Kristina Bryk

Fingers as a Marker of Prenatal Androgen Exposure

Interest in biological substrates of sex-related variations in psychological and physiological characteristics has led to a search for biomarkers of prenatal hormone exposure that can be measured postnatally. There has been particular interest in digit ratio, the relative lengths of the second and fourth fingers (2D:4D), but its validity as a measure of prenatal androgen has not been established. We report the strongest evaluation of the value of 2D:4D as a biomarker for early androgen exposure. Individuals with 46,XY karyotype but no effective prenatal androgen exposure due to complete androgen insensitivity syndrome had digit ratios that were feminized: they were higher than those of typical men and similar to those of typical women. Nevertheless, the effect was modest in size, and there was considerable within-group variability and between-group overlap, indicating that digit ratio is not a good marker of individual differences in prenatal androgen exposure.

Early Androgen Effects on Spatial and Mechanical Abilities: Evidence from Congenital Adrenal Hyperplasia

There is considerable controversy about the origins of sex differences in cognitive abilities, particularly the male superiority in spatial abilities. We studied effects of early androgens on spatial and mechanical abilities in adolescents and young adults with congenital adrenal hyperplasia (CAH). On tests of three-dimensional mental rotations, geography, and mechanical knowledge, females with CAH scored higher than their unaffected sisters, and males with CAH scored lower than their unaffected brothers. Exploratory regression analyses suggest that androgens affect spatial ability in females directly and through male-typed activity interests. Findings indicate that early androgens influence spatial and mechanical abilities, and that androgen effects on abilities may occur in part through effects on sex-typed activity interests.

Brain responses to sexual images in 46,XY women with complete androgen insensitivity syndrome are female-typical

Androgens, estrogens, and sex chromosomes are the major influences guiding sex differences in brain development, yet their relative roles and importance remain unclear. Individuals with complete androgen insensitivity syndrome (CAIS) offer a unique opportunity to address these issues. Although women with CAIS have a Y chromosome, testes, and produce male-typical levels of androgens, they lack functional androgen receptors preventing responding to their androgens. Thus, they develop a female physical phenotype, are reared as girls, and develop into women. Because sexually differentiated brain development in primates is determined primarily by androgens, but may be affected by sex chromosome complement, it is currently unknown whether brain structure and function in women with CAIS is more like that of women or men. In the first functional neuroimaging study of (46,XY) women with CAIS, typical (46,XX) women, and typical (46, XY) men, we found that men showed greater amygdala activation to sexual images than did either typical women or women with CAIS. Typical women and women with CAIS had highly similar patterns of brain activation, indicating that a Y chromosome is insufficient for male-typical human brain responses. Because women with CAIS produce male-typical or elevated levels of testosterone which is aromatized to estradiol these results rule out aromatization of testosterone to estradiol as a determinate of sex differences in patterns of brain activation to sexual images. We cannot, however, rule out an effect of social experience on the brain responses of women with CAIS as all were raised as girls.

Normal Intelligence in Female and Male Patients with Congenital Adrenal Hyperplasia

We provide evidence regarding the nature, causes, and consequences of intelligence in patients with 21-hydroxylase deficient congenital adrenal hyperplasia (CAH). Intelligence and quality of life (psychological adjustment) were measured on multiple occasions from childhood to young adulthood in 104 patients with CAH (62 females, 42 males) and 88 unaffected relatives (31 females, 57 males). Information on disease severity (CAH type, age at diagnosis, genital virilization for girls) and salt-wasting crises was obtained from medical records. There was no evidence of intellectual deficit in either female or male patients with CAH. Intelligence was not significantly associated with psychological adjustment or disease characteristics. CAH itself does not appear to increase risk for poor intellectual function. In a sample of patients with generally good disease control, intelligence is not related to adjustment problems, disease severity, or salt-wasting crises.