Brief report Tryptophan hydroxylase gene (TPH1) and peripheral tryptophan levels in depression Richard J. Porter a, ⁎ , Roger T. Mulder a , Peter R. Joyce a , Allison L. Miller b , Martin Kennedy b a Departments of Psychological Medicine, University of Otago, Christchurch, Christchurch, New Zealand b Pathology, University of Otago, Christchurch, Christchurch, New Zealand Received 18 October 2007; received in revised form 23 November 2007; accepted 23 November 2007 Available online 21 February 2008 Abstract Background: Genetic variants have been discovered in two genes encoding for tryptophan hydroxylase (TPH)—TPH1 and TPH2. Low tryptophan (TRP) levels are associated with depression and may arise because of stress. Evidence suggests that hypothalamic and peripheral 5HT systems have a significant role in appetite regulation, possibly a homeostatic mechanism in regulating peripheral TRP levels. Methods: We examined the association between a polymorphism in intron 7 of TPH1, 218A N C and plasma total TRP levels in 118 patients with major depression. Results: There was an interaction between 218A N C and gender in determining plasma TRP whereby presence of the 218C allele, in women, was associated with markedly reduced plasma TRP. Limitations: The study investigated only the TRP1 gene and did not use a haplotype analysis. The results only apply to a population of subjects suffering from major depression. Conclusions: TPH1 may be associated with the regulation of peripheral tryptophan levels and therefore availability of tryptophan to the brain. This may have relevance to a range of neuropsychiatric conditions. © 2007 Published by Elsevier B.V. Keywords: Tryptophan; Depressive disorder; Tryptophan hydroxylase; Serotonin; Genotype 1. Introduction Conversion of tryptophan (TRP) into 5-hydroxytryp- tophan (5HTP) by the enzyme tryptophan hydroxylase is the rate limiting step in 5HT synthesis. Two genes have been discovered which encode for tryptophan hydro- xylase isoforms (TPH1 and TPH2). A polymorphism in intron 7 of TPH1, 218A N C (rs1800532), has been extensively examined in association studies, the A allele being found to be associated with, for instance, self harm (Pooley et al., 2003) and anxiety symptoms in depression (Du et al., 2001). Furthermore, a haplotype-based study has suggested a strong association between TPH1 and stress induced depression (Gizatullin et al., 2006) but no association between TPH2 and stress induced depression (Gizatullin et al., 2008). Another recent report suggests an interaction between lack of social support and TPH1 in the development of depressive symptoms (Jokela et al., 2007). Journal of Affective Disorders 109 (2008) 209 – 212 www.elsevier.com/locate/jad ⁎ Corresponding author. Department of Psychological Medicine, University of Otago, Christchurch, P O Box 4345, Christchurch, New Zealand. Tel.: +64 3 372 0400; fax: +64 3 372 0407. E-mail address: richard.porter@otago.ac.nz (R.J. Porter). 0165-0327/$ - see front matter © 2007 Published by Elsevier B.V. doi:10.1016/j.jad.2007.11.010