Clinical and biochemical assessment of depressive symptoms in patients with Alkaptonuria before and after two years of treatment with nitisinone

Davison, AS ORCID: 0000-0001-5501-4475, Harrold, JA ORCID: 0000-0002-0899-4586, Hughes, G, Norman, B ORCID: 0000-0001-9293-4852, Devine, J, Usher, J, Hughes, AT, Khedr, M ORCID: 0000-0002-4998-2397, Gallagher, JA ORCID: 0000-0002-0852-279X, Milan, AM ORCID: 0000-0002-0452-2338
et al (show 2 more authors) (2018) Clinical and biochemical assessment of depressive symptoms in patients with Alkaptonuria before and after two years of treatment with nitisinone. Molecular Genetics and Metabolism, 125 (1-2). pp. 135-143.

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Objective:Concerns exist over hypertyrosinaemia that is observed following treatment with nitisinone. It hasbeen suggested that tyrosine may compete with tryptophan for uptake into the central nervous system, and orinhibit tryptophan hydroxylase activity reducing serotonin production. At the National Alkaptonuria (AKU)Centre nitisinone is being used off-licence to treat AKU, and there is uncertainty over whether hypertyrosinaemiamay alter mood. Herein results from clinical and biochemical assessments of depression in patients with AKUbefore and after treatment with nitisinone are presented.Patients and methods:63 patients were included pre-nitisinone treatment, of these 39 and 32 patients werefollowed up 12 and 24 months after treatment. All patients had Becks Depression Inventory-II (BDI-II) assess-ments (scores can range from 0 to 63, the higher the score the more severe the category of depression), andwhere possible urinary monoamine neurotransmitter metabolites and serum aromatic amino acids were mea-sured as biochemical markers of depression.Results:Mean ( ± standard deviation) BDI-II scores pre-nitisinone, and after 12 and 24 months were 10.1(9.6);9.8(10.0) and 10.5(9.9) (p≥0.05, all visits). Paired scores (n = 32), showed a significant increase at 24 monthscompared to baseline 10.5(9.9) vs. 8.6 (7.8) (p = 0.03). Serum tyrosine increased at least 6-fold following ni-tisinone (p≤0.0001, all visits), and urinary 3-methoxytyramine (3-MT) increased at 12 and 24 months(p≤0.0001), and 5-hydroxyindole acetic acid (5-HIAA) decreased at 12 months (p = 0.03).Conclusions:BDI-II scores were significantly higher following 24 months of nitisinone therapy in patients thatwere followed up, however the majority of these patients remained in the minimal category of depression. Serumtyrosine and urinary 3-MT increased significantly following treatment with nitisinone. In contrast urinary 5-HIAA did not decrease consistently over the same period studied. Together thesefindings suggest nitisinone doesnot cause depression despite some observed effects on monoamine neurotransmitter metabolism.

Item Type: Article
Uncontrolled Keywords: Alkaptonuria, Beck's depression inventory-II, Metadrenalines, 5-Hydroxyindole acetic acid
Depositing User: Symplectic Admin
Date Deposited: 30 Jul 2018 09:28
Last Modified: 19 Jan 2023 01:30
DOI: 10.1016/j.ymgme.2018.07.008
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