Plasma Tetrahydrobiopterin Levels in Patients with Psychiatric Disorders

Ozaki, Norio; Ohta, Tatsuro; Kasahara, Yoriko; Kaneda, Norio; Nagatsu, T

doi:10.1159/000119441

Cited by 25 publications

(11 citation statements)

References 17 publications

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“…Theoretically, this rise could compromise BH (4) synthesis, but consistent with our earlier research, we found no change in total BIOP, the sum of BH (4) and its oxidative products, dihydrobiopterin and biopterin. However, we cannot exclude a shift, within total BIOP, from BH (4) to these oxidative products [15]. Again in accordance with our earlier data in IFN-a, the increased PHE:TYR ratio of the treated group versus controls in turn points to a lower activity of the enzyme phenylalanine hydroxylase, for which BH (4) is also a cofactor.…”

Section: Discussionsupporting

confidence: 74%

Pegylated interferon-α2b treatment in melanoma patients: influence on amino acids, 5-hydroxyindolacetic acid and pteridine plasma concentrations

Gool¹,

Ojik²,

Kruit³

et al. 2004

Anti-Cancer Drugs

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Our objective was to study the influence of pegylated interferon-alpha2b (PEG-IFN-alpha) on the metabolism of amino acids and pteridines. We used an exploratory study into plasma concentrations of large neutral amino acids, 5-hydroxyindolacetic acid (5-HIAA), total biopterin (BIOP) and neopterin (NEOP) in 40 high-risk melanoma patients. Patients were randomized to treatment with PEG-IFN-alpha once a week in a dose of 6 microg/kg/week s.c. during 8 weeks, followed by a maintenance treatment of 3 microg/kg/week s.c. or to observation only. We found that treatment with PEG-IFN-alpha decreases tryptophan (TRP) concentrations in the first 3 months of treatment to a maximum of 25.3% compared to controls [95% confidence interval (CI): 14.9 to 34.4]. The TRP:LNAA ratio, an index for the availability of TRP to the central nervous system (CNS), decreases during 6 months with 18.8% (95% CI: 11.9 to 25.2). Concentrations of NEOP rose; however, concentrations of BIOP, the sum of tetrahydrobiopterin [BH4] and its oxidative products, did not decrease. The ratio of phenylalanine to tyrosine was increased with 11.7% (95% CI: 1.0 to 23.5) during 6 months. We conclude that, like conventional IFN-alpha, PEG-IFN-alpha lowers TRP concentrations and decreases the availability of TRP to the CNS. PEG-IFN-alpha has a similar influence on pteridine metabolism as standard IFN-alpha. If a lowered availability of TRP and a consequent decrease of serotonergic neurotransmission are indeed a mechanism underlying neuropsychiatric side-effects of IFN-alpha, patients on PEG-IFN-alpha are not at a lower risk of developing neuropsychiatric side-effects as patients on conventional IFN-alpha.

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Section: Discussionsupporting

confidence: 74%

Pegylated interferon-α2b treatment in melanoma patients: influence on amino acids, 5-hydroxyindolacetic acid and pteridine plasma concentrations

Gool¹,

Ojik²,

Kruit³

et al. 2004

Anti-Cancer Drugs

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“…[18][19][20][21] Others have also found a decrease in levels of tetrahydrobiopterin, a natural cofactor for TH, in depressed patients. [22][23][24][25] This evidence seems to indicate that adaptive changes in TH and the onset of action of various antidepressants are linked.…”

Section: Role Of Th In Depressionmentioning

confidence: 94%

Stress, norepinephrine and depression

Leonard

2002

Acta Neuropsychiatr.

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Journal of Psychiatry & Neuroscience S11Stress is an important precipitant factor in depression, and the changes in various body systems that occur in depression are similar to those observed in response to stress. This paper discusses the interactions among the immune, endocrine and norepinephrine systems that are evident in patients with depression, as well as those affected by stress. Many of the stress-induced changes can be reversed by antidepressants, particularly norepinephrine reuptake inhibitors.Le stress est un important facteur catalyseur dans les cas de dépression et les changements subis par les divers systèmes corporels au cours de la dépression ressemblent à ceux qu'on observe face au stress. Cette communication porte sur les interactions entre les systèmes immunitaire, endocrinien et celui de la norépinéphrine, qui sont évidentes chez les patients atteints de dépression, ainsi que chez ceux qui sont touchés par le stress. Il est possible d'inverser un grand nombre de ces changements causés par le stress en utilisant des antidépresseurs et en particulier des inhibiteurs du recaptage de la norépinéphrine.Norepinephrine in depression and mood disorders La norépinéphrine dans la dépression et les troubles psychiques

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“…Changes in the levels of plasma biopterins in patients with depression could be a disease or a symptom effect, because these changes were observed only in patients with affective disorders or in patients with panic disorder with depressive mood [21]. But in spite of our various experi ments, the main source of plasma biopterin, and the mechanism of the changes of plasma biopterin in depres sion remains unknown.…”

Section: Plasma Tetrahydrobiopterin Levels In Depressivesmentioning

confidence: 95%

Changes in Plasma Tetrahydrobiopterin Levels of Depressives in Depressive and Remission Phases: Reconfirmed by Measurement with an Internal Standard

Mizutani¹,

Ohta

Nakazawa³

et al. 1994

Neuropsychobiology

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Plasma total biopterin and tetrahydrobiopterin levels of 10 normal controls and 10 patients with monopolar depression were measured with and without internal standard. The levels did not differ between the two methods. A significant increase of total biopterin levels and the lower ratio of tetrahydrobiopterin to total biopterin in the depressive phase were observed in the plasma of patients with depression compared to normal controls, and these changes in plasma biopterin tended to normalize in the remission phase.

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Plasma Tetrahydrobiopterin Levels in Patients with Psychiatric Disorders

Cited by 25 publications

References 17 publications

Pegylated interferon-α2b treatment in melanoma patients: influence on amino acids, 5-hydroxyindolacetic acid and pteridine plasma concentrations

Pegylated interferon-α2b treatment in melanoma patients: influence on amino acids, 5-hydroxyindolacetic acid and pteridine plasma concentrations

Stress, norepinephrine and depression

Changes in Plasma Tetrahydrobiopterin Levels of Depressives in Depressive and Remission Phases: Reconfirmed by Measurement with an Internal Standard

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