Increased cerebrospinal fluid corticotropin-releasing factor concentrations during tryptophan depletion in healthy adults. |
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Authors: | Audrey R Tyrka Linda L Carpenter Christopher J McDougle Paul D Kirwin Michael J Owens Charles B Nemeroff David R Strong Lawrence H Price |
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Affiliation: | Department of Psychiatry and Human Behavior, Brown Medical School, Providence, Rhode Island, USA. Audrey_Tyrka@Brown.edu |
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Abstract: | BACKGROUND: Brain serotonin neurotransmission and hypothalamic-pituitary-adrenal axis function are implicated in the pathophysiology of depression, and these systems interact in a reciprocal modulatory fashion. This study examined the effect of tryptophan depletion, which acutely reduces brain serotonin concentrations, on serial cerebrospinal fluid concentrations of corticotropin-releasing factor in healthy humans. METHODS: Five subjects completed a standard tryptophan depletion protocol, and four subjects participated in a comparison condition. Subjects underwent continuous sampling of cerebrospinal fluid via lumbar peristaltic pump. Concentrations of cerebrospinal fluid corticotropin-releasing factor were measured by radioimmunoassay. RESULTS: No mood changes were observed in either group. Tryptophan-depleted subjects exhibited significantly greater increases in corticotropin-releasing factor concentrations over time than subjects in the comparison condition. CONCLUSIONS: These findings highlight the potential importance of corticotropin-releasing factor and serotonin interactions and suggest that activation of corticotropin-releasing-factor-containing neurons could play a role in the emergence of mood symptoms following tryptophan depletion in vulnerable individuals. |
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Keywords: | Cerebrospinal fluid corticotropin-releasing factor CRF CSF depression HPA hypothalamic-pituitary-adrenal neuroendocrine tryptophan depletion |
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