Urinary sulphatoxymelatonin as a biomarker of serotonin status in biogenic amine-deficient patients

Abstract

Melatonin is synthesized from serotonin and it is excreted as sulphatoxymelatonin in urine. We aim to evaluate urinary sulphatoxymelatonin as a biomarker of brain serotonin status in a cohort of patients with mutations in genes related to serotonin biosynthesis. We analized urinary sulphatoxymelatonin from 65 healthy subjects and from 28 patients with genetic defects. A total of 18 patients were studied: 14 with autosomal dominant and recessive guanosine triphosphate cyclohydrolase-I deficiency; 3 with sepiapterin reductase deficiency; and 1 with aromatic L-amino acid decarboxylase deficiency. Further 11 patients were studied after receiving serotoninergic treatment (serotonin precursors, monoamine oxidase inhibitors, selective serotonin re-uptake inhibitors): 5 with aromatic L-amino acid decarboxylase deficiency; 1 with sepiapterin reductase deficiency; 3 with dihydropteridine reductase deficiency; and 2 with 6-pyruvoyltetrahydropterin synthase deficiency. Among the patients without therapy, 6 presented low urinary sulphatoxymelatonin values, while most of the patients with guanosine triphosphate cyclohydrolase-I deficiency showed normal values. 5 of 11 patients under treatment presented low urine sulphatoxymelatonin values. Thus, decreased excretion of sulphatoxymelatonin is frequently observed in cases with severe genetic disorders affecting serotonin biosynthesis. In conclusion, sulphatoxymelatonin can be a good biomarker to estimate serotonin status in the brain, especially for treatment monitoring purposes.

Melatonin ameliorates ANIT‑induced cholestasis by activating Nrf2 through a PI3K/Akt‑dependent pathway in rats

“…Melatonin has also emerged as a valuable biomarker for estimating the serotonin status in the brain, particularly for treatment monitoring purposes (20). Evidence indicates that the prolonged administration of melatonin attenuates the increase in total and low-density lipoprotein cholesterol concentration and the decrease in high-density lipoprotein cholesterol concentration in the serum of rats fed a hypercholesterolemic diet (21). In addition, orally administered melatonin was found to reduce the increase in serum total cholesterol concentration and attenuate the disruption of serum cholesterol status in rats with ANIT-induced acute liver injury with cholestasis; this protective effect may be due to its antioxidant action and its inhibitory action against neutrophil infiltration (22–24).…”

Low melatonin as a contributor to SARS-CoV-2 disease

“…In addition to these numerous variations in synthetic genes in individuals without any reported disorder, there is a subgroup of patients with autism spectrum disorder (ASD) who have alterations in ASMT resulting in decreased in MT and 6SM levels (135)(136)(137); this subgroup may correspond to a similar one that shows alterations in the immune system (138). Several individuals with genetic defects in the serotonin synthetic pathway also have decreased levels of 6SM (139). It may be advisable to keep a close eye on such individuals for signs of the disease.…”

“…Another issue may be the decrease of MT and 6SM levels with age in man (122,(139)(140)(141)(142)(143)(144)(145). An extensive review concludes that there is a major drop that is virtually complete by age 35; although the huge variability persists (122), thus reduction in MT may lie at the root of increased susceptibility found in those over that age (121).…”

Prevalence of sleep disorders in early-treated phenylketonuric children and adolescents. Correlation with dopamine and serotonin status

“…RE54021). 24 We also evaluated concurrent Phe levels, and variability in Phe (standard deviation of Phe levels) and IDC (median Phe levels in blood) for the last year. The blood tests were performed after fasting in the morning and urine tests were collected in the first sample in the morning.…”