2 resultados para Ruta

em CentAUR: Central Archive University of Reading - UK


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Molecular and behavioural evidence points to an association between sex-steroid hormones and autism spectrum conditions (ASC) and/or autistic traits. Prenatal androgen levels are associated with autistic traits, and several genes involved in steroidogenesis are associated with autism, Asperger Syndrome and/or autistic traits. Furthermore, higher rates of androgen-related conditions (such as Polycystic Ovary Syndrome, hirsutism, acne and hormone-related cancers) are reported in women with autism spectrum conditions. A key question therefore is if serum levels of gonadal and adrenal sex-steroids (particularly testosterone, estradiol, dehydroepiandrosterone sulfate and androstenedione) are elevated in individuals with ASC. This was tested in a total sample of n=166 participants. The final eligible sample for hormone analysis comprised n=128 participants, n=58 of whom had a diagnosis of Asperger Syndrome or high functioning autism (33 males and 25 females) and n=70 of whom were age- and IQ-matched typical controls (39 males and 31 females). ASC diagnosis (without any interaction with sex) strongly predicted androstenedione levels (p<0.01), and serum androstenedione levels were significantly elevated in the ASC group (Mann-Whitney W=2677, p=0.002), a result confirmed by permutation testing in females (permutation-corrected p=0.02). This result is discussed in terms of androstenedione being the immediate precursor of, and being converted into, testosterone, dihydrotestosterone, or estrogens in hormone-sensitive tissues and organs.

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Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism.