Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-12-03T19:15:56.210Z Has data issue: false hasContentIssue false
  • English
  • Français

Pteridines and affective disorders

Published online by Cambridge University Press:  24 June 2014

R. Hoekstra  and
D. Fekkes
R. Hoekstra*
Affiliation:
Delta Psychiatric Hospital, MFC-Zuid, Rotterdam
D. Fekkes
Affiliation:
Department of Psychiatry, Section Pathophysiology of Behavior, Erasmus University, Rotterdam, the Netherlands
*
Delta Psychiatric Hospital, MFC-Zuid, Postbus 800, 3170 DZ Poortugaal, the Netherlands. Tel: 010 4936515; Fax: 010 4936514; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

The pteridine tetrahydrobiopterin (BH4) is an essential cofactor in the biosynthesis of dopamine, (nor)epinephrine, serotonin and nitric oxide (NO). Furthermore, BH4 has a direct influence on release mechanisms of these neurotransmitters and on serotonin receptor binding activity immunology. The synthesis of BH4 is stimulated by interferon-gamma and hence there is a close relationship with the immune system HPA-axis. In animal experiments it was also found that the hypothalamus–pituitary–adrenal axis influences the pteridine metabolism. In clinical studies, so far, no evidence has been found for this relationship diseases. A congenital biopterin deficiency results in atypical phenylketonuria with severe neuropsychiatric symptoms. In several neurological diseases, such as Parkinson's disease, decreased levels of BH4 are found depression. Since 1984 there have been reports on decreased biopterin and increased neopterin levels in urine and plasma of depressed patients. Conflicting results have also been found, however, due probably to methodological problems therapy. Until now, oral administration of BH4 to depressed patients has been performed by two investigators, which resulted in mainly temporal clinical improvement discussion. Understanding of biochemical mechanisms in which pteridines are involved may contribute to our knowledge of the pathogenesis and treatment of affective disorders. This paper aims to provide an overview of the relevant literature and warrant for further research on this intriguing compound.

Keywords

affective disordersbiopterindepressionneopterintetrahydrobiopterin
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 14 , Issue 3 , June 2002 , pp. 120 - 126
Copyright
Copyright © Acta Neuropsychiatrica 2002

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Praag van, H . Neurotransmitters and CNS disease: depression. Lancet 1982;ii: 1259–1264. CrossRefGoogle Scholar
Thöny, B, Auerbach, G, Blau, N. Tetrahydrobiopterin biosynthesis, regeneration and functions. Biochem J 2000;347: 1–16.CrossRefGoogle ScholarPubMed
Levine, RA. Tetrahydrobiopterin and biogenic amine metabolism in neuropsychiatry, immunology, and aging. Ann NY Acad Sci 1988;521: 129–139.CrossRefGoogle Scholar
Koshimura, K, Miwa, S, Lee, K, Fujiwara, M, Watanabe, Y. Enhancement of dopamine release in vivo from the rat striatum by dialytic perfusion of 6R-l-erythro-5,6,7,8–tetrahydrobiopterin. J Neurochem 1990;54: 1391–1397.CrossRefGoogle Scholar
Wolf, WA, Ziaja, E, Arthur, RA Jr,Anastasiadis, PZ, Levine, RA, Kuhn, DM. Effect of tetrahydrobiopterin on serotonin synthesis, release, and metabolism in superfused hippocampal slices. J Neurochem 1991;57: 1191–1197.CrossRefGoogle ScholarPubMed
Auerbach, G, Nar, H. The pathway from GTP to tetrahydrobiopterin: three dimensional structures of GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase. Biol Chem 1997;378: 185–192.Google ScholarPubMed
Leeming, RJ, Blair, JA. The effects of pathological and normal physiological processes on biopterin derivative levels in man. Clin Chim Acta 1980;108: 103–111.CrossRefGoogle ScholarPubMed
Bullard, WP, Guthrie, PB, Russo, PV, Mandell, AJ. Regional and subcellular distribution and some factors in the regulation of reduced pterins in rat brain. J Pharmacol Exp Ther 1978;206: 4–20.Google ScholarPubMed
Kapatos, G, Hirayama, K, Lentz, SI, Zhu, M, Stegenga, S. Differential metabolism of tetrahydrobiopterin in monoamine neurons: a hypothesis based upon clinical and basic research. Adv Exp Med Biol 1993;338: 217–222.CrossRefGoogle Scholar
Lentz, SI, Kapatos, G. Tetrahydrobiopterin biosynthesis in the rat brain: heterogeneity of GTP cyclohydrolase I mRNA expression in monoamine-containing neurons. Neurochem Int 1996;28: 569–582.CrossRefGoogle ScholarPubMed
Miwa, S, Watanabe, Y, Hayaishi, O. 6R-l-erythro-5,6,7,8–tetrahydrobiopterin as a regulator of dopamine and serotonin biosynthesis in the rat brain. Arch Biochem Biophys 1985;239: 234–241.CrossRefGoogle ScholarPubMed
Maes, M, Scharpé, S, Meltzer, HYet al. Increased neopterin and interferon-gamma secretion and lower availability of l-tryptophan in major depression: further evidence for an immune response. Psychiatr Res 1994;54: 143–160. CrossRefGoogle ScholarPubMed
Amsterdam van, JGC, Opperhuizen, A. Nitric oxide and biopterin in depression and stress. Psychiatr Res 1999;85: 33–38. CrossRefGoogle Scholar
Mayer, B, Werner, ER. In search of a function for tetrahydrobiopterin in the biosynthesis of nitric oxide. Naunyn-Schmiedeberg's Arch Pharmacol 1995;351: 453–463. CrossRefGoogle ScholarPubMed
Maier, W, Cosentino, F, Lûtolf, RBet al. Tetrahydrobiopterin improves endothelial function in patients with coronary artery disease. J Cardiovasc Pharmacol 2000;35: 173–178.DOI: 10.1097/00005344-200002000-00001CrossRefGoogle ScholarPubMed
Heitzer, T, Krohn, K, Albers, S, Meinertz, T. Tetrahydrobiopterin improves endothelium-dependent vasodilation by increasing nitric oxide actvitiy in patients with Type II diabetes mellitus. Diabetologica 2000;43: 1435–1438. CrossRefGoogle Scholar
Stroes, E, Kastelein, J, Cosentino, Fet al. Tetrahydrobiopterin restores endothelial function in hypercholesterolemia. J Clin Invest 1997;99: 41–46.CrossRefGoogle ScholarPubMed
Dunbar, PR, Hill, J, Neale, TJ, Mellsop, GW. Neopterin measurement provides evidence of altered cell-mediated immunity in patients with depression, but not with schizophrenia. Psychol Med 1992;22: 1051–1057.CrossRefGoogle Scholar
Natelson, BH, Denny, T, Zhou, XDet al. Is depression associated with immune activation? J Affect Disord 1999;53: 179–184.CrossRefGoogle ScholarPubMed
Rapaport, MH. Immune parameters in euthymic bipolar patients and normal volunteers. J Affect Disord 1994;32: 149–156.CrossRefGoogle ScholarPubMed
West van, D, Maes, M. Psycho-immunologie van affectieve stoornissen. In: Den Boer, JA, Ormel, J, Van Praag, HM, Westenberg, HGM, D'haenen, H, eds. Handboek Stemmingsstoornissen. Maarssen: Elsevier/De Tijdstroom, 1999: 179–183. Google Scholar
Matsuda, J, Gohchi, K, Gotoh, N. Serum concentrations of 2′,5′-oligo-adenylate synthetase, neopterin, and Beta-glucan in patients with chronic fatigue syndrome and in patients with major depression[Letters to the Editor]. J. Neurology, Neurosurgery & Psychiatry 1994: 57: 1015–1016. Google Scholar
Bonaccorso, S, Lin, A, Verkerk, Ret al. Immune markers in fibromyalgia: comparison with major depressed patients and normal volunteers. J Affect Disord 1998;48: 75–82.CrossRefGoogle ScholarPubMed
Hattori, Y, Akimoto, K, Nakanishi, N, Kasai, K. Glucocorticoid regulation of nitric oxide and tetrahydrobiopterin in a rat model of endotoxic shock. Biochem Biophys Res Commun 1997;240: 298–303.DOI: 10.1006/bbrc.1997.7653CrossRefGoogle Scholar
O'Toole, SM, Chiappelli, F, Rubin, RT. Plasma neopterin in major depression: relationship to basal and stimulated pituitary-adrenal cortical axis function. Psychiatr Res 1998;79: 21–29. CrossRefGoogle ScholarPubMed
Garbutt, JC, Duch, DS, Nichol, CA, Woolf, JH. Urinary biopterin and neopterin excretion and pituitary-adrenal activity in psychiatric patients. Psychiatr Res 1985;16: 181–187. CrossRefGoogle ScholarPubMed
Mataga, N, Imamura, K, Watanabe, Y. 6R-Tetrahydrobiopterin perfusion enhances dopamine, serotonin, and glutamate outputs in dialysate from rat striatum and frontal cortex. Brain Res 1991;551: 64–71.CrossRefGoogle ScholarPubMed
Muguruma, K, Imamura, K, Watanabe, Y. Repeated peripheral administration of 6R-l-erythro-5,6,7,8–tetrahydrobiopterin alters the binding activities of 5–HT1A and 5–HT2 receptors in rat brain. Biochem Biophys Res Commun 1996;227: 794–799.DOI: 10.1006/bbrc.1996.1587CrossRefGoogle ScholarPubMed
Blau, N, De Klerk, JBC, Thöny, Bet al. Tetrahydrobiopterin loading test in xanthine dehydrogenase and molybdenum cofactor deficiencies. Biochem Mol Med 1996;58: 199–203.CrossRefGoogle ScholarPubMed
Blaskovics, M, Giudici, TA. A new variant of biopterin deficiency. N Engl J Med 1988;319: 1611–1612.Google ScholarPubMed
Kaufman, S. Genetic disorders involving recycling and formation of tetrahydrobiopterin. Adv Pharmacol 1998;42: 41–43.CrossRefGoogle ScholarPubMed
Pogson, D. Issues for consideration in dihydropteridine reductase (DHPR) deficiency. a variant form of hyperphenylalaninaemia. J Intell Disabil Res 1997;41: 208–214. CrossRefGoogle Scholar
Williams, AC. Dopamine, dystonia, and the deficient co-factor. Lancet 1995;345: 1130.CrossRefGoogle Scholar
Curtius, H-CH, Müldner, H, Niederwieser, A. Tetrahydrobiopterin: efficacy in endogenous depression and Parkinson's disease. J Neural Transm 1982;55: 301–308. CrossRefGoogle Scholar
Morar, C, Whitburn, SB, Blair, JA. Tetrahydrobiopterin metabolism in senile dementia of Alzheimer type. J Neurol Neurosurg Psychiatry 1983;46: 582–590.CrossRefGoogle ScholarPubMed
Kay, AD, Milstien, S, Kaufman, Set al. Cerebrospinal fluid biopterin is decreased in Alzheimer's disease. Arch Neurol 1986;43: 996–999.CrossRefGoogle ScholarPubMed
Blair, JA, Barford, PA, Morar, Cet al. Tetrahydrobiopterin metabolism in depression. Lancet 1984;2: 163.CrossRefGoogle ScholarPubMed
Coppen, A, Swade, C, Jones, SA, Armstrong, RA, Blair, JA, Leeming, RJ. Depression and tetrahydrobiopterin: the folate connection. J Affect Disord 1989;16: 103–107.CrossRefGoogle ScholarPubMed
Hashimoto, R, Ozaki, N, Ohta, T, Kasahara, Y, Kaneda, N, Nagatsu, T. The plasma tetrahydrobiopterin levels in patients with affective disorders. Biol Psychiatry 1990;28: 526–528.CrossRefGoogle ScholarPubMed
Anderson, DN, Abou-Saleh, MT, Collins, Jet al. Pterin metabolism in depression: an extension of the amine hypothesis and possible marker of response to ECT. Psychol Med 1992;22: 863–869.CrossRefGoogle Scholar
Abou-Saleh, MT, Anderson, DN, Collins, Jet al. The role of pterins in depression and the effects of antidepressive therapy. Biol Psychiatry 1995;38: 458–463.CrossRefGoogle ScholarPubMed
Hoekstra, R, Van Den Broek, WW, Fekkes, D, Bruijn, J A, Mulder, PGH, Pepplinkhuizen, L. Effect of ECT treatment on biopterin and large neutral amino acids in severe, medication resistant depression. Psychiatr Res 2001;103: 115–123. CrossRefGoogle Scholar
Knapp, S, Irwin, M. Plasma levels of tetrahydrobiopterin and folate in major depression. Biol Psychiatry 1989;26: 156–162.CrossRefGoogle ScholarPubMed
Duch, DS, Woolf, JH, Nichol, CA, Davidson, JR, Garbutt, JC. Urinary excretion of biopterin and neopterin in psychiatric disorders. Psychiatr Res 1984;11: 83–89. CrossRefGoogle ScholarPubMed
Kaufman, S, Kapatos, G, McInnes, RR, Schulman, JD, Rizzo, WB. Use of tetrahydropterins in the treatment of hyperphenylalaninemia due to defective synthesis of tetrahydrobiopterin: evidence that peripherally administered tetrahydropterin enter the brain. Pediatrics 1982;70: 376–380.Google Scholar
Levine, RA, Zoephel, GP, Niederwieser, A, Curtius, H-C. Entrance of tetrahydropterin derivatives in brain after peripheral administration: effect on biogenic amine metabolism. J Pharmacol Exp Therap 1987;242: 514–522. Google ScholarPubMed
Fernell, E, Watanabe, Y, Adolfsson, Iet al. Possible effects of tetrahydrobiopterine treatment in six children with autism — clinical and positron emission tomography data: a pilot study. Dev Med Child Neurol 1997;39: 313–318.CrossRefGoogle Scholar
Sakai, T, Antoku, Y, Matsuishi, T, Iwashita, H. Tetrahydrobiopterin double-blind, crossover trial in Machado–Joseph disease. J Neurol Sci 1996;136: 71–72.CrossRefGoogle ScholarPubMed
Curtius, H-CH, Niederwieser, A, Levine, RA, Lovenberg, W, Woggon, B, Angst, J. Successful treatment of depression with tetrahydrobiopterin. Lancet 1983;19: 657–658. CrossRefGoogle Scholar
Fleischhacker, WW, Meise, U, Schubert, H. Re-evaluation of antidepressant effect of tetrahydrobiopterine. Lancet 1985;17: 387. CrossRefGoogle Scholar
Aziz, AA, Leeming, RJ, Blair, JA. Tetrahydrobiopterin metabolism in senile dementia of Alzheimer type. J Neurol Neurosurg Psychiatry 1983;46: 410–413.CrossRefGoogle ScholarPubMed
Nagatsu, T, Yamaguchi, T, Rashman, MKet al. Catecholamine-related enzymes and the biopterin cofactor in Parkinson's disease and related extrapyramidal diseases. Adv Neurol 1984;40: 467–473.Google ScholarPubMed
Bottiglieri, T, Hyland, K, Laundy, Met al. Folate deficiency, biopterin and monoamine metabolism in depression. Psychol Med 1992;22: 871–876.CrossRefGoogle ScholarPubMed
Van Kammen, DP, Levine, R, Sternberg, D. Preliminary evaluation of hydroxylase cofactor in human spinal fluid: potential biochemical and clinical relevance for psychiatric disorders. Psychopharmacol Bull 1978;14: 51–52.Google ScholarPubMed
Kellner, CH, Rakita, RM, Rubinow, DA, Gold, PW, Ballenger, JC, Post, RM. Tetrahydrobiopterin levels in cerebrospinal fluid of affectively ill patients. Lancet 1980;ii: 55–56. Google Scholar