Increased cerebrospinal fluid corticotropin-releasing factor concentrations during tryptophan depletion in healthy adults

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.