Early hormonal influences on cognitive functioning in congenital adrenal hyperplasia (original) (raw)
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Early androgen exposure modulates spatial cognition in congenital adrenal hyperplasia (CAH)
Psychoneuroendocrinology, 2008
Major questions remain about the exact role of hormones in cognition. Furthermore, the extent to which early perturbation in steroid function affects human brain development continues to be a wide open area of research. Congenital Adrenal Hyperplasia (CAH), a genetic disorder of steroid dysfunction characterized in part by in utero over-production of testosterone, was used as a natural model for addressing this question. Here, CAH (n=54, mean age = 17.53, 31 female) patients were compared to healthy age-and sex-matched individuals (n=55, mean age = 19.02, 22 female) on a virtual equivalent of the Morris Water Maze task , an established measure of sex differences in spatial cognition in rodents. Findings revealed that females with CAH with the most severe form of the disease and expected highest level of in utero exposure to androgens were found to perform similarly to both healthy males and CAH males, whereas strong sex differences were apparent in milder forms of the disorder and in controls. Moreover, advanced bone age, an indicator of long-term childhood exposure to testosterone was correlated with improved performance. The results indicate that individuals exposed to both excess androgens prenatally and prolonged exposure during childhood may manifest long-lasting changes in cognitive function. Such finding suggests a pivotal role of hormonal function on brain development in humans, mirroring results from the animal literature.
Archives of Sexual Behavior, 2008
Hormonal manipulations indicate that early androgens organize sex differences in spatial ability in laboratory rats. In humans, spatial ability is also sexually dimorphic, and information about the effects of prenatal androgens on spatial ability can be obtained from studies of congenital adrenal hyperplasia (CAH) and the ratio of the second and fourth finger lengths (2D:4D). CAH is characterized by prenatal overproduction of adrenal androgens and several lines of evidence suggest that 2D:4D reflects prenatal androgen exposure. Some studies have found that these proxy measures of prenatal androgens predict spatial ability, others have found no significant relationship, and yet others have obtained results in the opposite direction. In light of these mixed findings, we conducted meta-analyses of published literature and unpublished results to determine if, across studies, either of these indicators of prenatal androgens predicts performance on spatial tasks that show a male advantage. In addition, we applied a trim and fill analysis to the data in search of asymmetry that might be an indication of publication bias. Results indicated that females with CAH perform better on these spatial tasks, and CAH males perform worse, than do controls. Little or no relationship exists between 2D:4D and spatial ability. Implications for possible hormonal contributions and the developmental timing of sex differences in spatial cognition are discussed.
Hormones, context, and “Brain Gender”: A review of evidence from congenital adrenal hyperplasia
Social Science & Medicine, 2012
Brain organization theory suggests that steroid hormones during fetal development permanently organize the brain for gender, including patterns of sexuality, cognition, temperament, and interests that differ by sex. This widely-accepted theory has important implications for health, ranging from medical management of infants with intersex conditions to suggested etiologies for sex differences in autism, depression, and other mental health problems. Studies of genetic females with congenital adrenal hyperplasia (CAH), in which high prenatal androgens have been linked to both atypical genitals and "masculine" patterns of gender and sexuality, are particularly important. Based on a comprehensive review of research on CAH, this article demonstrates that such studies have neglected four broad categories of variables that plausibly affect psychosexual development: 1) physiological effects of CAH, including complex disruption of steroid hormones from early development onwards; 2) intensive medical intervention and surveillance, which many women with CAH describe as traumatic; 3) direct effects of genital morphology on sexuality (versus indirect effects that "masculine" genitals may have on gender socialization); and 4) expectations of masculinization that likely affect both the development and evaluation of gender and sexuality in CAH. Complex and iterative interactions among postnatal biological variables, medical interventions, and social context provide a more plausible explanation for atypicalities in psychology and behavior that have been reported for genetic females with CAH than the conventional explanation that early androgens have "masculinized" their brains.
Psychoneuroendocrinology, 2015
Girls and women with classical congenital adrenal hyperplasia (CAH) experience elevated androgens prenatally and show increased male-typical development for certain behaviors. Further, individuals with CAH receive glucocorticoid (GC) treatment postnatally, and this GC treatment could have negative cognitive consequences. We investigated two alternative hypotheses, that: (a) early androgen exposure in females with CAH masculinizes (improves) spatial perception and quantitative abilities at which males typically outperform females, or (b) CAH is associated with performance decrements in these domains, perhaps due to reduced short-term-memory (STM). Adolescent and adult individuals with CAH (40 female and 29 male) were compared with relative controls (29 female and 30 male) on spatial perception and quantitative abilities as well as on Digit Span (DS) to assess STM and on Vocabulary to assess general intelligence. Females with CAH did not perform better (more male-typical) on spatial perception or quantitative abilities than *
The Journal of Clinical Endocrinology & Metabolism, 2002
Previous studies have shown that girls with congenital adrenal hyperplasia (CAH), a syndrome resulting in overproduction of adrenal androgens from early fetal life, are behaviorally masculinized. We studied play with toys in a structured play situation and correlated the results with disease severity, assessed by CYP21 genotyping, and age at diagnosis. Girls with CAH played more with masculine toys than controls when playing alone. In addition, we could demonstrate a doseresponse relationship between disease severity (i.e. degree of fetal androgen exposure) and degree of masculinization of behavior. The presence of a parent did not influence the CAH girls to play in a more masculine fashion. Four CAH girls with late diagnosis are also described. Three of the four girls played exclusively with one of the masculine toys, a constructional toy. Our results support the view that prenatal androgen exposure has a direct organizational effect on the human brain to determine certain aspects of sex-typed behavior.
General intelligence and cognitive profile in women with congenital adrenal hyperplasia (CAH)
Psychoneuroendocrinology, 1994
To investigate possible effects of prenatal androgen exposure on cognitive functions, general intelligence and cognitive profile were studied in 22 women, 17-34 years old, with prenatal virilization due to congenital adrenal hyperplasia (CAH) (21-hydroxylase deficiency) and 22 healthy controls matched for region and date of birth. The tests were selected to measure abilities where gender differences repeatedly had been observed or that had earlier shown differences between CAH subjects and controls. The following cognitive functions were tested: Verbal, Visuo-Spatial, Visuo-Motor, Arithmetical, Logical Inductive abilities, and Field Dependence. Contrary to earlier reports, the mean general intelligence level of the CAH (22) group was significantly lower than the controls' and the earlier observed inferiority for calculation abilities in female CAH subjects was not supported by the results of the present study. A possible verbal disadvantage with significantly inferior results was noted for the two verbal tests for the CAH (22) group. For the 13 CAH/ control pairs with equal general intelligence levels, the discrepancy between the inferior verbal vs. visual, arithmetic, and logical category scores was significantly larger for the CAH group than the controls. These results may suggest that CAH women develop a more masculine cognitive pattern under the influence of increased prenatal androgen exposure.