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.
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.
Authors: Francisco A Moreno; Damian Parkinson; Craig Palmer; Wm Lesley Castro; John Misiaszek; Aram El Khoury; Aleksander A Mathé; Ron Wright; Pedro L Delgado Journal: Eur Neuropsychopharmacol Date: 2010-01 Impact factor: 4.600
Authors: J S Labus; E A Mayer; J Jarcho; L A Kilpatrick; T O C Kilkens; E A T Evers; W H Backes; R-J M Brummer; M A van Nieuwenhoven Journal: Gut Date: 2011-03-14 Impact factor: 23.059
Authors: Oliver J Robinson; Cassie Overstreet; Phillip S Allen; Daniel S Pine; Christian Grillon Journal: Neuropsychopharmacology Date: 2012-04-11 Impact factor: 7.853
Authors: Jeremy D Coplan; Chadi G Abdallah; Joan Kaufman; Joel Gelernter; Eric L P Smith; Tarique D Perera; Andrew J Dwork; Arie Kaffman; Jack M Gorman; Leonard A Rosenblum; Michael J Owens; Charles B Nemeroff Journal: Psychoneuroendocrinology Date: 2010-08-06 Impact factor: 4.905