1. Appelgren M, Persson K, Bahtsevani C, Borglin G. Swedish registered nurses’ perceptions of caring for patients with intellectual and developmental disability: A qualitative descriptive study. Health & social care in the community. 2022; 30(3): 1064-76.

Patients with intellectual and developmental disability (IDD) are often misinterpreted and misunderstood. Studies show that, in general, healthcare professionals have limited knowledge about IDD, and registered nurses (RNs) often report feeling unprepared to support this group of patients. Therefore, more knowledge about how to adequately address care for this patient group is warranted. This qualitative study employs an interpretative descriptive design to explore and describe Swedish RNs’ perceptions of caring for patients with IDD, here in a home-care setting. Twenty RNs were interviewed between September 2018 and May 2019, and the resulting data were analysed through an inductive qualitative content analysis. The study adheres to consolidated criteria for reporting qualitative research (COREQ). Our analysis found that nurses’ perceptions of caring for patients with an IDD could be understood from three overarching categories: nursing held hostage in the context of care, care dependent on intuition and proven experience and contending for the patients’ right to adequate care. Our findings show that the home-care context and organisation were not adjusted to the needs of the patients. This resulted in RNs feeling unable to provide care in accordance with their professional values. They also explained that they had not mastered the available augmentative and alternative communication tools, instead using support staff as interpreters for their patients. Finally, on a daily basis, the RNs caring for this group of patients took an active stance and fought for the patients’ right to receive the right care at the right time by the right person. This was particularly the case with issues involving psychiatric care.

Lien vers le texte intégral (Open Access ou abonnement)

2. Ballen K, Kurtzberg J. Exploring new therapies for children with autism: « Do no harm » does not mean do not try. Stem cells translational medicine. 2021; 10(6): 823-5.

Lien vers le texte intégral (Open Access ou abonnement)

3. Blowers AP, Luczynski KC, McKeown CA. Effects of differential observing responses on observational learning across multiple contingencies. Journal of applied behavior analysis. 2021; 54(4): 1385-404.

Whether a child with autism spectrum disorder will exhibit observational learning may depend on their attention to and the stimulus modalities of the observed contingency. We used multiple-probe and repeated-acquisition designs to test observational learning across a diverse set of contingencies, which included hidden edible, hidden toy, hidden video, tact, receptive identification, and intraverbal contingencies. During preteaching, 2 children with autism spectrum disorder showed observational learning with some contingencies. After learning to engage in differential observing responses for observed behaviors and consequences with the hidden-video contingency, 1 child showed generalization of observational learning with receptive identification and intraverbals. Neither child showed generalization with the tact contingency. Thus, teaching was initiated with the tact contingency, which led to generalization of observational learning with tacts. The efficacy of teaching differential observing responses over observational learning was demonstrated. Inconsistent observational learning across contingencies suggests scientist-practitioners should assess observational learning across a variety of contingencies.

Lien vers le texte intégral (Open Access ou abonnement)

4. Brunetti S, Malerba L, Giordano L, Parrini E, Guerrini R, Palumbo G, Parazzini C, Bestetti I, Accorsi P. Cerebral folate transporter deficiency syndrome in three siblings: Why genetic testing for developmental and epileptic encephalopathies should be performed early and include the FOLR1 gene. American journal of medical genetics Part A. 2021; 185(8): 2526-31.

Cerebral folate transporter deficiency syndrome, caused by FOLR-1 mutations is characterized by late infantile onset, severe developmental regression, epilepsy, and leukodystrophy. An extremely low concentration of 5-methyltetrahydrofolate in the cerebrospinal fluid provides a crucial clue to its diagnosis and is a treatment target. Oral or intravenous folinic acid (5-formyltetrahydrofolate) administration improves clinical symptoms and brain magnetic resonance imaging (MRI) findings. We describe three siblings carrying a novel homozygous FOLR1 nonsense mutation, that were referred due to intractable epilepsy and progressive neurological decline. Brain MRI showed hypomyelination and cerebellar atrophy. Folinic acid (oral and intravenous) supplementation, initiated after over 15 years illness, has failed to result in any sizeable clinical or neurophysiological improvement. Cerebral folate transport deficiency bears overlapping clinical features with many severe developmental encephalopathies. It is crucial to recognize FOLR1 signs and establish an early clinical and molecular diagnosis in order to provide timely folinic acid treatment and improve outcome.

Lien vers le texte intégral (Open Access ou abonnement)

5. Cheng P, Qiu Z, Du Y. Potassium channels and autism spectrum disorder: An overview. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 2021; 81(6): 479-91.

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by impaired social interaction and communication, and restricted, repetitive patterns of behaviors, interests, or activities. It had been demonstrated that potassium channels played a key role in regulating neuronal excitability, which was closely associated with neurological diseases including epilepsy, ataxia, myoclonus, and psychiatric disorders. In recent years, a growing body of evidence from whole-genome sequencing and whole-exome sequencing had identified several ASD susceptibility genes of potassium channels in ASD subjects. Genetically dysfunction of potassium channels may be involved in altered neuronal excitability and abnormal brain function in the pathogenesis of ASD. This review summarizes current findings on the features of ASD-risk genes (KCND2, KCNQ2, KCNQ3, KCNH5, KCNJ2, KCNJ10, and KCNMA1) and further expatiate their potential role in the pathogenicity of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

6. Cissne MN, Kester LE, Gunn AJM, Bodner KE, Miles JH, Christ SE. Brief Report: A Preliminary Study of the Relationship between Repetitive Behaviors and Concurrent Executive Function Demands in Children with Autism Spectrum Disorder. Journal of autism and developmental disorders. 2022; 52(4): 1896-902.

The present study evaluated the hypothesis that the strength of the relationship between executive function (EF) and repetitive behaviors and restricted interests (RBRI) symptomatology is moderated by the degree to which concurrent demands are placed on multiple aspects of EF. An eye movement task was used to evaluate inhibition and task switching ability (both together and in isolation) in a sample of 22 children with autism spectrum disorder (ASD). The Repetitive Behavior Scale-Revised (RBS-R) was used to assess the severity of RBRI symptoms. Results provide preliminary support for the aforementioned hypothesis. RBS-R scores were significantly correlated with task performance when simultaneous demands were placed on switching and inhibition; however, no such relationship was found for inhibition-only or switching-only task conditions.

Lien vers le texte intégral (Open Access ou abonnement)

7. Finlay-Morreale H. Invasive therapy for children with autism is not justified. Stem cells translational medicine. 2021; 10(6): 826.

Lien vers le texte intégral (Open Access ou abonnement)

8. Gangi DN, Hill MM, Maqbool S, Young GS, Ozonoff S. Measuring social-communication difficulties in school-age siblings of children with autism spectrum disorder: Standardized versus naturalistic assessment. Autism research : official journal of the International Society for Autism Research. 2021; 14(9): 1913-22.

Younger siblings of children with autism spectrum disorder (ASD; high-risk siblings) are at elevated risk for developing the broader autism phenotype (BAP), which consists of subclinical features of ASD. We examined conversational skills in a naturalistic context and standardized assessments of pragmatic language and communication skills in high-risk and low-risk school-age children with BAP (n = 22) and ASD (n = 18) outcomes, as well as comparison children without ASD or BAP (n = 135). Children with BAP characteristics exhibited lower conversational skills than comparison children, but did not differ on any of three standardized measures. Only the conversational ratings significantly predicted membership in the BAP versus Comparison group. This suggests that naturalistic tasks are crucial when assessing social-communication difficulties in children with a family history of ASD. LAY SUMMARY: The broader autism phenotype (BAP) consists of subclinical features of autism spectrum disorder (ASD) and is more common among family members of those with ASD. School-age children with BAP characteristics exhibited lower conversational skills than comparison children, but did not differ on standardized language measures tapping similar abilities. This suggests that naturalistic tasks may be more sensitive to the social-communication difficulties seen in some children with a family history of ASD than the standardized language tests used in most evaluations.

Lien vers le texte intégral (Open Access ou abonnement)

9. Hall HA, Speyer LG, Murray AL, Auyeung B. Prenatal Maternal Infections and Children’s Neurodevelopment in the UK Millennium Cohort Study: A Focus on ASD and ADHD. Journal of attention disorders. 2022; 26(4): 616-28.

OBJECTIVE: No clear answer has yet been attained as to the influence of prenatal exposure to infection on autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), either alone or as co-occurring issues. The current study examined links between hospital-recorded and maternal-reported prenatal infections and ASD, ADHD, and co-occurring ASD and ADHD. METHODS: Participants were n = 15,462 children and mother pairs from the Millennium Cohort Study (MCS), a population-representative UK sample. RESULTS: Findings show associations between maternal-reported infections and ASD, and some evidence of links with ADHD and co-occurring ASD and ADHD. Hospital-recorded infections were not found to be associated with ASD, ADHD, or their co-occurrence. Agreement between hospital-recorded and maternal-reported infections was low, which may explain the discrepant findings. CONCLUSION: Prenatal maternal infections may be associated with increased odds of ASD and ADHD. Findings point to the importance of drawing on multiple sources of information when ascertaining prenatal infection status.

Lien vers le texte intégral (Open Access ou abonnement)

10. Kalb LG, Holingue C, Pfeiffer D, Reetzke R, Dillon E, Azad G, Freedman B, Landa R. Parental relationship status and age at autism spectrum disorder diagnosis of their child. Autism : the international journal of research and practice. 2021; 25(8): 2189-98.

Autism spectrum disorder (ASD) can be diagnosed as early as 18 months of age. However, the average age at diagnosis in the United States is over 2 years later. A lot has been written about the many barriers families face when seeking a diagnosis for their child. One area of research that has received no attention is whether separation between a child’s biological parents affects the age at which a child is diagnosed with ASD. This study was conducted among 561 children who were receiving an ASD diagnosis for the first time. On average, these children were 5 years of age. The study took place in an urban, outpatient specialty autism clinic in the United States. Biological parents self-reported their relationship status during the evaluation. This was categorized as either « together » (married or living together but not married) or « not together » (separated, divorced, or never married). At the time of diagnosis, most children’s biological parents were together (69%). We found children of parents who were together were diagnosed 1.4 years earlier than those who were not together. These findings have important implications for providing support to families that separate early in a child’s life, with the goal of reducing the age at ASD evaluation among single parents and those who have been separated from their child’s other biological parent. Providing support to these families is important since earlier age at diagnosis leads to earlier intervention, which can improve long-term outcomes for the child, family, and community as a whole.

Lien vers le texte intégral (Open Access ou abonnement)

11. Lervåg A. Editorial: Is there a core deficit in specific learning disabilities?. Journal of child psychology and psychiatry, and allied disciplines. 2021; 62(6): 677-9.

Difficulties with learning mathematics and learning to read have for a long time been categorised into diagnostic categories like dyscalculia and dyslexia. This categorization has been based on ideas that some core deficits underlie and cause the difficulties. However, no clear and sufficient core deficit has been found for these difficulties and no qualitative differences has been identified distinguishing those assigned to the diagnoses from people not assigned to the diagnoses – thus, the diagnostic cut-offs are arbitrary. In addition, several of the factors associated with one disorder are also associated with other disorders. These issues favour a multi-factored view of the diagnoses that have implication for both clinical practice and research.

Lien vers le texte intégral (Open Access ou abonnement)

12. Morton SU, Maleyeff L, Wypij D, Yun HJ, Rollins CK, Watson CG, Newburger JW, Bellinger DC, Roberts AE, Rivkin MJ, Grant PE, Im K. Abnormal Right-Hemispheric Sulcal Patterns Correlate with Executive Function in Adolescents with Tetralogy of Fallot. Cerebral cortex (New York, NY : 1991). 2021; 31(10): 4670-80.

Neurodevelopmental disabilities are the most common noncardiac conditions in patients with congenital heart disease (CHD). Executive function skills have been frequently observed to be decreased among children and adults with CHD compared with peers, but a neuroanatomical basis for the association is yet to be identified. In this study, we quantified sulcal pattern features from brain magnetic resonance imaging data obtained during adolescence among 41 participants with tetralogy of Fallot (ToF) and 49 control participants using a graph-based pattern analysis technique. Among patients with ToF, right-hemispheric sulcal pattern similarity to the control group was decreased (0.7514 vs. 0.7553, P = 0.01) and positively correlated with neuropsychological testing values including executive function (r = 0.48, P < 0.001). Together these findings suggest that sulcal pattern analysis may be a useful marker of neurodevelopmental risk in patients with CHD. Further studies may elucidate the mechanisms leading to different alterations in sulcal patterning.

Lien vers le texte intégral (Open Access ou abonnement)

13. Nakashima H, Tsujimura K, Irie K, Imamura T, Trujillo CA, Ishizu M, Uesaka M, Pan M, Noguchi H, Okada K, Aoyagi K, Andoh-Noda T, Okano H, Muotri AR, Nakashima K. MeCP2 controls neural stem cell fate specification through miR-199a-mediated inhibition of BMP-Smad signaling. Cell reports. 2021; 35(7): 109124.

Rett syndrome (RTT) is a severe neurological disorder, with impaired brain development caused by mutations in MECP2; however, the underlying mechanism remains elusive. We know from previous work that MeCP2 facilitates the processing of a specific microRNA, miR-199a, by associating with the Drosha complex to regulate neuronal functions. Here, we show that the MeCP2/miR-199a axis regulates neural stem/precursor cell (NS/PC) differentiation. A shift occurs from neuronal to astrocytic differentiation of MeCP2- and miR-199a-deficient NS/PCs due to the upregulation of a miR-199a target, Smad1, a downstream transcription factor of bone morphogenetic protein (BMP) signaling. Moreover, miR-199a expression and treatment with BMP inhibitors rectify the differentiation of RTT patient-derived NS/PCs and development of brain organoids, respectively, suggesting that facilitation of BMP signaling accounts for the impaired RTT brain development. Our study illuminates the molecular pathology of RTT and reveals the MeCP2/miR-199a/Smad1 axis as a potential therapeutic target for RTT.

Lien vers le texte intégral (Open Access ou abonnement)

14. Norouzi N, Garza CM. Architecture for Children With Autism Spectrum Disorder and Their Therapists. Herd. 2021; 14(4): 147-56.

OBJECTIVES: The objective of this study is to identify an architectural design framework that can be applied to create adaptable, transformative therapy rooms that benefit children with autism and their therapists. BACKGROUND: Previous research suggests that environment shapes and influences human behavior. However, there remains a lack of evidence of effective design for pediatric rehabilitation therapy rooms. This study specifically focuses on how the design of the therapy room influences the patient’s level of comfort and participation as well as the therapists’ quality and efficiency of treatment to improve the overall therapeutic experience. METHOD: Two different surveys were conducted to improve the design of a therapeutic room based on professional therapist experiences. A grounded theory approach was employed to identify specific codes and categories. RESULTS: The result of this study is an architectural framework based on specific design tenets and their properties that not only can be utilized by architects and interior designers for building a new therapy center but could also be used for remodeling existing therapy rooms.

Lien vers le texte intégral (Open Access ou abonnement)

15. O’Connor C, Brassil M, O’Sullivan S, Seery C, Nearchou F. How does diagnostic labelling affect social responses to people with mental illness? A systematic review of experimental studies using vignette-based designs. Journal of mental health (Abingdon, England). 2022; 31(1): 115-30.

BACKGROUND: An outstanding question in the stigma literature is the extent to which negative responses are provoked by diagnostic labels, rather than observable symptoms of mental illness. Experimental studies frequently use vignettes to identify the unique effects of diagnostic labels on social responses to people with mental illness, independent of their behaviour or socio-demographic characteristics. AIMS: The current article identifies, evaluates, and synthesises the body of experimental vignette studies of labelling effects. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies were subjected to quality evaluation and narrative synthesis. RESULTS: Of 1511 articles screened, 22 met inclusion criteria. Most studies focused on the diagnostic categories of attention deficit hyperactivity disorder, schizophrenia spectrum disorders, and autism spectrum disorder. The literature reported diverse effects, with diagnostic disclosure either exacerbating, mitigating, or not affecting stigma. The quality of studies was generally acceptable but the review identified an over-reliance on convenience sampling and unvalidated measures. CONCLUSIONS: Results highlight the complexity of labelling effects, which diverge across diagnostic categories and social contexts. The review emphasises the need for expansion of diagnostic labels and contexts studied, standardisation of validated attitude scales, incorporation of behavioural outcomes, and diversification of samples.

Lien vers le texte intégral (Open Access ou abonnement)

16. Pavăl D, Micluția IV. The Dopamine Hypothesis of Autism Spectrum Disorder Revisited: Current Status and Future Prospects. Developmental neuroscience. 2021; 43(2): 73-83.

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. Despite intensive research, its etiopathogenesis remains largely unclear. Although studies consistently reported dopaminergic anomalies, a coherent dopaminergic model of ASD was lacking until recently. In 2017, we provided a theoretical framework for a « dopamine hypothesis of ASD » which proposed that autistic behavior arises from a dysfunctional midbrain dopaminergic system. Namely, we hypothesized that malfunction of 2 critical circuits originating in the midbrain, that is, the mesocorticolimbic and nigrostriatal pathways, generates the core behavioral features of ASD. Moreover, we provided key predictions of our model along with testing means. Since then, a notable number of studies referenced our work and numerous others provided support for our model. To account for these developments, we review all these recent data and discuss their implications. Furthermore, in the light of these new insights, we further refine and reconceptualize our model, debating on the possibility that various etiologies of ASD converge upon a dysfunctional midbrain dopaminergic system. In addition, we discuss future prospects, providing new means of testing our hypothesis, as well as its limitations. Along these lines, we aimed to provide a model which, if confirmed, could provide a better understanding of the etiopathogenesis of ASD along with new therapeutic strategies.

Lien vers le texte intégral (Open Access ou abonnement)

17. Peristeri E, Baldimtsi E, Vogelzang M, Tsimpli IM, Durrleman S. The cognitive benefits of bilingualism in autism spectrum disorder: Is theory of mind boosted and by which underlying factors?. Autism research : official journal of the International Society for Autism Research. 2021; 14(8): 1695-709.

This study examined whether bilingualism boosts Theory of Mind as measured by a non-verbal false belief (FB) task in children with autism spectrum disorder (ASD), and how this potential boost may stem from improvements in a variety of other domains, namely executive functions (EFs), language, metalinguistic awareness skills, as well as autism severity. One hundred and three children with ASD (7- to 15-year-olds) (43 bilingual and 60 age- and IQ-matched monolingual children) were tested on a nonverbal task of attentional switching, working memory and updating task, and an online, low-verbal first-order FB task. Results showed a clear FB benefit for bilingual children with ASD as compared with their monolingual peers. There were also boosts in EF, however, there is no evidence that these EF boosts drove the FB advantage. Enhanced FB was not explained either by language, metalinguistic skills, or lower autism severity. While the results do not conclusively settle the debate on what triggers the ToM advantage in bilingual children with ASD, the empirical picture of the current study suggests that the ToM component of FB understanding in bilingual children with ASD is enhanced by the bilingual experience per se. LAY SUMMARY: The current study aimed to determine if and how bilingualism may improve the ability to understand others’ beliefs in children with autism spectrum disorder (ASD). We assessed their belief reasoning alongside a series of other skills hypothesized to be beneficial for such reasoning, namely understanding, producing, and thinking about language, recalling and switching between information, and the severity of their autistic symptoms. The overall findings highlight advantages for bilingual children with ASD over their monolingual peers for grasping beliefs, thus suggesting that pursuing bilingualism may be beneficial for cognition in ASD. Other boosts were also associated with bilingualism, such as recalling and switching between information, but these boosts were not directly related to belief understanding, highlighting the beneficial role of bilingualism per se.

Lien vers le texte intégral (Open Access ou abonnement)

18. Polfuss M, Marston E, Pridham K, Brown R, McPherson AC. Relationship between Stress and Feeding Behaviors in Parents of Children with Developmental Disabilities. Childhood obesity (Print). 2021; 17(7): 457-66.

Background: Controlling feeding practices are associated with negative child eating behaviors and an increased risk of obesity. Parental stress may be related to feeding practices. Children with developmental disabilities have increased obesity prevalence, and families may also experience increased stress. This study examined the relationship between family stress and parental feeding practices in children with developmental disabilities and how concern for the child’s weight may moderate this relationship. Methods: Secondary analysis using a descriptive cross-sectional design was employed. Parents of children aged 5 to 15 years, with autism spectrum disorder (ASD), Down syndrome (DS), or spina bifida (SB) were recruited nationally. Demographics, the Child Feeding Questionnaire, and the Questionnaire on Resources and Stress were completed online. Analysis included regression with an empirical Bayesian effects model. Results: Five hundred twenty-three parents, 186 (ASD), 173 (DS) and 164 (SB), participated. Family stressors were associated with the use of controlling feeding practices. Direct effects included: (1) physical incapacitation on restriction and pressure to eat (ASD and DS); (2) pessimism (ASD) and concerns about child overweight (SB) on pressure to eat; and (3) parent/family problems on restriction (DS). Concern for child overweight moderated these relationships and resulted in two interactions (DS and SB). Conclusion: Understanding the relationship of family stressors with parental feeding practices and the role of parental concern for child overweight can potentially optimize feeding in this high-risk population. This study highlights the need to provide family-centered care with awareness of stress and its potential association with daily activities and children’s health.

Lien vers le texte intégral (Open Access ou abonnement)

19. Reimann GE, Walsh C, Csumitta KD, McClure P, Pereira F, Martin A, Ramot M. Gauging facial feature viewing preference as a stable individual trait in autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2021; 14(8): 1670-83.

Eye tracking provides insights into social processing deficits in autism spectrum disorder (ASD), especially in conjunction with dynamic, naturalistic free-viewing stimuli. However, the question remains whether gaze characteristics, such as preference for specific facial features, can be considered a stable individual trait, particularly in those with ASD. If so, how much data are needed for consistent estimations? To address these questions, we assessed the stability and robustness of gaze preference for facial features as incremental amounts of movie data were introduced for analysis. We trained an artificial neural network to create an object-based segmentation of naturalistic movie clips (14 s each, 7410 frames total). Thirty-three high-functioning individuals with ASD and 36 age- and IQ-equated typically developing individuals (age range: 12-30 years) viewed 22 Hollywood movie clips, each depicting a social interaction. As we evaluated combinations of one, three, five, eight, and 11 movie clips, gaze dwell times on core facial features became increasingly stable at within-subject, within-group, and between-group levels. Using a number of movie clips deemed sufficient by our analysis, we found that individuals with ASD displayed significantly less face-centered gaze (centralized on the nose; p < 0.001) but did not significantly differ from typically developing participants in eye or mouth looking times. Our findings validate gaze preference for specific facial features as a stable individual trait and highlight the possibility of misinterpretation with insufficient data. Additionally, we propose the use of a machine learning approach to stimuli segmentation to quickly and flexibly prepare dynamic stimuli for analysis. LAY SUMMARY: Using a data-driven approach to segmenting movie stimuli, we examined varying amounts of data to assess the stability of social gaze in individuals with autism spectrum disorder (ASD). We found a reduction in social fixations in participants with ASD, driven by decreased attention to the center of the face. Our findings further support the validity of gaze preference for face features as a stable individual trait when sufficient data are used.

Lien vers le texte intégral (Open Access ou abonnement)

20. Steubler V, Erdinger S, Back MK, Ludewig S, Fässler D, Richter M, Han K, Slomianka L, Amrein I, von Engelhardt J, Wolfer DP, Korte M, Müller UC. Loss of all three APP family members during development impairs synaptic function and plasticity, disrupts learning, and causes an autism-like phenotype. The EMBO journal. 2021; 40(12): e107471.

The key role of APP for Alzheimer pathogenesis is well established. However, perinatal lethality of germline knockout mice lacking the entire APP family has so far precluded the analysis of its physiological functions for the developing and adult brain. Here, we generated conditional APP/APLP1/APLP2 triple KO (cTKO) mice lacking the APP family in excitatory forebrain neurons from embryonic day 11.5 onwards. NexCre cTKO mice showed altered brain morphology with agenesis of the corpus callosum and disrupted hippocampal lamination. Further, NexCre cTKOs revealed reduced basal synaptic transmission and drastically reduced long-term potentiation that was associated with reduced dendritic length and reduced spine density of pyramidal cells. With regard to behavior, lack of the APP family leads not only to severe impairments in a panel of tests for learning and memory, but also to an autism-like phenotype including repetitive rearing and climbing, impaired social communication, and deficits in social interaction. Together, our study identifies essential functions of the APP family during development, for normal hippocampal function and circuits important for learning and social behavior.

Lien vers le texte intégral (Open Access ou abonnement)

21. van der Meer HA, Sheftel-Simanova I, Kan CC, Trujillo JP. Translation, Cross-Cultural Adaptation, and Validation of a Dutch Version of the Actions and Feelings Questionnaire in Autistic and Neurotypical Adults. Journal of autism and developmental disorders. 2022; 52(4): 1771-7.

The actions and feelings questionnaire (AFQ) provides a short, self-report measure of how well someone uses and understands visual communicative signals such as gestures. The objective of this study was to translate and cross-culturally adapt the AFQ into Dutch (AFQ-NL) and validate this new version in neurotypical and autistic populations. Translation and adaptation of the AFQ consisted of forward translation, synthesis, back translation, and expert review. In order to validate the AFQ-NL, we assessed convergent and divergent validity. We additionally assessed internal consistency using Cronbach’s alpha. Validation and reliability outcomes were all satisfactory. The AFQ-NL is a valid adaptation that can be used for both autistic and neurotypical populations in the Netherlands.

Lien vers le texte intégral (Open Access ou abonnement)

22. van Eijk L, Zietsch BP. Testing the extreme male brain hypothesis: Is autism spectrum disorder associated with a more male-typical brain?. Autism research : official journal of the International Society for Autism Research. 2021; 14(8): 1597-608.

Autism spectrum disorder (ASD) is more common in males than females and has been linked to male-typical behavior. Accordingly, the « Extreme Male Brain » hypothesis suggests that ASD is associated with an exaggeratedly male-typical brain. To test this hypothesis, we derived a data-driven measure of individual differences along a male-female dimension based on sex differences in subcortical brain shape (i.e., brain maleness) by training our algorithm on two population samples (Queensland Twin IMaging study and Human Connectome Project; combined N = 2153). We then applied this algorithm to two clinical datasets (Autism Brain Imaging Data Exchange I and II; ASD N = 1060; neurotypical controls N = 1166) to obtain a brain maleness score for each individual, representing maleness of their brain on a male-female continuum. Consistent with the Extreme Male Brain hypothesis, we found a higher mean brain maleness score in the ASD group than in controls (d = 0.20 [0.12-0.29]), parallel to higher scores for control males than control females (d = 1.17 [1.05-1.29]). Further, brain maleness was positively associated with autistic symptoms. We tested the possibility this finding was driven by the ASD group’s larger brains than controls (d = 0.17 [0.08-0.25]), given that males had larger brains than females (d = 0.96 [0.84-1.07]). Indeed, after adjusting for differences in brain size, the brain maleness difference between the ASD group and controls disappeared, and no association with autistic symptoms remained (after controlling for multiple comparisons), suggesting greater maleness of the autistic brain is driven by brain size. Brain maleness may be influenced by the same factors that influence brain size. LAY SUMMARY: A popular theory proposes that individuals with autistic spectrum disorder (ASD) have an « extreme male brain », but this has not been subject to rigorous, direct tests. We developed a measure of individual differences along a male-female dimension and then derived this measure for 1060 individuals with ASD and 1166 neurotypical controls. Individuals with ASD had slightly more male-type brains. However, this difference is accounted for by males and individuals with ASD having relatively larger brains than females and controls, respectively.

Lien vers le texte intégral (Open Access ou abonnement)

23. Vasa RA, Singh V, McDonald RG, Mazefsky C, Hong JS, Keefer A. Dysregulation in Children and Adolescents Presenting to a Multidisciplinary Autism Clinic. Journal of autism and developmental disorders. 2022; 52(4): 1762-70.

Research indicates that children with autism spectrum disorder (ASD) frequently exhibit dysregulation, which refers to poorly coordinated affective, behavioral, and cognitive responses to a given situation. We examined the characteristics of dysregulation in children presenting to a multidisciplinary ASD clinic for an ASD diagnostic evaluation. Sixty percent of children presenting for an ASD evaluation exhibited dysregulation. Dysregulation prevalence was higher in children without ASD versus with ASD (69% versus 56%). Severe dysregulation was higher in children without ASD (29% versus 16%). Both groups with severe dysregulation were equally likely to be taking psychiatric medications, however, children with ASD were less likely to be receiving therapy. These findings highlight the importance of implementing dysregulation screening and treatment protocols in ASD centers.

Lien vers le texte intégral (Open Access ou abonnement)

24. Wang ZJ, Rein B, Zhong P, Williams J, Cao Q, Yang F, Zhang F, Ma K, Yan Z. Autism risk gene KMT5B deficiency in prefrontal cortex induces synaptic dysfunction and social deficits via alterations of DNA repair and gene transcription. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2021; 46(9): 1617-26.

Large-scale genetic screening has identified KMT5B (SUV420H1), which encodes a histone H4 K20 di- and tri-methyltransferase highly expressed in prefrontal cortex (PFC), as a top-ranking high-risk gene for autism. However, the biological function of KMT5B in the brain is poorly characterized, and how KMT5B deficiency is linked to autism remains largely unknown. Here we knocked down Kmt5b in PFC and examined behavioral and electrophysiological changes, as well as underlying molecular mechanisms. Mice with Kmt5b deficiency in PFC display social deficits, a core symptom of autism, without the alteration of other behaviors. Kmt5b deficiency also produces deficits in PFC glutamatergic synaptic transmission, which is accompanied by the reduced synaptic expression of glutamate receptor subunits and associated proteins. Kmt5b deficiency-induced reduction of H4K20me2 impairs 53BP1-mediated DNA repair, leading to the elevation of p53 expression and its target gene Ddit4 (Redd1), which is implicated in synaptic impairment. RNA-sequencing data indicate that Kmt5b deficiency results in the upregulation of genes enriched in cellular stress response and ubiquitin-dependent protein degradation. Collectively, this study has revealed the functional role of Kmt5b in the PFC, and suggests that Kmt5b deficiency could cause autistic phenotypes by inducing synaptic dysfunction and transcriptional aberration.

Lien vers le texte intégral (Open Access ou abonnement)