Investigating the Role of Serotonin in Emotional Processing Through the Use of Tryptophan Depletion
Data Collection
Summary
Study start date: August 31, 2004
Actual date on which the first participant was enrolled.Objective The goal of this protocol is to use a targeted serotonergic manipulation \[acute tryptophan depletion (ATD)\] and specific neurocognitive and neuroimaging paradigms to consider the role of serotonin (5-HT) in emotional processing. In particular, we wish to evaluate claims that serotonin has a role in the effective processing of aversive signals. Additionally, we wish to examine whether tryptophan depletion will attenuate the neural response to aversive material. Study population Healthy human adult volunteers, ages 20-50 years old, with no DSM-IV-defined Axis I mental disease and who fulfill the remainder of the inclusion/exclusion criteria. Design This is a prospective, randomized, double-blind, placebo-controlled, single-dose, outpatient study in eligible, healthy volunteers. Participants will be randomly assigned in a 1:1 ratio to single doses of drug (ATD) or placebo. The National Institutes of Health (NIH) Clinical Center Pharmacy will facilitate randomization and supply the randomization code to the Clinical Center s Metabolic Nutrition Department (see below). All subjects will be monitored for adverse events. Participants will give written, informed consent prior to any assessments and procedures covered by this protocol. The study will be conducted in the NIH Clinical Center 5SW Day Hospital and the NMRF center (for the imaging arm of the study). Subjects will arrive in the morning of the testing day and complete baseline measurements (i.e., mood and anxiety ratings and serum tryptophan levels). Participants will then receive an oral dose of ATD capsules or placebo. Participants will consume two meals during the study day; the placebo group (control subjects) will be given high-tryptophan meals and tryptophan-depleted subjects will receive low-tryptophan meals. Meals will be designed and supplied by the NIH Clinical Center Metabolic Nutrition Department. At specified times, subjects will complete primary measures \[either neurocognitive or neuroimaging (fMRI) paradigms\] and secondary measures (mood and anxiety ratings and serum levels of tryptophan) as detailed in the protocol. Adverse events will be monitored throughout the study day. A post-study evaluation will occur prior to discharging the participant to verify that he/she is physically and mentally well and fit to leave the Clinical Center. Outcome Measures Primary Outcome Measures: * Neurocognitive Paradigms: Behavioral measures including reaction time and accuracy * Neuroimaging Paradigms: Blood-oxygen-level-dependent (BOLD) response Secondary Outcome Measurements: * Serum tryptophan levels * Mood and Anxiety Rating Scales
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.91 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 20 to 50 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Criteria
* INCLUSION CRITERIA: Age: Participants will be males and females, 20-50 years of age. IQ: IQ, as measured by 4 subscales from the Wechsler Adult Intelligence Scale-Revised (WAIS-R), must be greater than 80. Participants will be able to comprehend the purpose and procedures of the study. They will be able to provide written, informed consent for all study procedures. EXCLUSION CRITERIA: Psychiatric history: Participants will be assessed using DSM-IV criteria via standardized psychiatric interviews conducted by trained examiners (SCID). All participants will be free of any current or past major affective disorder, psychotic disorder, substance dependence, anorexia nervosa or bulimia. All participants will be free of any current anxiety disorders with the exception of specific phobias and free of current somatoform disorders. In addition, participants with a first degree relative with major depressive disorder will be excluded. Severe acute and chronic medical illnesses (e.g., cardiac disease, diabetes, epilepsy). CNS disease: History of brain abnormalities (e.g., neoplasms, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g., abscess), or other neurological disease, or history of head trauma (defined as loss of consciousness greater than 3 min). Currently on any regular medication that would interfere with study results (with exception of contraceptive pill). Current use of psychotropic medication or benzodiazepine Currently breast feeding or pregnant (as documented by pregnancy testing done within 24 hr of the study starting) Subjects who are lactose intolerant will be excluded as the placebo capsules contain lactose. Also, those subjects who cannot consume the diets provided by metabolic nutrition on the study day will be excluded. ADDITIONAL EXCLUSION CRITERIA FOR fMRI STUDIES: Metal or electronic objects: Metal plates, certain types of dental braces, cardiac pacemakers, etc., that are sensitive to electromagnetic fields contraindicate MRI scans. Claustrophobia: participants will be questioned about potential discomfort in being in an enclosed space, such as an MRI scanner.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, United StatesSee the location