Altered ghrelin levels in boys with autism: a novel finding associated with hormonal dysregulation

Abstract

Autism is a neurodevelopmental disorder with unclear pathogenesis. Many clinical observations and hormone studies have suggested the involvement of the neuroprotective hormone ghrelin in autism. The current study aimed to investigate the potential role of ghrelin in autism and to elucidate the associated hormonal dysregulation. This case-control study investigated acyl ghrelin (AG), des-acyl ghrelin (DG), total testosterone (TT), free testosterone (FT), leptin and growth hormone (GH) levels in 31 male children with autism and 28 healthy age and sex-matched controls. Hormone levels were measured in the blood using enzyme-linked immunosorbent assay and chemiluminescence immunoassay kits. AG, DG and GH levels were significantly lower in the autism group than in the control group (p ≤ 0.001, p ≤ 0.005 and p ≤ 0.05, respectively). However, TT, FT and leptin levels were significantly higher in the autism group than in the control group (p ≤ 0.05, p ≤ 0.001 and p ≤ 0.01, respectively). Our results for the first time demonstrate low AG and DG levels in autistic children. Considering the capacity of ghrelin to affect neuroinflammatory and apoptotic processes that are linked to autism, this study suggests a potential role for the hormone ghrelin in the pathogenesis of autism.

Cord and Early Childhood Plasma Adiponectin Levels and Autism Risk: A Prospective Birth Cohort Study

“…Since leptin is linked to ASD in several studies (Ashwood et al 2008; Blardi et al 2010; Rodrigues et al 2014; Al-Zaid et al 2014; Essa M.M. et al 2011), including ours, and adiponectin-leptin ratio is considered as a marker of metabolic syndrome (Inoue et al 2005), we assessed the association between log-transformed adiponectin-leptin ratio and subsequent ASD risk.…”

Fetal and Infancy Growth Pattern, Cord and Early Childhood Plasma Leptin, and Development of Autism Spectrum Disorder in the Boston Birth Cohort

“…Beyond leptin's role in prenatal and postnatal weight gain, this pleiotropic cytokine has been shown to be important in the regulation of the immune system, neurodevelopment including neuron excitability, synaptic plasticity, neural differentiation and promoting migration of neuronal lineage cells to the cortical plate [Ashwood et al, ; Blardi et al, ; Harvey, ; Harvey, Solovyova, & Irving, ; Paz‐Filho et al, ]. Emerging evidence suggests that children (2–15 years) with ASD have significantly higher plasma leptin levels than controls [Al‐Zaid, Alhader, & Al‐Ayadhi, ; Ashwood et al, ; Blardi et al, ; Essa et al, ; Rodrigues et al, ]. Among a few studies that have researched leptin‐ASD association in children, most were done after ASD diagnosis [Ashwood et al, ; Blardi et al, ], thus unable to assess the temporal relationship.…”

Sex Bias in Autism

“…The significant increase of free testosterone in a magnitude higher than that of total testosterone is explained by the lack of concomitant increase in SHBG. Both total testosterone and free testosterone were positively and strongly correlated with each other and both of which had a positive strong correlation with DHEA, which was also significantly elevated in autistic children by 50% suggesting an adrenal source of the elevated androgens [35]. Significant elevation of those androgens has been reported in American autistic children in comparison with laboratory reference values by Geier's study, which reported 158% increase in total testosterone, 214% increase in serum free testosterone, and 192% increase in DHEA [34].…”

“…In the light of EMB theory of autism, numerous studies were conducted to investigate postnatal testosterone levels in autistic children. Although it has been demonstrated by some studies that children with autism have significantly elevated androgen levels [34,35], other studies by Tordjman et al [36] and Lutchmaya et al [37] have not found significant differences in testosterone levels in autism. Moreover, postpubertal androgen levels were found to be lower than controls in autistic children [38].…”