Morning Plasma Melatonin Differences in Autism: Beyond the Impact of Pineal Gland Volume.

Anna Maruani,Guillaume Dumas,Nicolas Traut,Anita Beggiato,Monique Elmaleh,Thomas Bourgeron,David Germanaud,Jean-Marie Launay,Alicia Cohen-Freoua,Frédérique Amsellem,Roberto Toro,Hugo Peyre,Richard Delorme

doi:10.3389/fpsyt.2019.00011

Abstract

While low plasma melatonin, a neuro-hormone synthesized in the pineal gland, has been frequently associated with autism, our understanding of the mechanisms behind it have remained unclear. In this exploratory study, we hypothesized that low melatonin levels in ASD could be linked to a decrease of the pineal gland volume (PGV). PGV estimates with magnetic resonance imaging (MRI) with a voxel-based volumetric measurement method and early morning plasma melatonin levels were evaluated for 215 participants, including 78 individuals with ASD, 90 unaffected relatives, and 47 controls. We first found that both early morning melatonin level and PGV were lower in patients compared to controls. We secondly built a linear model and observed that plasma melatonin was correlated to the group of the participant, but also to the PGV. To further understand the relationship between PGV and melatonin, we generated a normative model of the PGV relationship with melatonin level based on control participant data. We found an effect of PGV on normalized melatonin levels in ASD. Melatonin deficit appeared however more related to the group of the subject. Thus, melatonin variations in ASD could be mainly driven by melatonin pathway dysregulation.

Highlights

Autism spectrum disorders (ASD) are a heterogeneous group of conditions characterized by a deficit in social communication and the presence of restrictive and repetitive behaviors and interest (DSM-5), affecting more than 1% of the general population [1, 2]
Melatonin plasma level was assessed in the early morning in individuals with ASD, their first-degree unaffected relatives and in a sample of typically developing individuals
We found that 55% of the participants with ASD had low melatonin levels corrected for pineal gland volume (PGV) ( +2SD) (Figure 2B)

Summary

Introduction

Autism spectrum disorders (ASD) are a heterogeneous group of conditions characterized by a deficit in social communication and the presence of restrictive and repetitive behaviors and interest (DSM-5), affecting more than 1% of the general population [1, 2]. One of the most frequent complains of individuals with ASD and their families is sleep disorders, ranging from 40 to 86% of the patients [3,4,5,6]. Sleep disturbances significantly impact the daily functioning of patients, affecting their cognitive resources (mainly attention, flexibility, or working memory), and altering their abilities to regulate their emotions and their behaviors [5].

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