Elsevier

Psychoneuroendocrinology

Volume 33, Issue 7, August 2008, Pages 973-980
Psychoneuroendocrinology

Early androgen exposure modulates spatial cognition in congenital adrenal hyperplasia (CAH)

https://doi.org/10.1016/j.psyneuen.2008.04.005Get rights and content

Summary

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 [Morris, R., 1984. Developments of a water-maze procedure for studying spatial learning in the rat. J. Neurosci. Methods 11, 47–60], 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.

Section snippets

Subjects

The CAH patients consisted of three groups: 25 (14 males and 11 females) patients with the salt wasting (SW) form, 13 (7 males and 6 females) patients with the simple virilizing (SV) form, and 16 patients (5 males and 11 females) with the non-classic form. Patients were classified according to clinical and endocrinological evaluation at presentation and all classifications were confirmed by genotype. Additionally, 55 healthy control subjects (22 females and 33 males) participated in the study.

Latency

All participants became faster at finding the platform over the course of the trials as indicated by a significant main effect of Block on latency (F(3, 300) = 2.76, p < .05). In addition, males were significantly faster in reaching the platform than females (main effect of Sex F(1, 100) = 12.23, p = .001). Most importantly, a significant Sex by Diagnosis interaction (F(3, 100) = 3.52, p < .05) indicated that the sex-related differences in latency were modulated by diagnosis. To follow up on this

Discussion

The study examined spatial cognition using an ecologically valid virtual water maze task in patients with androgen excess due to CAH. Two main findings emerged: (1) the severity of the disease and (2) the history of long-term excess androgen exposure during childhood modulated performance on a spatial task. These findings support the hypothesis of a direct impact of sex steroids on human spatial cognition.

We hypothesized that if prenatal androgen exposure was critical, females with the more

Role of the funding sources

This research was supported (in part) by the Intramural Research Program of the National Institutes of Health and (in part) by the Congenital Adrenal Hyperplasia Research, Education and Support (CARES) Foundation.

Conflicts of interest

The authors have no conflicts of interest to declare.

References (33)

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These authors contributed equally to this work.

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