Blood 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and melatonin levels in patients with either Huntington’s disease or chronic brain injury J. Christofides,* M. Bridel,* M. Egerton,* G. M. Mackay, C. M. Forrest, N. Stoy,à L. G. Darlington§ and T. W. Stone  *West Park Biochemistry Laboratories, Epsom General Hospital, Epsom, Surrey, UK  Institute of Biomedical & Life Sciences, University of Glasgow, Glasgow, UK àRoyal Hospital for Neuro-disability, Putney, London, UK §Epsom General Hospital, Epsom, Surrey, UK Abstract Following a study of oxidative tryptophan metabolism to kynurenines, we have now analysed the blood of patients with either Huntington’s disease or traumatic brain injury for levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and melatonin. There were no differences in the baseline levels of these compounds between patients and healthy controls. Tryptophan depletion did not reduce 5-HT levels in either the controls or in the patients with Huntington’s disease, but it increased 5-HT levels in patients with brain injury and lowered 5-HIAA in the control and Huntington’s disease groups. An oral tryptophan load did not modify 5-HT levels in the patients but increased 5-HT in control subjects. The tryptophan load restored 5-HIAA to baseline levels in controls and patients with brain injury, but not in those with Huntington’s disease, in whom 5-HIAA remained significantly depressed. Melatonin levels increased on tryptophan loading in all subjects, with levels in patients with brain injury increasing significantly more than in controls. Baseline levels of neopterin and lipid peroxidation products were higher in patients than in controls. It is concluded that both groups of patients exhibit abnormalities in tryptophan metabolism, which may be related to increased inflammatory status and oxidative stress. Interactions between the kynurenine, 5-HT and mela- tonin pathways should be considered when interpreting changes of tryptophan metabolism. Keywords: Huntington’s disease, 5-hydroxyindoleacetic acid (5-HIAA), 5-hydroxytryptamine (5-HT), oxidative stress, peroxi- dation, tryptophan. J. Neurochem. (2006) 97, 1078–1088. Huntington’s disease is an autosomal dominant disorder characterized by neuronal loss in the striatum and neocortex. Its clinical phenotype includes a complex movement disorder, psychiatric manifestations and a progressive decline in cog- nitive function. Genetic studies have indicated the probable involvement of a 349-kDa protein, huntingtin, bearing an abnormally expanded series of glutamine residues close to its N-terminus, and the relationship between this protein and neurochemical changes in the CNS remain the subject of intense investigation (Kuemmerle et al. 1999; Bates 2003). Although a major feature of Huntington’s disease seems to be a loss of GABA-containing neurones from the striatum, there is evidence that other transmitter systems may be affected either as part of the primary diseases mechanism or as secondary to the loss of GABA-ergic neurones. We have been particularly interested in the metabolism of tryptophan in Huntington’s disease, and have recently reported on changes in the kynurenine pathway metabolites of tryptophan in patients with this disorder (Stoy et al. 2005) as well as in patients with traumatic brain injury (Mackay et al. 2006). Received August 31, 2005; revised manuscript received January 25, 2006; accepted January 25, 2006. Address correspondence and reprint requests to Prof T. W. Stone, West Medical Building, University of Glasgow, Glasgow, G12 8QQ, UK. E-mail: t.w.stone@bio.gla.ac.uk Abbreviations used: BDNF, brain-derived neurotrophic factor; 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, 5-hydroxytryptamine; HD, Huntington’s disease; IDO, Indoleamine 2,3-dioxygenase; NAD, nico- tinamide adenine dinucleotide; SSRI, selective serotonin reuptake inhibitor antidepressant. Journal of Neurochemistry , 2006, 97, 1078–1088 doi:10.1111/j.1471-4159.2006.03807.x 1078 Journal Compilation Ó 2006 International Society for Neurochemistry, J. Neurochem. (2006) 97, 1078–1088 Ó 2006 The Authors