5‐Hydroxytryptophol in Human Cerebrospinal Fluid: Conjugation, Concentration Gradient, Relationship to 5‐Hydroxyindoleacetic Acid, and Influence of Hereditary Factors

Abstract

The serotonin metabolite 5-hydroxytryptophol was studied in human cerebrospinal fluid. A minor fraction (approximately 13%) was found in conjugated form from which it was liberated by treatment with sulphatase containing beta-glucuronidase activity. A concentration gradient of 5-hydroxytryptophol concentration was shown on lumbar tapping and the concentration in ventricular CSF was about 2.5 times higher than that in lumbar CSF. 5-Hydroxytryptophol and 5-hydroxyindoleacetic acid concentrations were significantly correlated in healthy, psychotic, and depressed subjects, but not in alcoholics. 5-Hydroxytryptophol concentrations in CSF of psychotic and depressed subjects were not different from those of healthy controls (4.22 pmol/ml +/- 0.15, SEM). In healthy subjects, hereditary factors seemed to have little influence on the CSF level of 5-hydroxytryptophol.

Pharmacogenetic insights to monoaminergic dysfunction in alcohol dependence

“…In adult non-human primates, heritability of serotonin turnover was 42% (Kaplan et al 2000) and in humans, heritability accounts for about 35% of the variance in CSF 5-HIAA concentrations (Beck et al 1984;Oxenstierna et al 1986). Therefore, environmental factors that have long-lasting effects on serotonergic neurotransmission are of particular interest.…”

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

“…The decreased levels of 5-HT metabolites in cerebrospinal fluid (CSF), coupled with the mood-lowering effects of tryptophan depletion and the efficacy of serotonin-modulating antidepressants, have supported the theory that dysfunctions of the 5-HT system are involved in the pathogenesis of MDD (Jans et al 2007). Genetic polymorphisms are among the innate factors that modulate 5-HTergic neurotransmission, given that heritability has been reported to account for approximately 35% of the variance in CSF 5-hydroxyindoleace-tic acid (5-HIAA), the main metabolite of 5-HT levels (Beck et al 1984;Oxenstierna et al 1986). …”

Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence

“…Given the predominance of the MAO-ALDH pathway in 5-HT metabolism, urinary levels of 5-HIAA are used as an index for measurement of plasma 5-HT content (with diagnostic value as a biomarker for carcinoid syndrome, a paraneoplastic disorder caused by gastrointestinal apudomas secreting 5-HT). Small amounts of 5-HT (1–5%) are converted into 5-hydroxyindolethanol (5-HIET, also termed 5-hydroxytryptophol) by either ALR or ADH (Feldstein and Williamson, 1968; Beck et al , 1984; Consalvi et al , 1986; Svensson et al , 1999) (Table I). Interestingly, the amount of 5-HIET can be enhanced by compounds that compete with endogenous 5-HT metabolite for ALDH, such as ethanol (Helander et al , 1993).…”