Sex differences in placenta-derived markers and later autistic traits in children.

Autism is more prevalent in males and males on average score higher on measures of autistic traits. Placental function is affected significantly by the sex of the fetus. It is unclear if sex differences in placental function are associated with sex differences in the occurrence of autistic traits postnatally. To assess this, concentrations of angiogenesis-related markers, placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) were assessed in maternal plasma of expectant women in the late 1st (mean= 13.5 [SD = 2.0] weeks gestation) and 2nd trimesters (mean=20.6 [SD = 1.2] weeks gestation), as part of the Generation R Study, Rotterdam, the Netherlands. Subsequent assessment of autistic traits in the offspring at age 6 was performed with the 18-item version of the Social Responsiveness Scale (SRS). Associations of placental protein concentrations with autistic traits were tested in sex-stratified and cohort-wide regression models. Cases with pregnancy complications or a later autism diagnosis (n = 64) were also assessed for differences in placenta-derived markers. sFlt-1 levels were significantly lower in males in both trimesters but showed no association with autistic traits. PlGF was significantly lower in male pregnancies in the 1st trimester, and significantly higher in the 2nd trimester, compared to female pregnancies. Higher PlGF levels in the 2nd trimester and the rate of PlGF increase were both associated with the occurrence of higher autistic traits (PlGF-2nd: n = 3469,b = 0.24 [SE = 0.11], p = 0.03) in both unadjusted and adjusted linear regression models that controlled for age, sex, placental weight and maternal characteristics. Mediation analyses showed that higher autistic traits in males compared to females were partly explained by higher PlGF or a faster rate of PlGF increase in the second trimester (PlGF-2nd: n = 3469, ACME: b = 0.005, [SE = 0.002], p = 0.004). In conclusion, higher PlGF levels in the 2nd trimester and a higher rate of PlGF increase are associated with both being male, and with a higher number of autistic traits in the general population.

Autistic People's Perinatal Experiences II: A Survey of Childbirth and Postnatal Experiences.

Qualitative accounts indicate there are sensory and communication related barriers to adequate childbirth and postnatal healthcare for autistic people. However, little quantitative work has explored the topic. This online survey study explored childbirth and postnatal experiences among 384 autistic and 492 non-autistic people. Compared with non-autistic people, autistic people were more likely to find the sensory aspects of birth overwhelming, and experienced lower satisfaction with birth-related and postnatal healthcare. Autistic people were more likely to experience postnatal depression and anxiety. The findings highlight that sensory and communication adjustments should be made to birth and postnatal healthcare for autistic people. The findings indicate the need for greater autism understanding among professionals and greater postnatal mental health support for autistic people.

Evaluation of data imputation strategies in complex, deeply-phenotyped data sets: the case of the EU-AIMS Longitudinal European Autism Project.

An increasing number of large-scale multi-modal research initiatives has been conducted in the typically developing population, e.g. Dev. Cogn. Neur. 32:43-54, 2018; PLoS Med. 12(3):e1001779, 2015; Elam and Van Essen, Enc. Comp. Neur., 2013, as well as in psychiatric cohorts, e.g. Trans. Psych. 10(1):100, 2020; Mol. Psych. 19:659-667, 2014; Mol. Aut. 8:24, 2017; Eur. Child and Adol. Psych. 24(3):265-281, 2015. Missing data is a common problem in such datasets due to the difficulty of assessing multiple measures on a large number of participants. The consequences of missing data accumulate when researchers aim to integrate relationships across multiple measures. Here we aim to evaluate different imputation strategies to fill in missing values in clinical data from a large (total N = 764) and deeply phenotyped (i.e. range of clinical and cognitive instruments administered) sample of N = 453 autistic individuals and N = 311 control individuals recruited as part of the EU-AIMS Longitudinal European Autism Project (LEAP) consortium. In particular, we consider a total of 160 clinical measures divided in 15 overlapping subsets of participants. We use two simple but common univariate strategies-mean and median imputation-as well as a Round Robin regression approach involving four independent multivariate regression models including Bayesian Ridge regression, as well as several non-linear models: Decision Trees (Extra Trees., and Nearest Neighbours regression. We evaluate the models using the traditional mean square error towards removed available data, and also consider the Kullback-Leibler divergence between the observed and the imputed distributions. We show that all of the multivariate approaches tested provide a substantial improvement compared to typical univariate approaches. Further, our analyses reveal that across all 15 data-subsets tested, an Extra Trees regression approach provided the best global results. This not only allows the selection of a unique model to impute missing data for the LEAP project and delivers a fixed set of imputed clinical data to be used by researchers working with the LEAP dataset in the future, but provides more general guidelines for data imputation in large scale epidemiological studies.

Brain charts for the human lifespan.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

The relevance of the interpersonal theory of suicide for predicting past-year and lifetime suicidality in autistic adults.

BACKGROUND: While there are known risk factors for suicidality in autistic adults, these are often unconnected from theoretical frameworks that might explain why risk is elevated and guide clinical interventions. The present study investigated the relevance of constructs from the Interpersonal Theory of Suicide (ITS), including perceived burdensomeness, thwarted belongingness and acquired capability for suicide, and explored mechanisms through which certain risk factors (relationship status, age at diagnosis) might elevate suicide risk. METHODS: Autistic adults (n = 314) completed an online study including measures of depression, anxiety and constructs from the ITS. Linear and multinomial regression analysis disentangled contributions of ITS variables from effects of depression and anxiety for past-year suicide ideation, past-year and lifetime suicide attempts. Mediation analyses examined associations between risk factors and these suicide outcomes via mechanisms proposed by the ITS. RESULTS: Past-year suicide ideation was associated with burdensomeness, mental rehearsal of suicide plans (a facet of acquired capability), and depression. Greater feelings of burdensomeness, and reduced fear of death, marked out participants who had attempted suicide in comparison to those who had experienced suicide ideation in the past year. Relationship status was indirectly associated with past-year suicide ideation via the mediators of depression and burdensomeness, and was associated with past-year attempts via its effect on ideation. Age at diagnosis was unrelated to any variables. LIMITATIONS: Cross-sectional research is insensitive to causality and temporal dynamics, which is likely why interaction hypotheses from the ITS were unsupported. Normative measures may be invalid in autistic samples. There was no control group. The autistic sample was unrepresentative of the whole population, particularly autistic people with intellectual disabilities, ethnic/racial minorities, and gender minorities. CONCLUSIONS: Perceived burdensomeness and acquired capability appear potentially important to suicide in autistic people, and may mediate the effects of some risk factors. Future research should explore the temporal dynamics of suicide trajectories in longitudinal, prospective designs.

Levels of Self-representation and Their Sociocognitive Correlates in Late-Diagnosed Autistic Adults.

The cognitive representation of oneself is central to other sociocognitive processes, including relations with others. It is reflected in faster, more accurate processing of self-relevant information, a "self-prioritisation effect" (SPE) which is inconsistent across studies in autism. Across two tasks with autistic and non-autistic participants, we explored the SPE and its relationship to autistic traits, mentalizing ability and loneliness. A SPE was intact in both groups, but together the two tasks suggested a reduced tendency of late-diagnosed autistic participants to differentiate between familiar and unfamiliar others and greater ease disengaging from the self-concept. Correlations too revealed a complex picture, which we attempt to explore and disentangle with reference to the inconsistency across self-processing studies in autism, highlighting implications for future research.

Preference for biological motion is reduced in ASD: implications for clinical trials and the search for biomarkers.

BACKGROUND: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology. METHODS: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL). RESULTS: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline. LIMITATIONS: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons. CONCLUSIONS: Biological motion preference elicits small-to-medium-sized case-control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear.

Maternal steroid levels and the autistic traits of the mother and infant.

BACKGROUND: Prenatal sex steroids have been associated with autism in several clinical and epidemiological studies. It is unclear how this relates to the autistic traits of the mother and how early this can be detected during pregnancy and postnatal development. METHODS: Maternal serum was collected from pregnant women (n = 122) before or during their first ultrasound appointment [mean = 12.7 (SD = 0.7) weeks]. Concentrations of the following were measured via immunoassays: testosterone, estradiol, dehydroepiandrosterone sulphate, progesterone; and sex hormone-binding globulin which was used to compute the free fractions of estradiol (FEI) and testosterone (FTI). Standardised human choriogonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) values were obtained from clinical records corresponding to the same serum samples. Mothers completed the Autism Spectrum Quotient (AQ) and for their infants, the Quantitative Checklist for Autism in Toddlers (Q-CHAT) when the infants were between 18 and 20 months old. RESULTS: FEI was positively associated with maternal autistic traits in univariate (n = 108, Pearson's r = 0.22, p = 0.019) and multiple regression models (semipartial r = 0.19, p = 0.048) controlling for maternal age and a diagnosis of PCOS. Maternal estradiol levels significantly interacted with fetal sex in predicting infant Q-CHAT scores, with a positive relationship in males but not females (n = 100, interaction term: semipartial r = 0.23, p = 0.036) after controlling for maternal AQ and other covariates. The opposite was found for standardised hCG values and Q-CHAT scores, with a positive association in females but not in males (n = 151, interaction term: r = -0.25, p = 0.005). LIMITATIONS: Sample size of this cohort was small, with potential ascertainment bias given elective recruitment. Clinical covariates were controlled in multiple regression models, but additional research is needed to confirm the statistically significant findings in larger cohorts. CONCLUSION: Maternal steroid factors during pregnancy are associated with autistic traits in mothers and their infants.

Links between self-injury and suicidality in autism.

BACKGROUND: Autistic individuals without intellectual disability are at heightened risk of self-injury, and appear to engage in it for similar reasons as non-autistic people. A wide divergence of autistic perspectives on self-injury, including those who frame it as a helpful coping mechanism, motivate investigating the link between self-injury, suicide ideation, and attempts which has been reported in typically developing individuals. METHOD: One hundred three autistic participants completed the Non-Suicidal Self-Injury Assessment Tool (NSSI-AT), the Suicide Behaviors Questionnaire (SBQ-R), and the Interpersonal Social Evaluation List (ISEL-12) across two online studies. Logistic regression was conducted to predict self-harming status via responses to questions on suicidality, and to predict whether certain self-injurious behaviors, including cutting, were especially associated with suicide ideation and attempts. Non-parametric correlation analysis examined relationships between suicide ideation/attempts and other variables that might characterize self-harmers especially at risk of suicidality. These included perceived access to social support, purposes or reasons for self-injury, the number of different self-injurious behaviors engaged in, the duration and lifetime incidence of self-injury, and the individual's feelings about their self-injury. RESULTS: While self-injuring status was significantly predicted by responses to a question on suicide ideation and attempts, there was no relationship between suicide ideation/attempts and a participant's personal feelings about their self-injury. The method of cutting was also predicted by suicide ideation and attempts, though other methods common in autistic people were at borderline significance. Use of self-injury for the regulation of low-energy emotional states like depression, for self-punishment or deterrence from suicide, and for sensory stimulation, was associated with suicide ideation and attempts, as was the number of self-injurious behaviors engaged in. There was no significant relationship between suicide ideation/attempts and the duration and lifetime incidence of self-injury or social support. CONCLUSIONS: These preliminary data suggest that while individuals might frame their self-injury as a positive or neutral thing, there remains a concerning relationship between self-injury and suicidality which exists regardless of individual feelings on self-injury. This is consistent with the theoretical perspective that self-injury can be a "gateway" through which individuals acquire capability for lethal suicidal behaviors. The data highlight that particular methods (cutting) and reasons for self-injury may be of significant concern, but this information, which might be of extreme value for clinicians, requires further investigation and validation.

A comparative study of autistic and non-autistic women's experience of motherhood.

Background: Autism is a lifelong neurodevelopmental difference and disability, yet there is limited research examining parenting in autistic mothers. Objective: To explore autistic mothers' experience of the perinatal period and parenthood. This includes pregnancy, childbirth, the postpartum period, self-perception of parenting strengths and weaknesses, communication with professionals in relation to one's child, mental health difficulties and the social experience of motherhood. It also includes disclosing one's diagnosis of autism in parenting contexts. Methods: We used a community-based participatory research model, and recruited an advisory panel, with whom we co-developed an anonymous, online survey for autistic mothers. The online survey was completed by autistic and non-autistic mothers, and we compared their responses using Chi-squared analysis. Sample: Autistic mothers (n = 355), and non-autistic mothers (n = 132), each of whom had at least one autistic child, were included in our final analysis. Results: There were differences in education, gender identity and age of mother at birth of first child. Autistic mothers were more likely to have experienced additional psychiatric conditions, including pre- or post-partum depression, and reported greater difficulties in areas such as multi-tasking, coping with domestic responsibilities and creating social opportunities for their child. They were also more likely to report feeling misunderstood by professionals, and reported greater anxiety, higher rates of selective mutism, and not knowing which details were appropriate to share with professionals. They were also more likely to find motherhood an isolating experience, to worry about others judging their parenting, or feel unable to turn to others for support in parenting. However, despite these challenges, autistic mothers were able to act in the best interest of their child, putting their child's needs first. Conclusions: Autistic mothers face unique challenges and the stigma associated with autism may further exacerbate communication difficulties. Greater understanding and acceptance amongst individuals who interact with autistic mothers is needed, and autistic mothers would benefit from additional and better-tailored support.

Autistic traits, resting-state connectivity, and absolute pitch in professional musicians: shared and distinct neural features.

Background: Recent studies indicate increased autistic traits in musicians with absolute pitch and a higher proportion of absolute pitch in people with autism. Theoretical accounts connect both of these with shared neural principles of local hyper- and global hypoconnectivity, enhanced perceptual functioning, and a detail-focused cognitive style. This is the first study to investigate absolute pitch proficiency, autistic traits, and brain correlates in the same study. Sample and methods: Graph theoretical analysis was conducted on resting-state (eyes closed and eyes open) EEG connectivity (wPLI, weighted phase lag index) matrices obtained from 31 absolute pitch (AP) and 33 relative pitch (RP) professional musicians. Small-worldness, global clustering coefficient, and average path length were related to autistic traits, passive (tone identification) and active (pitch adjustment) absolute pitch proficiency, and onset of musical training using Welch two-sample tests, correlations, and general linear models. Results: Analyses revealed increased path length (delta 2-4 Hz), reduced clustering (beta 13-18 Hz), reduced small-worldness (gamma 30-60 Hz), and increased autistic traits for AP compared to RP. Only clustering values (beta 13-18 Hz) were predicted by both AP proficiency and autistic traits. Post hoc single connection permutation tests among raw wPLI matrices in the beta band (13-18 Hz) revealed widely reduced interhemispheric connectivity between bilateral auditory-related electrode positions along with higher connectivity between F7-F8 and F8-P9 for AP. Pitch-naming ability and pitch adjustment ability were predicted by path length, clustering, autistic traits, and onset of musical training (for pitch adjustment) explaining 44% and 38% of variance, respectively. Conclusions: Results show both shared and distinct neural features between AP and autistic traits. Differences in the beta range were associated with higher autistic traits in the same population. In general, AP musicians exhibit a widely underconnected brain with reduced functional integration and reduced small-world property during resting state. This might be partly related to autism-specific brain connectivity, while differences in path length and small-worldness reflect other ability-specific influences. This is further evidenced for different pathways in the acquisition and development of absolute pitch, likely influenced by both genetic and environmental factors and their interaction.

A 'choice', an 'addiction', a way 'out of the lost': exploring self-injury in autistic people without intellectual disability.

Background: Non-suicidal self-injury (NSSI) describes a phenomenon where individuals inflict deliberate pain and tissue damage to their bodies. Self-injurious behaviour is especially prevalent across the autism spectrum, but little is understood about the features and functions of self-injury for autistic individuals without intellectual disability, or about the risk factors that might be valuable for clinical usage in this group. Methods: One hundred and three autistic adults who responded to an online advertisement were classified as current, historic or non-self-harmers in accordance with responses to the Non-Suicidal Self-Injury Assessment Tool (NSSI-AT). Multinomial regression aimed to predict categorisation of participants in accordance with scores on tests of autistic traits, alexithymia, depression, anxiety, mentalising and sensory sensitivity. Linear regression examined relationships between these predictors and the range, frequency, lifetime occurrence and functional purposes of NSSI. Qualitative analysis explored the therapeutic interventions that participants had found helpful, and what they wished people understood about self-injury. Results: Current, historic and non-self-harming participants did not differ in age, age at diagnosis, male-to-female ratio, level of employment or education (the majority qualified to at least degree level). The most common function of NSSI was the regulation of low-energy affective states (depression, dissociation), followed by the regulation of high-energy states such as anger and anxiety. Alexithymia significantly predicted the categorisation of participants as current, historic or non-self-harmers, and predicted use of NSSI for regulating high-energy states and communicating distress to others. Depression, anxiety and sensory-sensitivity also differentiated participant groups, and sensory differences also predicted the range of bodily areas targeted, lifetime incidence and frequency of NSSI. Sensory differences, difficulty expressing and identifying emotions also emerged as problematic in the qualitative analysis, where participants expressed the need for compassion, patience, non-judgement and the need to recognise diversity between self-harmers, with some participants perceiving NSSI as a practical, non-problematic coping strategy. Conclusions: Alexithymia, depression, anxiety and sensory differences may place some autistic individuals at especial risk of self-injury. Investigating the involvement of these variables and their utility for identification and treatment is of high importance, and the voices of participants offer guidance to practitioners confronted with NSSI in their autistic clients.

Child, Maternal and Demographic Factors Influencing Caregiver-Reported Autistic Trait Symptomatology in Toddlers.

Current research on children's autistic traits in the general population relies predominantly on caregiver-report, yet the extent to which individual, caregiver or demographic characteristics are associated with informants' ratings has not been sufficiently explored. In this study, caregivers of 396 Singaporean two-year-olds from a birth cohort study completed the Quantitative Checklist for Autism in Toddlers. Children's gender, cognitive functioning and birth order, maternal age, and ethnic group membership were not significant predictors of caregiver-reported autistic traits. Poorer child language development and higher maternal depressive symptoms significantly predicted more social-communicative autistic traits, while lower maternal education predicted more behavioural autistic traits. Children's language and informants' educational level and depressive symptomatology may need to be considered in caregiver-reports of autistic traits.

Understanding the role of steroids in typical and atypical brain development: Advantages of using a "brain in a dish" approach.

Steroids have an important role in growth, development, sexual differentiation and reproduction. All four classes of steroids, androgens, oestrogens, progestogens and glucocorticoids, have varying effects on the brain. Androgens and oestrogens are involved in the sexual differentiation of the brain, and also influence cognition. Progestogens such as progesterone and its metabolites have been shown to be involved in neuroprotection, although their protective effects are timing-dependent. Glucocorticoids are linked with stress and memory performance, also in a dose- and time-dependent manner. Importantly, dysfunction in steroid function has been implicated in the pathogenesis of disease. Moreover, regulating steroid-signalling has been suggested as potential therapeutic avenue for the treatment of a number of neurodevelopmental, psychiatric and neurodegenerative disorders. Therefore, clarifying the role of steroids in typical and atypical brain function is essential for understanding typical brain functions, as well as determining their potential use for pharmacological intervention in the atypical brain. However, the majority of studies have thus far have been conducted using animal models, with limited work using native human tissue or cells. Here, we review the effect of steroids in the typical and atypical brain, focusing on the cellular, molecular functions of these molecules determined from animal models, and the therapeutic potential as highlighted by human studies. We further discuss the promise of human-induced pluripotent stem cells, including advantages of using three-dimensional neuronal cultures (organoids) in high-throughput screens, in accelerating our understanding of the role of steroids in the typical brain, and also with respect to their therapeutic value in the understanding and treatment of the atypical brain.

Genome-wide meta-analysis of cognitive empathy: heritability, and correlates with sex, neuropsychiatric conditions and cognition.

We conducted a genome-wide meta-analysis of cognitive empathy using the 'Reading the Mind in the Eyes' Test (Eyes Test) in 88,056 research volunteers of European Ancestry (44,574 females and 43,482 males) from 23andMe Inc., and an additional 1497 research volunteers of European Ancestry (891 females and 606 males) from the Brisbane Longitudinal Twin Study. We confirmed a female advantage on the Eyes Test (Cohen's d=0.21, P<2.2 × 10-16), and identified a locus in 3p26.1 that is associated with scores on the Eyes Test in females (rs7641347, Pmeta=1.58 × 10-8). Common single nucleotide polymorphisms explained 5.8% (95% CI: 4.5%-7.2%; P=1.00 × 10-17) of the total trait variance in both sexes, and we identified a twin heritability of 28% (95% CI: 13%-42%). Finally, we identified significant genetic correlation between the Eyes Test and anorexia nervosa, openness (NEO-Five Factor Inventory), and different measures of educational attainment and cognitive aptitude.

Structural Covariance Networks in Children with Autism or ADHD.

Background: While autism and attention-deficit/hyperactivity disorder (ADHD) are considered distinct conditions from a diagnostic perspective, clinically they share some phenotypic features and have high comorbidity. Regardless, most studies have focused on only one condition, with considerable heterogeneity in their results. Taking a dual-condition approach might help elucidate shared and distinct neural characteristics. Method: Graph theory was used to analyse topological properties of structural covariance networks across both conditions and relative to a neurotypical (NT; n = 87) group using data from the ABIDE (autism; n = 62) and ADHD-200 datasets (ADHD; n = 69). Regional cortical thickness was used to construct the structural covariance networks. This was analysed in a theoretical framework examining potential differences in long and short-range connectivity, with a specific focus on relation between central graph measures and cortical thickness. Results: We found convergence between autism and ADHD, where both conditions show an overall decrease in CT covariance with increased Euclidean distance between centroids compared with a NT population. The 2 conditions also show divergence. Namely, there is less modular overlap between the 2 conditions than there is between each condition and the NT group. The ADHD group also showed reduced cortical thickness and lower degree in hub regions than the autism group. Lastly, the ADHD group also showed reduced wiring costs compared with the autism groups. Conclusions: Our results indicate a need for taking an integrated approach when considering highly comorbid conditions such as autism and ADHD. Furthermore, autism and ADHD both showed alterations in the relation between inter-regional covariance and centroid distance, where both groups show a steeper decline in covariance as a function of distance. The 2 groups also diverge on modular organization, cortical thickness of hub regions and wiring cost of the covariance network. Thus, on some network features the groups are distinct, yet on others there is convergence.

Sex differences in frontal lobe connectivity in adults with autism spectrum conditions.

Autism spectrum conditions (ASC) are more prevalent in males than females. The biological basis of this difference remains unclear. It has been postulated that one of the primary causes of ASC is a partial disconnection of the frontal lobe from higher-order association areas during development (that is, a frontal 'disconnection syndrome'). Therefore, in the current study we investigated whether frontal connectivity differs between males and females with ASC. We recruited 98 adults with a confirmed high-functioning ASC diagnosis (61 males: aged 18-41 years; 37 females: aged 18-37 years) and 115 neurotypical controls (61 males: aged 18-45 years; 54 females: aged 18-52 years). Current ASC symptoms were evaluated using the Autism Diagnostic Observation Schedule (ADOS). Diffusion tensor imaging was performed and fractional anisotropy (FA) maps were created. Mean FA values were determined for five frontal fiber bundles and two non-frontal fiber tracts. Between-group differences in mean tract FA, as well as sex-by-diagnosis interactions were assessed. Additional analyses including ADOS scores informed us on the influence of current ASC symptom severity on frontal connectivity. We found that males with ASC had higher scores of current symptom severity than females, and had significantly lower mean FA values for all but one tract compared to controls. No differences were found between females with or without ASC. Significant sex-by-diagnosis effects were limited to the frontal tracts. Taking current ASC symptom severity scores into account did not alter the findings, although the observed power for these analyses varied. We suggest these findings of frontal connectivity abnormalities in males with ASC, but not in females with ASC, have the potential to inform us on some of the sex differences reported in the behavioral phenotype of ASC.

Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women.

Oxytocin may influence various human behaviors and the connectivity across subcortical and cortical networks. Previous oxytocin studies are male biased and often constrained by task-based inferences. Here, we investigate the impact of oxytocin on resting-state connectivity between subcortical and cortical networks in women. We collected resting-state functional magnetic resonance imaging (fMRI) data on 26 typically developing women 40 min following intranasal oxytocin administration using a double-blind placebo-controlled crossover design. Independent components analysis (ICA) was applied to examine connectivity between networks. An independent analysis of oxytocin receptor (OXTR) gene expression in human subcortical and cortical areas was carried out to determine plausibility of direct oxytocin effects on OXTR. In women, OXTR was highly expressed in striatal and other subcortical regions, but showed modest expression in cortical areas. Oxytocin increased connectivity between corticostriatal circuitry typically involved in reward, emotion, social communication, language and pain processing. This effect was 1.39 standard deviations above the null effect of no difference between oxytocin and placebo. This oxytocin-related effect on corticostriatal connectivity covaried with autistic traits, such that oxytocin-related increase in connectivity was stronger in individuals with higher autistic traits. In sum, oxytocin strengthened corticostriatal connectivity in women, particularly with cortical networks that are involved in social-communicative, motivational and affective processes. This effect may be important for future work on neurological and psychiatric conditions (for example, autism), particularly through highlighting how oxytocin may operate differently for subsets of individuals.