An increase in the neurotransmitter gamma-aminobutyric acid (GABA) has similar effects in mice to widely used antidepressants, but they are achieved much more rapidly. If the same proves true for humans, the discovery could open up a path to producing antidepressants that work faster and may have fewer side effects than those currently available.
Existing antidepressants make more serotonin available to transmit signals between brain cells. Despite major benefits for some people, the drugs have serious side-effects and appear not to be more effective than placebos for patients under the age of 25. Yet such is the epidemic of depression in society that they are some of the most profitable drugs of all time.
Professor Bernhard Lüscher of Penn State University is seeking a radically different approach to altering brain chemistry. "GABA is the major inhibitory neurotransmitter in the brain – it acts as the 'brakes' of neural activity – and its dysfunction is implicated in a wide range of neuropsychiatric disorders," Lüscher said in a statement. "Increasing evidence suggests that dysfunction of GABA is also a major culprit in major depressive disorder (MDD), the most common and costly brain disorder and a principal cause of suicide, the primary cause of death among young people."
Lüscher disabled the GABA receptors of mouse somatostatin-positive GABAergic (SST+) interneurons, a type of brain cell thought to play a role in MDD. Somewhat ironically, inability to receive GABA causes SST+ interneurons to produce more GABA themselves, affecting other types of nearby neurons. The findings were reported in Molecular Psychiatry.