Geffner, M. E. | Search bioRxiv

bioRxiv2020

No Difference in 2D:4D Ratio between Youth with Elevated Prenatal Androgen Exposure due to Congenital Adrenal Hyperplasia and Controls

The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine 513 serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: {square} = -0.001 (-0.008, 0.006)]; females: {square} = -0.004 [-0.015, 0.007]; males: {square} = 0.001, [-0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.

developmental biology↗

bioRxiv2019

Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia

ContextClassical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency results in hormone imbalances present both prenatally and postnatally that may impact the developing brain.\n\nObjectiveTo characterize gray matter morphology in the prefrontal cortex and subregion volumes of the amygdala and hippocampus in youth with CAH, compared to age- and sex-matched controls.\n\nDesignA cross-sectional study of 27 CAH youth (16 female; 12.6 {+/-} 3.4 year) and 35 typically developing, age- and sex-matched healthy controls (20 female; 13.0 {+/-} 2.8 year) with 3-T magnetic resonance imaging scans. Brain volumes of interest included bilateral prefrontal cortex, and eight amygdala and six hippocampal subregions. Between-subject effects of group (CAH vs control) and sex, and their interaction (group-by-sex) on brain volumes were studied, while controlling for intracranial volume (ICV) and group differences in body mass index and bone age.\n\nResultsCAH youth had smaller ICV and increased cerebrospinal fluid volume compared to controls. In fully-adjusted models, CAH youth had smaller bilateral, superior and caudal middle frontal volumes, and smaller left lateral orbito-frontal volumes compared to controls. Medial temporal lobe analyses revealed the left hippocampus was smaller in fully-adjusted models. CAH youth also had significantly smaller lateral nucleus of the amygdala and hippocampal subiculum and CA1 subregions.\n\nConclusionsThis study replicates previous findings of smaller medial temporal lobe volumes in CAH patients, and suggests that lateral nucleus of the amygdala, as well as subiculum and subfield CA1 of the hippocampus are the most affected regions in CAH youth.\n\nPrecisWe collected brain scans of 27 youth with classical CAH and 35 healthy controls. Portions of the prefrontal cortex, amygdala, and hippocampus were smaller in CAH youth compared to controls.\n\nDisclosure SummaryMEG receives grant support from Novo Nordisk; consultant fees from Daiichi Sankyo, Ferring, Novo Nordisk, Nutrition & Growth Solutions, Pfizer, Sandoz, and Spruce Biosciences; serves on data safety monitoring boards for Ascendis, Millendo, and Tolmar; and receives royalties from McGraw-Hill and UpToDate.

neuroscience↗