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      Salivary serotonin does not correlate with central serotonin turnover in adult phenylketonuria (PKU) patients

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          Abstract

          Introduction

          Phenylketonuria (PKU) is an inborn error of metabolism associated with an increased risk of behavioural and mood disorders. There are currently no reliable markers for monitoring mood in PKU. The purpose of this study was to evaluate salivary serotonin as a possible non-invasive marker of long-term mood symptoms and central serotonin activity in patients with PKU.

          Methods

          20 patients were recruited from our Adult Metabolic Diseases Clinic. Age, sex, plasma phenylalanine (Phe) level, DASS (Depression Anxiety Stress Scales) depression score, DASS anxiety score, BMI, salivary serotonin, salivary cortisol, 2-year average Phe, 2-year average tyrosine (Tyr), and 2-year average Phe:Tyr ratio were collected for each patient. Spearman's ρ correlation analysis was used to determine if there was any relationship between any of the parameters.

          Results

          There were positive correlations between DASS anxiety and DASS depression scores (Spearman's ρ = 0.8708, p-value < 0.0001), BMI and plasma Phe level (Spearman's ρ = 0.6228, p-value = .0034), and 2-year average Phe and BMI (Spearman's ρ = 0.5448, p-value = .0130). There was also a negative correlation between salivary cortisol and plasma Phe level (Spearman's ρ = −0.5018, p-value = .0338). All other correlations were not statistically significant.

          Conclusion

          Salivary serotonin does not correlate with peripheral phenylalanine levels, DASS depression scale scores, or DASS anxiety scale scores, implying that salivary serotonin does not reflect central serotonin turnover. Additionally, this study suggests that salivary serotonin is not a suitable marker for monitoring dietary control, mood, or anxiety in PKU.

          Synopsis

          Salivary serotonin does not correlate with peripheral phenylalanine levels, DASS depression scale scores, or DASS anxiety scale scores, suggesting that salivary serotonin is not a suitable marker for monitoring dietary control, mood, or anxiety in PKU.

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          Most cited references39

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          A unique central tryptophan hydroxylase isoform

          Biochemical Pharmacology, 66(9), 1673-1680
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            Psychometric properties of the Depression Anxiety Stress Scales (DASS) in clinical samples.

            The psychometric properties of the Depression Anxiety Stress Scales (DASS) were evaluated in two studies using large clinical samples (N = 437 and N = 241). In Study 1, the three scales comprising the DASS were shown to have excellent internal consistency and temporal stability. An exploratory factor analysis (principal components extraction with varimax rotation) yielded a solution that was highly consistent with the factor structure previously found in nonclinical samples. Between-groups comparisons indicated that the DASS distinguished various anxiety and mood disorder groups in the predicted direction. In Study 2, the conceptual and empirical latent structure of the DASS was upheld by findings from confirmatory factor analysis. Correlations between the DASS and other questionnaire and clinical rating measures of anxiety, depression, and negative affect demonstrated the convergent and discriminant validity of the scales. In addition to supporting the psychometric properties of the DASS in clinical anxiety and mood disorders samples, the results are discussed in the context of current conceptualizations of the distinctive and overlapping features of anxiety and depression.
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              White matter pathology in phenylketonuria.

              Early-treated phenylketonuria (PKU) is associated with a range of neuropsychological impairments. Proposed mechanisms for these impairments include dopamine depletion and white matter pathology. Neuroimaging studies demonstrate high-signal intensity in the periventricular white matter in most PKU patients, which can extend into subcortical and frontal regions in more severe cases. A review of histopathology and neuroimaging studies reveals that diffuse white matter pathology in untreated PKU patients is likely to reflect hypomyelination (lack of myelin formation), while in early-treated patients white matter abnormalities observed on magnetic resonance imaging (MRI) is likely to reflect intramyelinic edema. Research demonstrates that this pathology is associated with metabolic control and may be reversed with adherence to a strict low-phenylalanine (Phe) diet. While the functional significance of white matter pathology in PKU is not certain, there is some evidence that these abnormalities are associated with functional impairments when the pathology extends into subcortical and frontal regions.
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                Author and article information

                Contributors
                Journal
                Mol Genet Metab Rep
                Mol Genet Metab Rep
                Molecular Genetics and Metabolism Reports
                Elsevier
                2214-4269
                05 April 2018
                June 2018
                05 April 2018
                : 15
                : 100-105
                Affiliations
                [a ]UBC Department of Medicine, Division of Endocrinology, Canada
                [b ]Vancouver Coastal Health, Adult Metabolic Diseases Clinic, Canada
                [c ]UBC Department of Pediatrics, Division of Biochemical Diseases, Canada
                Author notes
                [* ]Corresponding author at: 4th Floor, Gordon and Leslie Diamond Health Care Centre, 2775 Laurel Street, Vancouver, BC V5Z 1M9, Canada. gabriella.horvath@ 123456cw.bc.ca
                Article
                S2214-4269(18)30014-4
                10.1016/j.ymgmr.2018.03.008
                6047111
                b88c1b61-0ab1-45f2-b08f-a1c906d82f98
                © 2018 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 14 January 2018
                : 20 March 2018
                : 21 March 2018
                Categories
                Research Paper

                phenylketonuria (pku),salivary serotonin,salivary cortisol,depression,anxiety,mood disorders

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