A new drug target to treat depression and other mood disorders could lie in a group of GABA neurons, which have been shown to contribute to symptoms like social withdrawal and increased anxiety.
A preclinical study, from the lab of Olivier Berton, PhD, an assistant professor in the department of Psychiatry, in collaboration with Sheryl Beck, PhD, a professor in the department of Anesthesiology at Children's Hospital of Philadelphia, found that bullying and other social stresses triggered symptoms of depression in mice by activating GABA neurons, in a never-before-seen direct relationship between social stimuli and this neural circuitry.
AdvertisementActivation of those neurons, they found, directly inhibited levels of serotonin, long known to play a vital role in behavioural responses-without it, a depressed person is more likely to socially withdrawal.
Less serotonin elicits socially defensive responses like avoidance or submission, where enhancement-the main goal of antidepressants-induces a positive shift in the perception of socio-affective stimuli, promoting affiliation and dominance.
These new findings point to GABA neurons as a new, neural drug target that could help treat the other patients who don't respond to today's treatment.
For the study, "avoidant" mice were exposed to brief bouts of aggression from trained "bully" mice. By comparing gene expression in the brains of resilient and avoidant mice, Berton and colleagues discovered that bullying in avoidant mice puts GABA neurons in a state where they become more excitable and the mice exhibit signs of social defeat. Resilient mice, however, had no change in neuron levels and behavior.
The study has been published in the Journal of Neuroscience.