Study sheds new light on the mechanics of depression
A joint French and US research team has discovered what makes a brain particularly vulnerable to depression and anxiety and less likely to respond to antidepressant treatment. The study was published in the journal Neuron and may lead to new treatments for such conditions. Depression is one of the most common health problems in the world; its many symptoms include irritability, inability to concentrate, lack of interest in life and in other people, lack of energy and poor sleep patterns. Treatments vary and commonly include antidepressant medication, counselling and making lifestyle changes. The mechanism behind depression is not yet fully understood, but recent research results point to a combination of stressful events in life and predisposing biological factors. Current treatment is mostly with antidepressant drugs including selective serotonin reuptake inhibitors (SSRIs), which increase serotonin levels in the brain. Serotonin is a neurotransmitter (a chemical that sends signals between a neuron and another cell); low levels of serotonin are believed to contribute to depression. 'Unfortunately, more than half of all depressed patients fail to respond to their first drug treatment,' explained one of the authors of the study, Dr René Hen from Columbia University in the US, whose team carried out the research alongside the pharmacy department at the University of Paris-Sud 11. 'The reasons for this treatment resistance remain enigmatic,' he added. 'Elucidating the exact nature of both of the factors predisposing to depression and the mechanisms underlying treatment resistance remains an important and unmet need.' Previous studies on serotonin have suggested that regulation of serotonin receptors may be linked to depression and to how a person responds to antidepressant treatment. The serotonin-1A (5-HT1A) receptors are found in the serotonin neurons (autoreceptors), where they inhibit serotonin release, and in target areas that receive heteroreceptors (receptors that respond to neurotransmitters). The autoreceptors are vital for setting the 'serotonergic tone' in the brain. Recent research has identified a genetic alteration in human beings that may regulate 5-HT1A autoreceptor levels, and this has been linked with susceptibility to depression and an impaired response to antidepressant treatment. The research team carried out experiments on mice in which they manipulated autoreceptors without altering heteroreceptors. Their results showed that mice with higher levels of autoreceptors showed a blunted physiological response to acute stress, increased levels of despairing behaviour and no response to antidepressants. But when 5-HT1A autoreceptor levels were reduced before antidepressant therapy, the mice began responding to the treatment. 'Taken together, our results establish a causal relationship between 5-HT1A autoreceptor levels, resilience under stress and response to antidepressants,' said Dr Hen. 'We predict that treatments aimed at increasing serotonergic tone prior to beginning SSRI administration might prove to be efficacious and possibly faster-acting antidepressant therapies, particularly for individuals with higher autoreceptor levels.'
Countries
France, United States