Low serum sphingolipids in children with attention deficit-hyperactivity disorder.

Marcela P Henríquez-Henríquez,Richard J Deckelbaum,Teresa Quiroga,Benjamin I Kim,Tilla S Worgall,Sandra Solari

doi:10.3389/fnins.2015.00300

Abstract

Background: Attention deficit-hyperactivity disorder (ADHD) is the most prevalent neuropsychiatric condition in childhood. ADHD is a multifactorial trait with a strong genetic component. One neurodevelopmental hypothesis is that ADHD is associated with a lag in brain maturation. Sphingolipids are essential for brain development and neuronal functioning, but their role in ADHD pathogenesis is unexplored. We hypothesized that serum sphingolipid levels distinguish ADHD patients from unaffected subjects.Methods: We characterized serum sphingolipid profiles of ADHD patients and two control groups: non-affected relatives and non-affected subjects without a family history of ADHD. Sphingolipids were measured by LC-MS/MS in 77 participants (28 ADHD patients, 28 related controls, and 21 unrelated controls). ADHD diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR). Diagnostic criteria were assessed by two independent observers. Groups were compared by parametrical statistics.Results: Serum sphingomyelins C16:0, C18:0, C18:1, C24:1, ceramide C24:0, and deoxy-ceramide C24:1 were significantly decreased in ADHD patients at 20–30% relative reductions. In our sample, decreased serum sphingomyelin levels distinguished ADHD patients with 79% sensitivity and 78% specificity.Conclusions: Our results showed lower levels of all major serum sphingomyelins in ADHD. These findings may reflect brain maturation and affect neuro-functional pathways characteristic for ADHD.

Highlights

Attention deficit-hyperactivity disorder (ADHD) is a neurobehavioral condition characterized by persistent, cross-situational and developmentally inappropriate levels of inattention, hyperactivity, and impulsiveness (American Psychiatric, 2000)
Pairwise comparisons confirmed significant differences between ADHD patients and both control groups for all the species, except for sphingomyelin C18:1, where ADHD patients were significantly different only when compared to related controls
The biggest relative difference was observed for sphingomyelin C24:1, which was 21% lower in ADHD patients

Summary

Introduction

Attention deficit-hyperactivity disorder (ADHD) is a neurobehavioral condition characterized by persistent, cross-situational and developmentally inappropriate levels of inattention, hyperactivity, and impulsiveness (American Psychiatric, 2000). A recent genome-wide association study suggested that exploration of alternative/complementary etiological factors related to neuritic outgrowth and maturation should be considered (Bralten et al, 2013) This is in line with neuroimaging studies, which increasingly suggest white/gray matter anomalies in prefrontal cortex, temporo-parietal regions, striatum, and cerebellum in ADHD patients (Casey et al, 2007; Silk et al, 2009; Helpern et al, 2011; Nagel et al, 2011; Peterson et al, 2011; de Zeeuw et al, 2012; Cortese et al, 2013; Greven et al, 2015). We hypothesized that serum sphingolipid levels distinguish ADHD patients from unaffected subjects

Methods

Results

Conclusion