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

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.

Cerebrospinal fluid inflammatory cytokines and biomarkers of injury severity in acute human spinal cord injury.

There is an urgent need for both the scientific development and clinical validation of novel therapies for acute spinal cord injury (SCI). The scientific development of novel therapies would be facilitated by a better understanding of the acute pathophysiology of human SCI. Clinical validation of such therapies would be facilitated by the availability of biomarkers with which to stratify injury severity and predict neurological recovery. Cerebrospinal fluid (CSF) samples were obtained over a period of 72 h in 27 patients with complete SCI (ASIA A) or incomplete SCI (ASIA B or C). Cytokines were measured in CSF and serum samples using a multiplex cytokine array system and standard enzyme-linked immunosorbent assay (ELISA) techniques. Neurological recovery was monitored, and patient-reported neuropathic pain was documented. IL-6, IL-8, MCP-1, tau, S100beta, and glial fibrillary acidic protein (GFAP) were elevated in a severity-dependent fashion. A biochemical model was established using S100beta, GFAP, and IL-8 to predict injury severity (ASIA A, B, or C). Using these protein concentrations at 24-h post injury, the model accurately predicted the observed ASIA grade in 89% of patients. Furthermore, segmental motor recovery at 6 months post injury was better predicted by these CSF proteins than with the patients' baseline ASIA grade. The pattern of expression over the first 3 to 4 days post injury of a number of inflammatory cytokines such as IL-6, IL-8, and MCP-1 provides invaluable information about the pathophysiology of human SCI. A prediction model that could use such biological data to stratify injury severity and predict neurological outcome may be extremely useful for facilitating the clinical validation of novel treatments in acute human SCI.

Normal-appearing white matter in patients with phenylketonuria: water content, myelin water fraction, and metabolite concentrations.

PURPOSE: To prospectively assess relative water content (RWC), myelin water fraction (MWF), and hydrogen 1 magnetic resonance (MR) spectroscopy findings in the white matter (WM) of patients with phenylketonuria (PKU). MATERIALS AND METHODS: This study was approved by the institution's investigational review board, and informed consent was obtained. T2 water relaxation data were acquired by using a 48-echo measurement in a transverse plane through the genu and splenium of the corpus callosum in 16 patients (six men, 10 women; age range, 18-40 years) with PKU and 16 age- and sex-matched control subjects. MR spectroscopy was performed in a voxel (94x70x15 mm) above the ventricles. WM in control subjects (defined as normal WM) was compared with normal-appearing WM (NAWM) and diffuse WM lesions in patients with PKU by using a Student t test. RESULTS: Patients with PKU had two forms of NAWM: (a) areas that looked normal on intermediate-weighted (IW) and T2-weighted MR images and long T2 maps and (b) areas that looked normal on IW and T2-weighted MR images but were hyperintense on long T2 maps. Both forms of NAWM showed increased RWC (up to 2.5%, P<.001) and reduced MWF (up to 56%, P<.001) relative to normal WM; these changes paralleled those seen in diffuse WM lesions. Approximately 9% of the water in diffuse WM lesions was in a reservoir with a long T2 time of 200-800 msec. Myoinositol concentrations were reduced by 14% (P=.003) in patients with PKU. CONCLUSION: In patients with PKU, NAWM and diffuse WM lesions have altered RWC and MWF relative to normal WM, and diffuse WM lesions show a redistribution of water into an extracellular reservoir with a long T2 time.