Genetic impediments to treating depression
A fascinating new study in Neuron reports a novel genetic approach to treating depression. Patients suffering from depression often don’t respond well to initial treatments. It has been suggested that a gene variant in the human serotonin receptor 5-HT1A decreases treatment response and increases susceptibility to depression. When these receptors occur on serotonin releasing neurons, they function as autoreceptors and inhibit serotonin release when serotonin levels rise. The researchers have developed a strategy to manipulate these 5-HT1A autoreceptors without affecting the other 5-HT1A receptors. Mice with high autoreceptor levels showed increased signs of depression and resistance to treatment. By lowering autoreceptor levels, mice responded to drug treatments.
See Jesse W. Richardson-Jones et al. “5-HT1A Autoreceptor Levels Determine Vulnerability to Stress and Response to Antidepressants,” Neuron 65 (2010): 40–52. (requires subscription—no obvious free abstract.) Nice general discussion of it here: Pierre Blier, “Altered Function of the Serotonin 1A Autoreceptor and the Antidepressant Response” Neuron 65 (2010): 1–2 (again, it seems a subscription is required)