Androgens in Health and Disease.pdf - E Library

300 Cherrier and Craft
gen excess results from loss of cortisol negative feedback regulation of ACTH secretion.
About 75% of children with CAH have an associated deficiency in aldosterone
production. The salt-wasting variety results in hyponatremia, hyperkalemia, and volume
depletion that is usually present within the first 2 wk of life. The condition affects
approx 1 in 5000 to 15,000 live births. The clinical presentation in genetic females
includes pseudohermaphroditism, whereas affected males tend to have normal or early
sexual development. Exposure to excess androgens during early development of the
organism provides a unique opportunity to examine the organizational effects of hormones
in humans.
There is some indication that individuals with CAH may demonstrate greater cerebral
lateralization, as evidenced by a higher incidence of sinistrality (left-handedness) (82,83).
However, other studies have failed to support this (84). MRI examination of CAH
patients has revealed mixed findings with some evidence of atypical lateralization,
abnormal white-matter distribution, or temporal lobe atrophy in about one-third of
patients (85–87). However, these abnormalities do not appear to be related to any detrimental
neuropsychological performance or treatment status (85,86). Increased incidence
of learning disorders has been found in CAH patients, along with decrements in
general intelligence quotient (IQ) level and verbal intelligence quotient (VIQ), suggesting
that prenatal exposure to androgens may adversely affect the development of the left
hemisphere or hemispheric lateralization, which would adversely affect verbal abilities
(85,87–91). For example, female CAH patients demonstrate significantly lower VIQ
scores compared to unaffected sisters (83,88,90). However, some evidence also supports
a higher level of general intelligence in CAH patients (85,92,93). In addition, studies of
dichotic listening, a task that is sensitive to hemispheric lateralization, are not supportive
of an atypical lateralization pattern in CAH patients (84,94). In a dichotic listening task,
different auditory inputs are simultaneously presented to each ear through headphones.
In normal individuals with an intact corpus callosum, visual and auditory inputs sent to
one hemisphere are quickly shared with the other. This task has been used to discover
the typical pattern of left-hemisphere dominance for language.
One possible explanation for these findings may be that androgens specifically affect
spatial abilities. In particular, if androgens are specific to spatial abilities, one would
expect that CAH females would evidence superior spatial abilities compared to matched
controls, whereas male CAH patients would evidence modest or no appreciable increase
in spatial abilities compared to male controls. A study by Resnick et al. (1986) found
CAH adolescent girls performed better than matched familial controls on tests of spatial
ability (e.g., the Hidden Patterns Test, Card Rotations, and Mental Rotations) (93). A
more recent study by Hampson et al. (1998) also provides evidence that spatial abilities
are specifically increased in CAH girls compared to controls (95). This study examined
a relatively young population of CAH patients (mean age 10 yr) matched for IQ level
with controls. Participants were administered the Perceptual Speed Test, a task on which
females typically outperform males, and the Spatial Relations Test, from the Primary
Mental Abilities Test, a measure of spatial visualization on which males typically outperform
females. CAH girls performed less well than controls on the perceptual speed
task but outperformed the controls on the spatial test. This effect was large, nearly one
standard deviation (see Fig. 6) and there was no difference between salt-wasters vs nonsalt-wasters.
Thus, the atypical advantage of CAH girls on the spatial task and a failure
to find a typical advantage on the perceptual speed task represents a double-dissociation