Papers by Simon Baron-Cohen
With autistic people at increased risk of dying by suicide, understanding barriers to help-seekin... more With autistic people at increased risk of dying by suicide, understanding barriers to help-seeking is crucial for suicide prevention efforts. Using an online survey designed in consultation with autistic people, we examined reasons why autistic adults living in the United Kingdom did not seek help from the National Health Service (NHS) when they last experienced suicidal thoughts or behaviours. Participants who disaffirmed help-seeking from the NHS (n = 754) were able to select from a prepopulated list of 20 reasons why and to enter their own. The three most commonly endorsed reasons were 'I tried to cope and manage my feelings by myself', 'I did not think they could help me' and 'The waiting list is too long -no point'. Endorsement of reasons differed significantly with gender identity, age group and degree of lifetime suicidality. Four themes emerged from analysis of free-form responses: NHS is ineffective, NHS as antagonistic, Fear and consequences and Barriers to access. These findings highlight the need to foster more flexible healthcare systems capable of supporting autistic people, and that autistic people view as trustworthy and effective, to enable help-seeking behaviours with the potential to save lives.
Molecular Autism, 2025
Background Sensory processing requires selectivity to salient sensory input. Many autistic indivi... more Background Sensory processing requires selectivity to salient sensory input. Many autistic individuals report different sensory processing, which has been associated with altered sensory selectivity. The locus-coeruleus norepinephrine (LC-NE) system modulates the neuronal gain of sensory input, which represents a neurophysiological mechanism of sensory selectivity. In autistic individuals, we hypothesized that LC-NE tonic upregulation reduces sensory selectivity and underlies different sensory processing. Methods Autistic (n = 139) and non-autistic (n = 98) individuals were assessed during a passive auditory oddball task with pupillometry and electroencephalography. For every trial, a baseline pupil size (BPS) assessed LC-NE tonic activity that coincides with current arousal, while a stimulus-evoked pupillary response (SEPR) assessed LC-NE phasic activity that estimated sensory selectivity. Electroencephalography assessed amplitudes of mismatch negativity (MMN-amp) that estimated pre-attentive change detection as a brain-activity readout of sensory selectivity. Measures were modeled between groups within the task by combining Frequentist and Bayesian approaches. Across groups, higher BPS was associated with more negative MMN-amp to standards and oddballs. A more negative MMN-amp to standards was associated with a higher SEPR to standards. Controlling for these associations, autistic versus non-autistic individuals showed a higher SEPR in response to standards. In addition, a positive association of BPS and SEPR to standards was specific to autistic individuals. With task progression, autistic versus non-autistic individuals showed a higher initial increase and subsequently steeper decrease of BPS. This was supported by Bayesian posterior distribution estimates. Limitations A short trial duration required concatenating trials to epochs and applying a linear-time invariant filter to capture the slow pupil changes. Without an LC-NE manipulation, we cannot rule out that pupil changes are evoked by other cortical pathways than the LC-NE.
Communications Biology, 2025
We explore neurodevelopmental heterogeneity in Autism Spectrum Disorder (ASD) through normative m... more We explore neurodevelopmental heterogeneity in Autism Spectrum Disorder (ASD) through normative modeling of cross-cultural cohorts. By leveraging large-scale datasets from Autism Brain Imaging Data Exchange (ABIDE) and China Autism Brain Imaging Consortium (CABIC), our model identifies two ASD subgroups with distinct brain morphological abnormalities: subgroup "L" is characterized by generally smaller brain region volumes and higher rates of abnormality, while subgroup "H" exhibits larger volumes with less pronounced deviations in specific areas. Key areas, such as the isthmus cingulate and transverse temporal gyrus, were identified as critical for subgroup differentiation and ASD trait correlations. In subgroup H, the regional volume of the isthmus cingulate cortex showed a direct correlation with individuals' autistic mannerisms, potentially corresponding to its slower postpeak volumetric declines during development. These findings offer insights into the biological mechanisms underlying ASD and support the advancement of subgroup-driven precision clinical practices.
Cognitive Neuroscience and Neuroimaging, 2025
BACKGROUND: Neurodevelopmental conditions, such as autism, are highly heterogeneous at both the m... more BACKGROUND: Neurodevelopmental conditions, such as autism, are highly heterogeneous at both the mechanistic and phenotypic levels. Therefore, parsing heterogeneity is vital for uncovering underlying processes that could inform the development of targeted, personalized support. We aimed to parse heterogeneity in autism by identifying subgroups that converge at both the phenotypic and molecular levels. METHODS: An imaging transcriptomics approach was used to link neuroanatomical imaging-derived phenotypes in autism to whole-brain gene expression signatures provided by the Allen Human Brain Atlas. Neuroimaging and clinical data of 359 autistic participants ages 6 to 30 years were provided by EU-AIMS (European Autism Interventions) LEAP (Longitudinal European Autism Project). Individuals were stratified using data-driven clustering techniques based on the correlation between brain phenotypes and transcriptomic profiles. The resulting subgroups were characterized on the clinical, neuroanatomical, and molecular levels. RESULTS: We identified 3 subgroups of autistic individuals based on the correlation between imaging-derived phenotypes and transcriptomic profiles that showed different clinical phenotypes. The individuals with the strongest transcriptomic associations with imaging-derived phenotypes showed the lowest level of symptom severity. The gene sets most characteristic for each subgroup were significantly enriched for genes previously implicated in autism etiology, including processes such as synaptic transmission and neuronal communication, and mapped onto different gene ontology categories. CONCLUSIONS: Autistic individuals can be subgrouped based on the transcriptomic signatures associated with their neuroanatomical fingerprints, which reveal subgroups that show differences in clinical measures. The study presents an analytical framework for linking neurodevelopmental and clinical diversity in autism to underlying molecular mechanisms, thus highlighting the need for personalized support strategies.
Autism, Sep 2, 2022
The Autism-Spectrum Quotient is a self-report scale, used to assess autistic traits. It was teste... more The Autism-Spectrum Quotient is a self-report scale, used to assess autistic traits. It was tested cross-culturally, and a short version was created to clinically refer adults for an autism assessment. This study aimed to examine the properties of the Hebrew version of the Autism-Spectrum Quotient and to create a short version suitable for Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Ninety-three clinically diagnosed autistic adults (24 females) aged 18-53, and 147 comparable controls (34 females) completed the Hebrew version of the Autism-Spectrum Quotient. Ten clinicians specializing in diagnosing autism in adults classified the Autism-Spectrum Quotient's items according to Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria. The Hebrew version of the Autism-Spectrum Quotient showed good internal consistency (Kuder-Richardson 20 = 0.90). Based on the prevalence of autism among clinically referred adults (70%), receiver operating characteristic analysis yielded area under the curve of 0.94. A cutoff of 21 demonstrated high sensitivity (0.90), specificity (0.76), positive predictive value (0.90), and negative predictive value (0.77). The short version of the Hebrew Autism-Spectrum Quotient included five social communication and five restricted, repetitive behavior items, which represented two social communication and two restricted, repetitive behavior criteria of Diagnostic and Statistical Manual of Mental Disorders (5th ed.). It showed good internal consistency (Kuder-Richardson 20 = 0.86), and receiver operating characteristic analysis yielded area under the curve of 0.95. An optimal clinical cutoff of five showed high sensitivity (0.90), specificity (0.82), positive predictive value (0.92), and negative predictive value (0.78). The Hebrew version of the Autism-Spectrum Quotient and the short version of the Hebrew Autism-Spectrum Quotient can be effectively used to help screen for autism in clinically referred adults.
Molecular Autism
Background Many empirical studies suggest that higher maternal age increases the likelihood of ha... more Background Many empirical studies suggest that higher maternal age increases the likelihood of having an autistic child. However, little is known about factors that may explain this relationship or if higher maternal age is related to the number of autistic-like traits in offspring. One possibility is that mothers who have a higher number of autistic-like traits, including greater challenges performing mentalizing skills, are delayed in finding a partner. The goal of our study is to assess the relationship between maternal age, mentalizing skills and autistic-like traits as independent predictors of the number of autistic-like traits in offspring. Methods In a population-based study in the Netherlands, information on maternal age was collected during pre- and perinatal enrolment. Maternal mentalizing skills and autistic-like traits were assessed using the Reading the Mind in the Eyes Test and the Autism Spectrum Quotient, respectively. Autistic-like traits in children were assessed ...
Psychoneuroendocrinology, 2021
Prenatal testosterone (pT) is a crucial component in physiological masculinization in humans. In ... more Prenatal testosterone (pT) is a crucial component in physiological masculinization in humans. In line with the Prenatal Sex Steroid Theory of autism, some studies have found a positive correlation between pT and autistic traits in childhood. However, effects in adolescence have not been explored. Hormonal and environmental changes occurring during puberty may alter the strength or the nature of prenatal effects on autistic traits. The current study examines if pT relates to autistic traits in a non-clinical sample of adolescents and young adults (N = 97, 170 observations; age 13-21 years old). It also explores pT interactions with pubertal stage and timing. PT concentrations were measured from amniotic fluid extracted in the 2nd trimester of gestation via amniocentesis conducted for clinical purposes. Autistic traits were measured by self-and parent-reports on the Autism Spectrum Quotient (AQ) which provides a total score and 5 sub-scores (social skills, communication, imagination, attention switching and attention to detail). Self-reported pubertal stage was regressed on age to provide a measure of relative timing. We found no statistical evidence for a direct association between pT and autistic traits in this adolescent sample (males, females or full sample). Exploratory analyses suggested that pT correlated positively with autistic traits in adolescents with earlier puberty-onset, but statistical robustness of this finding was limited. Further exploratory post-hoc tests suggested the pT-by-pubertal timing interaction was stronger in males relative to females, in self-reported compared to parent-reported AQ and specifically for social traits. These findings require replication in larger samples. Findings have implications for understanding the effects of pT on human behavior, specifically existence of effects in adolescence.
Improving the recognition of autism in children and adults Allison C, Baron-Cohen S. Improving th... more Improving the recognition of autism in children and adults Allison C, Baron-Cohen S. Improving the recognition of autism in children and adults.
Molecular Autism, 2020
Background Autistic individuals without intellectual disability are at heightened risk of self-in... more 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 suici...
The core diagnostic criteria for autism comprise two symptom domains – social and communication d... more The core diagnostic criteria for autism comprise two symptom domains – social and communication difficulties, and unusually repetitive and restricted behaviour, interests and activities. There is some evidence to suggest that these two domains are dissociable, yet, this hypothesis has not been tested using molecular genetics. We test this using a GWAS of a non-social autistic trait, systemizing (N = 51,564), defined as the drive to analyse and build systems. We demonstrate that systemizing is heritable and genetically correlated with autism. In contrast, we do not identify significant genetic correlations between social autistic traits and systemizing. Supporting this, polygenic scores for systemizing are significantly positively associated with restricted and repetitive behaviour but not with social difficulties in autistic individuals. These findings strongly suggest that the two core domains of autism are genetically dissociable, and point at how to fractionate the genetics of au...
Molecular Autism, 2019
Background: Non-suicidal self-injury (NSSI) describes a phenomenon where individuals inflict deli... more 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.
Molecular Autism, 2019
Background: Autism is a highly varied and heritable neurodevelopmental condition, and common vari... more Background: Autism is a highly varied and heritable neurodevelopmental condition, and common variants explain approximately 50% of the genetic variance of autism. One of the genes implicated in autism is the oxytocin receptor (OXTR). The current study combined genetic and brain imaging (fMRI) data to examine the moderating effect of genotype on the association between diagnosis and brain activity in response to a test of cognitive empathy. Methods: Participants were adolescents (mean age = 14.7 ± 1.7) who were genotyped for single nucleotide polymorphisms (SNPs) within the OXTR and underwent functional brain imaging while completing the adolescent version of the 'Reading the Mind in the Eyes' Test (Eyes Test). Results: Two (rs2254298, rs53576) of the five OXTR SNPs examined were significantly associated with brain activity during the Eyes Test, and three of the SNPs (rs2254298, rs53576, rs2268491) interacted with diagnostic status to predict brain activity. All of the effects localized to the right supramarginal gyrus (rSMG) and an overlap analysis revealed a large overlap of the effects. An exploratory analysis showed that activity within an anatomically defined rSMG and genotype can predict diagnostic status with reasonable accuracy. Conclusions: This is one of the first studies to investigate OXTR and brain function in autism. The findings suggest a neurogenetic mechanism by which OXTR-dependent activity within the rSMG is related to the aetiology of autism. 
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Papers by Simon Baron-Cohen