Elevated fetal steroidogenic activity in autism

TLDR

Autism disproportionately affects males, suggesting that steroid hormones influencing early fetal brain development may be a key early biological risk factor. Using the Danish Historic Birth Cohort, the authors measured Δ4 sex steroids and cortisol in amniotic fluid from 128 male infants later diagnosed with autism or related disorders and matched controls by liquid chromatography tandem mass spectrometry. Principal component analysis identified a single latent steroidogenic factor that was significantly elevated (Cohen’s d = 0.37, P = 0.0009) in the autism group across all hormones, providing the first direct evidence of heightened fetal steroidogenic activity in autism and implicating potential epigenetic programming mechanisms.

Abstract

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.