Autistic Features Research Articles

Multiparametric Assays Capture Sex- and Environment-Dependent Modifiers of Behavioral Phenotypes in Autism Mouse Models

BackgroundCurrent phenotyping approaches for murine autism models often focus on one selected behavioral feature, making the translation onto a spectrum of autistic characteristics in humans challenging. Furthermore, sex and environmental factors are rarely considered. Here, we aimed to capture the full spectrum of behavioral manifestations in 3 autism mouse models to develop a “behavioral fingerprint” that takes environmental and sex influences under consideration. MethodsTo this end, we employed a wide range of classical standardized behavioral tests and 2 multiparametric behavioral assays—the Live Mouse Tracker and Motion Sequencing—on male and female Shank2, Tsc1, and Purkinje cell–specific Tsc1 mutant mice raised in standard or enriched environments. Our aim was to integrate our high dimensional data into one single platform to classify differences in all experimental groups along dimensions with maximum discriminative power. ResultsMultiparametric behavioral assays enabled a more accurate classification of experimental groups than classical tests, and dimensionality reduction analysis demonstrated significant additional gains in classification accuracy, highlighting the presence of sex, environmental, and genotype differences in our experimental groups. ConclusionsTogether, our results provide a complete phenotypic description of all tested groups, suggesting that multiparametric assays can capture the entire spectrum of the heterogeneous phenotype in autism mouse models.

"Don't talk to me like Iam an illness": exploring patients' needs using the communication passport in an eating disorder service.

Social challenges are common in patients with eating disorders (ED). The presence of autistic characteristics often exacerbates social difficulties within this group, potentially affecting treatment outcomes. This study investigates the communication preferences, challenges, dislikes, and support needs of patients with ED, both with and without autistic traits, using acommunication passport in anational inpatient ED service. An explorative qualitative analysis of 38 completed communication passports was conducted to investigate patients' communication preferences, sensory needs, struggles and dislikes, and areas of support required, paying particular attention to the distinct needs of patients with high levels of autistic traits. The communication passport provided valuable insights into patients' communication preferences, sensory sensitivities, challenges, and support needed. Patients also used the passports to share information about their strengths, personal identity, and life beyond the hospital. The communication passport fosters adeeper understanding of patients' needs and may support clinicians in care planning and communication strategies tailored to each patient's needs. Regular evaluation and updates are warranted to ensure its usability and accessibility by the wider care team.

Exploring cross-linguistic differences in parental input and their associations with child expressive language in ASD: Bulgarian versus English comparison.

Parental input plays a central role in typical language acquisition and development. In autism spectrum disorder (ASD), characterized by social communicative and language difficulties, parental input presents an important avenue for investigation as a target for intervention. A rich body of literature has identified which aspects of grammatical complexity and lexical diversity are most associated with child language ability in both typical development and autism. Yet, the majority of these studies are conducted with English-speaking children, thus potentially overlooking nuances in parental input derived from cross-linguistic variation. To examine the differences in verbal parental input to Bulgarian- and English-speaking children with ASD. To examine whether aspects of verbal parental input found to be concurrent predictors of English-speaking children's expressive language ability are also predictors of the expressive language of Bulgarian-speaking children with ASD. We compared parental input to Bulgarian-speaking (N=37; 2;7-9;10 years) and English-speaking (N=37; 1;8-4;9 years) children with ASD matched on expressive language. Parent-child interactions were collected during free play with developmentally appropriate toys. These interactions were transcribed, and key measures of parental input were extracted. English-speaking parents produced more word tokens and word types than Bulgarian-speaking parents. However, Bulgarian parents produced more verbs in relation to nouns and used more statements and exclamations but asked fewer questions than English-speaking parents. In addition, child age and parents' use of questions were significant concurrent predictors of child expressive vocabulary. This is one of the first studies to conduct a cross-linguistic comparison of parental input in ASD. The differences found emphasize the need to further study parental input to Bulgarian children and adapt naturalistic parent-mediated interventions to the local language and its specific characteristics. What is already known on the subject A rich body of literature has identified the specific aspects of grammatical complexity, lexical diversity, and question-asking that are concurrently and longitudinally associated with the language ability of children with typical development and of children with ASD. Yet, the majority of these studies are conducted with English-speaking children. What this paper adds to the existing knowledge The present study finds that there are specific differences in verbal parental input to Bulgarian- and English-speaking children with autism in terms of lexical composition and question-asking. Bulgarian parents used more verbs than nouns, and the opposite pattern was found for English-speaking parents. In addition, Bulgarian parents asked fewer questions but used more statements and exclamations. Nevertheless, parental question use was significantly correlated with children's language ability across both groups, suggesting that question-asking should be further examined as a potential target for parent-mediated language interventions for Bulgarian children with autism. What are the potential or actual clinical implications of this work? Most language and social communication interventions for autism are designed and piloted with English-speaking children. These interventions are often simply translated and used in different countries, with different populations and in different contexts. However, considering that one of the defining characteristics of autism is language difficulty, more studies should examine (1) how these language difficulties manifest in languages other than English, and (2) what characterizes verbal parental input in these other contexts. Such research investigations should inform future language and social communication interventions. The present study emphasizes the cross-linguistic differences between Bulgarian- and English-speaking parents' verbal input to their children with autism.

Applying a User-Centered Design Framework to Develop a Remote Research Assessment Protocol for a Randomized Clinical Trial for Toddlers with Early Autism Characteristics.

COVID-19 required many research teams to shift from in-person to remote assessments, which posed both procedural and theoretical challenges. While research has explored the utility of remote assessments for autism diagnosis from the perspective of families and clinicians, less is known about their application in clinical trials. This paper describes the development of a remote research assessment protocol for a randomized clinical trial focusing on the implementation of reciprocal imitation teaching (RIT) with toddlers in Part C early intervention. This project spans two phases. For Phase 1, our team developed and documented a series of steps utilizing user-centered design (UCD) strategies (e.g., recruiting potential users, creating a prototype, engaging in iterative development) for the purpose of redesigning an assessment protocol for a remote environment. For Phase 2, we examined preliminary outcomes of the redesign process. Primary end users (assessors) rated post-redesign usability and acceptability, while acceptability was examined using attrition data from secondary end users (family participants). Preliminary fidelity of implementation was also examined. The iterative redesign process allowed the research team to refine aspects of the assessment that ultimately led to promising preliminary ratings of usability, acceptability, and feasibility, as well as high fidelity. Preliminary data suggest that the redesigned assessment appears to be an acceptable, feasible, and usable tool for autism clinical trial research and that assessors can use it with fidelity. Further research is needed to examine the reliability and validity of the assessment, as well as implementation characteristics on a larger scale.

The experience of autism from the perspective of autistic adolescents

The aim of this study is to explore with autistic adolescents, their perspectives and experiences related to autism. Situated in Australia, the study uses a qualitative methodology and a narrative approach. The findings illustrate a rich and nuanced understanding of autism for adolescents. Autistic adolescents place greater emphasis on difference and diversity rather than difficulty and highlight the positives and strengths of autism characteristics. The findings encourage the framing and conceptualisation of autism in relation to adolescents’ strengths and abilities whilst acknowledging experiences of anger, stress, and anxiety. Most adolescents describe feeling disconnected, emotionally and physically from others. The findings of this study indicate a need for increased awareness and practice of a strengths use in autism. This is to enhance understandings of autism, improve upon the wellbeing and mental health of autistic adolescents and to promote greater connectedness and belonging for this group amongst family, peers, and wider society.

Clinical characteristics and multimodal imaging can help diagnosing and treating mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy.

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a recently described, histopathologically and molecularly defined (SLC35A2-mutated) type of cortical malformation. Although increasingly recognized, the diagnosis of MOGHE remains a challenge. We present the characteristics of the first six patients diagnosed in Bulgaria, with the aim to facilitate identification, proper presurgical evaluation, and surgical treatment approach in this disease. Revision of histopathological specimens of 202 patients operated on for drug-resistant focal epilepsy identified four cases with MOGHE. Another two were suggested, based on clinical characteristics and subsequently, were histologically confirmed. Sanger SLC35A2 sequencing on paraffin-embedded or fresh-frozen brain tissue was performed. Analysis of seizure types, neuropsychological profiles, electroencephalographic (EEG), imaging features and epilepsy surgery outcomes was done. Three out of the six cases (50%) harbored pathogenic SLC35A2 mutations. One patient had a heterozygous somatic variant with uncertain significance. Clinical characteristics included epilepsy onset in infancy (in 100% under 3 years of age), multiple seizure types, and moderate or severe intellectual/developmental delay. Epileptic spasms with hypsarrhythmia on EEG were the initial seizure type in five patients. The subsequent seizure types resembled those in Lennox-Gastaut syndrome. The majority of the patients (n = 4) presented prominent and persisting autistic features. Magnetic resonance imaging (MRI) showed multilobar (n = 6) and bilateral (n = 3) lesions, affecting the frontal lobes (n = 5; bilaterally in three) and characterized by increased signal on T2/fluid-attenuated inversion recovery (FLAIR). Voxel-based morphometric MRI post-processing and positron emission tomography helped determining the localization and extent of the lesions and presumed epileptogenic zones. After surgery, four patients (66.7%) were seizure-free ≥2 years. Interestingly, all seizure-free patients carried somatic SLC35A2-alterations. Epileptic spasms, early prominent neuropsychological disturbances, MRI-T2/FLAIR hyperintense lesions with cortico-subcortical blurring, frequently multilobar and especially frontal, can preoperatively help to suspect MOGHE. Epilepsy surgery is still the only successful treatment option in MOGHE.

Stabilizing axin leads to optic nerve hypoplasia in a mouse model of autism

Autism spectrum disorder (ASD) is a group of neurodevelopment disorders characterized by deficits in social interaction and communication, and repetitive or stereotyped behavior. Autistic children are more likely to have vision problems, and ASD is unusually common among blind people. However, the mechanisms behind the vision disorders in autism are unclear. Stabilizing WNT-targeted scaffold protein Axin2 by XAV939 during embryonic development causes overproduction of cortical neurons and leads to autistic-like behaviors in mice. In this study, we investigated the relationship between vision abnormality and autism using an XAV939-induced mouse model of autism. We found that the mice receiving XAV939 had decreased amplitude of bright light-adaptive ERG. The amplitudes and latency of flash visual evoked potential recorded from XAV939-treated mice were lower and longer, respectively than in the control mice, suggesting that XAV939 inhibits visual signal processing and conductance. Anatomically, the diameters of RGC axons were reduced when Axin2 was stabilized during the development, and the optic fibers had defective myelin sheaths and reduced oligodendrocytes. The results suggest that the WNT signaling pathway is crucial for optic nerve development. This study provides experimental evidence that conditions interfering with brain development may also lead to visual problems, which in turn might exaggerate the autistic features in humans.

Challenges of Treating a Patient with Autism and Hodgkin’s Lymphoma

Abstract Hodgkin’s lymphoma (HL) and autism spectrum disorder (ASD) are a rare combination. Diagnosing and treating patients with this combination is challenging. Here, we report the case of a 19-year-old male with ASD and HL. Upon initial presentation to our clinic, the patient was very active with the clinical features of autism. Pathology confirmed stage IVBs HL of the mixed cellularity subtype. He received six cycles of Adriamycin, bleomycin sulfate, vinblastine sulfate, and dacarbazine and has been in remission for the last 4 years. This report presents the challenges in the diagnosis and treatment of a young patient with ASD and cancer and how to overcome them.

Clinical, cognitive, and functional characteristics of recent-onset psychosis with autistic features: A 2-year longitudinal study

Though categorized as separate illnesses, schizophrenia and autism are known to exhibit shared characteristics. This study explored the distinctions in clinical, cognitive, and functional characteristics among individuals with recent-onset psychosis, considering the severity of their autistic symptoms, involving longitudinal examinations. We analyzed 671 patients with recent-onset psychosis from Korean Early Psychosis Cohort Study (KEPS), and used the PANSS Autism Severity Score (PAUSS) to categorize patient into ‘autistic’, ‘moderate’, and ‘non-autistic’ groups. The autistic group had the highest rate of schizophrenia diagnosis, and the lowest incidence of comorbid psychiatric disorders. Schizophrenia diagnosis predicted membership of the autistic group. More severe autistic symptoms correlated with worse overall symptoms and functional outcomes, which significantly predicted membership of the autistic group. Cognitive impairments and emotional recognition difficulties increased with the severity of autistic symptoms. 2-year longitudinal assessments demonstrated that group differences in autistic features and overall symptoms, and functional outcomes remained consistent, and membership of the autistic group significantly predicted symptomatic remission and functional recovery. In conclusion, the presence of autistic symptoms has a significant impact on the overall symptomatology and functional capabilities. They are enduring attributes rather than temporary state variables, and serve as a significant predictor for both symptomatic and functional recovery.

Resting state EEG in young children with Tuberous Sclerosis Complex.

Tuberous Sclerosis Complex (TSC) manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations. Such a biomarker could be useful in clinical trials as an endpoint or predictor of treatment response. However, seizures and antiepileptic medications also affect resting neural oscillatory activity and could undermine the utility of resting state EEG features as biomarkers in neurodevelopmental disorders such as TSC. This paper compares resting state EEG features in a cross-sectional cohort of young children with TSC (n=49, ages 12-37 months) to 49 age- and sex-matched typically developing controls. Within children with TSC, associations were examined between resting state EEG features, seizure severity composite score, and use of GABA agonists. Compared to matched typically developing controls, children with TSC showed significantly greater alpha and beta power in permutation cluster analyses iterated across a broad frequency range (2-50Hz). Children with TSC also showed significantly greater aperiodic offset after power spectra were parameterized using SpecParam into aperiodic and periodic components. Within children with TSC, greater seizure severity was significantly related to increased periodic peak beta power. Use of GABA agonists was also independently and significantly associated with increased periodic peak beta power; the interaction between seizure severity and GABA agonist use had no significant effect on peak beta power. The elevated peak beta power observed in children with TSC compared to matched typically developing controls may be driven by both seizures and GABA agonist use. It is recommended to collect seizure and mediation data alongside EEG data for clinical trials. These results highlight the challenge of using resting state EEG features as biomarkers in trials with neurodevelopmental disabilities when epilepsy and anti-epileptic medication are common.

Distinguishing between autism and the consequences of early traumatisation during diagnostic assessment: a clinical case study

PurposeDistinguishing between autism characteristics and trauma-related symptoms may be clinically challenging, particularly in individuals who have experienced early traumatisation. Previous studies have described a risk that trauma-related symptoms are misinterpreted and/or misattributed to autism. This study aims to describe and explore assessment strategies to distinguish autism and early traumatisation in the case of a young woman with mild intellectual disability.Design/methodology/approachA clinical case study outlining assessment strategies, diagnostic decision-making and initial intervention.FindingsA multi-informant interdisciplinary assessment using multiple assessment tools, together with a comprehensive review of records from previous assessments and contacts with various services, was helpful in distinguishing between autism and trauma. This included specific assessment tools for autism and trauma. Autism characteristics and trauma-related symptoms appeared to interact, not merely co-occur.Originality/valueThe current case demonstrates that diagnostic overshadowing may occur for autism in the context of early trauma. The case further highlights the importance of not ascribing trauma-related symptoms to autism, as service provision and treatment need to take account of both. Overlooking autism in individuals who have experienced early traumatisation may result in a risk that intervention and care are not appropriately adapted, which may involve a risk of exacerbating trauma symptoms.

Sleep correlates of behavior functioning in Cornelia de Lange syndrome.

Pathogenic variants in the cohesin genes, NIPBL and SMC1A, both cause Cornelia de Lange syndrome (CdLS), a rare genetic disorder associated with developmental delay and intellectual disability. This study aimed to compare sleep behaviors across individuals with CdLS caused by a variant in NIPBL or SMC1A, and identify relationships between sleep and behavior functioning. A total of 31 caregivers of individuals with a variant in NIPBL (N = 22) or SMC1A (N = 9) completed questionnaires regarding their child's sleep behaviors, behavior regulation, attention, and autistic features (repetitive behaviors and social communication difficulties) as part of the Coordination of Rare Diseases (CoRDS) registry. Findings showed a trend of increased behavior regulation difficulties and repetitive behaviors in the NIPBL compared to the SMC1A participants. Both groups presented with a similar degree of attention, social communication, and sleep challenges. In the whole sample, sleep disturbance was strongly correlated with more behavior regulation difficulties, a relationship that was more robust in the NIPBL sample. In brief, study results support our prior observations of greater behavior difficulties among those with a variant in NIPBL as compared to SMC1A. Preliminary findings point to unique associations between sleep and behavior regulation in the NIPBL group, suggesting sleep interventions may yield differential effects on behavior management across variants.

The associations between autistic characteristics and microtransaction spending

Microtransactions provide optional, virtual, video game goods that, for an additional cost to the player, provide additional game content and alter the gameplay experience. Loot boxes—a specific form of microtransaction—offer randomised rewards in exchange for payment, and are argued to be structurally and psychologically similar to gambling. Nascent research suggests that a link exists between autism and both problematic gaming and problematic gambling. Here, we investigated the relationships between autistic characteristics and experiences, and excessive video gaming and microtransaction expenditure. A sample of 1178 adults from Australia, Aotearoa, and The United States were recruited from Prolific Academic, and completed a survey measuring in-game expenditure, autistic characteristics and experiences, problematic gaming, problematic gambling, and risky loot box use. Analyses showed positive associations between autistic characteristics and experiences with problematic gaming and problem gambling symptomatology. However, results also showed a small, negative association between autistic characteristics and experiences and spending on loot boxes when problem gambling symptoms, problematic gaming, and risky loot box use were statistically controlled for. These results suggest that autistic gamers may be vulnerable to problematic gaming and gambling, but that this effect does not extend to the purchasing of microtransactions.

Prevalence of autism in first-episode psychosis in two Hong Kong teaching hospitals.

Autistic features are commonly observed in children and adolescents with first-episode psychosis, but they are sometimes overlooked by clinicians and caregivers. By comprehensively examining the clinical profiles of 103 children and adolescents (below 18 years old) with first-episode psychosis and conducting the Autism Diagnostic Interview-Revised (the 'gold standard' autism diagnostic tool) with their primary caregivers, we showed that around 28% of patients with first-episode psychosis had a comorbid autism diagnosis, and boys were 3.57 times more likely to have first-episode psychosis-autism spectrum disorder comorbidity than girls. After administering the Autism Diagnostic Interview-Revised, we also observed that an additional 30% of patients with first-episode psychosis met the autism spectrum disorder diagnostic cut-off; their autism spectrum disorder symptoms were probably overshadowed by prodromal psychotic symptoms and left undetected before this study. The co-occurrence of autism and first-episode psychosis might be more common than we previously thought. Careful autism screening and assessment is highly recommended for clinicians working with patients with psychosis.

A follow-up study of peer relationships in autistic and non-autistic youths: Mediating effects from autistic, emotional and behavioral symptoms

BackgroundLittle is known about how clinical features prospectively influence peer relationships in autistic populations. AimsThis study investigated the clinical symptoms mediating the link between autism spectrum disorder (ASD) diagnosis and peer relationships at follow-up, i.e. the second time evaluation of this study. MethodsThe sample consisted of 366 autistic youths and 134 non-autistic comparisons. The autistic traits and emotional/behavioral problems were measured at baseline by Social Responsiveness Scale (SRS) and Child Behavior Checklist (CBCL). The interactions and problems with peers were assessed by the Social Adjustment Inventory for Children and Adolescents (SAICA) at follow-up. ResultsEach subscore of SRS and CBCL showed significant mediation effects. Multiple mediation analyses showed atypical social communication, social awareness problems, and delinquent behaviors mediated the link from ASD to less active peer interactions after controlling for sex, age, and IQ. Moreover, atypical social communication, social-emotional problems, and attention difficulties predicted problems with peers. After considering these mediation effects, the diagnosis of ASD still demonstrated a significantly direct effect on peer relationships at follow-up. Conclusions and implicationsOur findings support that social-related autistic features, attention problems, and delinquent behaviors mediated a link between ASD and peer relationships. These mediators are potential measures for improving interactions and decreasing difficulties with peers in the autistic population.

Moral distress and moral injury in the context of autism

PurposeClinically, it is often observed that autistic people may have a heightened need for rules and may find rule violations very distressing. It is clinically plausible that autistic individuals may be prone to hyper-morality and greater reactivity and adverse experiences arising from moral threats and violations. Such adverse experiences may, in some instances, lead to moral distress (MD) or in more extreme cases moral injury. Thus, this study aims to examine how MD can operate in the context of autism.Design/methodology/approachThe authors explore clinical hypotheses on how MD can intersect with different features of autism by drawing on clinical and research knowledge of autism spectrum disorder and how it contextualises experiences of morality.FindingsBased on a review of the literature and theory, the authors hypothesise that autistic individuals may be more prone to MD where they have a lower threshold for MD. As a result of this lower threshold, they may have more frequent exposure to MD, experience more immediate and intense subjective reactions to moral transgressions, for more protracted periods. Also, they may find it more difficult to over-ride and neutralise moral outrage. As a result, they may be more susceptible to mental health sequelae and impaired social and occupational functioning. Practical recommendations are made for clinicians supporting people with autism with a propensity for MD or moral injury, to improve their quality of life.Practical implicationsPractical recommendations are made for clinicians supporting people with autism with a propensity for MD or moral injury, to improve their quality of life.Originality/valueUnderstanding MD in an autistic context is important for detecting and treating the adverse impacts of MD on autistic individuals. Importantly, erroneous preconceptions about moral reasoning in autism need to be mitigated to fully understand the moral experiences and harness the many strengths of people with autism.

Recovery of adults with autism spectrum disorder during intensive inpatient treatment: a qualitative study.

Although some adults with autism spectrum disorder (ASD) require intensive and specialized ASD treatment, there is little research on how these adults experience the recovery process. Recovery is defined as the significant improvement in general functioning compared to the situation prior to treatment. This qualitative study describes the recovery process from the perspective of adults on the autism spectrum during intensive inpatient treatment. Semi-structured interviews (n = 15) were carried out and analyzed according to the principles of grounded theory. Our results indicate that, given the specific characteristics of autism, therapeutic interventions and goal-oriented work cannot be carried out successfully, and the recovery process cannot begin, if no good working relationship has been established, and if care is not organized in ways that a person on the autism spectrum finds clear and predictable.

Improving Emergency Department Care for Suicidality in Autism: Perspectives from Autistic Youth, Caregivers, and Clinicians.

In this pilot study, we conducted semi-structured interviews with 17 key members of the autism community (i.e., autistic youth with a history of suicidality, caregivers of autistic youth with a history of suicidality, autism specialist clinicians, ED clinicians) to inform the development of recommendations for modifying ED care for autistic patients, with a focus on suicide risk screening and management. Participants reported on challenges they encountered receiving or providing care and/or recommendations for improving care. Participant perspectives were aligned, and four main categories emerged: accounting for autism features, connection and youth engagement in care, caregiver and family involvement, and service system issues. As research continues in the development of autism-specific suicide risk assessment tools and management strategies, it is essential we better equip providers to address suicide risk in autistic patients, particularly in ED settings.

Predicting Intervention Use in Youth with Rare Variants in Autism-Associated Genes.

Specialized multidisciplinary supports are important for long-term outcomes for autistic youth. Although family and child factors predict service utilization in autism, little is known with respect to youth with rare, autism-associated genetic variants, who frequently have increased psychiatric, developmental, and behavioral needs. We investigate the impact of family factors on service utilization to determine whether caregiver (autistic features, education, income) and child (autistic features, sex, age, IQ, co-occurring conditions) factors predicted service type (e.g., speech, occupational, behavioral) and intensity (hours/year) among children with autism-associated variants (N = 125), some of whom also had a confirmed ASD diagnosis. Analyses revealed variability in the types of services used across a range of child demographic, behavioral, and mental health characteristics. Speech therapy was the most received service (87.2%). Importantly, behavior therapy was the least received service and post-hoc analyses revealed that use of this therapy was uniquely predicted by ASD diagnosis. However, once children received a particular service, there was largely comparable intensity of services, independent of caregiver and child factors. Findings suggest that demographic and clinical factors impact families' ability to obtain services, with less impact on the intensity of services received. The low receipt of therapies that specifically address core support needs in autism (i.e., behavior therapy) indicates more research is needed on the availability of these services for youth with autism-associated variants, particularly for those who do not meet criteria for an ASD diagnosis but do demonstrate elevated and impactful child autistic features as compared to the general population.

Is autism a PIN1 deficiency syndrome? A proposed etiological role for glyphosate.

Autism is a neurodevelopmental disorder, the prevalence of which has increased dramatically in the United States over the past two decades. It is characterized by stereotyped behaviors and impairments in social interaction and communication. In this paper, we present evidence that autism can be viewed as a PIN1 deficiency syndrome. Peptidyl-prolyl cis/trans isomerase, NIMA-Interacting 1 (PIN1) is a peptidyl-prolyl cis/trans isomerase, and it has widespread influences in biological organisms. Broadly speaking, PIN1 deficiency is linked to many neurodegenerative diseases, whereas PIN1 over-expression is linked to cancer. Death-associated protein kinase 1 (DAPK1) strongly inhibits PIN1, and the hormone melatonin inhibits DAPK1. Melatonin deficiency is strongly linked to autism. It has recently been shown that glyphosate exposure to rats inhibits melatonin synthesis as a result of increased glutamate release from glial cells and increased expression of metabotropic glutamate receptors. Glyphosate's inhibition of melatonin leads to a reduction in PIN1 availability in neurons. In this paper, we show that PIN1 deficiency can explain many of the unique morphological features of autism, including increased dendritic spine density, missing or thin corpus callosum, and reduced bone density. We show how PIN1 deficiency disrupts the functioning of powerful high-level signaling molecules, such as nuclear factor erythroid 2-related factor 2 (NRF2) and p53. Dysregulation of both of these proteins has been linked to autism. Severe depletion of glutathione in the brain resulting from chronic exposure to oxidative stressors and extracellular glutamate leads to oxidation of the cysteine residue in PIN1, inactivating the protein and further contributing to PIN1 deficiency. Impaired autophagy leads to increased sensitivity of neurons to ferroptosis. It is imperative that further research be conducted to experimentally validate whether the mechanisms described here take place in response to chronic glyphosate exposure and whether this ultimately leads to autism.