Psychopharmacology (2003) 169:104–107 DOI 10.1007/s00213-003-1479-x ORIGINAL INVESTIGATION M.-J. Attenburrow · C. Williams · J. Odontiadis · A. Reed · J. Powell · P. J. Cowen · C. J. Harmer Acute administration of nutritionally sourced tryptophan increases fear recognition Received: 17 January 2003 / Accepted: 18 March 2003 / Published online: 29 April 2003  Springer-Verlag 2003 Abstract Rationale: The serotonin precursor tryptophan (TRP) has been widely used as a nutritional supplement and antidepressant. Recently, however, the use of TRP has been severely restricted due to its association with the eosinophilic myalgic syndrome, an autoimmune disorder probably caused by ingestion of a contaminant produced in certain TRP manufacturing processes. Objectives: To determine the bioavailability of a nutritional source of TRP obtained from milk protein and to assess whether administration of this material produced neuroendocrine and neuropsychological effects consistent with increased brain serotonin activity. Methods: We studied 24 healthy subjects who ingested approximately 1.8 g of nutrition- ally-sourced TRP or placebo in a double-blind, parallel group, design. We carried out venous sampling for amino acid and hormone estimation and performed a test of emotional processing using a facial expression recogni- tion task. Results: The nutritionally-sourced TRP caused a substantial increase in the availability of TRP in plasma. Relative to placebo the TRP material produced some evidence of an increase in plasma cortisol, and enhanced the perception of fearful and happy facial expressions. Conclusions: A nutritional source of TRP increased the availability of TRP for brain serotonin synthesis and produced endocrine and neuropsychological changes consistent with increased brain serotonin function. The effect of TRP on emotional processing may be relevant to its reported activity in primate studies of social behaviour. Keywords Tryptophan · Serotonin · Fear · Cortisol Introduction Tryptophan (TRP), an amino acid contained in dietary protein, is a precursor of the neurotransmitter serotonin (5-HT) (see Bender 1982). While administration of TRP clearly increases brain 5-HT synthesis, there has long been debate as to whether TRP administered in pharma- cological doses increases brain 5-HT function (Green and Grahame-Smith 1976; Sharp et al. 1992). Despite these reservations TRP was, until recently, widely available as a health food supplement and was licensed as an antide- pressant agent in several countries (Byerly and Risch 1985; Young 1986). Subsequently TRP treatment was linked to the eosinophilic myalgic syndrome, an autoim- mune disorder probably caused by a contaminant pro- duced during TRP manufacture (Kilbourne et al. 1996). The medicinal use of TRP was subsequently severely restricted. The aim of the present study was two-fold. First we assessed the bioavailability in plasma of a nutritional source of TRP produced from milk protein. Second, we tested the hypothesis that a single dose of this material would produce effects consistent with increased brain 5- HT function as judged by previously validated neuroen- docrine and psychological markers of brain neurotrans- mission. Thus we predicted that nutritional TRP would increase the secretion of the anterior pituitary hormones, growth hormone (GH), prolactin (PRL) and cortisol (CORT) (Cowen et al. 1985; Yatham and Steiner 1993). In addition, based on a recent study with acute SSRI treatment, we predicted that acute TRP ingestion would increase the detection of fearful and happy facial expres- sions (Harmer et al. 2003a). Materials and methods Subjects We studied 24 women (mean age 36.2 years, range 19–53 years) who were determined by standard clinical examination and the Structured Clinical Interview for DSM-IV (SCID) to be free of M.-J. Attenburrow · C. Williams · J. Odontiadis · A. Reed · P. J. Cowen ( ) ) · C. J. Harmer University Department of Psychiatry, Warneford Hospital, Oxford, OX3 7JX, UK e-mail: phil.cowen@psych.ox.ac.uk Tel.: +44-1865-226394 Fax: +44-1865-251076 J. Powell Unilever Research, Colworth House, Sharnbrook, Bedford, MK44 1LQ, UK