Marked elevation of adrenal steroids, especially androgens, in saliva of prepubertal autistic children

Abstract

Autism is diagnosed on the basis of behavioral manifestations, but its biomarkers are not well defined. A strong gender bias typifying autism (it is 4–5 times more prevalent in males) suggests involvement of steroid hormones in autism pathobiology. In order to evaluate the potential roles of such hormones in autism, we compared the salivary levels of 22 steroids in prepubertal autistic male and female children from two age groups (3–4 and 7–9 years old) with those in healthy controls. The steroids were analyzed using gas chromatography–mass spectrometry and radioimmunoassay. Statistical analysis (ANOVA) revealed that autistic children had significantly higher salivary concentrations of many steroid hormones (both C21 and C19) than control children. These anomalies were more prominent in older autistic children and in boys. The levels of androgens (androstenediol, dehydroepiandrosterone, androsterone and their polar conjugates) were especially increased, indicative of precocious adrenarche and predictive of early puberty. The concentrations of the steroid precursor, pregnenolone, and of several pregnanolones were also higher in autistic than in healthy children, but cortisol levels were not different. Some steroids, whose levels are raised in autism (allopregnanolone, androsterone, pregnenolone, dehydroepiandrosterone and their sulfate conjugates) are neuroactive and modulate GABA, glutamate, and opioid neurotransmission, affecting brain development and functioning. These steroids may contribute to autism pathobiology and symptoms such as elevated anxiety, sleep disturbances, sensory deficits, and stereotypies among others. We suggest that salivary levels of selected steroids may serve as biomarkers of autism pathology useful for monitoring the progress of therapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s00787-013-0472-0) contains supplementary material, which is available to authorized users.

Assessment of plasma amino acid profile in autism using cation-exchange chromatography with postcolumn derivatization by ninhydrin

“…Peripherally, glutamate was found to affect taste sensation, skin pain sensation, and pancreatic exocrine function (15). The rise in serum glutamic acid was in part attributed to the failure of its conversion to glutamine due to vitamin B6 deficiency in such patients (15), in addition to the modulatory effect of neuroactive steroids on glutamate level (11). Such findings of high glutamate led some researchers to consider glutamate as a diagnostic tool for early detection of autism (26).…”

Neuroactive Steroids and Related Steroids in Autism Spectrum Disorders

“…There should be reduced emotional changes compared to collecting blood samples and thus possibly increased accuracy of results [121]. Saliva samples have proved appropriate in the past for determining levels of several neuroactive and related steroids [72,[122][123][124][125][126].…”

“…This is further evidence of dysregulation and is referred to as the absence of the typical sexual dimorphism. Majewska et al [72] found that saliva androstenedione levels in ASD subjects are no different in a 7-9 year old group or a 3-4 year old group and HCs. Tordjman et al…”

“…Majewska et al [72] showed that compared with HCs, salivary levels of pregnenolone and allopregnanolone were elevated in a 7-9 year old group, but they found no difference between a 3-4 year old group and HCs. However, an increasing number of investigators have become interested in the relationship between pregnenolone and ASD.…”

“…However, Ruta et al [58] reported that the serum DHEAS levels in adult ASD are no different than those in HCs, and Strous et al [71] reported that the plasma DHEAS levels in adult ASD are significantly decreased compared to HCs and that there was no difference in plasma levels of DHEA compared to HCs. Majewska et al [72] compared ASD subjects with HCs and found that levels of DHEA were elevated in a 7-9 year old group but found no difference in a 3-4 year old group when measuring levels in saliva samples.…”