Malfunction in GABA and Glutamate as Pathways to Depression: A Review of the Evidence

With nearly one fifth of the population experiencing depression sometime during their lives, plus the recent finding that depression rivals smoking in its association with mortality, the search for effective pharmacological treatments for depression remains urgent. However, despite this heavy disease burden upon society, the various waves of antidepressants developed in the last 40 years have shown significant side effects and little specific efficacy over placebo. One potential treatment may be via re-establishment of glutamate and GABA neurotransmitter systems that have been shown to malfunction in depressed patients. The literature describing possible causal links between GABA and/or glutamate malfunction and depression is reviewed, plus those studies which provide experimental data to confirm this hypothesis. While there is plausible support for the links between malfunction of these neurotransmitters and depression, few data exist yet regarding development of effective antidepressant medications based upon these findings.