Longitudinal Associations Between Autistic Traits, Self-compassion, Anxiety and Depression in Autistic and Non-autistic Adults Without Intellectual Disability.

PURPOSE: Previous cross-sectional research suggests self-compassion may mediate associations between autistic traits and mental health in autistic and non-autistic adults. However, no research to date has examined these relationships longitudinally. In this study, we used a cross-lagged panel analysis to examine correlations over time between autistic traits, self-compassion, and anxiety/depression. METHODS: Participants were from the UK and included autistic (n = 228 at T1, n = 156 at T2, and n = 165 at T3) and non-autistic adults (n = 228 at T1, n = 122 at T2, and n = 124 at T3) without intellectual disability. Participants were recruited through an online participation platform and completed demographics, the Autism Spectrum Quotient (AQ), the Self-Compassion Scale (SCS), and the Hospital Anxiety and Depression Scale (HADS) at baseline (T1), 6 months (T2), and 12 months (T3). RESULTS: In the autistic sample, negative correlations were observed between self-compassion and subsequent anxiety/depression across all models and timepoints, and these relationships were not reciprocal (i.e., earlier depression and anxiety did not predict future self-compassion). In the non-autistic sample, the findings generally suggested bi-directional relationships between self-compassion and anxiety/depression. In both groups, an indirect pathway between T1 autistic traits and T3 anxiety/depression via T2 self-compassion was confirmed. CONCLUSION: Considering the high prevalence of anxiety and depression among autistic people, and that self-compassion can be cultivated through practice, these findings suggest that self-compassion could be a useful therapeutic target to promote mental health in the autistic population.

Handedness in twins reared apart: A review of the literature and new data.

Reared-apart twin studies are a powerful means for identifying the relative contributions of heredity and environment to variation in human physical and behavioural traits. One such characteristic is handedness, for which it has long been noted that approximately 20% of twin pairs are comprised of one right-handed cotwin and one left-handed cotwin. Reared-together twin studies suggest a slightly greater concordance in monozygotic (MZT) than dizygotic (DZT) twins, implying that genetics influences hand preference. We report here two studies of handedness in reared-apart twins. Study 1 synthesizes the available data and estimates that at least N = 560 same-sex reared-apart twin pairs (for which zygosity is known with reasonable confidence) have been identified. Of these, handedness data are available for both members of n = 415 pairs. We observed similar levels of concordance/discordance for reared-apart monozygotic (MZA) and dizygotic (DZA) twins. However, although direction of handedness (right or left) has frequently been examined, strength of handedness (strong or weak) has not. Study 2 examined strength of hand preference and relative hand skill, as well as right- and left-hand speed, information available for participants in the Minnesota Study of Twins Reared Apart (MISTRA). We provide evidence of heritability for right-hand and left-hand speed. We also found hand preference strength was more alike than chance in DZA, but not MZA, twins. Findings are discussed in relation to genetic and environmental influences on human handedness.

The association of prenatal amniotic sex hormones and digit ratio (2D:4D) in children aged 5 to 70 months: A longitudinal study.

The sex difference of the 2D:4D digit ratio (female > male)-a proposed marker for prenatal testosterone exposure-is well established. Studies suggest it already exists in utero and is of moderate effect size in adulthood. However, evidence for the claim that 2D:4D reflects prenatal androgen action is limited, and the sex difference may exhibit lability during childhood. In the present study, 244 mothers were recruited in the course of an amniocentesis examination (performed between gestational weeks 14 and 18). Prenatal testosterone (T) and estradiol (E) levels were determined from amniotic fluid for boys and girls. The majority (97.4%, n = 114) of available female T levels (n = 117) were found below the level of quantification. Therefore, only male amniotic fluid data (n = 117) could be included for the analysis of associations between amniotic sex hormones (T levels and T to E ratio (T/E)) and 2D:4D. The families were then invited to each of the five consecutive follow-ups (ages: 5, 9, 20, 40, and 70 months) where children's 2D:4D was measured for both hands. The alternative marker D[r-l] reflects the directional asymmetry of 2D:4D (right subtracted by left 2D:4D) and was subsequently calculated as an additional measure for prenatal T exposure. No significant correlations between amniotic T or the T/E ratio (measured between week 14 and 18 of gestation) with 2D:4D respectively D[r-l] were observed for any time point. There was a significant sex difference (females > males) and a significant age effect with moderate correlations of 2D:4D between time points. 2D:4D increased between 20 and 40 months and between 40 and 70 months of age. The findings raise questions regarding the applicability of 2D:4D as a marker for prenatal androgen action and are discussed in terms of the reliability of obtained digit ratio data as well as in terms of the developmental timing of amniocentesis.

Ten simple rules for implementing open and reproducible research practices after attending a training course.

Open, reproducible, and replicable research practices are a fundamental part of science. Training is often organized on a grassroots level, offered by early career researchers, for early career researchers. Buffet style courses that cover many topics can inspire participants to try new things; however, they can also be overwhelming. Participants who want to implement new practices may not know where to start once they return to their research team. We describe ten simple rules to guide participants of relevant training courses in implementing robust research practices in their own projects, once they return to their research group. This includes (1) prioritizing and planning which practices to implement, which involves obtaining support and convincing others involved in the research project of the added value of implementing new practices; (2) managing problems that arise during implementation; and (3) making reproducible research and open science practices an integral part of a future research career. We also outline strategies that course organizers can use to prepare participants for implementation and support them during this process.

The indirect effect of self-compassion in the association between autistic traits and anxiety/depression: A cross-sectional study in autistic and non-autistic adults.

LAY ABSTRACT: Previous research on non-autistic adults suggests self-compassion may serve to reduce mental health problems and promote psychological well-being. Correlations between autistic traits and self-compassion have been observed in non-clinical populations. In this study, we were interested in extending previous research by exploring relationships between autistic traits, self-compassion and anxiety/depression in autistic adults without intellectual disability. The findings revealed that on average autistic people reported lower self-compassion than non-autistic people. Once we accounted for levels of self-compassion in our statistical model, this resulted in a complete loss of statistical significance in the relationships between autistic traits and anxiety/depression. Self-compassion may be a useful target for clinical intervention in autistic adults with co-occurring mental health difficulties.

Technostress, Coping, and Anxious and Depressive Symptomatology in University Students During the COVID-19 Pandemic.

The COVID-19 pandemic raised many challenges for university staff and students, including the need to work from home, which resulted in a greater reliance on technology. We collected questionnaire data from university students (N = 894) in three European countries: Greece, Italy, and the United Kingdom. Data were collected between 7th April 2020 and 19th June 2020, representing a period covering the first lockdown and university closures in these countries and across Europe generally. We tested the hypotheses that technology-related stressors (techno-overload, work-home conflict, techno-ease, techno-reliability, techno-sociality, and pace of change) would be associated with anxiety and depressive symptoms, and that coping styles (problem-focused, emotion-focused, and avoidance) would mediate these relationships. Results showed significant positive associations between techno-overload, work-home conflict and anxiety and depressive symptoms, and significant negative associations between techno-reliability, techno-ease and anxiety and depressive symptoms. A significant negative association was found between techno-sociality and depressive symptoms but not anxiety symptoms. No evidence was found for an association between pace of change and anxiety or depressive symptoms. Multiple mediation analyses revealed significant direct effects of techno-overload, work-home conflict and techno-ease on anxiety symptoms, and of work-home conflict and techno-ease on depressive symptoms. Work-home conflict had significant indirect effects on anxiety and depressive symptoms through avoidance coping. Techno-overload and techno-ease both had significant indirect effects on anxiety symptoms through problem- and emotion-focused coping. Techno-ease also had a significant indirect effect on depressive symptoms through problem-focused coping. The findings add to the body of evidence on technostress amongst university students and provide knowledge on how technostress translates through coping strategies into anxious and depressive symptoms during the disruption caused by the outbreak of a pandemic disease.

Evidence of assortative mating for theory of mind via facial expressions but not language.

Assortative mating is a phenomenon in which romantic partners typically resemble each other at a level greater than chance. There is converging evidence that social behaviours are subject to assortative mating, though less is known regarding social cognition. Social functioning requires the ability to identify and understand the mental states of others, i.e., theory of mind. The present study recruited a sample of 102 heterosexual couples via an online survey to test if theory of mind as measured using facial expressions (Reading the Mind in the Eyes Test) or language (Stiller-Dunbar Stories Task) is associated with assortative mating. Results provide evidence of assortative mating for theory of mind via facial expressions, though there was no such effect for theory of mind via language. Assortative mating for theory of mind via facial expressions was not moderated by length of relationship nor by partner similarity in age, educational attainment, or religiosity, all variables relevant to social stratification. This suggests assortative mating for theory of mind via facial expressions is better explained by partners being alike at the start of their relationship (initial assortment) rather than becoming similar through sustained social interaction (convergence), and by people seeking out partners that are like themselves (active assortment) rather than simply pairing with those from similar demographic backgrounds (social homogamy).

The associations between autistic traits and disordered eating/drive for muscularity are independent of anxiety and depression in females but not males.

Previous research has shown a positive correlation between autistic traits and eating disorder symptoms, and this relationship appears to be independent of co-occurring mental health status. The current study followed a pre-registered analysis plan with the aim to investigate a previously unconsidered factor in the relationship between autistic traits and disorders of eating and body image: the drive for muscularity. Participants (N = 1068) completed the Autism Spectrum Quotient (AQ), Hospital Anxiety and Depression Scale (HADS), Eating Attitudes Test-26 (EAT-26) and Drive for Muscularity Scale (DMS). Positive correlations between AQ and EAT-26 and AQ and DMS were observed. In females, AQ remained significantly correlated with EAT-26 and DMS when controlling for co-occurring anxiety and depression symptoms, but this was not the case in males. These findings demonstrate the moderating role of sex, and the need to consider autistic traits in individuals diagnosed with, or at a heightened risk for, disorders of eating and body image.

Digit ratio (2D:4D) and maternal testosterone-to-estradiol ratio measured in early pregnancy.

The ratio of index to ring finger (2D:4D) has been hypothesised to indicate prenatal androgen exposure, yet evidence for its validity is lacking. We report the first pre-registered study to investigate mothers' early pregnancy sex hormone concentrations in relation to their children's digit ratios measured at 18-22-month follow-up. Although the testosterone (T) to estradiol (E) ratio correlated negatively with right hand digit ratio (R2D:4D) and directional asymmetry (right-minus-left) in digit ratio (D[R-L]), neither effect remained statistically significant once demographic and obstetric covariates were controlled for. Nevertheless, the multivariate level of analysis did reveal that T correlated positively with left hand digit ratio (L2D:4D) and negatively with D[R-L]. However, the first of these effects is in the opposite direction to that predicted by theory. Taken together, the results of our study suggest research with larger samples is required to determine whether digit ratios are valid proxies for maternal sex hormone exposure.

A longitudinal examination of perinatal testosterone, estradiol and vitamin D as predictors of handedness outcomes in childhood and adolescence.

The developmental origins of handedness remain elusive, though very early emergence suggests individual differences manifesting in utero could play an important role. Prenatal testosterone and Vitamin D exposure are considered, yet findings and interpretations remain equivocal. We examined n = 767 offspring from a population-based pregnancy cohort (The Raine Study) for whom early biological data and childhood/adolescent handedness data were available. We tested whether 18-week maternal circulatory Vitamin D (25[OH]D), and testosterone and estradiol from umbilical cord blood sampled at birth predicted variance in direction of hand preference (right/left), along with right- and left-hand speed, and the strength and direction of relative hand skill as measured by a finger-tapping task completed at 10 (Y10) and/or 16 (Y16) years. Although higher concentrations of Vitamin D predicted more leftward and less lateralized (regardless of direction) relative hand skill profiles, taken as a whole, statistically significant findings typically did not replicate across time-point (Y10/Y16) or sex (male/female) and were rarely detected across different (bivariate/multivariate) levels of analysis. Considering the number of statistical tests and generally inconsistent findings, our results suggest that perinatal testosterone and estradiol contribute minimally, if at all, to subsequent variance in handedness. Vitamin D, however, may be of interest in future studies.

Targeting the adrenomedullin-2 receptor for the discovery and development of novel anti-cancer agents.

INTRODUCTION: Adrenomedullin (AM) is a peptide responsible for many physiological processes including vascular health and hormone regulation. Dysregulation of AM signaling can stimulate cancers by promoting proliferation, angiogenesis and metastasis. Two AM receptors contribute to tumor progression in different ways. Adrenomedullin-1 receptor (AM1R) regulates blood pressure and blocking AM signaling via AM1R would be clinically unacceptable. Therefore, antagonizing adrenomedullin-2 receptor (AM2R) presents as an avenue for anti-cancer drug development. AREAS COVERED: We review the literature to highlight AM's role in cancer as well as delineating the specific roles AM1R and AM2R mediate in the development of a pro-tumoral microenvironment. We highlight the importance of exploring the residue differences between the receptors that led to the development of first-in-class selective AM2R small molecule antagonists. We also summarize the current approaches targeting AM and its receptors, their anti-tumor effects and their limitations. EXPERT OPINION: As tool compounds, AM2R antagonists will allow the dissection of the functions of CGRPR (calcitonin gene-related peptide receptor), AM1R and AM2R, and has considerable potential as a first-in-class oncology therapy. Furthermore, the lack of detectable side effects and good drug-like pharmacokinetic properties of these AM2R antagonists support the promise of this class of compounds as potential anti-cancer therapeutics.

Evidence of partner similarity for autistic traits, systemizing, and theory of mind via facial expressions.

It has been hypothesised that romantic partners are more similar than chance in relation to autistic traits. To test this theory, we recruited n = 105 heterosexual couples and examined within-couple correlations for autistic traits [measured using the Autism Spectrum Quotient (AQ)], empathizing [measured using the Empathy Quotient (EQ)], and systemizing [measured using the Systemizing Quotient-Revised (SQ-R)]. For a subsample that attended the lab (n = 58 couples), we also investigated theory of mind via facial expressions using the Reading the Mind in the Eyes Test (RMET) and attention to detail, a component within systemizing, using the Embedded Figures Task (EFT). Variable-centred analyses revealed positive within-couple correlations for all measures except EQ, although these effects were only statistically significant for unmarried couples and not for married/engaged couples. Follow-up analyses indicated that the observed couple similarity effects are likely consistent with people pairing with those more similar than chance (initial assortment) rather than becoming alike over time (convergence), and to seeking out self-resembling partners (active assortment) rather than pairing in this manner via social stratification processes (social homogamy). Additionally, a significant within-couple correlation for autistic traits was observed at the meta-analytic level. However, it should be noted that the meta-analytic effect size estimate was small (r = 0.153) and indicates that only ~ 2% of variance in a person's score on a phenotypic measure of autistic traits can be predicted by that of their partner.

Autistic Traits, Empathizing-Systemizing, and Gender Diversity.

Previous research indicates a link between autism and transgender and gender-diverse identities, though the association is not yet fully understood. The current study examined autistic traits (Autism Spectrum Quotient [AQ]), empathizing (Empathizing Quotient-Short [EQ-S]), and systemizing (Systemizing Quotient-Short [SQ-S]) in a sample of 89 adults and aimed to test whether gender-diverse individuals exhibit cognitive profiles consistent with predictions derived from the Extreme Male Brain (EMB) theory. As most research has considered only cisgender people, we recruited a more diverse sample by contacting > 200 UK LGBTQ+ organizations and posting on social media. A range of non-cisgender identities (e.g., transgender male, transgender female, non-binary, genderqueer, transmasculine) and non-heterosexual orientations (e.g., bisexual) were represented, and participants were categorized into one of four groups: (1) assigned female at birth but does not identify as female (transgender AFAB) (n = 32), (2) cisgender female (n = 21), (3) assigned male at birth but does not identify as male (transgender AMAB) (n = 18), and (4) cisgender male (n = 18). After controlling for age and autism diagnostic status, transgender AFAB participants had marginally higher AQ scores, and significantly higher SQ-S and systemizing-relative-to-empathizing (D) scores, compared with the cisgender female group. No such differences were detected between the transgender AMAB and cisgender male groups. Our findings are broadly in line with predictions derived from the EMB theory, though as no transgender AFAB participants reported being heterosexual, it was not possible to determine whether these effects relate specifically to gender identity, to sexual orientation, or to both.

Autism and autistic traits in those who died by suicide in England.

BACKGROUND: Autism and autistic traits are risk factors for suicidal behaviour. AIMS: To explore the prevalence of autism (diagnosed and undiagnosed) in those who died by suicide, and identify risk factors for suicide in this group. METHOD: Stage 1: 372 coroners' inquest records, covering the period 1 January 2014 to 31 December 2017 from two regions of England, were analysed for evidence that the person who died had diagnosed autism or undiagnosed possible autism (elevated autistic traits), and identified risk markers. Stage 2: 29 follow-up interviews with the next of kin of those who died gathered further evidence of autism and autistic traits using validated autism screening and diagnostic tools. RESULTS: Stage 1: evidence of autism (10.8%) was significantly higher in those who died by suicide than the 1.1% prevalence expected in the UK general alive population (odds ratio (OR) = 11.08, 95% CI 3.92-31.31). Stage 2: 5 (17.2%) of the follow-up sample had evidence of autism identified from the coroners' records in stage 1. We identified evidence of undiagnosed possible autism in an additional 7 (24.1%) individuals, giving a total of 12 (41.4%); significantly higher than expected in the general alive population (1.1%) (OR = 19.76, 95% CI 2.36-165.84). Characteristics of those who died were largely similar regardless of evidence of autism, with groups experiencing a comparably high number of multiple risk markers before they died. CONCLUSIONS: Elevated autistic traits are significantly over-represented in those who die by suicide.

Judgements of attractiveness of the opposite sex and nostril differences in self-rated mood: The effects of androstenol.

Androstenol has been reported to influence judgements of attractiveness and to affect participants' mood. In the present study, participants were asked to sniff androstenol or a control odour (pure ethanol) unilaterally with the left or right nostril. Subsequently, they rated the attractiveness of photographs of the opposite sex and their own feelings on four mood scales. Participants rated the photographs as significantly more attractive after sniffing androstenol compared with the control odour. This did not depend upon androstenol being perceived as pleasant. Androstenol made male participants feel more lively, and both male and female participants more sexy, when sniffed through the right compared with the left nostril. Participants rated themselves as more irritable and aggressive when exposed to androstenol through the left nostril. The findings are discussed in relation to the effects of arousal on attraction and in the context of current theories of hemispheric differences in emotion.

Investigating the reliability and sex differences of digit lengths, ratios, and hand measures in infants.

Hands and digits tend to be sexually dimorphic and may reflect prenatal androgen exposure. In the past years, the literature introduced several hand and digit measures, but there is a lack of studies in prepubertal cohorts. The available literature reports more heterogeneous findings in prepubertal compared to postpubertal cohorts. The comparability of the available studies is further limited by the study design and different measurement techniques. The present study compared the reliability and sex differences of available hand and digit measures, namely digit lengths of 2D, 3D, 4D, 5D, digit ratios 2D:4D, 2D:5D, 3D:4D, 3D:5D, 4D:5D, relative digit lengths rel2, rel3, rel4, rel5, directional asymmetry of right and left 2D:4D (Dr-l), hand width, length, and index of 399 male and 364 female 6-month-old German infants within one study using only indirect and computer-assisted measurements. The inter-examiner reliability was excellent while the test-retest reliability of hand scans was only moderate to high. Boys exhibited longer digits as well as wider and longer hands than girls, but smaller digit ratios, with ratios comprising the fifth digit revealing the largest effect sizes. Other hand and digit ratios revealed sex differences to some extent. The findings promote the assumption of sexual dimorphic hand and digit measures. However, by comparing the results of the available literature, there remains an uncertainty regarding the underlying hypothesis. Specifically in prepubertal cohorts, i.e. before the influence of fluctuating hormones, significant effects should be expected. It seems like other factors than the influence of prenatal androgens contribute to the sexual dimorphism in hand and digit lengths.

Discovery of a First-In-Class Small Molecule Antagonist against the Adrenomedullin-2 Receptor: Structure-Activity Relationships and Optimization.

Class B G-protein-coupled receptors (GPCRs) remain an underexploited target for drug development. The calcitonin receptor (CTR) family is particularly challenging, as its receptors are heteromers comprising two distinct components: the calcitonin receptor-like receptor (CLR) or calcitonin receptor (CTR) together with one of three accessory proteins known as receptor activity-modifying proteins (RAMPs). CLR/RAMP1 forms a CGRP receptor, CLR/RAMP2 forms an adrenomedullin-1 (AM1) receptor, and CLR/RAMP3 forms an adrenomedullin-2 (AM2) receptor. The CTR/RAMP complexes form three distinct amylin receptors. While the selective blockade of AM2 receptors would be therapeutically valuable, inhibition of AM1 receptors would cause clinically unacceptable increased blood pressure. We report here a systematic study of structure-activity relationships that has led to the development of first-in-class AM2 receptor antagonists. These compounds exhibit therapeutically valuable properties with 1000-fold selectivity over the AM1 receptor. These results highlight the therapeutic potential of AM2 antagonists.

Where next for laterality research? Looking back and looking forward.

While paying attention to the recommendations of Ocklenburg, Berretz, Packheiser, and Friedrich (2020) in the target article, researchers in the field of laterality should attempt to: (1) solve the long-standing puzzle of the relationship between handedness and language lateralization; (2) further explore the genetic bases of manual and cerebral asymmetry and of their associations with psychiatric and neurodevelopmental conditions; (3) explore the adaptive significance of laterality for humans and non-humans and elucidate the relationships of asymmetry across species; and (4) embrace developing technologies to investigate the interaction between the hemispheres during the performance of everyday tasks.

Digit ratio (2D:4D) and handedness: A meta-analysis of the available literature.

The Geschwind-Behan-Galaburda and sexual differentiation models predict an association between elevated foetal androgen exposure and left-handedness whereas the callosal hypothesis predicts the opposite. We present a meta-analysis of correlations between handedness and digit ratio (2D:4D), a putative marker of prenatal testosterone. Left-handedness predicted low (male-typical) right-hand digit ratio (R2D:4D), high (female-typical) left-hand digit ratio (L2D:4D), and low R2D:4D-L2D:4D directional asymmetry (D[R-L]). Effect sizes were extremely small and not moderated by sex or method of measuring handedness or 2D:4D. The same general pattern was observed after excluding the very large study (110,329 males, 90,412 females) of Manning and Peters ([2009]. Digit ratio (2D:4D) and hand preference for writing in the BBC Internet Study. Laterality: Asymmetries of Body, Brain and Cognition, 14(5), 528-540. doi:10.1080/13576500802637872); however, no significant effects for R2D:4D were observed once these samples were removed. The results do not confirm any theory linking prenatal androgens with handedness, so we speculate they instead reflect the mechanical action of writing causing subtle changes in the musculature and/or fat pads of the fingers. Gripping a pen/pencil might cause an increase in 2D relative to 4D (and/or decrease in 4D relative to 2D) resulting in higher ratios on the writing-hand; furthermore, this could differ between left- and right-handers due to writing in the left-to-right direction (as in English) having asymmetrical effects depending on which hand is used.

Digit ratio (2D:4D) and amniotic testosterone and estradiol: an attempted replication of Lutchmaya et al. (2004).

The ratio of length between the second (index) and fourth (ring) fingers (digit ratio or 2D:4D) is frequently employed as a retrospective marker of prenatal sex hormone exposure. Lutchmaya et al. (2004) reported that the ratio of testosterone (T) to estradiol (E) present in second-trimester amniotic fluid was negatively correlated with digit ratios for the right hand (but not the left hand) in a sample of 29 children at 2-year follow-up. This observation is frequently cited as evidence for the measure's validity but has not been replicated. We therefore present the findings of another study of amniotic T and E that did not find evidence for these effects at 4½-year follow-up. The confidence intervals were large, the direction of correlations observed was generally erratic, and the overall findings question the premise that second-trimester sex hormones affect the development of digit length ratios in humans.