1. {{Erratum: Children with autism spectrum disorders and selective mutism [Corrigendum]}}. {Neuropsychiatric disease and treatment}. 2018; 14: 2305.
[This corrects the article on p. 1163 in vol. 14, PMID: 29765220.].
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2. Ajram LA, Pereira AC, Durieux AMS, Velthius HE, Petrinovic MM, McAlonan GM. {{The contribution of [1H] magnetic resonance spectroscopy to the study of excitation-inhibition in autism}}. {Progress in neuro-psychopharmacology & biological psychiatry}. 2018; 89: 236-44.
Autism spectrum disorder (ASD) affects over 1:100 of the population and costs the UK more than pound32bn and the USA more than $175bn ( pound104bn) annually. Its core symptoms are social and communication difficulties, repetitive behaviours and sensory hyper- or hypo-sensitivities. A highly diverse phenotypic presentation likely reflects its etiological heterogeneity and makes finding treatment targets for ASD challenging. In addition, there are no means to identify biologically responsive individuals who may benefit from specific interventions. There is hope however, and in this review we consolidate how findings from magnetic resonance spectroscopy (MRS) add to the evidence that differences in the brain’s excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) balance may be both a key biomarker and a tractable treatment target in ASD.
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3. Bennett AE, Miller JS, Stollon N, Prasad R, Blum NJ. {{Autism Spectrum Disorder and Transition-Aged Youth}}. {Current psychiatry reports}. 2018; 20(11): 103.
PURPOSE OF REVIEW: This article discusses common issues surrounding transition to adulthood in youth with autism spectrum disorder (ASD). We review recent evidence on co-occurring medical and mental health conditions and topics of education and employment, sexuality and relationships, independent living, and financial support. RECENT FINDINGS: Transitioning individuals with ASD have increased risk for several medical and behavioral health comorbidities and should be routinely screened for co-occurring conditions. Evidence on interventions for mental health disorders is limited but emerging, particularly with respect to mindfulness training and cognitive behavioral therapy. Many autistic adults or their families express a desire for independent living, participation in education/employment, and intimacy and social relationships, but they often lack skills and/or resources to successfully achieve these outcomes. The time of transition to adulthood for adolescents with ASD is an opportunity for physicians to provide anticipatory guidance and necessary supports around issues of community participation. To allow time for planning, these discussions should occur well before the child reaches adulthood. Clinicians should also routinely screen for and address medical and/or behavioral health comorbidities.
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4. Chapin S, McNaughton D, Boyle S, Babb S. {{Effects of Peer Support Interventions on the Communication of Preschoolers with Autism Spectrum Disorder: A Systematic Review}}. {Seminars in speech and language}. 2018.
Many young children with autism spectrum disorders (ASDs) experience difficulty in the development of communication skills. Teaching peers to make use of communication support behaviors has been investigated as a strategy to increase communication for young children with ASD in early childhood settings. The purpose of this systematic review was to examine (1) the overall effects of peer support interventions on the communication of young children with ASD and (2) any possible moderating variables related to participant and intervention characteristics. The social support model was used as a framework for the study of intervention components. Eighteen single-case experimental design studies (48 children with ASD) met the inclusion criteria and were advanced to the full coding and analysis phase of the investigation. Descriptive analyses and effect size estimations using the improvement rate difference (IRD) metric were conducted. Overall, peer support interventions were found to be effective across a range of young children with ASD and intervention approaches. Evidence was also identified for the use of the social support model as a framework to guide the development of peer interventions in early childhood settings. The use of friendship groups, the selection of play materials based on the interests of the child with ASD, and the provision of augmentative and alternative communication appeared to be associated with positive communication outcomes.
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5. Donato C, Spencer E, Arthur-Kelly M. {{A critical synthesis of barriers and facilitators to the use of AAC by children with autism spectrum disorder and their communication partners}}. {Augmentative and alternative communication (Baltimore, Md : 1985)}. 2018: 1-12.
The aim of this review was to critically synthesize barriers and facilitators to the use of AAC systems by children with autism spectrum disorder (ASD) and their communication partners. Qualitative data related to barriers and facilitators were synthesized from 42 studies located using a systematic search. A diverse range of studies was examined in order to identify the span of barriers and facilitators reported in the literature. Included studies comprised quasi-experimental, non-experimental, and qualitative study designs. The full range of unaided, low-tech aided, and high-tech aided AAC systems were reported across the included studies. The critical synthesis identified 5 themes to which barriers and facilitators are related: (a) Intervention Services and Service Providers, (b) AAC Systems and Technologies (c), Communication Partners of Children with ASD, (d) Parents of Children with ASD, and (e) Children with ASD. The findings suggest that barriers and facilitators to the use of AAC vary across individuals, AAC modalities, and environments. By identifying barriers and facilitators to the use of AAC experienced by children with ASD and their communication partners, service providers might be better equipped to support these children and their communication partners. Clinical implications and future research directions are discussed.
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6. Green J, Aldred C, Charman T, Le Couteur A, Emsley RA, Grahame V, Howlin P, Humphrey N, Leadbitter K, McConachie H, Parr JR, Pickles A, Slonims V, Taylor C. {{Paediatric Autism Communication Therapy-Generalised (PACT-G) against treatment as usual for reducing symptom severity in young children with autism spectrum disorder: study protocol for a randomised controlled trial}}. {Trials}. 2018; 19(1): 514.
BACKGROUND: Prior evidence shows that behaviours closely related to the intervention delivered for autism are amenable to change, but it is more difficult to generalise treatment effects beyond the intervention context. We test an early autism intervention designed to promote generalisation of therapy-acquired skills into home and school contexts to improve adaptive function and reduce symptoms. A detailed mechanism study will address the process of such generalisation. Objective 1 will be to test if the PACT-G intervention improves autism symptom outcome in the home and school context of the intervention as well as in the primary outcome research setting. Objective 2 will use the mechanism analysis to test for evidence of acquired skills from intervention generalizing across contexts and producing additive effects on primary outcome. METHODS/DESIGN: This is a three-site, two-parallel-group, randomised controlled trial of the experimental treatment plus treatment as usual (TAU) versus TAU alone. Children aged 2-11 years (n = 244 (122 intervention/122 TAU; ~ 82/site) meeting criteria for core autism will be eligible. The experimental intervention builds on a clinic-based Pre-school Autism Communication Treatment model (PACT), delivered with the primary caregiver, combined with additional theory- and evidence-based strategies designed to enhance the generalisation of effects into naturalistic home and education contexts. The control intervention will be TAU. PRIMARY OUTCOME: autism symptom outcome, researcher-assessed using a standardised protocol. SECONDARY OUTCOMES: autism symptoms, child interaction with parent or teacher, language and reported functional outcomes in home and school settings. Outcomes measured at baseline and 12-month endpoint in all settings with interim interaction measurements (7 months) to test treatment effect mechanisms. Primary analysis will estimate between-group difference in primary outcome using analysis of covariance with test of homogeneity of effect across age group. Mechanism analysis will use regression models to test for mediation on primary outcome by parent-child and teaching staff-child social interaction. DISCUSSION: This is an efficacy and mechanism trial of generalising evidence-based autism treatment into home and school settings. It will provide data on whether extending treatment across naturalistic contexts enhances overall effect and data on the mechanism in autism development of the generalisation of acquired developmental skills across contexts. TRIAL REGISTRATION: ISRCTN, ID: 25378536 . Prospectively registered on 9 March 2016.
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7. Hayward DA, Fenerci C, Ristic J. {{An investigation of global-local processing bias in a large sample of typical individuals varying in autism traits}}. {Consciousness and cognition}. 2018; 65: 271-9.
Although individuals with an autism spectrum disorder display impaired function across several social and behavioral domains, they possess intact, and often superior visual processing abilities for local relative to global aspects of their visual environment. To address whether differences in visual processing similarly vary within typical individuals as a function of their level of social competence, using the Navon hierarchical figures task, here we examined the relationship between global-local visual processing style and the number of autism-like traits in a large sample of 434 typically developed persons. In line with the existing literature, our data indicated an overall global processing bias. However, this overall visual processing style did not vary with participants’ number of autism-like traits. These results suggest that the visual processing of Navon figures may be different in typical individuals vs. those with an autism spectrum disorder, with those differences potentially reflecting specific stimulus and task settings.
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8. Jun E, Kang E, Choi J, Suk HI. {{Modeling regional dynamics in low-frequency fluctuation and its application to Autism spectrum disorder diagnosis}}. {NeuroImage}. 2018.
With the advent of neuroimaging techniques, many studies in the literature have validated the use of resting-state fMRI (rs-fMRI) for understanding functional mechanisms of the brain, as well as for identifying brain disorders or diseases. One of the main streams in recent studies of modeling and analyzing rs-fMRI data is to account for the dynamic characteristics of a brain. In this study, we propose a novel method that directly models the regional temporal BOLD fluctuations in a stochastic manner and estimates the dynamic characteristics in the form of likelihoods. Specifically, we modeled temporal BOLD fluctuation of individual Regions Of Interest (ROIs) by means of Hidden Markov Models (HMMs), and then estimated the ‘goodness-of-fit’ of each ROI’s BOLD signals to the corresponding trained HMM in terms of a likelihood. Using estimated likelihoods of the ROIs over the whole brain as features, we built a classifier that can discriminate subjects with Autism Spectrum Disorder (ASD) from Typically Developing (TD) controls at an individual level. In order to interpret the trained HMMs and a classifier from a neuroscience perspective, we also conducted model analysis. First, we investigated the learned weight coefficients of a classifier by transforming them into activation patterns, from which we could identify the ROIs that are highly associated with ASD and TD groups. Second, we explored the characteristics of temporal BOLD signals in terms of functional networks by clustering them based on sequences of the hidden states decoded with the trained HMMs. We validated the effectiveness of the proposed method by achieving the state-of-the-art performance on the ABIDE dataset and observed insightful patterns related to ASD.
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9. Nguyen HTN, Kato H, Masuda K, Yamaza H, Hirofuji Y, Sato H, Pham TTM, Takayama F, Sakai Y, Ohga S, Taguchi T, Nonaka K. {{Impaired neurite development associated with mitochondrial dysfunction in dopaminergic neurons differentiated from exfoliated deciduous tooth-derived pulp stem cells of children with autism spectrum disorder}}. {Biochemistry and biophysics reports}. 2018; 16: 24-31.
Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder characterized by impaired social interactions, restrictive interests, and repetitive stereotypic behaviors. Among the various mechanisms underlying the pathogenesis of ASD, dysfunctions of dopaminergic signaling and mitochondria have been hypothesized to explain the core symptoms of children with ASD. However, only a few studies focusing on the pathological association between dopaminergic neurons (DN) and mitochondria in ASD have been performed using patient-derived stem cells and in vitro differentiated neurons. Stem cells from human exfoliated deciduous teeth (SHED) are neural crest-derived mesenchymal stem cells present in the dental pulp of exfoliated deciduous teeth; these cells can differentiate into dopaminergic neurons (DN) in vitro. This study aimed to investigate the pathological association between development of DN and mitochondria in ASD by using SHED as a disease- or patient-specific cellular model. The SHED obtained from three children with ASD and three typically developing children were differentiated into DN, and the neurobiology of these cells was examined. The DN derived from children with ASD showed impaired neurite outgrowth and branching, associated with decreased mitochondrial membrane potential, ATP production, number of mitochondria within the neurites, amount of mitochondria per cell area and intracellular calcium level. In addition, impaired neurite outgrowth and branching of ASD-derived DN were not improved by brain-derived neurotrophic factor (BDNF), suggesting impairment of the BDNF signaling pathway in ASD. These results imply that intracerebral dopamine production may have decreased in these children. The earliest age at which deciduous teeth spontaneously exfoliate in humans, and SHED can be noninvasively collected, is approximately 6 years. Our results suggest that in vitro analysis of SHED-derived DN obtained from children with ASD provides neurobiological information that may be useful in determining treatment strategies in the early stages of ASD.
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10. Ocak E, Eshraghi RS, Danesh A, Mittal R, Eshraghi AA. {{Central Auditory Processing Disorders in Individuals with Autism Spectrum Disorders}}. {Balkan medical journal}. 2018; 35(5): 367-72.
The etiology and the underlying pathogenetic mechanisms of autism spectrum disorders are still largely unknown. This article provides a comprehensive review of the studies that are relevant to autism spectrum disorders and central auditory processing disorders and also discusses the relationship between autism spectrum disorders and central auditory processing disorders in the light of recent studies on this subject, which may provide new pathways in a therapeutic perspective. Several studies confirm that most of the individuals with an autism spectrum disorder have some degree of sensory dysfunction related to disorders of processing auditory, visual, vestibular, and/or tactile stimuli. Among these studies, some have addressed central auditory processing disorders. There is an increasing amount of effort for studies regarding the link between autism spectrum disorders and central auditory processing disorders. Most of the studies investigating central auditory processing disorders in patients with autism spectrum disorders have used electrophysiological measurements such as mismatch negativity and P300 event-related potentials. In addition to these, several studies have reported deterioration in speech perception and expression in patients with autism spectrum disorders, which may also be related to central auditory processing disorders in this unique group of individuals.
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11. Overweg J, Hartman CA, Hendriks P. {{Temporarily Out of Order: Temporal Perspective Taking in Language in Children With Autism Spectrum Disorder}}. {Frontiers in psychology}. 2018; 9: 1663.
Clinical reports suggest that children with autism spectrum disorder (ASD) struggle with time perception, but few studies have investigated this. This is the first study to examine these children’s understanding of before and after. These temporal conjunctions have been argued to require additional cognitive effort when conjoining two events in a clause order that is incongruent with their order in time. Given the suggested time perception impairment and well-established cognitive deficits of children with ASD, we expected them to have difficulties interpreting temporal conjunctions, especially in an incongruent order. To investigate this, the interpretation of before and after in congruent and incongruent orders was examined in 48 children with ASD and 43 typically developing (TD) children (age 6-12). Additional tasks were administered to measure Theory of Mind (ToM), working memory (WM), cognitive inhibition, cognitive flexibility, IQ, and verbal ability. We found that children with ASD were less accurate in their interpretation of temporal conjunctions than their TD peers. Contrary to our expectations, they did not have particular difficulties in an incongruent order. Furthermore, older children showed better overall performance than younger children. The difference between children with ASD and TD children was explained by WM, ToM, IQ, and verbal ability, but not by cognitive inhibition and flexibility. These cognitive functions are more likely to be impaired in children with ASD than in TD children, which could account for their poorer performance. Thus, the cognitive factors found to affect the interpretation of temporal language in children with ASD are likely to apply in typical development as well. Sufficient WM capacity and verbal ability may help children to process complex sentences conjoined by a temporal conjunction. Additionally, ToM understanding was found to be related to children’s interpretation of temporal conjunctions in an incongruent order, indicating that perspective taking is required when events are presented out of order. We conclude from this that perspective-taking abilities are needed for the interpretation of temporal conjunctions, either to shift one’s own perspective as a hearer to another point in time, or to shift to the perspective of the speaker to consider the speaker’s linguistic choices.
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12. Pejovic-Milovancevic M, Stankovic M, Mitkovic-Voncina M, Rudic N, Grujicic R, Herrera AS, Stojanovic A, Nedovic B, Shih A, Mandic-Maravic V, Daniels A. {{Perceptions on Support, Challenges and Needs among Parents of Children with Autism: the Serbian Experience}}. {Psychiatria Danubina}. 2018; 30(Suppl 6): 354-64.
BACKGROUND: Autism spectrum disorders (ASD) significantly impact lives of affected individuals and their families. They confront daunting challenges and multiple demands in their daily life, when compared to parents of children with other disabilities or parents of typically developing children. SUBJECTS AND METHODS: Participants completed The Caregiver Needs Survey, the survey intended for parents or primary caregivers of children with a diagnosis of ASD. During the study, 231 parents were interviewed; 167 mothers and 64 fathers. Parents were recruited from the patient database comprised of families from the two largest cities in Serbia. All of them were contacted before the study, either via phone or at the child’s regular check-in visit. RESULTS: Over 90 percent of the parents reported that additional support at schools, home, and improved relationships with service providers are necessary and important. The most important challenges related to care were child’s communication difficulties, social interaction difficulties, and problems with daily living skills. The significant predictors of lower overall satisfaction were parent’s higher education, having a first concern related to problems of the child’s interaction with others or playing alone, and parent frustration with accessing services in the past 12 months. Greater overall satisfaction, on the other hand, was related to having an in-school tutor training or assistance in managing child’s needs or implementing treatments, and having primary care doctor or pediatrician as a source of information on autism. CONCLUSIONS: Future efforts to develop ASD-related policies and services should also take the following into consideration: the low level of awareness among caregivers and health care providers about the early signs of autism; disparities in access to services; educational problems and significant levels of dissatisfaction with the overall care and stigma.
13. Pujol CN, Pellissier LP, Clement C, Becker JAJ, Le Merrer J. {{Back-translating behavioral intervention for autism spectrum disorders to mice with blunted reward restores social abilities}}. {Translational psychiatry}. 2018; 8(1): 197.
The mu opioid receptor (MOR) plays a critical role in modulating social behavior in humans and animals. Accordingly, MOR null mice display severe alterations in their social repertoire as well as multiple other behavioral deficits, recapitulating core and secondary symptoms of autism spectrum disorder (ASD). Such behavioral profile suggests that MOR dysfunction, and beyond this, altered reward processes may contribute to ASD etiopathology. Interestingly, the only treatments that proved efficacy in relieving core symptoms of ASD, early behavioral intervention programs, rely principally on positive reinforcement to ameliorate behavior. The neurobiological underpinnings of their beneficial effects, however, remain poorly understood. Here we back-translated applied behavior analysis (ABA)-based behavioral interventions to mice lacking the MOR (Oprm1(-/-)), as a model of autism with blunted reward processing. By associating a positive reinforcement, palatable food reward, to daily encounter with a wild-type congener, we were able to rescue durably social interaction and preference in Oprm1(-/-) mice. Along with behavioral improvements, the expression of marker genes of neuronal activity and plasticity as well as genes of the oxytocin/vasopressin system were remarkably normalized in the reward/social circuitry. Our study provides further evidence for a critical involvement of reward processes in driving social behavior and opens new perspectives regarding therapeutic intervention in ASD.
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14. Rais M, Binder DK, Razak KA, Ethell IM. {{Sensory Processing Phenotypes in Fragile X Syndrome}}. {ASN neuro}. 2018; 10: 1759091418801092.
Fragile X syndrome (FXS) is a neurodevelopmental disorder that causes intellectual disability. It is a leading known genetic cause of autism. In addition to cognitive, social, and communication deficits, humans with FXS demonstrate abnormal sensory processing including sensory hypersensitivity. Sensory hypersensitivity commonly manifests as auditory, tactile, or visual defensiveness or avoidance. Clinical, behavioral, and electrophysiological studies consistently show auditory hypersensitivity, impaired habituation to repeated sounds, and reduced auditory attention in humans with FXS. Children with FXS also exhibit significant visuospatial impairments. Studies in infants and toddlers with FXS have documented impairments in processing texture-defined motion stimuli, temporal flicker, perceiving ordinal numerical sequence, and the ability to maintain the identity of dynamic object information during occlusion. Consistent with the observations in humans with FXS, fragile X mental retardation 1 ( Fmr1) gene knockout (KO) rodent models of FXS also show seizures, abnormal visual-evoked responses, auditory hypersensitivity, and abnormal processing at multiple levels of the auditory system, including altered acoustic startle responses. Among other sensory symptoms, individuals with FXS exhibit tactile defensiveness. Fmr1 KO mice also show impaired encoding of tactile stimulation frequency and larger size of receptive fields in the somatosensory cortex. Since sensory deficits are relatively more tractable from circuit mechanisms and developmental perspectives than more complex social behaviors, the focus of this review is on clinical, functional, and structural studies that outline the auditory, visual, and somatosensory processing deficits in FXS. The similarities in sensory phenotypes between humans with FXS and animal models suggest a likely conservation of basic sensory processing circuits across species and may provide a translational platform to not just develop biomarkers but also to understand underlying mechanisms. We argue that preclinical studies in animal models of FXS can facilitate the ongoing search for new therapeutic approaches in FXS by understanding mechanisms of basic sensory processing circuits and behaviors that are conserved across species.
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15. Tsai HJ, Cebula K, Liang SH, Fletcher-Watson S. {{Siblings’ experiences of growing up with children with autism in Taiwan and the United Kingdom}}. {Research in developmental disabilities}. 2018; 83: 206-16.
BACKGROUND: A child’s diagnosis of autism impacts their whole family, in both positive and negative ways, that may be influenced by cultural beliefs. AIMS: We aimed to describe the experiences of mothers and typically-developing siblings of children with autism in two cultural contexts. METHODS: Fourteen mother-sibling dyads from Taiwan and the UK participated in semi-structured interviews. RESULTS: Whilst there were similarities in sibling experiences, a negative tone regarding the influence of autism was more evident in Taiwan, where families also cited societal judgement and cultural-specific expectations. In the UK, a more balanced tone was apparent: mothers emphasised educating and involving the siblings. It is speculated that UK siblings had a greater understanding of their parents’ stress, leading to more adaptive family dynamics. Various types of support service were mentioned in the UK, whereas the availability of social services and support appeared to be relatively limited in Taiwan. IMPLICATIONS: Our data suggest that cultural context may have a significant impact on the responses of the family members. This is mediated by both differences in attitudes and traditions, and availability of resources. Support for family members needs to be sensitive to such cultural differences, as well as recognising positive experiences.
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16. Tsilimingras D, Gibson Scipio W, Clancy K, Hudson L, Liu X, Mendez J, Benkert R. {{Interprofessional education during an autism session}}. {Journal of communication disorders}. 2018; 76: 71-8.
Interprofessional education (IPE) gained a strong foothold in the beginning of the twenty-first century as an effort to improve care to patients through enhanced teamwork. The aim of this study was to compare attitudes and experiences of the learners, which included graduate students, physicians in training, and practicing healthcare professionals, before and after an interprofessional clinical practice (IPCP) six-h autism didactic and experiential training session. The training session consisted of a 1-h lecture on Autism Spectrum Disorder (ASD), a 2-h behavior review meeting consisting of four different case study discussions among the learners, a 1-h lunch, a 1-h therapy session with children diagnosed with ASD, and a 1-h discussion among the learners. The IPCP learners (n = 63) completed a pre- and post-learning questionnaire of the Readiness for Interprofessional Learning Scale (RIPLS) and 12 Statements instruments and both showed an overall significant improvement in the learners interprofessional education after completing the training session. This study was able to show that students, professional trainees, and practicing professionals from different backgrounds led by an expert in the field can exchange ideas and role perceptions in an interprofessional didactic and experiential session, and develop improved attitudes toward IPCP. Moving forward, interprofessional education research needs to focus more on professional trainees and practicing professionals working together in combined didactic and experiential environments for children diagnosed with ASD.
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17. Xavier J, Gauthier S, Cohen D, Zahoui M, Chetouani M, Villa F, Berthoz A, Anzalone S. {{Interpersonal Synchronization, Motor Coordination, and Control Are Impaired During a Dynamic Imitation Task in Children With Autism Spectrum Disorder}}. {Frontiers in psychology}. 2018; 9: 1467.
Background: Impairments in imitation abilities have been commonly described in children with autism spectrum disorder (ASD). How motricity in interpersonal coordination impacts imitation, during long lasting semi-ecological conditions, has not been carefully investigated. Methods: Eighty-five children and adolescents (39 controls with typical development, TD; 29 patients with ASD; 17 patients with developmental coordination disorder, DCD), aged 6 to 20 years, participated to a behavioral paradigm in which participants, standing and moving, interacted with a virtual tightrope walker standing and moving as well. During the protocol, we measured automatically and continuously bodily postures and movements from RGB sensor recording to assess participants’ behavioral imitation. Results: We show that (1) interpersonal synchronization (as evidenced by the synchrony between the participant’s and the tightrope walker’s bars) and (2) motor coordination (as evidenced by the synchrony between the participant’s bar and its own head axis) increased with age and were more impaired in patients with ASD. Also, motor control as evidenced by the movement angle standard deviations of participants’ bar and head were significantly impaired in ASD compared to TD or DCD. Conclusion: Interpersonal synchronization and motor coordination during ecological interaction show both subtle impairment in children with ASD as compared to children with TD or DCD. These results questioned how motricity mature in terms of motor control and proprioception in children with ASD.
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18. Yan J, Porch MW, Court-Vazquez B, Bennett MVL, Zukin RS. {{Activation of autophagy rescues synaptic and cognitive deficits in fragile X mice}}. {Proceedings of the National Academy of Sciences of the United States of America}. 2018.
Fragile X syndrome (FXS) is the most frequent form of heritable intellectual disability and autism. Fragile X (Fmr1-KO) mice exhibit aberrant dendritic spine structure, synaptic plasticity, and cognition. Autophagy is a catabolic process of programmed degradation and recycling of proteins and cellular components via the lysosomal pathway. However, a role for autophagy in the pathophysiology of FXS is, as yet, unclear. Here we show that autophagic flux, a functional readout of autophagy, and biochemical markers of autophagy are down-regulated in hippocampal neurons of fragile X mice. We further show that enhanced activity of mammalian target of rapamycin complex 1 (mTORC1) and translocation of Raptor, a defining component of mTORC1, to the lysosome are causally related to reduced autophagy. Activation of autophagy by delivery of shRNA to Raptor directly into the CA1 of living mice via the lentivirus expression system largely corrects aberrant spine structure, synaptic plasticity, and cognition in fragile X mice. Postsynaptic density protein (PSD-95) and activity-regulated cytoskeletal-associated protein (Arc/Arg3.1), proteins implicated in spine structure and synaptic plasticity, respectively, are elevated in neurons lacking fragile X mental retardation protein. Activation of autophagy corrects PSD-95 and Arc abundance, identifying a potential mechanism by which impaired autophagy is causally related to the fragile X phenotype and revealing a previously unappreciated role for autophagy in the synaptic and cognitive deficits associated with fragile X syndrome.
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19. Zalla T, Korman J. {{Prior Knowledge, Episodic Control and Theory of Mind in Autism: Toward an Integrative Account of Social Cognition}}. {Frontiers in psychology}. 2018; 9: 752.
Over the last 30 years, research has explored theory of mind (ToM), the ability to attribute mental states to oneself and to others. Work on ToM in typical and atypical populations has shed light on the neurocognitive mechanisms underlying social understanding and interaction. The ToM hypothesis has long been regarded as one comprehensive explanation of the severe cognitive and behavioral impairments encountered by individuals with autism. However, high-functioning individuals can often pass both first-order and second-order false belief tasks using cognitive compensation strategies. To provide more sensitive measures of mental state attribution abilities, researchers have introduced more difficult, « advanced » theory of mind tasks. In this article, we argue that in attempting to bypass compensation strategies, these new advanced ToM tasks, such as the Faux Pas and the Strange Stories tasks, impose cognitive demands beyond those specific to the domain of ToM. We then provide an integrative account of social deficits in autism that takes into account several distinct components of mental state understanding, including both general cognitive capacities and processes specific to ToM. We argue that a number of related cognitive abilities, including episodic cognitive control and inferencing from prior knowledge, are necessary to understand how both people with autism and typical development navigate challenging, real-life social situations.
