Reduced short term memory in congenital adrenal hyperplasia (CAH) and its relationship to spatial and quantitative performance

Abstract

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 control females, failing to support the hypothesis of cognitive masculinization. Rather, in the sample as a whole individuals with CAH scored lower on spatial perception (p ≤ .009), a quantitative composite (p ≤ .036), and DS (p ≤ .001), despite no differences in general intelligence. Separate analyses of adolescent and adult participants suggested the spatial and quantitative effects might be present only in adult patients with CAH; however, reduced DS performance was found in patients with CAH regardless of age group. Separate regression analyses showed that DS predicted both spatial perception and quantitative performance (both p ≤ .001), when age, sex, and diagnosis status were controlled. Thus, reduced STM in CAH patients versus controls may have more general cognitive consequences, potentially reducing spatial perception and quantitative skills. Although hyponatremia or other aspects of salt-wasting crises, or additional hormone abnormalities cannot be ruled out as potential contributors, elevated GCs appear to be the most likely contributor to reductions in STM. Additional efforts to monitor GC administration protocols may help achieve optimal cognitive outcomes. Educational intervention for individuals with CAH might also be useful.

Early contributions to infants’ mental rotation abilities

“…At least a dozen studies have reported increased male‐typical childhood play behavior, reduced heterosexual interest, and reduced female gender identity in girls with CAH (Hines, ). However, findings regarding mental rotation performance in females with CAH have been inconsistent (Hines, ), perhaps because hormones used in the medical treatment of CAH cause reduced working memory and reduced performance on spatial tasks (Browne et al., ; Collaer, Hindmarsh, Pasterski, Fane, & Hines, ).…”

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

“…Alternatively, a lack of association between brain volumes and exposures due to treatment or hormone concentrations may be muddled by individual differences in glucocorticoid-related genes, which may otherwise complicate hormone concentrations and clearance, as well as physiological neural responses (51). In addition, neurologic impairments, including possible brain injury, may result from adrenal crises associated with CAH which merits further study (7). More research is needed to better understand the biological mechanisms that may contribute to regional atrophy of the amygdala, hippocampus, and PFC in youth with CAH.…”

“…Lastly, the current study was designed to examine structural differences in a priori gray matter in CAH vs control youth. However, studies have also suggested impairments in white matter (15,39) as well as brain function (7,8,10,11,13) in patients with CAH. Thus, studies are currently underway to probe additional brain structural and functional abnormalities as a focus of future research.…”

“…Several studies have begun to examine brain and behavioral alterations associated with CAH, with reported differences in emotional and memory processes in CAH patients. These include moderate-to-large reductions in short-term and working memory, which involve the hippocampus (7,8). Utilizing neuroimaging, abnormal amygdala volumes have been reported in children with CAH (9), with affected females exhibiting greater amygdala activity during functional magnetic resonance imaging (fMRI) emotional tasks (10) compared to control females (11).…”

Methodological Issues for Psychological Evaluation across the Lifespan of Individuals with a Difference/Disorder of Sex Development

“…For example, 2 studies including children and adults with congenital adrenal hyperplasia have shown reduced short term memory [Browne et al, 2015;Collaer et al, 2016], with the working hypothesis that long-term treatment with glucocorticoids may impair hippocampal function. The implications here are obvious.…”