Clinical, socio-demographic, and parental correlates of early autism traits in a community cohort of toddlers.

Identifying factors linked to autism traits in the general population may improve our understanding of the mechanisms underlying divergent neurodevelopment. In this study we assess whether factors increasing the likelihood of childhood autism are related to early autistic trait emergence, or if other exposures are more important. We used data from 536 toddlers from London (UK), collected at birth (gestational age at birth, sex, maternal body mass index, age, parental education, parental language, parental history of neurodevelopmental conditions) and at 18 months (parents cohabiting, measures of socio-economic deprivation, measures of maternal parenting style, and a measure of maternal depression). Autism traits were assessed using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) at 18 months. A multivariable model explained 20% of Q-CHAT variance, with four individually significant variables (two measures of parenting style and two measures of socio-economic deprivation). In order to address variable collinearity we used principal component analysis, finding that a component which was positively correlated with Q-CHAT was also correlated to measures of parenting style and socio-economic deprivation. Our results show that parenting style and socio-economic deprivation correlate with the emergence of autism traits at age 18 months as measured with the Q-CHAT in a community sample.

The 'PSILAUT' protocol: an experimental medicine study of autistic differences in the function of brain serotonin targets of psilocybin.

BACKGROUND: The underlying neurobiology of the complex autism phenotype remains obscure, although accumulating evidence implicates the serotonin system and especially the 5HT2A receptor. However, previous research has largely relied upon association or correlation studies to link differences in serotonin targets to autism. To directly establish that serotonergic signalling is involved in a candidate brain function our approach is to change it and observe a shift in that function. We will use psilocybin as a pharmacological probe of the serotonin system in vivo. We will directly test the hypothesis that serotonergic targets of psilocybin - principally, but not exclusively, 5HT2A receptor pathways-function differently in autistic and non-autistic adults. METHODS: The 'PSILAUT' "shiftability" study is a case-control study autistic and non-autistic adults. How neural responses 'shift' in response to low doses (2 mg and 5 mg) of psilocybin compared to placebo will be examined using multimodal techniques including functional MRI and EEG. Each participant will attend on up to three separate visits with drug or placebo administration in a double-blind and randomized order. RESULTS: This study will provide the first direct evidence that the serotonin targets of psilocybin function differently in the autistic and non-autistic brain. We will also examine individual differences in serotonin system function. CONCLUSIONS: This work will inform our understanding of the neurobiology of autism as well as decisions about future clinical trials of psilocybin and/or related compounds including stratification approaches. TRIAL REGISTRATION: NCT05651126.

Retinal GABAergic Alterations in Adults with Autism Spectrum Disorder.

Alterations in γ-aminobutyric acid (GABA) have been implicated in sensory differences in individuals with autism spectrum disorder (ASD). Visual signals are initially processed in the retina, and in this study, we explored the hypotheses that the GABA-dependent retinal response to light is altered in individuals with ASD. Light-adapted electroretinograms were recorded from 61 adults (38 males and 23 females; n = 22 ASD) in response to three stimulus protocols: (1) the standard white flash, (2) the standard 30 Hz flickering protocol, and (3) the photopic negative response protocol. Participants were administered an oral dose of placebo, 15 or 30 mg of arbaclofen (STX209, GABAB agonist) in a randomized, double-blind, crossover order before the test. At baseline (placebo), the a-wave amplitudes in response to single white flashes were more prominent in ASD, relative to typically developed (TD) participants. Arbaclofen was associated with a decrease in the a-wave amplitude in ASD, but an increase in TD, eliminating the group difference observed at baseline. The extent of this arbaclofen-elicited shift significantly correlated with the arbaclofen-elicited shift in cortical responses to auditory stimuli as measured by using an electroencephalogram in our prior study and with broader autistic traits measured with the autism quotient across the whole cohort. Hence, GABA-dependent differences in retinal light processing in ASD appear to be an accessible component of a wider autistic difference in the central processing of sensory information, which may be upstream of more complex autistic phenotypes.

Neonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment.

Brain dynamic functional connectivity characterises transient connections between brain regions. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n = 324) and preterm-born (n = 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age.

Editorial Perspective: Bridging the translational neuroscience gap in autism - development of the 'shiftability' paradigm.

Clinical trials of pharmacological candidates targeting the core features of autism have largely failed. This is despite evidence linking differences in multiple neurochemical systems to brain function in autism. While this has in part been explained by the heterogeneity of the autistic population, the field has largely relied upon association studies to link brain chemistry to function. The only way to directly establish that a neurotransmitter or neuromodulator is involved in a candidate brain function is to change it and observe a shift in that function. This experimental approach dominates preclinical neuroscience, but not human studies. There is little direct experimental evidence describing how neurochemical systems modulate information processing in the living human brain. Thus, our understanding of how neurochemical differences contribute to neurodiversity is limited, impeding our ability to translate findings from animal studies into humans. Here, we introduce our 'shiftability' paradigm, an approach to bridge the translational gap in autism research. We provide an overview of the guiding principles and methodologies we use to directly test the hypothesis that neurochemical systems function differently in autistic and non-autistic individuals.

Genetic relationship between the immune system and autism.

Autism spectrum disorder (ASD) is a common and complex neurodevelopmental condition. The pathophysiology of ASD is poorly defined; however, it includes a strong genetic component and there is increasing evidence to support a role of immune dysregulation. Nonetheless, it is unclear which immune phenotypes link to ASD through genetics. Hence, we investigated the genetic correlation between ASD and diverse classes of immune conditions and markers; and if these immune-related genetic factors link to specific autistic-like traits in the population. We estimated global and local genetic correlations between ASD (n = 55,420) and 11 immune phenotypes (n = 14,256-755,406) using genome-wide association study summary statistics. Subsequently, polygenic scores (PGS) for these immune phenotypes were calculated in a population-based sample (n = 2487) and associated to five autistic-like traits (i.e., attention to detail, childhood behaviour, imagination, rigidity, social skills), and a total autistic-like traits score. Sex-stratified PGS analyses were also performed. At the genome-wide level, ASD was positively correlated with allergic diseases (ALG), and negatively correlated with lymphocyte count, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) (FDR-p = 0.01-0.02). At the local genetic level, ASD was correlated with RA, C-reactive protein, and granulocytes and lymphocyte counts (p = 5.8 × 10-6-0.002). In the general population sample, increased genetic liability for SLE, RA, ALG, and lymphocyte levels, captured by PGS, was associated with the total autistic score and with rigidity and childhood behaviour (FDR-p = 0.03). In conclusion, we demonstrated a genetic relationship between ASD and immunity that depends on the type of immune phenotype considered; some increase likelihood whereas others may potentially help build resilience. Also, this relationship may be restricted to specific genetic loci and link to specific autistic dimensions (e.g., rigidity).

Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder.

Altered reactivity and responses to auditory input are core to the diagnosis of autism spectrum disorder (ASD). Preclinical models implicate ϒ-aminobutyric acid (GABA) in this process. However, the link between GABA and auditory processing in humans (with or without ASD) is largely correlational. As part of a study of potential biosignatures of GABA function in ASD to inform future clinical trials, we evaluated the role of GABA in auditory repetition suppression in 66 adults (n = 28 with ASD). Neurophysiological responses (temporal and frequency domains) to repetitive standard tones and novel deviants presented in an oddball paradigm were compared after double-blind, randomized administration of placebo, 15 or 30 mg of arbaclofen (STX209), a GABA type B (GABAB) receptor agonist. We first established that temporal mismatch negativity was comparable between participants with ASD and those with typical development (TD). Next, we showed that temporal and spectral responses to repetitive standards were suppressed relative to responses to deviants in the two groups, but suppression was significantly weaker in individuals with ASD at baseline. Arbaclofen reversed weaker suppression of spectral responses in ASD but disrupted suppression in TD. A post hoc analysis showed that arbaclofen-elicited shift in suppression was correlated with autistic symptomatology measured using the Autism Quotient across the entire group, though not in the smaller sample of the ASD and TD group when examined separately. Thus, our results confirm: GABAergic dysfunction contributes to the neurophysiology of auditory sensory processing alterations in ASD, and can be modulated by targeting GABAB activity. These GABA-dependent sensory differences may be upstream of more complex autistic phenotypes.

Immunogenetics of autism spectrum disorder: A systematic literature review.

The aetiology of autism spectrum disorder (ASD) is complex and, partly, accounted by genetic factors. Nonetheless, the genetic underpinnings of ASD are poorly defined. The presence of immune dysregulations in autistic individuals, and their families, supports a role of the immune system and its genetic regulators. Albeit immune responses belong either to the innate or adaptive arms, the overall immune system genetics is broad, and encompasses a multitude of functionally heterogenous pathways which may have different influences on ASD. Hence, to gain insights on the immunogenetic underpinnings of ASD, we conducted a systematic literature review of previous immune genetic and transcription studies in ASD. We defined a list of immune genes relevant to ASD and explored their neuro-immune function. Our review confirms the presence of immunogenetic variability in ASD, accounted by inherited variations of innate and adaptive immune system genes and genetic expression changes in the blood and post-mortem brain of autistic individuals. Besides their immune function, the identified genes control neurodevelopment processes (neuronal and synaptic plasticity) and are highly expressed in pre/peri-natal periods. Hence, our synthesis bolsters the hypothesis that perturbation in immune genes may contribute to ASD by derailing the typical trajectory of neurodevelopment. Our review also helped identifying some of the limitations of prior immunogenetic research in ASD. Thus, alongside clarifying the neurodevelopment role of immune genes, we outline key considerations for future work into the aetiology of ASD and possible novel intervention targets.

Bridge-building between communities: Imagining the future of biomedical autism research.

A paradigm shift in research culture is required to ease perceived tensions between autistic people and the biomedical research community. As a group of autistic and non-autistic scientists and stakeholders, we contend that through participatory research, we can reject a deficit-based conceptualization of autism while building a shared vision for a neurodiversity-affirmative biomedical research paradigm.

Comparison of an online adaptation of the Autism Diagnostic Observation Schedule-2 with its in-person version in an adult autism diagnostic service.

BACKGROUND: Restrictions on in-person assessments during the COVID-19 pandemic were a challenge for an adult autism diagnostic service receiving over 600 referrals annually. The service sought to adapt the Autism Diagnostic Observation Schedule (ADOS-2) for online administration. AIMS: To investigate whether an online adaptation of the ADOS-2 performed comparably to the in-person ADOS-2. To obtain qualitative feedback from patients and clinicians regarding experiences of the online alternative. METHOD: Online ADOS-2 assessments were completed for 163 referred individuals. A matched-comparison group comprised 198 individuals seen for an in-person ADOS-2 assessment prior to COVID-19 restrictions. A two-way analysis of variance (ANOVA) was run to explore any effect of assessment type (online or in-person ADOS-2) and gender on total ADOS score. Qualitative feedback was collected from 46 patients and 8 clinicians involved in diagnostic decision-making after the online ADOS-2 assessment. RESULTS: A two-way ANOVA found no significant effect of assessment type or gender and no assessment type × gender interaction effect on total ADOS score. Qualitative feedback suggested that only 27% of patients would have preferred an in-person assessment. Nearly all clinicians reported gains from offering an online alternative. CONCLUSIONS: This is the first study to examine an online adaptation of ADOS-2 within an adult autism diagnostic service. It performed comparably to the in-person ADOS-2, making it a viable alternative when in-person assessments are not possible. As this clinic group has high rates of comorbid mental health difficulties, we encourage further work to determine whether online assessment approaches generalise to other services to increase options for patients and efficiencies for service delivery.

Development of neonatal brain functional centrality and alterations associated with preterm birth.

Formation of the functional connectome in early life underpins future learning and behavior. However, our understanding of how the functional organization of brain regions into interconnected hubs (centrality) matures in the early postnatal period is limited, especially in response to factors associated with adverse neurodevelopmental outcomes such as preterm birth. We characterized voxel-wise functional centrality (weighted degree) in 366 neonates from the Developing Human Connectome Project. We tested the hypothesis that functional centrality matures with age at scan in term-born babies and is disrupted by preterm birth. Finally, we asked whether neonatal functional centrality predicts general neurodevelopmental outcomes at 18 months. We report an age-related increase in functional centrality predominantly within visual regions and a decrease within the motor and auditory regions in term-born infants. Preterm-born infants scanned at term equivalent age had higher functional centrality predominantly within visual regions and lower measures in motor regions. Functional centrality was not related to outcome at 18 months old. Thus, preterm birth appears to affect functional centrality in regions undergoing substantial development during the perinatal period. Our work raises the question of whether these alterations are adaptive or disruptive and whether they predict neurodevelopmental characteristics that are more subtle or emerge later in life.

From mechanisms to markers: novel noninvasive EEG proxy markers of the neural excitation and inhibition system in humans.

Brain function is a product of the balance between excitatory and inhibitory (E/I) brain activity. Variation in the regulation of this activity is thought to give rise to normal variation in human traits, and disruptions are thought to potentially underlie a spectrum of neuropsychiatric conditions (e.g., Autism, Schizophrenia, Downs' Syndrome, intellectual disability). Hypotheses related to E/I dysfunction have the potential to provide cross-diagnostic explanations and to combine genetic and neurological evidence that exists within and between psychiatric conditions. However, the hypothesis has been difficult to test because: (1) it lacks specificity-an E/I dysfunction could pertain to any level in the neural system- neurotransmitters, single neurons/receptors, local networks of neurons, or global brain balance - most researchers do not define the level at which they are examining E/I function; (2) We lack validated methods for assessing E/I function at any of these neural levels in humans. As a result, it has not been possible to reliably or robustly test the E/I hypothesis of psychiatric disorders in a large cohort or longitudinal patient studies. Currently available, in vivo markers of E/I in humans either carry significant risks (e.g., deep brain electrode recordings or using Positron Emission Tomography (PET) with radioactive tracers) and/or are highly restrictive (e.g., limited spatial extent for Transcranial Magnetic Stimulation (TMS) and Magnetic Resonance Spectroscopy (MRS). More recently, a range of novel Electroencephalography (EEG) features has been described, which could serve as proxy markers for E/I at a given level of inference. Thus, in this perspective review, we survey the theories and experimental evidence underlying 6 novel EEG markers and their biological underpinnings at a specific neural level. These cheap-to-record and scalable proxy markers may offer clinical utility for identifying subgroups within and between diagnostic categories, thus directing more tailored sub-grouping and, therefore, treatment strategies. However, we argue that studies in clinical populations are premature. To maximize the potential of prospective EEG markers, we first need to understand the link between underlying E/I mechanisms and measurement techniques.

From bench to bedside: The mGluR5 system in people with and without Autism Spectrum Disorder and animal model systems.

The metabotropic glutamate receptor 5 (mGluR5) is a key regulator of excitatory (E) glutamate and inhibitory (I) γ-amino butyric acid (GABA) signalling in the brain. Despite the close functional ties between mGluR5 and E/I signalling, no-one has directly examined the relationship between mGluR5 and glutamate or GABA in vivo in the human brain of autistic individuals. We measured [18F] FPEB (18F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile) binding in 15 adults (6 with Autism Spectrum Disorder) using two regions of interest, the left dorsomedial prefrontal cortex and a region primarily composed of left striatum and thalamus. These two regions were mapped out using MEGA-PRESS voxels and then superimposed on reconstructed PET images. This allowed for direct comparison between mGluR5, GABA + and Glx. To better understand the molecular underpinnings of our results we used an autoradiography study of mGluR5 in three mouse models associated with ASD: Cntnap2 knockout, Shank3 knockout, and 16p11.2 deletion. Autistic individuals had significantly higher [18F] FPEB binding (t (13) = -2.86, p = 0.047) in the left striatum/thalamus region of interest as compared to controls. Within this region, there was a strong negative correlation between GABA + and mGluR5 density across the entire cohort (Pearson's correlation: r (14) = -0.763, p = 0.002). Cntnap2 KO mice had significantly higher mGlu5 receptor binding in the striatum (caudate-putamen) as compared to wild-type (WT) mice (n = 15, p = 0.03). There were no differences in mGluR5 binding for mice with the Shank3 knockout or 16p11.2 deletion. Given that Cntnap2 is associated with a specific striatal deficit of parvalbumin positive GABA interneurons and 'autistic' features, our findings suggest that an increase in mGluR5 in ASD may relate to GABAergic interneuron abnormalities.

The developing brain structural and functional connectome fingerprint.

In the mature brain, structural and functional 'fingerprints' of brain connectivity can be used to identify the uniqueness of an individual. However, whether the characteristics that make a given brain distinguishable from others already exist at birth remains unknown. Here, we used neuroimaging data from the developing Human Connectome Project (dHCP) of preterm born neonates who were scanned twice during the perinatal period to assess the developing brain fingerprint. We found that 62% of the participants could be identified based on the congruence of the later structural connectome to the initial connectivity matrix derived from the earlier timepoint. In contrast, similarity between functional connectomes of the same subject at different time points was low. Only 10% of the participants showed greater self-similarity in comparison to self-to-other-similarity for the functional connectome. These results suggest that structural connectivity is more stable in early life and can represent a potential connectome fingerprint of the individual: a relatively stable structural connectome appears to support a changing functional connectome at a time when neonates must rapidly acquire new skills to adapt to their new environment.

Cell line specific alterations in genes associated with dopamine metabolism and signaling in midbrain dopaminergic neurons derived from 22q11.2 deletion carriers with elevated dopamine synthesis capacity.

Microdeletions at the 22q11.2 locus are associated with increased risk for schizophrenia. Recent work has demonstrated that antipsychotic naïve 22q11.2 carriers display elevated levels of dopamine synthesis capacity (DSC) as assessed by 18F-DOPA PET imaging. While this is consistent with a role for abnormal dopamine function in schizophrenia, it is unclear what molecular changes may be associated with this neuro-imaging endophenotype, and moreover, if these alterations occur independently of clinical presentation. We therefore conducted a pilot study in which we generated human induced pluripotent stem cells (hiPSCs) from two 22q11.2 deletion carriers with elevated DSC in vivo, but distinct clinical presentations. From these and neurotypical control lines we were able to robustly generate midbrain dopaminergic neurons (mDA-neurons). We then assessed whether genes associated with dopamine synthesis, metabolism or signaling show altered expression between genotypes and further between the 22q11.2 deletion lines. Our data showed alterations in expression of genes associated with dopamine metabolism and signaling that differed between the two 22q11.2 hiPSC lines with distinct clinical presentations. This reinforces the importance of considering clinical, genetic and molecular information, when possible, when choosing which donors to generate hiPSCs from, to carry out mechanistic studies.

Attenuated transcriptional response to pro-inflammatory cytokines in schizophrenia hiPSC-derived neural progenitor cells.

Maternal immune activation (MIA) during prenatal development is an environmental risk factor for psychiatric disorders including schizophrenia (SZ). Converging lines of evidence from human and animal model studies suggest that elevated cytokine levels in the maternal and fetal compartments are an important indication of the mechanisms driving this association. However, there is variability in susceptibility to the psychiatric risk conferred by MIA, likely influenced by genetic factors. How MIA interacts with a genetic profile susceptible to SZ is challenging to test in animal models. To address this gap, we examined whether differential gene expression responses occur in forebrain-lineage neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (hiPSC) generated from three individuals with a diagnosis of schizophrenia and three healthy controls. Following acute (24 h) treatment with either interferon-gamma (IFNγ; 25 ng/µl) or interleukin (IL)-1ß (10 ng/µl), we identified, by RNA sequencing, 3380 differentially expressed genes (DEGs) in the IFNγ-treated control lines (compared to untreated controls), and 1980 DEGs in IFNγ-treated SZ lines (compared to untreated SZ lines). Out of 4137 genes that responded significantly to IFNγ across all lines, 1223 were common to both SZ and control lines. The 2914 genes that appeared to respond differentially to IFNγ treatment in SZ lines were subjected to a further test of significance (multiple testing correction applied to the interaction effect between IFNγ treatment and SZ diagnosis), yielding 359 genes that passed the significance threshold. There were no differentially expressed genes in the IL-1ß-treatment conditions after Benjamini-Hochberg correction. Gene set enrichment analysis however showed that IL-1ß impacts immune function and neuronal differentiation. Overall, our data suggest that a) SZ NPCs show an attenuated transcriptional response to IFNγ treatment compared to controls; b) Due to low IL-1ß receptor expression in NPCs, NPC cultures appear to be less responsive to IL-1ß than IFNγ; and c) the genes differentially regulated in SZ lines - in the face of a cytokine challenge - are primarily associated with mitochondrial, "loss-of-function", pre- and post-synaptic gene sets. Our findings particularly highlight the role of early synaptic development in the association between maternal immune activation and schizophrenia risk.

Differences in social brain function in autism spectrum disorder are linked to the serotonin transporter: A randomised placebo-controlled single-dose crossover trial.

BACKGROUND: Alterations in the serotonergic control of brain pathways responsible for facial emotion processing in people with autism spectrum disorder (ASD) may be a target for intervention. However, the molecular underpinnings of autistic-neurotypical serotonergic differences are challenging to access in vivo. Receptor-Enriched Analysis of functional Connectivity by Targets (REACT) has helped define molecular-enriched functional magnetic resonance imaging (fMRI) brain networks based on a priori information about the spatial distribution of neurochemical systems from available PET templates. METHODS: We used REACT to estimate the dominant fMRI signal related to the serotonin (5-HT) transporter (SERT) distribution during processing of aversive facial emotion in adults with and without ASD. We first predicted a group difference in baseline (placebo) functioning of this system. We next used a single 20 mg oral dose of citalopram, a serotonin reuptake inhibitor, to test the hypothesis that network activity in people with and without ASD would respond differently to inhibition of SERT. To confirm the specificity of our findings, we also repeated the analysis with 5-HT1A, 5-HT1B, 5-HT2A and 5-HT4 receptor maps. RESULTS: Using REACT with the SERT map, we found a baseline group difference in the SERT-enriched response to faces in the ventromedial prefrontal cortex. A single oral dose of citalopram 'shifted' the response in the ASD group towards the neurotypical baseline but did not alter response in the control group. Similar differences in SERT-enriched response were observed after controlling for other 5-HT maps. CONCLUSIONS: Our findings suggest that the SERT-enriched functional network is dynamically different in ASD during processing of socially relevant stimuli. Whether this acute neurobiological response to citalopram in ASD translates to a clinical target will be an important next step.

Neonatal multi-modal cortical profiles predict 18-month developmental outcomes.

Developmental delays in infanthood often persist, turning into life-long difficulties, and coming at great cost for the individual and community. By examining the developing brain and its relation to developmental outcomes we can start to elucidate how the emergence of brain circuits is manifested in variability of infant motor, cognitive and behavioural capacities. In this study, we examined if cortical structural covariance at birth, indexing coordinated development, is related to later infant behaviour. We included 193 healthy term-born infants from the Developing Human Connectome Project (dHCP). An individual cortical connectivity matrix derived from morphological and microstructural features was computed for each subject (morphometric similarity networks, MSNs) and was used as input for the prediction of behavioural scores at 18 months using Connectome-Based Predictive Modeling (CPM). Neonatal MSNs successfully predicted social-emotional performance. Predictive edges were distributed between and within known functional cortical divisions with a specific important role for primary and posterior cortical regions. These results reveal that multi-modal neonatal cortical profiles showing coordinated maturation are related to developmental outcomes and that network organization at birth provides an early infrastructure for future functional skills.

Adults with autism spectrum disorder and the criminal justice system: An investigation of prevalence of contact with the criminal justice system, risk factors and sex differences in a specialist assessment service.

LAY ABSTRACT: There has been growing interest in offending and contact with the criminal justice system (CJS) by people with autism spectrum disorder (ASD). However, it is not clear whether people with ASD offend more than those without ASD. Studies have started to look at whether there are particular offences people with ASD are more likely to commit and whether there are any factors that can affect whether someone comes into contact with the CJS as a potential suspect. This study looked at the patients who attended an ASD diagnostic service over a 17-year period to see the rate of contact with the CJS of those who were diagnosed with ASD and whether there were any particular factors that might increase the risk of CJS contact. Nearly a quarter of the ASD group had some contact with the CJS as a potential suspect. Factors that seemed to increase whether someone with ASD was more likely to have contact with the CJS were being male, being diagnosed with ADHD, and being diagnosed with psychosis. This study is one of the largest studies to investigate the rate of CJS contact as a potential suspect in a sample of adults with ASD in an attempt to give a clearer picture of what might influence someone with ASD to engage in offending behaviour in order to try to see what mental health services can offer to reduce the likelihood of someone with ASD coming into contact with the CJS, for example, treatment for another condition or support.