A prospective study of associations between early fearfulness and perceptual sensitivity and later restricted and repetitive behaviours in infants with typical and elevated likelihood of autism

Autism is diagnosed based on social and communication difficulties, restricted and repetitive behaviours and sensory anomalies. Existing evidence indicates that anxiety and atypical sensory features are associated with restricted and repetitive behaviours, but cannot clarify the order of emergence of these traits. This study uses data from a prospective longitudinal study of infants with and without a family history of autism ( N = 247; Elevated Likelihood N = 170 and Typical Likelihood N = 77). Longitudinal cross-lag models tested bidirectional pathways between parent-rated infant fear/shyness and perceptual sensitivity at 8, 14 and 24 months, and associations between these domains and parent-rated restricted and repetitive behaviours and social communication scores at 36 months. In addition to within-domain continuity, higher levels of fear/shyness at 14 months were associated with higher levels of perceptual sensitivity at 24 months. Higher levels of both fear/shyness and perceptual sensitivity at 24 months were associated with greater restricted and repetitive behaviours and social communication scores at 36 months. Results demonstrate the directionality of developmental pathways between fear/shyness and perceptual sensitivity in infancy and toddlerhood, but question theories that argue that these domains specifically underlie restricted and repetitive behaviours rather than autism. Identifying how early emerging anxiety and sensory behaviours relate to later autism is important for understanding pathways and developing targeted support for autistic children. Lay abstract Restricted interests and repetitive behaviours are central to the diagnosis of autism and can have profound effects on daily activities and quality of life. These challenges are also linked to other co-occurring conditions such as anxiety and sensory sensitivities. Here, we looked at whether early emerging signs of anxiety and sensory problems appear before symptoms of autism by studying infants with a family history of autism, as these infants are more likely to develop autism themselves. Studying infant siblings provides an opportunity for researchers to focus on early developmental markers of autism as these infants can be followed from birth. This study found that early infant signs of anxiety (e.g. fear/shyness) predicted later perceptual sensitivity, and those infants who scored higher on fear/shyness and sensitivity were more likely to experience more persistent repetitive behaviours, but also social and communication difficulties in toddlerhood. Early signs of anxiety and perceptual sensitivity may thus relate to both later social difficulties and repetitive behaviours. These findings support the importance of further research exploring the causal links between these domains in relation to autism, resulting in increased understanding of children who go onto develop autism in the future and guiding early interventions and supports.

AN OBSERVATIONAL STUDY TO ASSESS THE PARENTAL DOSHA PRAKRITI OF AUTISTIC CHILDREN

Prakriti refers to the genetically determined physical and mental constitution of an individual. Autism is a lifelong disability identified by impaired communication, social interaction and repetitive behaviours. The genetic, envi- ronmental and immunological factors play an important role in generating autism. Genetic factors are more pre- dominant in autism pathogenesis than the environmental factors that would modulate the phenotype. Until now, no interventions have proven widely effective in providing complete relief to autism. Therefore, the prevention of autism needs supreme attention. To a greater extent, prakriti of an individual can determine proneness to particu- lar diseases. To assess the prakriti of both parents of 30 diagnosed cases of autistic children attending the OPD and IPD of Govt. Ayurveda College, Kannur were randomly selected. They are subjected to detailed history taking based on specially prepared proforma and assessments were recorded. Their prakriti assessment was done using a validated computer-assisted questionnaire software Ayusoft developed by C-DAC Pune. The data was statistically analysed. In this study, Vata pitta prakriti was significantly seen in mothers of autistic children. Keywords: Prakriti, Autism

Genetic determinants of autism spectrum disorders - a review

Introduction: It is estimated that various types of abnormalities from the autistic spectrum disorder occur in up to 2% of the population. These include difficulties in maintaining relationships, communication, and repetitive behaviours. Literature describes them quite well, in contrast to the causes of these disorders, which include both environmental factors and a very long list of genetic aberrations. Materials and methods: The papers available on the PubMed platform and other sources were reviewed to describe the most important genetic factors responsible for the development of autism spectrum disorders. Results: There are many genes and their mutations associated with the prevalence of autism spectrum disorders in patients. One of the main factors is the SHANK gene family, with the type and degree of abnormality in patients depending on the damage to particular genes: SHANK1-SHANK3. Research also shows the potential of targeted symptom-relieving therapies in patients with SHANK3 mutations. A correlation with the occurrence of autism has also been demonstrated for genes responsible for calcium signaling - especially the group of IP3R calcium channels. Their calcium transmission is abnormal in the majority of patients with autism spectrum disorders. A number of mutations in the 7q region were discovered - including the AUTS2, GNAI1, RELN, KMT2E, BRAF genes - the occurrence of which is associated with the presence of symptoms of autism. Autism spectrum disorders occur in about 10% of patients suffering from monogenic syndromes such as fragile X chromosome syndrome, Timothy syndrome, tuberous sclerosis, Rett syndrome or hamartomatic tumor syndrome. Conclusions: Research shows that many mutations can contribute to the development of autism spectrum disorders. Further studies are necessary to discover their therapeutic and diagnostic potential for autism.

Reduced Axon Calibre in the Associative Striatum of the Sapap3 Knockout Mouse

Pathological repetitive behaviours are a common feature of various neuropsychiatric disorders, including compulsions in obsessive–compulsive disorder or tics in Gilles de la Tourette syndrome. Clinical research suggests that compulsive-like symptoms are related to associative cortico-striatal dysfunctions, and tic-like symptoms to sensorimotor cortico-striatal dysfunctions. The Sapap3 knockout mouse (Sapap3-KO), the current reference model to study such repetitive behaviours, presents both associative as well as sensorimotor cortico-striatal dysfunctions. Previous findings point to deficits in both macro-, as well as micro-circuitry, both of which can be affected by neuronal structural changes. However, to date, structural connectivity has not been analysed. Hence, in the present study, we conducted a comprehensive structural characterisation of both associative and sensorimotor striatum as well as major cortical areas connecting onto these regions. Besides a thorough immunofluorescence study on oligodendrocytes, we applied AxonDeepSeg, an open source software, to automatically segment and characterise myelin thickness and axon area. We found that axon calibre, the main contributor to changes in conduction speed, is specifically reduced in the associative striatum of the Sapap3-KO mouse; myelination per se seems unaffected in associative and sensorimotor cortico-striatal circuits.

The Mediating Effects of Alexithymia, Intolerance of Uncertainty, and Anxiety on the Relationship Between Sensory Processing Differences and Restricted and Repetitive Behaviours in Autistic Adults

Distress caused by sensory processing differences for autistic individuals may be reduced by repetitive behaviours (RRB), including repetitive motor (RMB) and insistence on sameness (ISB) behaviours. Intolerance of uncertainty (IU) and anxiety mediate the relationship between sensory processing and RRB in autistic children. We replicated this model in autistic adults, extending it to include alexithymia. Serial mediation, using data from 426 autistic adults, identified significant direct effects from sensory processing to RMB and ISB, and indirect effects through alexithymia-IU-anxiety for RMB, and IU alone, and alexithymia-IU for ISB. Different mechanisms may underpin RMB and ISB. Alexithymia alongside, IU and anxiety, should be considered when understanding the relationship between sensory processing and RRB, and when offering interventions to support autistic people.

Exploring the impact of adolescent cognitive inflexibility on emotional and behavioural problems experienced by autistic adults

Autistic young people experience high levels of co-occurring mental health difficulties, including anxiety, depression and behavioural difficulties, across their lifespan. Understanding the neuropsychological mechanisms which underlie these difficulties is vital in developing personalised supports and interventions. Cognitive inflexibility is one candidate mechanism which is associated with co-occurring mental health comorbidities but is also associated with other features of autism such as restricted and repetitive behaviours. This study investigates the distinct longitudinal association between cognitive inflexibility, measured using objective neuropsychological measures and emotional and behavioural problems across adolescence and early adulthood. Eighty-one autistic people from a population-based longitudinal study were assessed at 16 and 23 years on measures of emotional and behavioural problems, with cognitive inflexibility, restricted and repetitive behaviours and verbal intelligence quotient measured at 16 years. We used structural equation modelling to investigate the relationship between cognitive inflexibility and emotional and behavioural symptoms at both timepoints while accounting for the severity of restricted and repetitive behaviours and verbal intelligence quotient. Our results indicate an effect of cognitive inflexibility on increased behavioural problems at 16 years and emotional problems across timepoints, which is distinct from restricted and repetitive behaviours and verbal intelligence quotient. Exploratory mediation analyses suggest that cognitive inflexibility may be one mechanism through which emotional difficulties are maintained longitudinally. Lay abstract Autistic people experience high levels of co-occurring mental health difficulties. To develop more effective treatments, a greater understanding of the thinking processes that may lead to these difficulties is needed. Cognitive inflexibility, defined as a rigid pattern of thoughts and subsequently behaviours, is one possible thinking trait which has previously been associated with both co-occurring mental health difficulties but also other features of autism such as restricted and repetitive behaviours. Restricted and repetitive behaviours include repetitive movements, ritualistic behaviours, and/or highly focused interests. This study investigates the relationship between, cognitive inflexibility, measured using neuropsychological tasks, and emotional and behavioural problems across adolescence and early adulthood. Eighty-one autistic people who were recruited to be representative of the wider autism population were assessed at 16 and 23 years on measures of emotional and behavioural problems, with cognitive inflexibility, restricted and repetitive behaviours and verbal intelligence measured at 16 years. We used statistical modelling to investigate the relationship between cognitive inflexibility and emotional and behavioural symptoms at both timepoints while accounting for the possible relationship with restricted and repetitive behaviours and verbal intelligence quotient. Our results suggest that cognitive inflexibility may be an important factor associated with emotional difficulties across adolescence and early adulthood. This suggests that developing intervention approaches targeting cognitive inflexibility may be an important step in improving the mental health of those with autism.

Maternal Mid-Gestation Cytokine Dysregulation in Mothers of Children with Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a developmental disorder characterised by deficits in social interactions and communication, with stereotypical and repetitive behaviours. Recent evidence suggests that maternal immune dysregulation may predispose offspring to ASD. Independent samples t-tests revealed downregulation of IL-17A concentrations in cases, when compared to controls, at both 15 weeks (p = 0.02), and 20 weeks (p = 0.02), which persisted at 20 weeks following adjustment for confounding variables. This adds to the growing body of evidence that maternal immune regulation may play a role in foetal neurodevelopment.

Helping autistic children

Autism is a highly heritable neurodevelopmental condition, with prevalence estimated at 1 in 100 people worldwide (Elsabbagh et al., 2012). Autism is diagnosed by behavioural presentation, and although there is substantial variability both within autistic people across the lifespan, and between autistic individuals, a set of core diagnostic criteria are relied on by clinicians. These criteria are broadly categorised in two ways: (1) distinctive patterns of social communication and interactions with others, and (2) restricted or repetitive behaviours or interests (American Psychiatric Association, APA, 2013) (for a comprehensive overview of the current autism research, see: Fletcher-Watson & Happé, 2019).Given the emphasis on social and communication difficulties in the diagnostic criteria of autism, and the pivotal role they play in development generally, these domains are commonly key targets for autism interventions. Here, we first provide an overview of different types of traditional social interventions and evaluate their effectiveness and validity. We also present some of the possible risks associated with such interventions, and suggest a number of means for autistic children to develop social and communication capacities on their own terms, in both family and educational settings. We end by considering some other factors essential for understanding the social development of autistic children in context and informing development and delivery of supports.