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

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.

Autism Spectrum Disorder patients may be susceptible to COVID-19 disease due to deficiency in melatonin

“…Although both melatonin and PGV were lower in patients than controls, the melatonin deficit appeared to be more related to group than to PCV. The authors stated that the findings support a deficit in the melatonin synthetic pathway as a possible main cause [ 15 ],.…”

Mass‐spectrometry analysis of the human pineal proteome during night and day and in autism

“…We previously reported that taking as a threshold the 10th percentile of the control group, a large proportion (74%) of autistic patients displayed a reduced platelet ASMT activity, 37,65 but the mechanisms remain unknown. We also showed that the level of melatonin was highly inherited, 117 but was not correlated to the size of the pineal gland 118 . For a subset of patients, we could identify strongly deleterious ASMT mutations functionally associated with ASMT activity deficiency and low melatonin levels 37,91,119 .…”

“…We also showed that the level of melatonin was highly inherited, 117 but was not correlated to the size of the pineal gland. 118 For a subset of patients, we could identify strongly deleterious ASMT mutations functionally associated with ASMT activity deficiency and low melatonin levels. 37,91,119 But these rare mutations do not explain the deficit observed in a relatively large fraction of the individuals.…”

Melatonin and Sleep Problems in Children with Autism Spectrum Disorder

“…Some studies also attempted to find a link between melatonin level and pineal gland volume [59]. Maruani et al [59] evaluated 215 participants, including 78 children with ASD, 90 unaffected relatives, and 47 healthy controls. They found that both early morning melatonin levels and pineal gland volume were lower in patients compared to controls.…”

“…However, the effect of pineal gland volume was normalized when analyzed in relation to melatonin levels. Thus, melatonin variations in ASD might be driven mainly by dysregulation of the melatonin synthesis pathway [59]. The role of the pineal gland volume differences has not yet been clarified.…”