A response to the terms in Shah et al's 'Neurodevelopmental disorders and neurodiversity: definition of terms from Scotland's National Autism Implementation Team'.

The Scottish National Autism Implementation Team's neurodiversity terms are a valiant, but flawed, attempt to reconcile different worldviews on neurodiversity. The aim of harmonising different perspectives is laudable; however, we disagree with the use of 'societal norms' in the authors' framework of terms and challenge some of their proposed definitions.

Genetic and early environmental predictors of adulthood self-reports of trauma.

BACKGROUND: Retrospective self-reports of childhood trauma are associated with a greater risk of psychopathology in adulthood than prospective measures of trauma. Heritable reporter characteristics are anticipated to account for part of this association, whereby genetic predisposition to certain traits influences both the likelihood of self-reporting trauma and of developing psychopathology. However, previous research has not considered how gene-environment correlation influences these associations. AIMS: To investigate reporter characteristics associated with retrospective self-reports of childhood trauma and whether these associations are accounted for by gene-environment correlation. METHOD: In 3963 unrelated individuals from the Twins Early Development Study, we tested whether polygenic scores for 21 psychiatric, cognitive, anthropometric and personality traits were associated with retrospectively self-reported childhood emotional and physical abuse. To assess the presence of gene-environment correlation, we investigated whether these associations remained after controlling for composite scores of environmental adversity across development. RESULTS: Retrospectively self-reported childhood trauma was associated with polygenic scores for autism spectrum disorder (ASD), body mass index (BMI), post-traumatic stress disorder (PTSD) and risky behaviours. When composite scores of environmental adversity were controlled for, only associations with the polygenic scores for ASD and PTSD remained significant. CONCLUSIONS: Genetic predisposition to ASD and PTSD may increase liability to experiencing or interpreting events as traumatic. Associations between genetic predisposition for risky behaviour and BMI with self-reported childhood trauma may reflect gene-environment correlation. Studies of the association between retrospectively self-reported childhood trauma and later-life outcomes should consider that genetically influenced reporter characteristics may confound associations, both directly and through gene-environment correlation.

A full CIRCLE: inclusion of autistic doctors in the Royal College Of Psychiatrists' values and Equality Action Plan.

Autistic psychiatrists bring strengths and values to the workforce and ask to be acknowledged and supported as part of the Royal College of Psychiatrists' CIRCLE values and Equality Action Plan. Courage and collaboration are required to jointly learn and innovate, promoting well-being, resilience and excellence for autistic doctors.

The epilepsy-autism spectrum disorder phenotype in the era of molecular genetics and precision therapy.

Autism spectrum disorder (ASD) is frequently associated with infants with epileptic encephalopathy, and early interventions targeting social and cognitive deficits can have positive effects on developmental outcome. However, early diagnosis of ASD among infants with epilepsy is complicated by variability in clinical phenotypes. Commonality in both biological and molecular mechanisms have been suggested between ASD and epilepsy, such as occurs with tuberous sclerosis complex. This review summarizes the current understanding of causal mechanisms between epilepsy and ASD, with a particularly genetic focus. Hypothetical explanations to support the conjugation of the two conditions include abnormalities in synaptic growth, imbalance in neuronal excitation/inhibition, and abnormal synaptic plasticity. Investigation of the probable genetic basis has implemented many genes, although the main risk supports existing hypotheses in that these cluster to abnormalities in ion channels, synaptic function and structure, and transcription regulators, with the mammalian target of rapamycin (mTOR) pathway and "mTORpathies" having been a notable research focus. Experimental models not only have a crucial role in determining gene functions but are also useful instruments for tracing disease trajectory. Precision medicine from gene therapy remains a theoretical possibility, but more contemporary developments continue in molecular tests to aid earlier diagnoses and better therapeutic targeting.

Co-occurrence of autistic and psychotic traits: implications for depression, self-harm and suicidality.

BACKGROUND: There is increasing interest in the clinical and aetiological overlap between autism spectrum disorders and schizophrenia spectrum disorders, reported to co-occur at both diagnostic and trait levels. Individually, sub-clinical autistic and psychotic traits are associated with poor clinical outcomes, including increased depressive symptomatology, self-harming behaviour and suicidality. However, the implications when both traits co-occur remain poorly understood. The study aimed to (1) examine the relationship between autistic and psychotic traits and (2) determine if their co-occurrence increases depressive symptomatology, self-harm and suicidality. METHODS: Cross-sectional data from a self-selecting (online and poster advertising) sample of the adult UK population (n = 653) were collected using an online survey. Validated self-report measures were used to assess sub-clinical autistic and psychotic traits, depressive symptomatology, self-harming behaviour and suicidality. Correlation and regression analyses were performed. RESULTS: A positive correlation between sub-clinical autistic and positive psychotic traits was confirmed (rs = 0.509, p < 0.001). Overall, autistic traits and psychotic traits were, independently, significant predictors of depression, self-harm and suicidality. Intriguingly, however, depression was associated with a negative interaction between the autistic domain attention to detail and psychotic traits. CONCLUSIONS: This study supports previous findings that sub-clinical autistic and psychotic traits are largely independently associated with depression, self-harm and suicidality, and is novel in finding that their combined presence has no additional effect on depression, self-harm or suicidality. These findings highlight the importance of considering both autistic and psychotic traits and their symptom domains in research and when developing population-based depression prevention and intervention strategies.

The Novel Potential Therapeutic Utility of Montelukast in Alleviating Autistic Behavior Induced by Early Postnatal Administration of Thimerosal in Mice.

BACKGROUND AND AIM: Thimerosal (THIM) is a mercury-containing preservative widely used in many biological and medical products including many vaccines. It has been accused of being a possible etiological factor for some neurodevelopmental disorders such as autistic spectrum disorders (ASDs). In our study, the potential therapeutic effect of montelukast, a leukotriene receptor antagonist used to treat seasonal allergies and asthma, on THIM mice model (ASDs model) was examined. METHODOLOGY: Newborn mice were randomly distributed into three groups: (Group 1) Control (Cont.) group received saline injections. (Group 2) THIM-treated (THIM) group received THIM intramuscular (IM) at a dose of 3000 µg Hg/kg on postnatal days 7, 9, 11, and 15. (Group 3) Montelukast-treated (Monte) group received THIM followed by montelukast sodium (10 mg/kg/day) intraperitoneal (IP) for 3 weeks. Mice were evaluated for growth development, social interactions, anxiety, locomotor activity, and cognitive function. Brain histopathology, alpha 7 nicotinic acetylcholine receptors (α7nAChRs), nuclear factor kappa B p65 (NF-κB p65), apoptotic factor (Bax), and brain injury markers were evaluated as well. RESULTS: THIIM significantly impaired social activity and growth development. Montelukast mitigated THIM-induced social deficit probably through α7nAChRs upregulation, NF-κB p65, Bax, and brain injury markers downregulation, thus suppressing THIM-induced neuronal toxicity and inflammation. CONCLUSION: Neonatal exposure to THIM can induce growth retardation and abnormal social interactions similar to those observed in ASDs. Some of these abnormalities could be ameliorated by montelukast via upregulation of α7nAChRs that inhibited NF-κB activation and significant suppression of neuronal injury and the associated apoptosis.

Healthy Intimate Relationships and the Adult With Autism.

OBJECTIVE: An adult faces many challenges; however, one experience that is often taken for granted by neurotypical individuals is building intimate relationships. The purpose of this article is to discuss the barriers for healthy intimate relationships for an individual with autism, strategies to overcome these barriers, recommendations for future practice and research, and resources to improve knowledge of this important yet overlooked topic. METHOD: Data collection was done using research journals and databases such as EBSCO, SAGE Knowledge, MEDLINE, and CINAHL. The reviewed articles were published from 2015 to the present time. During the search process, the following key phrases were used: autism spectrum disorder, intimate relationships, sexuality education, and social skills. In total, 1,400 articles were found with an additional 52 sources found through other sources, of which 31 met inclusion criteria and were subsequently reviewed. RESULTS: Although those with autism have many strengths and talents, deficits in communication and social interaction can affect the formation of healthy adult relationships, including friendships and romantic relationships. In addition to social challenges, a lack of education regarding safe and healthy relationships can put an individual with autism at risk. CONCLUSIONS: It is imperative that that individuals with autism, their families, and health care professionals are educated about the barriers and able to access educational resources and specialized curricula on this topic.

Identifying schizophrenia patients who carry pathogenic genetic copy number variants using standard clinical assessment: retrospective cohort study.

BACKGROUND: Copy number variants (CNVs) play a significant role in disease pathogenesis in a small subset of individuals with schizophrenia (~2.5%). Chromosomal microarray testing is a first-tier genetic test for many neurodevelopmental disorders. Similar testing could be useful in schizophrenia. AIMS: To determine whether clinically identifiable phenotypic features could be used to successfully model schizophrenia-associated (SCZ-associated) CNV carrier status in a large schizophrenia cohort. METHOD: Logistic regression and receiver operating characteristic (ROC) curves tested the accuracy of readily identifiable phenotypic features in modelling SCZ-associated CNV status in a discovery data-set of 1215 individuals with psychosis. A replication analysis was undertaken in a second psychosis data-set (n = 479). RESULTS: In the discovery cohort, specific learning disorder (OR = 8.12; 95% CI 1.16-34.88, P = 0.012), developmental delay (OR = 5.19; 95% CI 1.58-14.76, P = 0.003) and comorbid neurodevelopmental disorder (OR = 5.87; 95% CI 1.28-19.69, P = 0.009) were significant independent variables in modelling positive carrier status for a SCZ-associated CNV, with an area under the ROC (AUROC) of 74.2% (95% CI 61.9-86.4%). A model constructed from the discovery cohort including developmental delay and comorbid neurodevelopmental disorder variables resulted in an AUROC of 83% (95% CI 52.0-100.0%) for the replication cohort. CONCLUSIONS: These findings suggest that careful clinical history taking to document specific neurodevelopmental features may be informative in screening for individuals with schizophrenia who are at higher risk of carrying known SCZ-associated CNVs. Identification of genomic disorders in these individuals is likely to have clinical benefits similar to those demonstrated for other neurodevelopmental disorders.

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The pathogenesis of autistic spectrum disorders is complicated and the exact etiology and pathogenesis remain unclear. Major advances in spatial information technology have revealed the potential of spatial information technology as an effective tool in research and treatment for children with autistic spectrum disorders. However, there are too many fragmented research topics. According to recent reports on spatial information technology, there is no precedent for the application of spatial information technology in autistic spectrum disorders in China. Space information technology analysis for autistic spectrum disorders can be divided into the following steps: pre analysis, spatial clustering analysis, spatial model analysis, and interpretation of related results. It is hopeful that the space information technology can provide proposals for the future research on the pathogenesis of autistic spectrum disorders in our country.

Autism spectrum disorder diagnosis in adults: phenotype and genotype findings from a clinically derived cohort.

BACKGROUND: The past decade has seen the development of services for adults presenting with symptoms of autism spectrum disorder (ASD) in the UK. Compared with children, little is known about the phenotypic and genetic characteristics of these patients. AIMS: This e-cohort study aimed to examine the phenotypic and genetic characteristics of a clinically presenting sample of adults diagnosed with ASD by specialist services. METHOD: Individuals diagnosed with ASD as adults were recruited by the National Centre for Mental Health and completed self-report questionnaires, interviews and provided DNA; 105 eligible individuals were matched to 76 healthy controls. We investigated demographics, social history and comorbid psychiatric and physical disorders. Samples were genotyped, copy number variants (CNVs) were called and polygenic risk scores were calculated. RESULTS: Of individuals with ASD, 89.5% had at least one comorbid psychiatric diagnosis, with depression (62.9%) and anxiety (55.2%) being the most common. The ASD group experienced more neurological comorbidities than controls, particularly migraine headache. They were less likely to have married or be in work, and had more alcohol-related problems. There was a significantly higher load of autism common genetic variants in the adult ASD group compared with controls, but there was no difference in the rate of rare CNVs. CONCLUSIONS: This study provides important information about psychiatric comorbidity in adult ASD, which may inform clinical practice and patient counselling. It also suggests that the polygenic load of common ASD-associated variants may be important in conferring risk within the non-intellectually disabled population of adults with ASD. DECLARATION OF INTEREST: None.

Commentary on the overlapping and distinct resting functional connectivity between autism spectrum disorder and attention-deficit hyperactivity disorder.

Altered neural connectivity in neurodevelopmental disorders is likely subtle, meaning that neuroimaging literature studying development has produced heterogeneous findings. A recent study, published in this issue, illustrates the translational potential of functional connectivity magnetic resonance imaging findings as a biomarker for attention-deficit hyperactivity disorder and autism spectrum disorder. Importantly, it highlights the overlap between disorders, emphasising the need for transdiagnostic and dimensional approaches in neurodevelopment.Declaration of interestNone.

Challenges in the Medical Care of Patients With Autism Spectrum Disorder: The Role of the Consultation-Liaison Psychiatrist.

BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder that affects one in 40 children. Individuals with ASD have high rates of medical comorbidity, excess mortality, high health care expenditures, and difficulty accessing coordinated medical care. As the prevalence of ASD rises, consultation-liaison (C-L) psychiatrists will be increasingly called upon to assist patients with ASD both in inpatient and outpatient medical settings. METHODS: In this article, we review the patient, provider, and systems factors that converge to create challenges for delivering high-quality, patient-centered medical care for patients with ASD. CONCLUSION: Strategies to optimize the care of patients with ASD in medical settings include previsit planning, anticipating and reducing sources of distress, facilitating a patient- and family-centered multidisciplinary approach, employing environmental interventions, and using psychopharmacologic treatments.

General Pathophysiology of Astroglia.

Astroglial cells are involved in most if not in all pathologies of the brain. These cells can change the morpho-functional properties in response to pathology or innate changes of these cells can lead to pathologies. Overall pathological changes in astroglia are complex and diverse and often vary with different disease stages. We classify astrogliopathologies into reactive astrogliosis, astrodegeneration with astroglial atrophy and loss of function, and pathological remodelling of astrocytes. Such changes can occur in neurological, neurodevelopmental, metabolic and psychiatric disorders as well as in infection and toxic insults. Mutation in astrocyte-specific genes leads to specific pathologies, such as Alexander disease, which is a leukodystrophy. We discuss changes in astroglia in the pathological context and identify some molecular entities underlying pathology. These entities within astroglia may repent targets for novel therapeutic intervention in the management of brain pathologies.

The Early Sociocognitive Battery: a clinical tool for early identification of children at risk for social communication difficulties and ASD?

BACKGROUND: A substantial proportion of preschool children referred to speech and language therapy (SLT) services have social communication difficulties and/or autistic spectrum disorders (SC&/ASD) that are not identified until late childhood. These 'late' diagnosed children miss opportunities to benefit from earlier targeted interventions. Prior evidence from a follow-up clinical sample showed that preschool performance on the Early Sociocognitive Battery (ESB) was a good predictor of children with social communication difficulties 7-8 years later. AIMS: The aims were three-fold: (1) to determine the impact of child/demographic factors on ESB performance in a community sample of young children; (2) to assess the ESB's concurrent validity and test-retest reliability; and (3) to use cut-offs for 'low' ESB performance derived from the community sample data to evaluate in a clinical sample the predictiveness of the ESB at 2-4 years for outcomes at 9-11 years, including parent-reported SC&/ASD diagnosis. METHODS & PROCEDURES: A community sample of 205 children aged 2-4 years was assessed on the ESB and a receptive vocabulary test. A subsample (n = 20) was retested on the ESB within 2 weeks. Parents completed a questionnaire providing background child/demographic information. The clinical sample from our previous study comprised 93 children assessed on the ESB at 2;6 to < 4;0 whose parents completed the Social Responsiveness Scale (SRS), our measure of social communication, when the children were 9-11 years. Cut-offs for 'low' ESB performance derived from the community sample were used to determine the predictive validity of 'low' ESB scores for social communication outcomes and parent-reported SC&/ASD diagnosis according to age of ESB assessment. OUTCOME & RESULTS: Findings from the community sample confirmed the ESB as psychometrically robust, sensitive to age and language delay, and, in contrast to the receptive vocabulary measure, unaffected by bilingualism. While overall associations between ESB performance and later social communication difficulties in the clinical sample were particularly strong for the youngest age group (2;6 to < 3;0; r = .71, p < .001), 'low' ESB performance was equally predictive across age groups and overall identified 89% of children with 'late' SC&/ASD diagnoses (sensitivity), and 75% of those without (specificity). CONCLUSIONS & IMPLICATIONS: Results indicate that the ESB is a valid preschool assessment suitable for use with children from diverse language backgrounds. It identifies deficits in key sociocognitive skills and is predictive of social communication difficulties in school-age children that had not been identified in preschool clinical assessment, supporting earlier targeted interventions for these children.

Multiple inflammasome complexes are activated in autistic spectrum disorders.

BACKGROUND: Inflammasomes are multimeric protein platforms involved in the regulation of inflammatory responses whose activity results in the production of proinflammatory cytokines. Because neuroinflammation is observed in autistic spectrum disorders (ASD), a neurologic condition of childhood resulting in a complex behavioural impairment, we analyzed the inflammasomes activity in ASD. Additionally we verified whether alterations of the gastrointestinal (GI) barriers might play a role in inflammasomes activation. METHODS: The activity of the inflammasomes, the concentration of the inflammasomes-derived proinflammatory cytokines interleukin (IL)-1ß and IL-18, and serum parameters of GI damage were analyzed in 25 ASD children, 23 healthy siblings (HS) and 30 unrelated age-matched healthy controls (HC). RESULTS: A significant upregulation of the AIM2 and the NLRP3 inflammasomes and an increased production of IL-1ß and IL-18 that was associated with a consistent reduction of IL-33, an anti inflammation cytokine were observed in ASD alone. Notably, in a possible immune-mediated attempt to dampen inflammation, IL-37, a suppressor of innate inflammatory responses, was significantly augmented in these same children. Finally, intestinal fatty acid binding protein (IFABP), an index of altered GI permeability, was significantly increased in serum of ASD and HS. CONCLUSIONS: These results show that the inflammasomes are activated in ASD and shed light on the molecular mechanisms responsible for ASD-associated neuroinflammation. The observation that GI alterations could be present as well in ASD offers a possible link between such alterations and neuroinflammation. Therapeutic strategies targeting inflammasome activation could be useful in ASD.

The epidemiology and global burden of autism spectrum disorders.

BACKGROUND: Autism spectrum disorders (ASDs) are persistent disabling neurodevelopmental disorders clinically evident from early childhood. For the first time, the burden of ASDs has been estimated for the Global Burden of Disease Study 2010 (GBD 2010). The aims of this study were to develop global and regional prevalence models and estimate the global burden of disease of ASDs. METHOD: A systematic review was conducted for epidemiological data (prevalence, incidence, remission and mortality risk) of autistic disorder and other ASDs. Data were pooled using a Bayesian meta-regression approach while adjusting for between-study variance to derive prevalence models. Burden was calculated in terms of years lived with disability (YLDs) and disability-adjusted life-years (DALYs), which are reported here by world region for 1990 and 2010. RESULTS: In 2010 there were an estimated 52 million cases of ASDs, equating to a prevalence of 7.6 per 1000 or one in 132 persons. After accounting for methodological variations, there was no clear evidence of a change in prevalence for autistic disorder or other ASDs between 1990 and 2010. Worldwide, there was little regional variation in the prevalence of ASDs. Globally, autistic disorders accounted for more than 58 DALYs per 100 000 population and other ASDs accounted for 53 DALYs per 100 000. CONCLUSIONS: ASDs account for substantial health loss across the lifespan. Understanding the burden of ASDs is essential for effective policy making. An accurate epidemiological description of ASDs is needed to inform public health policy and to plan for education, housing and financial support services.

Do Social Stories help to decrease disruptive behaviour in children with autistic spectrum disorders? A review of the published literature.

A structured search and identification of themes within the literature regarding the use of Social Stories to decrease disruptive behaviour in children with autistic spectrum disorders is presented. The examination of seven studies showed that the Social Story intervention was successful for the majority of the participants, although the level of success was variable. Overall, Social Stories appear to be an acceptable intervention for use in the classroom, however unplanned verbal prompting by teachers, in some studies, reduced confidence in the effectiveness of Social Stories when used in isolation. An increasing body of literature has indicated that Social Stories are an effective intervention for children diagnosed with autistic spectrum disorders, however very few studies have addressed the efficacy of Social Stories when used with children with other disabilities.

Combination of 15q24 Microdeletion Syndrome and Metabolic Imbalance in a Patient with Atypical Autism.

Autistic spectrum disorders (ASD) in children are becoming increasingly common, reaching epidemic proportions. Among the various causes contributing to the development of ASD, the leading place belongs to both chromosomal pathologies and genetic syndromes and their consequence - metabolic imbalance or severe metabolic disorders. Depending on the degree of metabolic pathway damage, certain phenotypes of ASD are formed. A deletion of ~3.1 Mb of chromosome 15q24 was detected in the examined 2-year-old boy with a "mild phenotype" of autism without an obvious delay in mental development. A wide range of additional studies included genetic testing of folate metabolism genes and analysis of metabolites of the methylation cycle and detection of antibodies to folic acid alpha receptors. A heterozygous variant of the MTHFR gene (rs1801133), moderate hyperhomocysteinemia, hypermethylation, and an increased titer of antibodies to alpha receptors of folic acid were revealed in the patient. This clinical case indicates the need for a multifaceted clinical and laboratory examination in children with ASD to identify the metabolic phenotype and prescribe personalized treatment. A personalized treatment strategy will improve the cognitive functions, psycho-emotional state, and social adaptation of individuals with ASD in the long term."

Psychometric Properties of the Chinese Version of the Core Symptom Index: A Study among Chinese Parents of Children with Autistic Spectrum Disorders.

(1) Background: Parents of children with autism spectrum disorders often experience psychological distress, which can affect the quality of childcare they provide. It is crucial to screen for psychiatric symptoms among these parents. The core symptom index (CSI) is a widely recognized tool used to assess general symptoms, including depression, anxiety, and somatic issues. It has proven validity and reliability across diverse Thai populations. Given the cultural similarities between Thai and Chinese populations, the CSI has been successfully implemented within the Chinese population. Nevertheless, it is crucial to research its validity and reliability in the general Chinese population. This study aimed to investigate the psychometric properties of the Chinese version of the CSI among parents of children with autism spectrum disorders using confirmatory factor analysis (CFA). (2) Methods: A total of 794 Chinese parents raising children with autism participated in this study. All completed the CSI, along with the social inhibition subscale of the Interpersonal Problems Inventory and the Couple Satisfaction Index. Factorial validity was assessed using CFA to determine how well the bifactor three-factor model fits the data. Various structural models were compared using model fit indices. Convergent and discriminant validity were examined by exploring correlations with the social inhibition subscale and the Couple Satisfaction Index. Invariance testing of the CSI was conducted across multiple groups based on gender, age, and education using CFA. The reliability of the CSI was evaluated using McDonald's omega coefficients. (3) Results: The bifactor model emerged as the best-fitting model for the data, suggesting that the total score of the CSI adequately represents overall psychiatric symptoms. The CSI exhibited significant correlations with the social inhibition subscale (r = 0.41, p < 0.01) and smaller correlation coefficients with the Couple Satisfaction Index (r = -0.16, p < 0.05), indicating both convergent and discriminant validity. The invariant test results support scalar invariance levels based on gender and age but only partial invariance for education. The Chinese version of the CSI demonstrated high consistency, with McDonald's omega coefficients ranging between 0.86 and 0.95. (4) Conclusions: The bifactor model of the Chinese version of the CSI is validated, making it a suitable tool for measuring depression, anxiety, and somatization symptoms among parent(s) of children with autism spectrum disorders. Further research on other Chinese populations is encouraged.