Melatonin in Epilepsy: A New Mathematical Model of Diurnal Secretion

Abstract

Purpose. The main objective of the study was to create a mathematical model that describes the melatonin circadian secretion and, then the functionality of the model was tested by a comparison of the melatonin secretions in children with and without epilepsy. Material and Methods. The patients were divided into the epilepsy group (EG, n = 52) and the comparison group (CG, n = 30). The melatonin level was assessed by a radioimmunoassay method. The diurnal melatonin secretion was described using a nonlinear least squares method. Spearman's rank correlation coefficient was chosen to estimate the dependence of the acquired data. The model reproduces blood concentration profiles and its parameters were statistically analyzed using the Mann-Whitney-Wilcoxon test and logistic regression. Results. The correlation analysis performed for the EG and CG groups showed moderate correlations between age and the melatonin secretion model parameters. Patients with epilepsy are characterized by an increased phase shift of melatonin release.

Melatonin in Tuberous Sclerosis Complex Analysis Using Modern Mathematical Modeling Methods

“…Our data suggest that not only disordered sleep but also the shift of melatonin secretion may be expected in TSC children with frequent seizures; unfortunately, this supposition is based on the results gathered from a small TSC group, too. However, our previous studies performed on the large epileptic group strongly confirm it [7, 26]. Examination of melatonin secretion in patients with epilepsy has shown higher nocturnal MLT concentration, increase of MLT concentration during or after seizure, shift or loss of MLT circadian rhythm, or comparable to controls [7, 26].…”

“…The methodology for determining individual parameters of melatonin cycle was based on our mathematical modeling of the diurnal melatonin secretion in children with epilepsy where the time dependencies of melatonin concentrations for each patient were approximated by the MLT( t ) function [7]: $\begin{array}{c}\mathrm{M}\mathrm{L}\mathrm{T}\left(t\right)=b_1+b_2\exp \left(-\frac{{\left(\cos \left(\left(\pi /12\right)t-\left(\pi /12\right)b_3\right)-1\right)}^2}{{\left(\cos \left(\left(\pi /24\right)b_4\right)-1/\sqrt{\ln 2}\right)}^2}\right).\end{array}$…”

A unified model of melatonin, 6‐sulfatoxymelatonin, and sleep dynamics

“…There have been several recent mechanism‐based and statistical models of melatonin dynamics . The statistical model had successfully fitted an exponential function to melatonin profile in plasma to track differences in melatonin features in children with and without epilepsy .…”

“…There have been several recent mechanism‐based and statistical models of melatonin dynamics . The statistical model had successfully fitted an exponential function to melatonin profile in plasma to track differences in melatonin features in children with and without epilepsy . Models based on mechanisms successfully simulate the dynamics of melatonin in plasma and saliva, including its amplitude and phase, as well as the effects of exogenous melatonin administration on resetting the circadian clock, including the endogenous melatonin rhythm .…”

“…[33][34][35][36] The statistical model had successfully fitted an exponential function to melatonin profile in plasma to track differences in melatonin features in children with and without epilepsy. 36 Models based on mechanisms successfully simulate the dynamics of melatonin in plasma and saliva, including its amplitude and phase, as well as the effects of exogenous melatonin administration on resetting the circadian clock, including the endogenous melatonin rhythm. [33][34][35] None of the models have accounted for the dynamics of aMT6s in urine, however, which is increasingly used as a phase marker or for the relationship between the dynamics of melatonin in different fluids, which can only be achieved by studying simultaneous recordings in plasma, saliva, and urine.…”