No evidence for a difference in 2D:4D ratio between youth with elevated prenatal androgen exposure due to congenital adrenal hyperplasia and controls.
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ABSTRACT:
SUBMITTER: Nave G
PROVIDER: S-EPMC8591085 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo determine whether the 2D:4D ratio (ratio of the second and fourth digit lengths), a proxy for lower prenatal androgen to estrogen ratio, differs in men with and without multiple sclerosis (MS) using a case-control study design.MethodsWe obtained 2 digital scans of the right hand for men with MS presenting to a scheduled clinic visit at a large MS referral center, and for men without autoimmune or endocrine diseases. All individuals were aged 18 to 65 years, right-handed, and reported no prior digit trauma. We calculated a mean 2D:4D ratio using digital calipers. In participants with MS, we assessed age at first MS symptoms, MS type, and the MS Severity Score; 51 had provided a testosterone level within 10 years of symptom onset. Our primary analysis was a cross-sectional comparison of the 2D:4D ratio between men with and without MS, using a 2-sample t test for independent samples assuming unequal variance.ResultsIn total, we scanned 137 men with MS and 145 men without MS. A statistically significant association between 2D:4D ratio and MS status was observed in the univariate logistic regression model (p<0.05). These differences were not associated with age or race, which differed between the 2 groups. In participants with MS, the 2D:4D ratio was not correlated with MS type, age at first symptoms, or MS Severity Score (p>0.15 for each), and it was not correlated with adult testosterone levels (r=0.06, p=0.68, n=51).ConclusionsDuring the prenatal period, low androgens could represent a risk factor for MS.
| S-EPMC4607599 | biostudies-literature
Project description:Spatial abilities contribute to life and occupational competencies, and certain spatial skills differ, on average, between males and females, typically favoring males when differences occur. Factors contributing to spatial skills could include prenatal as well as experiential/cultural influences, with biological and social influences likely interacting and difficult to disentangle. This meta-analysis examined the potential influence of prenatal androgen exposure on spatial skill by examining studies of patients with congenital adrenal hyperplasia (CAH). CAH involves elevated adrenal androgens prenatally, with overall androgen concentrations higher for females with CAH versus same-sex controls but with little overall difference between males with CAH versus controls. We hypothesized that, if androgens contribute prenatally to neurobehavioral development in humans as in many other species, females with CAH would show spatial enhancement versus control females, but with no definitive hypothesis for males. Meta-analysis of 12 studies examining overall spatial skill and three spatial subcategories failed to support enhanced spatial performance for females with CAH; males with CAH showed lower spatial ability compared to control males, at least for the category of overall spatial skill. Although statistical logic precludes accepting the null hypothesis for females, the meta-analysis failed to support the idea that prenatal exposure to androgens explains spatial gender/sex differences in humans. Alternative explanations for average gender/sex differences in some spatial tasks could include androgen exposure at other times, such as mini-puberty, or different social factors experienced by males and females. We also discuss possible explanations for the different outcomes seen in females versus males with CAH.
| S-EPMC8784244 | biostudies-literature
Project description:Positive social interactions are crucial for human well-being. Elevated prenatal exposure to testosterone as indicated by a low second-to-fourth finger length ratio (2D:4D) relates to more aggressive/hostile behavior in men of low 2D:4D, especially in challenging situations. How much people enjoy interacting with others is determined by the personality trait sociability. Given its role in approach and avoidance behavior, sociability might also be influenced by prenatal sex hormones, but studies are inconclusive so far. Here, we investigated the association between 2D:4D and the personality trait sociability complemented by personal social capital and personal social network size, in a population-based cohort of 4998 men. Lower 2D:4D correlated significantly with higher trait sociability, bigger personal social capital, and larger personal social network size. These effects were consistent across both hands separately and their mean value. Furthermore, both factors of sociability (1) liking party and company of friends and (2) isolation intolerance, correlated significantly with the prenatal testosterone marker. The exploratory analysis revealed no link between 2D:4D and responses to the personality trait aggression items or items of anti-social-personality disorder. Our data suggest that prenatal androgen exposure organizes the brain with lasting effects on social behavior.
| S-EPMC6906175 | biostudies-literature
Project description:The second to fourth digit (2D:4D) ratio is of interest in autism spectrum disorder (ASD). Studies on the relationship of this ratio with other neurodevelopmental disorders (NDDs) are lacking. Investigating the association between the ratio and NDDs in twins can provide insight into genetic and/or environmental factors driving the ratio. Hand images were collected in N?=?238 twins with NDDs or typical development from 70 monozygotic and 49 dizygotic pairs to examine ratios and their associations to DSM-5 defined categorical NDDs, autistic traits, zygosity, and sex. There were small associations for males between the ratios and any NDD and ADHD diagnoses. Males had lower ratios than females. Future studies exploring the ratio alongside physical anomalies could provide etiological insight into NDDs.
| S-EPMC6096789 | biostudies-other
Project description:The ratio of the lengths of an individual's second to fourth digit (2D:4D) is commonly used as a noninvasive retrospective biomarker for prenatal androgen exposure. In order to identify the genetic determinants of 2D:4D, we applied a genome-wide association approach to 1507 11-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in whom 2D:4D ratio had been measured, as well as a sample of 1382 12- to 16-year-olds from the Brisbane Adolescent Twin Study. A meta-analysis of the two scans identified a single variant in the LIN28B gene that was strongly associated with 2D:4D (rs314277: p = 4.1 x 10(-8)) and was subsequently independently replicated in an additional 3659 children from the ALSPAC cohort (p = 1.53 x 10(-6)). The minor allele of the rs314277 variant has previously been linked to increased height and delayed age at menarche, but in our study it was associated with increased 2D:4D in the direction opposite to that of previous reports on the correlation between 2D:4D and age at menarche. Our findings call into question the validity of 2D:4D as a simplistic retrospective biomarker for prenatal testosterone exposure.
| S-EPMC2850436 | biostudies-literature
Project description:BackgroundDespite the global increase in the prevalence of autism spectrum disorders (ASD), relevant research studies are lacking in Brunei Darussalam. Various studies have shown a significant association between a lowered 2D:4D ratio (ratio of second digit/index finger to the fourth digit/ring finger) and ASD, making it one of the potential phenotypic biomarkers for early detection of autism, which is important for early intervention and management.ObjectiveThe objective of this study is to explore the association between 2D:4D ratio and ASD in Brunei Darussalam, as a potential tool to complement early ASD diagnosis.MethodsWe conducted a case-control study comprising 28 ASD and 62 typically developing (TD) children in the case and control group, respectively (age range: 3-11 years old; median age: 6 years old). Median 2D:4D ratios were measured, compared and analysed between the two groups. Logistic regression models were used to explore potential associations between the median 2D:4D ratio and ASD in respective gender, for both left and right hands, independently.ResultsOur study shows that the median 2D:4D ratio of left hand in ASD males is significantly lower than those in TD males, after adjusting for ethnicity and age [Odds Ratio (OR) = 0.57 (95% Confidence Interval (CI): 0.31-0.96); p = 0.044]. For females, there is no association of ASD with the median left hand 2D:4D ratio [OR = 3.09 (95% CI: 0.98-19.86); p = 0.144] or the median right hand 2D:4D ratio [OR = 1.23 (95% CI: 0.42-3.88); p = 0.702]. Our study also shows a significant positive correlation and/or a reduced asymmetry between the average 2D:4D ratio of left hands and right hands in ASD males (Pearson's correlation (r) = 0.48; 95% CI: 0.076-0.75, p = 0.023).ConclusionsThere is significant association between a lowered median 2D:4D ratio of the left hand (in males only) and ASD diagnosis. Once validated in a larger sample size, a lowered median 2D:4D ratio on the left hand may be a potential tool to complement ASD diagnosis for males in our study population. There is no association between the median 2D:4D ratio (left or right hands) and ASD in females, which could be due to the small female sample size and/or the possibility of different aetiology for ASD in females. Reduced asymmetry between the average 2D:4D ratio of left and right hands observed in ASD males only (not in ASD females) also suggests the importance of considering gender-specific biomarkers for ASD diagnosis.
| S-EPMC8531075 | biostudies-literature
Project description:We replicate the Stanford marshmallow experiment with a sample of 141 preschoolers and find a correlation between lack of self-control and 2D:4D digit ratio. Children with low 2D:4D digit ratio are less likely to delay gratification. Low 2D:4D digit ratio may indicate high fetal testosterone. If this hypothesis is true, our finding means high fetal testosterone children are less likely to delay gratification.
| S-EPMC4260846 | biostudies-literature
Project description:Prior research has identified relations between prenatal testosterone exposure and various antisocial and criminal behaviors. However, less is known about the association between prenatal testosterone exposure and personality traits, such as psychopathy. This study used self-report and biometric data from a sample of undergraduates (n = 491) at a large southwestern university to examine the association between prenatal testosterone exposure (measured by the 2D:4D ratio) and three dimensions of psychopathy (i.e., callousness, egocentricity, and antisocial behavior). Analyses were stratified by sex to explore sex-specific biological underpinnings of psychopathy in young adulthood. Results showed that males scored significantly higher in psychopathic traits and reported significantly lower 2D:4D ratios, compared to females. Additionally, 2D:4D ratios were negatively associated with egocentricity in males, but not females. These findings contribute to a growing literature on the organizational effects that prenatal testosterone exposure may have on the development of different dimensions of psychopathy. Highlights • Psychopathy is higher for males compared to females.• Males exhibit lower 2D:4D ratios compared to females.• Low 2D:4D ratios were linked with higher levels of egocentricity in males compared to females.• Findings provide evidence that testosterone, measured by the 2D:4D ratio, may be implicated in certain domains of psychopathy. Psychopathy; 2D:4D ratio; Sex.
| S-EPMC9792753 | biostudies-literature
Project description:Prenatal androgen exposure affects the brain development of the fetus which may facilitate certain behaviors and decision patterns in the later life. The ratio between the lengths of second and the fourth fingers (2D:4D) is a negative biomarker of the ratio between prenatal androgen and estrogen exposure and men typically have lower ratios than women. In line with the typical findings suggesting that women are more risk averse than men, several studies have also shown negative relationships between 2D:4D and risk taking although the evidence is not conclusive. Previous studies have also reported that both men and women believe women are more risk averse than men. In the current study, we re-test the relationship between 2D:4D and risk preferences in a German student sample and also investigate whether the 2D:4D ratio is associated with people's perceptions about others' risk preferences. Following an incentivized risk elicitation task, we asked all participants their predictions about (i) others' responses (without sex specification), (ii) men's responses, and (iii) women's responses; then measured their 2D:4D ratios. In line with the previous findings, female participants in our sample were more risk averse. While both men and women underestimated other participants' (non sex-specific) and women's risky decisions on average, their predictions about men were accurate. We also found evidence for the false consensus effect, as risky choices are positively correlated with predictions about other participants' risky choices. The 2D:4D ratio was not directly associated either with risk preferences or the predictions of other participants' choices. An unexpected finding was that women with mid-range levels of 2D:4D estimated significantly larger sex differences in participants' decisions. This finding needs further testing in future studies.
| S-EPMC5810266 | biostudies-literature
Project description:The classic androgen synthesis pathway proceeds via dehydroepiandrosterone, androstenedione, and testosterone to 5?-dihydrotestosterone. However, 5?-dihydrotestosterone synthesis can also be achieved by an alternative pathway originating from 17?-hydroxyprogesterone (17OHP), which accumulates in congenital adrenal hyperplasia (CAH). Similarly, recent work has highlighted androstenedione-derived 11-oxygenated 19-carbon steroids as active androgens, and in CAH, androstenedione is generated directly from 17OHP. The exact contribution of alternative pathway activity to androgen excess in CAH and its response to glucocorticoid (GC) therapy is unknown.We sought to quantify classic and alternative pathway-mediated androgen synthesis in CAH, their diurnal variation, and their response to conventional GC therapy and modified-release hydrocortisone.We used urinary steroid metabolome profiling by gas chromatography-mass spectrometry for 24-hour steroid excretion analysis, studying the impact of conventional GCs (hydrocortisone, prednisolone, and dexamethasone) in 55 adults with CAH and 60 controls. We studied diurnal variation in steroid excretion by comparing 8-hourly collections (23:00-7:00, 7:00-15:00, and 15:00-23:00) in 16 patients with CAH taking conventional GCs and during 6 months of treatment with modified-release hydrocortisone, Chronocort.Patients with CAH taking conventional GCs showed low excretion of classic pathway androgen metabolites but excess excretion of the alternative pathway signature metabolites 3?,5?-17-hydroxypregnanolone and 11?-hydroxyandrosterone. Chronocort reduced 17OHP and alternative pathway metabolite excretion to near-normal levels more consistently than other GC preparations.Alternative pathway-mediated androgen synthesis significantly contributes to androgen excess in CAH. Chronocort therapy appears superior to conventional GC therapy in controlling androgen synthesis via alternative pathways through attenuation of their major substrate, 17OHP.
| S-EPMC5470768 | biostudies-literature