Serotonin and melatonin as marker for ASD subset

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kulkulkan
Posts: 2075
Joined: Tue Mar 13, 2012 1:37 pm

Serotonin and melatonin as marker for ASD subset

Postby kulkulkan » Thu Nov 13, 2014 10:32 am

Below has been shown in several other studies as well. Could very well be a big subgroup (50%). This one is more important given the larger sample size and researchers went further to show high sensitivity and specificity and more importantly, if you had high serotonin then melatonin was likely low (and also had previously found that the enzyme converting serotonin to melatonin was down regulated somehow).

http://www.nature.com/tp/journal/v4/n11 ... 4120a.html

The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders.

Authors
Pagan C1, Delorme R2, Callebert J3, Goubran-Botros H4, Amsellem F5, Drouot X6, Boudebesse C7, Le Dudal K8, Ngo-Nguyen N9, Laouamri H9, Gillberg C10, Leboyer M7, Bourgeron T11, Launay JM12.
Author information
Journal
Transl Psychiatry. 2014 Nov 11;4:e479. doi: 10.1038/tp.2014.120.

Affiliation
Abstract
Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35-46%) of patients), as well as the deficit in melatonin (51% (45-57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41-54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS-melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS-melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD.


kulkulkan
Posts: 2075
Joined: Tue Mar 13, 2012 1:37 pm

Re: Serotonin and melatonin as marker for ASD subset

Postby kulkulkan » Thu Nov 13, 2014 2:47 pm

Interestingly, this pathway was not linked to any level of ASD impairment / severity scores; just insomnia. I think it makes sense to supplement melatonin for this subgroup, which we do therapeutically even though our son doesn't have any sleep issues.

On ways to up-regulate the ASMT enzyme to convert serotonin to melatonin, perhaps retinoic acid might work (metabolite of Vitamin A retinol)? That was shown to increase activity of related enzyme 10x but it was in retinoblastoma cells.

http://www.ncbi.nlm.nih.gov/pubmed/8752 ... t=Abstract

Interestingly, retinoic acid was also found to upregulate CD38 transcription in ASD mouse model (for producing oxytocin). Could be why Vitamin A helps with socialization and eye contact more which we did see first time we introduce CLO with Vitamin A.

http://www.ncbi.nlm.nih.gov/pubmed/21528155


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