Major Depressive Disorder Clinical Trial
Official title:
Sensitivity of Short and Long Allele Carriers of the 5-HTTLPR to Environmental Threat Post Hydrocortisone Administration
The current study will test the causal relationship between elevated levels of cortisol and the serotonin transporter gene (5-HTTLPR) as these factors influence sensitivity to environmental threat. The investigators predict that carriers of the short allele of the serotonin transporter gene who have elevated cortisol levels will be most sensitive to threatening environments, whereas carriers of the long allele who do not have elevated cortisol (placebo subjects) will be least sensitive.
Depression vulnerability has been linked to certain variants of the serotonin transporter gene. Research indicates that a polymorphism of the serotonin transporter (5-HTTLPR) gene appears to moderate the association between life stress and depression onset. Life stress robustly predicts depression onset for individuals with two short 5-HTTLPR alleles. Individuals homozygous for the short 5-HTTLPR allele thus appear to be more sensitive to the effect of life stress, which in turn contributes to depression onset. A recent study showed that short allele carriers presented with a threat (social or other threats) who also had high levels of testosterone had elevated cortisol after exposure to the threat. There is neurobiological evidence that short allele status, elevated testosterone levels, and elevated cortisol levels are all linked to amygdala hyper-reactivity to the same classes of environmental threats. Thus, this study will test, for the first time, a potential interaction between 5-HTTLPR status and experimentally manipulated cortisol levels as risk factors for downstream mood and/or anxiety disorders by examining potential dysregulated stress responses among short allele carriers who have elevated cortisol levels. ;
Observational Model: Case Control
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