Sensitivity of Short and Long Allele Carriers of the 5-HTTLPR to Environmental Threat Post Hydrocortisone Administration

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Sensitivity of Short and Long Allele Carriers of the 5-HTTLPR to Environmental Threat Post Hydrocortisone Administration

Conditions
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Major Depressive Disorder, Anxiety Disorders

Intervention / Treatment
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* Drug: Hydrocortisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: None Exclusion Criteria: Are you under the age of 18 years old? Have you ever had an allergic reaction to hydrocortisone? Do you have diabetes or high blood pressure? Do you have any thyroid, liver, heart, lung, or kidney problems? Do you have herpes, HIV or any sexual transmitted disease? Are you currently pregnant or think you might be pregnant? Have you taken RU486, Plan B or Morning After Pill within the last 2 weeks? - Are you currently breastfeeding? Have you been sick within the last week? Do you have any fungal infections? Have you been exposed to measles or chicken pox in the last week? Have you ever had a seizure? Do you have any disease of bony tissue, such as osteoporosis? Do you have any autoimmune diseases, such as myasthenia gravis? Do you have multiple sclerosis? Do you have any condition that compromises you immune system function or causes you to be more likely to get sick? Have you had any recent surgeries? Do you have and gastrointestinal problems, such as ulcers, diverticulitis, colitis, hepatitis, or Crohn disease? Are you taking any of the following medications: nevirapine, telbivudine, sipuleucel-T (IV), natalizumab (IV)? Have you received any vaccinations within the last week? With the exception of vitamins, have you taken any medications in the last 3 days, including all over-the counter medications and/or supplements (e,g. Tylenol, ibuprofen, St. John's Wort, cold remedies)? Do you currently have or have you had in the past of any kind of cancer? Do you have any significant medical or psychiatric illnesses not listed above?

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo<br>Control group who will not receive hydrocortisone. Will act as a comparison group to the hydrocortisone group. | |
| Experimental: Hydrocortisone<br>Group will receive 20mg oral hydrocortisone | Drug: Hydrocortisone<br>* Each subject in this group will receive one 20mg hydrocortisone capsule to be taken by mouth.<br>* Other names: Hydrocortone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in testosterone concentration | Subjects will be administered hydrocortisone or placebo. One hour after administration, they will be exposed to an environmental threat manipulation. 20 minutes after this manipulation, saliva will be collected, and testosterone concentrations will be assessed and compared to pre-manipulation concentrations | 2 hours post hydrocortisone administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hydrocortisone, Cortisol, Testosterone, Stress, Serotonin, 5-HTTLPR, Amygdala, Depression