to know who will benefit and how long effects last.

Abstract

Excessive glutamate release has been linked to stress and many neurodegenerative diseases. Evidence indicates abnormalities of glutamatergic neurotransmission or glutamatergic dysfunction as playing an important role in the development of many major psychiatric disorders (e.g., schizophrenia, bipolar disorder, and major depressive disorder). Recently, ketamine, an N-methyl-d-aspartate antagonist, has been demonstrated to have promisingly rapid antidepressant efficacy for treatment-resistant depression. Many compounds that target the glutamate system have also become available that possess potential in the treatment of major psychiatric disorders. In this review, we update evidence from recent human studies that directly or indirectly measured glutamatergic neurotransmission and function in major psychiatric disorders using modalities such as magnetic resonance spectroscopy, positron emission tomography/single-photon emission computed tomography, and paired-pulse transcranial magnetic stimulation. The newer generation of antidepressants that target the glutamatergic system developed in human clinical studies is also reviewed.

Topics

Functional Brain Connectivity Studies Neuroscience and Neuropharmacology Research Treatment of Major Depression

Categories

Cognitive Neuroscience Life Sciences Neuroscience

Tags

Antidepressant Cognition Glutamate receptor Glutamatergic Hippocampus Internal medicine Major depressive disorder Medicine Neuroimaging Neuroscience Neurotransmission Psychiatry Psychology Receptor Schizophrenia (object-oriented programming) Stimulation Transcranial magnetic stimulation

Substances

Ketamine

Conditions & symptoms

Depression Lack of energy or motivation Sadness or low mood