Tetrahydroisoquinoline derivatives: a new perspective on monoaminergic dysfunction in children with ADHD?

Veit Roessner,Aribert Rothenberger,Regina Hünnerkopf,Andreas Moser,Franz Riederer,Manfred Gerlach,Susanne Walitza

doi:10.1186/1744-9081-3-64

Abstract

BackgroundThe dopamine-derived tetrahydroisoquinolines (TIQ) synthesized endogeneously from aldehydes and catecholamines have shown to modulate neurotransmission, central metabolism and motor activity. Converging evidence has implicated abnormalities of the dopamine metabolism to the pathophysiology of Attention-Deficit/Hyperactivity Disorder (ADHD). Therefore, four TIQ derivatives involved in central dopamine metabolism (salsolinol, N-methyl-salsolinol, norsalsolinol, N-methyl-norsalsolinol) have been analyzed for the first time in children and adolescents with ADHD and healthy controls.Methods42 children and adolescents with ADHD and 24 controls from three sites participated in this pilot study. Free and bound amounts of salsolinol, N-methyl-salsolinol, norsalsolinol, N-methyl-norsalsolinol have been analyzed in urine.ResultsIn the ADHD group, free and total amounts of the four TIQ derivatives in urine were significantly higher compared to urine levels of healthy controls. For N-methyl-salsolinolfree, most of the ADHD patients were identified correctly with a sensitivity of 92.5% (specificity 94.4%).ConclusionUrine levels of salsolinol, N-methyl-salsolinol, norsalsolinol and N-methyl-norsalsolinol are elevated in children and adolescents with ADHD and point to a new perspective on catecholaminergic dysfunction in ADHD. However, replication and extension of this pilot study would progress this innovative and promising field.

Highlights

The dopamine-derived tetrahydroisoquinolines (TIQ) synthesized endogeneously from aldehydes and catecholamines have shown to modulate neurotransmission, central metabolism and motor activity
Current models of Attention-Deficit/Hyperactivity Disorder (ADHD) propose a hypofunctioning of e.g. three interacting dopamine systems [3]: (1) the mesolimbic dopamine system primarily associated with altered reinforcement of novel behavior and deficient extinction of previously reinforced behavior, (2) the mesocortical dopamine system associated with deficient attention and poor behavioral organization and (3) the nigrostriatal dopamine system impairing motor functions and causing poor nondeclarative habit learning
In the ADHD group (n = 42), free and total concentrations of all measured TIQ derivatives were increased in urine samples compared to those of healthy controls (n = 24) (ANOVA, Table 1)

Summary

Introduction

The dopamine-derived tetrahydroisoquinolines (TIQ) synthesized endogeneously from aldehydes and catecholamines have shown to modulate neurotransmission, central metabolism and motor activity. Converging evidence has implicated abnormalities of the dopamine metabolism to the pathophysiology of Attention-Deficit/Hyperactivity Disorder (ADHD). Current models of ADHD propose a hypofunctioning of e.g. three interacting dopamine systems [3]: (1) the mesolimbic dopamine system primarily associated with altered reinforcement of novel behavior and deficient extinction of previously reinforced behavior, (2) the mesocortical dopamine system associated with deficient attention and poor behavioral organization and (3) the nigrostriatal dopamine system impairing motor functions and causing poor nondeclarative habit learning. Previous studies in ADHD found only a limited relationship of plasma and urine levels of dopamine metabolites to the activity of central dopamine metabolism as well as small effects of stimulant medication on urinary dopamine metabolites [5]. Studies on the levels of dopamine metabolites in the cerebrospinal fluid have been performed, but yielded mixed results of limited value [69]

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