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Treating Depression

Individual variations in antidepressant treatment outcomes.
There continues to be interest in the use of deep brain stimulation for the treatment of those with depression resistant to the usual medications. Further studies by Helen Mayberg and colleagues at Emory University may help reveal whether this treatment is effective in a broader range of patients. Among other approaches were studies of genetic factors that may influence the response to more conventional antidepressant treatments. Researchers led by Francis McMahon examined the genetic basis of individual variations in antidepressant treatment outcomes. By studying the DNA of 1,953 patients with major depressive disorder being treated with citalopram, a common antidepressant, they demonstrated a significant association between favorable treatment outcome and the A variant of a gene responsible for serotonin reception, HTR2A. The results of the study are reported in the American Journal of Human Genetics. Furthermore, this A variation was found to occur six times more frequently in Caucasian patients than in African-American patients, who correspondingly showed poorer response to citalopram treatment. The findings provide a compelling case for the role of this gene in antidepressant action, and may help to explain racial differences in responses to antidepressant treatments. Elsewhere, Myrna Weissman and colleagues illustrated an interesting phenomenon involving depression in children. It has long been known that children of depressed parents are at high risk for developing a depressive disorder of their own. Weissman’s group reported in the Journal of the American Medical Association that when mothers were successfully treated with medication for depression over three months, their children showed a reduction in depressive and other symptoms and diagnoses. Conversely, children of mothers who remained depressed suffered from an increased rate of symptoms. This suggests that environmental effects can also affect the psychopathology of this high-risk group of children. Teenage Suicide Researchers led by Mark Olfson looked at a different facet of antidepressant treatment: its relationship to suicide attempts and deaths in adults and children. The results of their matched case-control study, published in the Archives of General Psychiatry, revealed that although antidepressant treatment was not associated with either suicide attempts or deaths in adults, it was significantly associated with both suicide attempts and deaths in children and adolescents. This finding suggests at a minimum that drug treatment in younger patients needs to be closely supervised by clinicians, and parents. The neurobiology of stress-induced depression was the focus of Eric Nestler’s research group. In a study in Nature Neuroscience, mice were subjected to chronic social defeat stress, a frequent precursor to depressive disorders, followed by the chronic administration of imipramine, an antidepressant. Nestler’s group found that this defeat stress generated a decrease in a protein called brain-derived neurotrophic factor (BDNF) in the hippocampus as well as increased modifications to specific proteins associated with gene transcription, called histone methylation. The antidepressant agent reversed this effect, as did an infusion of BDNF itself. The findings suggest that histone methylation and the neurobiological processes related to it may provide a new area of therapeutic interest for depression treatment. Meanwhile, Michel Lazdunski and his collaborators identified a different area of interest for future antidepressant development. Writing in Nature Neuroscience, Lazdunski’s group reported their discovery that a background potassium channel regulated by serotonin, TREK-1, was implicated in depression resistance in mice. Those without the TREK-1 channel showed a resistance to depression under stress, suggesting that this channel may be a viable target for new drug interventions for depression.
depression, major, depressive, disorder, suicide, deep brain stimulation, bdnf, serotonin
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