Circulating anti-Müllerian hormone (AMH) associates with the maturity of boys' drawings: Does AMH slow cognitive development in males?

PURPOSE: High levels of circulating anti-Müllerian hormone are unique to developing males, but the function of anti-Müllerian hormone in boys is unknown. In mice, anti-Müllerian hormone contributes to the male biases in the brain, but its receptors are present throughout non-sexually dimorphic portions of the brain. In humans, the speed of maturation is the most overt difference between girls and boys. We postulate that this is because anti-Müllerian hormone slows the maturation of the male human brain. METHODS: One hundred and fourty three 5-year or 6-year-old boys and 38 age-matched girls drew a person and donated a blood sample. The children's drawings were blind-scored to generate a maturity index. The level of anti-Müllerian hormone and the other Sertoli cell hormone, inhibin B, were measured by ELISA. The relationship between the children's age, hormones and maturity index were examined by linear regression analysis. RESULTS: The girls drew more complex and realistic person than the boys (32%, p = 0.001), with their drawings also being larger (39%, p = 0.037) and more coloured-in (235%, p = 0.0005). The maturity index in boys correlated with age (+r = 0.43, p < 0.0005) and anti-Müllerian hormone level (-r = -0.29, p < 0.0005). The association between maturity index and anti-Müllerian hormone level persisted when corrected for age and for inhibin B (r = -0.24, p = 0.0005). The calculated effect of the median level of anti-Müllerian hormone (1 nM) was equal to 0.81 months of development. The size and colouring of the drawings did not correlate with the boys' age, anti-Müllerian hormone or inhibin B. CONCLUSIONS: This exploratory study provides the first indicative evidence that circulating anti-Müllerian hormone may influence the development of the human brain.

Body maps do not facilitate older children's report of touch.

In a single experiment, we assessed the effect of body maps on reports of touch by 5- and 6-year-olds, 9- and 10-year-olds, and adults. Children and adults participated in a staged event in which they were touched four times. Immediately following the event, children and adults were asked to either show using a body map or show using their own body where they had been touched. Consistent with prior research, body maps were ineffective with 5- and 6-year-olds. Furthermore, although older children and adults reported more touches and were more accurate than younger children, body maps did not enhance the quality of their reports. We conclude that the provision of a body map does not facilitate reports of touch by any age group, raising serious questions about their use in forensic contexts.

The level of serum anti-Müllerian hormone correlates with vitamin D status in men and women but not in boys.

CONTEXT: Anti-Müllerian hormone (AMH) is a gonad-specific hormone, which is extensively used as a marker of gonadal status. The level of serum AMH has a high variance in similar individuals for reasons that are unknown. The AMH gene promoter contains a vitamin D response element that may cause vitamin D status to influence serum AMH levels. AIM: The objective of the study was to determine whether serum levels of AMH are related to 25-hydroxyitamin D [25(OH)D)] status. SETTING: This was a correlative and intervention study. PARTICIPANTS: Three cohorts of participants were analyzed; mature men (n = 113), premenopausal women (n = 33), and 5- to 6-yr-old boys (n = 74). Women were given a daily supplement of ergocalciferol, cholecalciferol, or a placebo for 6 months and provided baseline and posttreatment blood samples. MAIN OUTCOME MEASURES: Serum AMH and 25(OH)D were measured and analyzed for covariation. RESULTS: Serum AMH positively correlated with 25(OH)D in men (r = 0.22, P = 0.02) but not boys. Both 25(OH)D and AMH levels exhibited seasonal variation in women, with an 18% decrease in AMH levels in winter compared with summer (P = 0.01). Change in AMH level correlated with the initial AMH level and the magnitude of change in vitamin D levels (r = 0.36, P = 0.004). Cholecalciferol supplementation prevented seasonal AMH change. CONCLUSION: Vitamin D may be a positive regulator of AMH production in adults, and vitamin D deficiency may confound clinical decisions based on AMH. Vitamin D deficiency should be considered when serum AMH levels are obtained for diagnosis.

The stature of boys is inversely correlated to the levels of their sertoli cell hormones: do the testes restrain the maturation of boys?

The testes of preadolescent boys appear to be dormant, as they produce only trace levels of testosterone. However, they release supra-adult levels of Müllerian Inhibiting Substance (MIS, anti-Müllerian hormone) and lesser levels of inhibin B (InhB), for unknown reasons. Boys have a variable rate of maturation, which on average is slower than girls. The height of children relative to their parents is an index of their maturity. We report here that a boy's level of MIS and InhB is stable over time and negatively correlates with his height and his height relative to his parent's height. This suggests that boy's with high levels of MIS and InhB are short because they are immature, rather than because they are destined to be short men. The levels of MIS and InhB in the boys did not correlate with known hormonal modulators of growth, and were additive with age and the growth hormone/IGF1 axis as predictors of a boy's height. If MIS and InhB were causal regulators of maturity, then the inter-boy differences in the levels of these hormone produces variation in maturation equivalent to 18-months of development. MIS and InhB may thus account for most of the variation in the rate of male development. If boys lacked these hormones, then an average 5-year-old boy would be over 5 cm taller than age-matched girls, making boys almost as dimorphic as men, for height. This indicates that boys have a high growth potential that is initially suppressed by their testes. The concept of the childhood testes suppressing an adult male feature appears paradoxical. However, the growth of children requires intergenerational transfer of nutrients. Consequently, the MIS/InhB slowing of male growth may have been historically advantageous, as it would minimizes any sex bias in the maternal cost of early child rearing.

The sex bias in novelty preference of preadolescent mouse pups may require testicular Müllerian inhibiting substance.

Male mouse pups exhibit elevated preference for novelty relative to their sisters. The testes of pups secrete high levels of Müllerian inhibiting substance (MIS, anti-Müllerian hormone), with neurons being a target of this hormone. We report here that Mis(+/+) male pups exhibit novelty preference, but their Mis(-/-) brothers and Mis(+/+) sisters do not. This suggests that MIS is one of the determinants of "boy"-specific behavior.

Age-related changes in visual recognition memory during infancy and early childhood.

Age-related changes in long-term memory during infancy and early childhood were examined using the Visual Recognition Memory (VRM) procedure. Independent groups of 1-, 2-, 3-, and 4-year-olds were familiarized with a visual stimulus and were tested either immediately or after a delay that ranged from 24 hr to 6 months. Although all age groups exhibited a significant novelty preference when tested immediately after familiarization, clear age-related differences emerged over longer retention intervals. We conclude that age-related increases in basic retention are a fundamental aspect of mammalian memory development and, in humans, these increases may play a vital role in the offset of childhood amnesia.

Iodine supplementation improves cognition in mildly iodine-deficient children.

BACKGROUND: The effects of severe iodine deficiency during critical periods of brain development are well documented. There is little known about the consequences of milder forms of iodine deficiency on neurodevelopment. OBJECTIVE: The objective was to determine whether supplementing mildly iodine-deficient children with iodine improves cognition. DESIGN: A randomized, placebo-controlled, double-blind trial was conducted in 184 children aged 10-13 y in Dunedin, New Zealand. Children were randomly assigned to receive a daily tablet containing either 150 microg I or placebo for 28 wk. Biochemical, anthropometric, and dietary data were collected from each child at baseline and after 28 wk. Cognitive performance was assessed through 4 subtests from the Wechsler Intelligence Scale for Children. RESULTS: At baseline, children were mildly iodine deficient [median urinary iodine concentration (UIC): 63 microg/L; thyroglobulin concentration: 16.4 microg/L]. After 28 wk, iodine status improved in the supplemented group (UIC: 145 microg/L; thyroglobulin: 8.5 microg/L), whereas the placebo group remained iodine deficient (UIC: 81 microg/L; thyroglobulin: 11.6 microg/L). Iodine supplementation significantly improved scores for 2 of the 4 cognitive subtests [picture concepts (P = 0.023) and matrix reasoning (P = 0.040)] but not for letter-number sequencing (P = 0.480) or symbol search (P = 0.608). The overall cognitive score of the iodine-supplemented group was 0.19 SDs higher than that of the placebo group (P = 0.011). CONCLUSIONS: Iodine supplementation improved perceptual reasoning in mildly iodine-deficient children and suggests that mild iodine deficiency could prevent children from attaining their full intellectual potential. The trial was registered with the Australia New Zealand Clinical Trials Register as ACTRN12608000222347.

Nonspecific verbal cues alleviate forgetting by young children.

Verbal reminders play a pervasive role in memory retrieval by human adults. In fact, relatively nonspecific verbal information (e.g. 'Remember the last time we ate at that restaurant?') will often cue vivid recollections of a past event even when presented outside the original encoding context. Although research has shown that memory retrieval by young children can be initiated by physical cues and by highly specific verbal cues, the effect of less specific verbal cues is not known. Using a Visual Recognition Memory (VRM) procedure, we examined the effect of nonspecific verbal cues on memory retrieval by 4-year-old children. Our findings showed that nonspecific verbal cues were as effective as highly specific nonverbal cues in facilitating memory retrieval after a 2-week delay. We conclude that, at least by 4 years of age, children are able to use nonspecific verbal reminders to cue memory retrieval, and that the VRM paradigm may be particularly valuable in examining the age at which this initially occurs.

The effect of encoding time on retention by infants and young children.

Using a Visual Recognition Memory (VRM) procedure, we examined the effect of encoding time on retention by 1- and 4-year olds. Irrespective of age, shorter familiarization time reduced retention, and longer familiarization time prolonged retention. The amount of familiarization that yielded retention after a given delay decreased as a function of age.

Age-related changes in memory reactivation by 1- and 2-year-old human infants.

In three experiments, we examined the effect of a single reactivation treatment on retention by 1- and 2-year-old human infants who were tested in the visual recognition memory (VRM) paradigm. In all experiments, infants were familiarized with a visual stimulus and were tested after a delay. In the absence of a reactivation treatment, infants of both ages exhibited forgetting but exposure to a reactivation treatment alleviated forgetting after the same delay. When the duration of the original familiarization period was only 10 s, the minimum duration of an effective reminder treatment was 1 s for 2-year-olds, but was 5 s for 1-year-olds. When the duration of the original familiarization period was increased to 30 s, however, a 1-s reminder also alleviated forgetting by 1-year-olds.