Endogenous hormones, androgen receptor CAG repeat length and fluid cognition in middle-aged and older men: results from the European Male Ageing Study.
ABSTRACT Data remain divergent regarding the activational effects of endogenous hormones on adult cognitive function. We examined the association between cognition, hormones and androgen receptor (AR) CAG repeat length in a large cohort of men.
Community-based, cross-sectional study of 3369 men aged 40-79 years.
Cognition tests were the Rey-Osterrieth Complex Figure, Camden Topographical Recognition Memory and Digit-Symbol Substitution. A fluid cognition (FC) z-score was computed from the individual tests. Testosterone, oestradiol (OE(2)) and 5alpha-dihydrotestosterone were measured by gas chromatography-mass spectrometry; DHEAS, LH, FSH and sex hormone-binding globulin (SHBG) by electrochemiluminescence. Free testosterone and OE(2) were calculated from total hormone, SHBG and albumin. CAG repeat lengths were assayed by PCR genotyping.
Total testosterone and free testosterone were associated with higher FC z-scores, LH and FSH with lower FC z-scores in age-adjusted linear regressions. After adjusting for health, lifestyle and centre, a modest association was only observed between DHEAS and a lower FC z-score (beta=-0.011, P=0.02), although this was driven by subjects with DHEAS levels >10 micromol/l. Locally weighted plots revealed no threshold effects between hormones and FC. There was no association between CAG repeat length and FC z-score after adjustment for age and centre (beta=-0.007, P=0.06), nor any interaction effect between CAG repeat length and hormones.
Our results suggest that endogenous hormones are not associated with a vision-based measure of FC among healthy, community-dwelling men. Further studies are warranted to determine whether 'high' DHEAS levels are associated with poorer performance on a broader range of neuropsychological tests.
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ABSTRACT: Androgens modulate brain functions such as cognition, emotions and ability. Several studies have shown a correlation between testosterone levels and mental rotation. The aim of the present study was to confirm the influence of salivary testosterone levels, 2D/4D ratio (such as a putative marker of prenatal testosterone), and sensitivity of androgen receptor on the mental rotation in healthy young men. Seventy-five healthy young men (age, 21.86 year) volunteered in this study. Mental rotation scores of our subjects were assessed using the Vandenberg and Kuse Mental Rotation Test. The 2D/4D finger length ratio as an indicator of prenatal testosterone was used as an average measurement of both hands. Correlation analysis revealed no correlation between salivary testosterone levels and mental rotation. However, we have observed a trend towards a negative correlation. There were no statistically significant results between 2D/4D ratio and mental rotation or between polymorphic three-nucleotide (CAG) repeats and mental rotation tests. Future studies should focus on other genetic determinants of spatial abilities, potentially genes involved in testosterone metabolism.General Physiology and Biophysics 03/2014; 33(3). DOI:10.4149/gpb_2014005 · 0.88 Impact Factor
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ABSTRACT: Testosterone was shown to organize brain structure and modulate cognitive functions. Higher prenatal testosterone exposure has been proposed to increase systemizing and to decrease empathizing. Whether intellectually gifted (IQ > 130) individuals differ in these aspects is largely unexplored. The aim of this paper is to compare the prenatal testosterone exposure (reflected by 2D:4D), the actual testosterone levels, and the ability of empathizing and systemizing in gifted boys (N = 66) and control boys of same age (N = 80). The comparison revealed significantly lower salivary testosterone levels (d = − 3.35, t = 2.46, p = 0.02) in gifted group compared to controls. Although the effect size was quite robust, this result did not remain significant after the correcting for multiple testing (new p value calculated after Bonferroni correction was 0.006). Lower left 2D:4D (standing for higher prenatal testosterone level; d = − 1.33, t = 4.96, p < 0.0001) was observed in intellectually gifted boys compared to control boys surviving the correction for multiple testing. No significant difference between groups was found in the number of CAG repeats in gene encoding the androgen receptor (d = − 0.06, t = 0.38, p = ns). Intellectually gifted boys achieved significantly lower score in reading mind in the eye test (d = − 0.75, t = 3.38, p = 0.003) that remained significant after correcting for multiple comparisons. It can be speculated that higher prenatal testosterone reflected by lower 2D:4D organizes the brain of gifted boys in a different way in comparison with controls. Consequences include differences in cognitive functions such as lower ability to mentalize—to understand the mental state of others. The physiological mechanisms of testosterone in intellectually gifted boys, especially at the molecular level remain to be elucidated.Intelligence 02/2015; 48. DOI:10.1016/j.intell.2014.11.002 · 2.67 Impact Factor
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ABSTRACT: Klinefelter syndrome (KS, 47,XXY) is associated with increased psychiatric morbidity and cognitive disabilities, although the neuropsychological phenotype shows great variability. Androgen receptor polymorphism (CAG repeat length), skewed X-chromosome inactivation and parent-of-origin of the extra X-chromosome have been suggested to influence cognitive function and psychological traits. These issues have not been clarified for KS patients. We studied X-chromosome inactivation pattern, CAG repeat length and parent-of-origin in relation to educational and cohabitation status, personality and autism traits, psychological distress, cognitive function and brain volumes in 73 KS patients and 73 controls. Grey matter (GM) volume of left insula was significantly decreased in KS patients with skewed X-inactivation (z = 5.78) and we observed a borderline significant difference in global brain matter volume where KS patients with skewed X-chromosome inactivation tended to have smaller brains. Skewed X-inactivation, CAG repeat length and parent-of-origin were not correlated with educational and marital status, personality traits, autism traits, and psychological distress, prevalence of depression and anxiety or cognitive function. Interestingly our results regarding brain volumes indicate that X-inactivation has an influence on GM volume in left insula and might also be related to global GM volume, indicating a possible effect of X-linked genes on the development of GM volume in KS patient. Skewed X-inactivation, CAG repeat length and parent-of-origin have no impact on the neuropsychological phenotype in KS (http://www.clinicaltrials.gov (Clinical trial NCT00999310)).Andrology 05/2014; DOI:10.1111/j.2047-2927.2014.00229.x · 3.37 Impact Factor