1. Aita C, Mizoguchi Y, Yamamoto M, Seguch IY, Yatsuga C, Nishimura T, Sugimoto Y, Takahashi D, Nishihara R, Ueno T, Nakayama M, Kuroki T, Nabeta H, Imamura Y, Monji A. {{Oxytocin levels and sex differences in autism spectrum disorder with severe intellectual disabilities}}. {Psychiatry Res}. 2018; 273: 67-74.
There were few reports of oxytocin (OXT) concentrations of autism spectrum disorder (ASD) patients with severe intellectual disabilities. We measured serum OXT concentrations in 79 hospitalized patients with severe intellectual disabilities (16-60 years old, 50 males and 29 females, 54 ASD patients) and investigated the associations between serum OXT concentration, symptom scores, sex differences, and autism spectrum disorder. There were no significant effects of diagnosis, severity of intellectual disabilities, and total score of the Japanese version of the Aberrant Behavior Checklist (ABC-J), the Childhood Autism Rating Scale-Tokyo Version (CARS-TV), and the Japanese version of the Repetitive Behavior Scale-Revised (RBS-R). However, there were sex differences in the correlations between OXT concentrations and subscale scores in the ASD group. The male ASD group (n=39) showed negative correlations between RBS-R Self-injurious and Sameness subscale scores and serum OXT concentrations. In the female ASD group(n=15), CARS-TV Nonverbal communication subscale scores and RBS-R Compulsive subscale scores were seen to positively correlate with serum OXT concentrations. These findings suggest that OXT functions differ in males and females with severe intellectual disabilities and that OXT partly affects autism and related to some of the repetitive behaviors and nonverbal communication, in ASD patients with severe intellectual disabilities.
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2. Bouvet L, Amsellem F, Maruani A, Tonus-Vic Dupont A, Mathieu A, Bourgeron T, Delorme R, Mottron L. {{Synesthesia & Autistic Features in a Large Family:evidence for spatial imagery as a common factor}}. {Behav Brain Res}. 2019.
BACKGROUND: Autism and synesthesia are neurodevelopmental conditions associated with variants of perceptual processing. They also share some genetic variants and include a large magnitude of intra-categorical variation: 60 types for synesthesia, as well as a spectrum for autism. In order to investigate the relationship between these two phenomena, we investigated the family of FC, an autistic individual who also possess savant abilities and synesthesia manifestations. METHOD: Autistic symptoms were assessed for the entire sample of participants entering the study (39 individuals) using the SRS. Participants above threshold were evaluated with standardized diagnostic tools. Synesthesia was explored in the entire participating sample using a self-reported questionnaire. Consistency tests were used for participants who reported synesthetic manifestations. RESULTS: In addition to FC, four individuals with ASD were detected. Fifteen participants self-reported synesthesia (15 sequence-space, 4 sound-shape, 4 lexical-color), among which nine sequence-space synesthetes satisfied the consistency criteria. Two participants possess both autism and synesthesia. CONCLUSION: This family illustrates the co-segregation of autism and synesthesia. This co-segregation is in favour of a partially overlapping genetic predisposition for both conditions, but also authorizes a large variety of manifestations in both conditions. The high prevalence of sequence-space synesthesia in this family strengthens the previous assumption that this form of synesthesia may be linked to autism. We discuss the potential role of spatial imagery in the development of this form of synesthesia and savant abilities.
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3. Goswami S, Cavalier S, Sridhar V, Huber KM, Gibson JR. {{Local cortical circuit correlates of altered EEG in the mouse model of Fragile X syndrome}}. {Neurobiology of disease}. 2019.
Electroencephalogram (EEG) recordings in Fragile X syndrome (FXS) patients have revealed enhanced sensory responses, enhanced resting « gamma frequency » (30-100Hz) activity, and a decreased ability for sensory stimuli to modulate cortical activity at gamma frequencies. Similar changes are observed in the FXS model mouse – the Fmr1 knockout. These alterations may become effective biomarkers for diagnosis and treatment of FXS. Therefore, it is critical to better understand what circuit properties underlie these changes. We employed Channelrhodopsin2 to optically activate local circuits in the auditory cortical region in brain slices to examine how changes in local circuit function may be related to EEG changes. We focused on layers 2/3 and 5 (L2/3 and L5). In Fmr1 knockout mice, light-driven excitation of L2/3 revealed hyperexcitability and increased gamma frequency power in both local L2/3 and L5 circuits. Moreover, there is increased synchrony in the gamma frequency band between L2/3 and L5. Hyperexcitability and increased gamma power were not observed in L5 with L5 light-driven excitation, indicating that these changes were layer-specific. A component of L2/3 network hyperexcitability is independent of ionotropic receptor mediated synaptic transmission and may be mediated by increased intrinsic excitability of L2/3 neurons. Finally, lovastatin, a candidate therapeutic compound for FXS that targets ERK signaling did not normalize changes in gamma activity. In conclusion, hyperactivity and increased gamma activity in local neocortical circuits, together with increased gamma synchrony between circuits, provide a putative substrate for EEG alterations observed in both FXS patients and the FXS mouse model.
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4. Hadoush H, Alafeef M, Abdulhay E. {{Automated identification for autism severity level: EEG analysis using empirical mode decomposition and second order difference plot}}. {Behav Brain Res}. 2019.
BACKGROUND: Previous automated EEG-based diagnosis of autism spectrum disorders (ASD) using various nonlinear EEG analysis methods were limited to distinguish only children with ASD from those normally developed without approaching their autistic features severity. OBJECTIVES: Identifying potential differences between children with mild and sever ASD based on EEG analysis using empirical mode decomposition (EMD) and second-order difference plot (SODP) models, and determining the accuracy of such model outcome measures to distinguish ASD severity levels. METHODS: Resting-state EEG data recorded for 36 children, who divided equally into two matched groups of mild and sever ASD. EMD analysis was applied to their EEG data to identify intrinsic mode functions (IMFs) features, SODP patterns, elliptical area and central tendency measure (CTM) values. Artificial neural network then used to determine the accuracy of this models outcome measures in distinguishing between the two ASD groups. RESULTS: Children with sever ASD showed smaller, less twitches and oscillation of IMFs features, more stochastic SODP plotting, less CTM values, and higher ellipse area values compared to the children with mild ASD, which indicates their greater EEG variabilities and their greater inability to suppress their improper behavior. ANN ended with model sensitivity and specificity of 100% and 94.7%, respectively, and 97.2% overall accuracy of distinguishing between ASD groups. CONCLUSION: Children with sever and mild ASD had different IMFs features, SODP plotting, elliptical area and CTM values. In addition, these EMD outcome measures could serve as a sensitive automated tool to distinguish different severity levels in children with ASD.
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5. Heyman M, Hauser-Cram P. {{The influence of the family environment on adaptive functioning in the classroom: A longitudinal study of children with developmental disabilities}}. {Res Dev Disabil}. 2019; 86: 20-30.
BACKGROUND: No study has examined trajectories of school-based adaptive functioning (AF) for children with developmental disabilities (DD). This is a critical gap in the literature, since AF is context dependent, and high levels of AF at school facilitate meaningful participation at school. AIMS: This study examined trajectories of school-based AF for 170 children with DD from age 3 to 15 years, and indicators of the early childhood home and family environment as predictors of these trajectories. METHODS: Multilevel modeling was used to explore trajectories of school-based AF and identify early childhood home and family predictors of these trajectories. RESULTS: Children’s school-based AF raw scores increased over time. There was significant variability in initial status and rate of change of AF. As hypothesized, higher quality mother-child interaction predicted more positive functioning. CONCLUSIONS: Findings indicate the influence of the early childhood home and family environment on school-based AF over time.
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6. Hirokawa K, Kimura T, Ikehara S, Honjo K, Sato T, Ueda K, Iso H. {{Associations between broader autism phenotype (BAP) and maternal attachment are moderated by maternal postpartum depression when infants are one month old: A prospective study of the Japan environment & children’s study}}. {Journal of affective disorders}. 2019; 243: 485-93.
BACKGROUND: Broader autism phenotype (BAP) refers to the expression of behavioral and cognitive dispositions similar to autism spectrum disorder. The present study investigated whether mothers’ BAP was prospectively associated with maternal attachment, and if postpartum depression modified this association. METHODS: The Japan Environment and Children’s Study (JECS) is a national and government-funded birth cohort study that began in January 2011. Among the 103,099 mothers enrolled, 87,369 mothers without a history of depression were included in the analysis. Self-administered questionnaires were used. These included: the Japanese version of the Autism Spectrum Quotient, the Mother to Infant Bonding Scale, and the Edinburgh Postnatal Depression Scale. Logistic regression analyses were performed. RESULTS: The BAP during the second or third trimester of pregnancy was linearly associated with an increased risk of postpartum depression and insecure maternal attachment when infants were one month old (p for trend<0.001), after adjusting for confounding variables. When stratified by postpartum depression, among the BAP subscales, deficiencies in social skills and communication were associated with an increased risk of insecure maternal attachment in mothers without postpartum depression. The relationships between the BAP subscales and maternal attachment were attenuated among mothers with postpartum depression. LIMITATIONS: Only five items of the Mother to Infant Bonding Scale were used in the present study, and thus the results should be interpreted with caution. CONCLUSIONS: Mothers' BAP was predictive of insecure maternal attachment toward their infant. Postpartum depression partially moderated the associations between mothers' BAP and insecure maternal attachment. Lien vers le texte intégral (Open Access ou abonnement)
7. Jones RM, Plesa Skwerer D, Pawar R, Hamo A, Carberry C, Ajodan EL, Caulley D, Silverman MR, McAdoo S, Meyer S, Yoder A, Clements M, Lord C, Tager-Flusberg H. {{How effective is LENA in detecting speech vocalizations and language produced by children and adolescents with ASD in different contexts?}}. {Autism Res}. 2019.
The LENA system was designed and validated to provide information about the language environment in children 0 to 4 years of age and its use has been expanded to populations with a number of communication profiles. Its utility in children 5 years of age and older is not yet known. The present study used acoustic data from two samples of children with autism spectrum disorders (ASD) to evaluate the reliability of LENA automated analyses for detecting speech utterances in older, school age children, and adolescents with ASD, in clinic and home environments. Participants between 5 and 18 years old who were minimally verbal (study 1) or had a range of verbal abilities (study 2) completed standardized assessments in the clinic (study 1 and 2) and in the home (study 2) while speech was recorded from a LENA device. We compared LENA segment labels with manual ground truth coding by human transcribers using two different methods. We found that the automated LENA algorithms were not successful (<50% reliable) in detecting vocalizations from older children and adolescents with ASD, and that the proportion of speaker misclassifications by the automated system increased significantly with the target-child's age. The findings in children and adolescents with ASD suggest possibly misleading results when expanding the use of LENA beyond the age ranges for which it was developed and highlight the need to develop novel automated methods that are more appropriate for older children. Autism Research 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Current commercially available speech detection algorithms (LENA system) were previously validated in toddlers and children up to 48 months of age, and it is not known whether they are reliable in older children and adolescents. Our data suggest that LENA does not adequately capture speech in school age children and adolescents with autism and highlights the need to develop new automated methods for older children. Lien vers le texte intégral (Open Access ou abonnement)
8. Kang E, Gadow KD, Lerner MD. {{Atypical Communication Characteristics, Differential Diagnosis, and the Autism Spectrum Disorder Phenotype in Youth}}. {J Clin Child Adolesc Psychol}. 2019: 1-13.
This study compared atypical communication characteristics (ACCs) in clinic-referred youth with and without autism spectrum disorder (ASD), identified subgroups based on different patterns of ACCs in youth with ASD, and determined if ACC subgroups result in meaningful clinical phenotypes in their relation to psychopathology and functional outcomes. Youth 6-18 years of age (N= 947; M age = 11.41; 72% male; 84% Caucasian) with and without ASD were assessed using Child and Adolescent Symptom Inventory-4R and the Parent Questionnaire, which included a checklist of ACCs. Prevalence of ACCs was examined and receiver operational characteristic analyses were used to estimate the diagnostic accuracy of number of ACCs for ASD. Latent class analysis was conducted to see if patterns of ACCs yielded clinically useful subgroups in youth with ASD. Youth with ASD exhibited higher rates of ACC than non-ASD psychiatry referrals, and a summary score of ACCs easily differentiated the two clinic-referred samples. Among youth with ASD, ACC subgroups exhibited differences in severity of psychiatric symptoms, ASD symptomatology, and functional outcomes. Our results suggest that ACCs are an important characteristic of the ASD clinical phenotype and may be a useful consideration for defining more precise ASD symptomatology, functional outcomes, and treatment targets.
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9. Liu T, Liu X, Yi L, Zhu C, Markey PS, Pelowski M. {{Assessing autism at its social and developmental roots: A review of Autism Spectrum Disorder studies using functional near-infrared spectroscopy}}. {Neuroimage}. 2019; 185: 955-67.
We review a relatively new method for studying the developing brain in children and infants with Autism Spectrum Disorder (ASD). Despite advances in behavioral screening and brain imaging, due to paradigms that do not easily allow for testing of awake, very young, and socially-engaged children-i.e., the social and the baby brain-the biological underpinnings of this disorder remain a mystery. We introduce an approach based on functional near-infrared spectroscopy (fNIRS), which offers a noninvasive imaging technique for studying functional activations by measuring changes in the brain’s hemodynamic properties. This further enables measurement of brain activation in upright, interactive settings, while maintaining general equivalence to fMRI findings. We review the existing studies that have used fNIRS for ASD, discussing their promise, limitations, and their technical aspects, gearing this study to the researcher who may be new to this technique and highlighting potential targets for future research.
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10. Liu TL, Wang PW, Yang YC, Hsiao RC, Su YY, Shyi GC, Yen CF. {{Deficits in facial emotion recognition and implicit attitudes toward emotion among adolescents with high functioning autism spectrum disorder}}. {Comprehensive psychiatry}. 2019; 90: 7-13.
OBJECTIVE: Impaired social interaction is one of the core characteristics of autism spectrum disorder (ASD). This study was conducted to compare the facial emotion recognition (FER) abilities and emotional interference of adolescents with and without high-functioning ASD by performing the FER Task (FERT) using the faces of Taiwanese people and the Implicit Association Test (IAT), respectively. METHODS: This study recruited 71 adolescents with high-functioning ASD who aged at 11 to 18years old as the ASD group and 63 adolescents without ASD from the Taiwanese community as the non-ASD group. We investigated FER abilities by conducting the FERT on six types of emotional expression with a three-level intensity rating, and we performed the IAT for evaluating the strength of a person’s automatic association with mental representations of emotions in memory. RESULTS: Compared with the non-ASD group, the ASD group performed significantly worse on facial emotion differentiation and the ranking and rating of emotional intensity in the FERT. The ASD group had higher IAT scores than the non-ASD group. CONCLUSION: The results suggest that adolescents with high-functioning ASD have subtle deficits in facial emotion processing and emotional interference.
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11. Lotan M. {{The cost of Rett syndrome}}. {Dev Med Child Neurol}. 2019.
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12. Miranda A, Berenguer C, Rosello B, Baixauli I. {{Relationships between the social communication questionnaire and pragmatic language, socialization skills, and behavioral problems in children with autism spectrum disorders}}. {Appl Neuropsychol Child}. 2019: 1-12.
The Social Communication Questionnaire (SCQ) is one of the most widely used screening instruments for autism spectrum disorder (ASD). This study examined the relationships between the reciprocal social interaction, communication, and repetitive/stereotyped factors on the Strength and Difficulties Questionnaire (SDQ) and pragmatic, socialization, and behavioral problems in children with ASD and children with typical development (TD). Participants were seven- to 11-year-old children with ASD without intellectual disability (n = 52) and with TD (n = 37). The two groups were matched on age and intelligence quotient. Significant differences were found between the two groups on the SCQ domains and the outcome measures (pragmatic language, socialization skills, and behavioral problems). Furthermore, multiple regression analysis exploring the relationships between the SCQ and the criterion variables showed that reciprocal social interaction and repetitive/stereotyped behaviors had an important weight in the prediction of daily life social skills in typically developing children (34%). However, the model with the highest percentage of explained variance in children with ASD involved pragmatic language, with reciprocal social interaction as the best predictor, even reaching 41%. The findings highlight the suitability of routinely including the SCQ in the first stage of assessment protocols for ASD, and, in particular, they show its capacity to predict a valuable repertoire of behaviors.
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13. Muller M. {{Disturbed redox homeostasis and oxidative stress: Potential players in the developmental regression in Rett syndrome}}. {Neurosci Biobehav Rev}. 2019.
Rett syndrome (RTT) is a neurodevelopmental disorder affecting mostly girls. A seemingly normal initial development is followed by developmental stagnation and regression, leading to severe mental impairment with autistic features, motor dysfunction, irregular breathing and epilepsy. Currently, a cure does not exist. Due to the close association of RTT with mitochondrial alterations, cellular redox-impairment and oxidative stress, compounds stabilizing mitochondrial function, cellular redox-homeostasis, and oxidant detoxification are increasingly considered as treatment concepts. Indeed, antioxidants and free-radical scavengers ameliorate certain aspects of the complex and severe clinical presentation of RTT. To further evaluate these strategies, reliable biosensors are needed to quantify redox-conditions in brain and peripheral organs of mouse models or in patient-derived cells. Genetically-encoded redox-sensors meet these requirements. Expressed in transgenic mouse-models such as our unique Rett-redox indicator mice, they will report for any cell type desired the severity of oxidant stress throughout the various disease stages of RTT. Furthermore, these sensors will be crucial to evaluate in vitro and in vivo the outcome of mitochondria- and redox-balance targeted treatments.
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14. Murray LE, O’Neill L. {{Neuroticism and extraversion mediate the relationship between having a sibling with developmental disabilities and anxiety and depression symptoms}}. {Journal of affective disorders}. 2019; 243: 232-40.
Background Children growing up with a sibling with disabilities report higher levels of depression and anxiety symptoms as adults. Here, we examined whether personality characteristics also play a part in mediating this relationship. Method We tested for differences in personality traits between 132 individuals who have a sibling with developmental disabilities and 132 closely matched comparisons. Results Differences in Big Five factors of personality were demonstrated across the disability groups and between the disability groups and the comparisons, especially in Extraversion, Neuroticism and Openness. Individuals growing up alongside a sibling with developmental disabilities have a higher tendency to experience anxiety and depression symptoms, and this research is the first demonstration that personality traits mediate this relationship. Specifically, Neuroticism is a strong mediator of anxiety while both Neuroticism and Extraversion contribute mediating effects toward the development of depression. Limitations Our study made use of self-report methodology which, although having recognized limitations, is more reliable than parental reports. Given the cross-sectional nature of our design, we were not able to examine pre-existing developmental factors that may have influenced the participant’s propensity to particular personality traits and affective disorders. However, we obtained a large sample and closely matched participants to examine differences between those with a sibling with disabilities and those without. Conclusions As such, differences in personality traits have important implications for the understanding and treatment of siblings presenting with anxiety and depression symptoms. We recommend that intervention should target those high in Neuroticism among individuals who have a sibling with disabilities, and that more social support is put in place for siblings to mitigate their tendency towards introversion and buffer them against psychological maladjustment.
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15. Niemczyk J, Fischer R, Wagner C, Burau A, Link T, von Gontard A. {{Detailed Assessment of Incontinence, Psychological Problems and Parental Stress in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2019.
Incontinence, psychological symptoms, parental stress and psychopathology were examined in 51 children (43 boys, mean age = 9.7 years) presented in an outpatient clinic for autism spectrum disorders (ASD) and in 53 matched controls (43 boys, mean age = 10.2 years). All children were clinically assessed for ASD, incontinence and psychopathology according to current guidelines. ASD was confirmed in 37 children and excluded in 14. Enuresis (16.2%) and daytime urinary incontinence (16.2%), but not fecal incontinence (8.2%) were more common in ASD than in controls. Children with ASD showed significantly more comorbid psychiatric disorders. Parents of children with ASD experience more stress. Parental stress was predicted by parental psychopathology, role restriction and group (patient/control), but not by incontinence.
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16. Sheinkopf SJ, Levine TP, McCormick CEB, Puggioni G, Conradt E, Lagasse LL, Lester BM. {{Developmental Trajectories of Autonomic Functioning in Autism from Birth to Early Childhood}}. {Biological psychology}. 2019.
Deficits in social engagement emerge in autism during the infant and toddler period and may be related to emotion regulation and stress response systems. This study examined patterns of growth in autonomic functioning related to autism diagnosis and addresses the hypothesis that there are differences in autonomic functioning related to autism in infancy. Heart rate (HR) and respiratory sinus arrhythmia (RSA) were measured at 8 time points from 1 to 72 months of age in infants later diagnosed with autism (n = 12) and a non-autistic comparison group (n = 106). Multilevel models were used to describe the developmental course of HR and RSA and to test the effect of autism diagnosis on growth trajectories. Both groups showed an expected age-related decrease in HR and increase in RSA. Groups did not differ in the rate of decrease of HR over time. However, infants with autism demonstrated a smaller linear increase in RSA, indicating slower growth in RSA over time in comparison to controls. These results suggest that differences in physiological regulation may develop with age in autism. The slowed RSA growth in autism was most evident after 18 months of age, at a time when behavioral symptoms become prominent. This is consistent with the view that RSA is a marker of functional status in autism rather than a cause of social deficits in autism.
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17. Tartaglione AM, Schiavi S, Calamandrei G, Trezza V. {{Prenatal valproate in rodents as a tool to understand the neural underpinnings of social dysfunctions in autism spectrum disorder}}. {Neuropharmacology}. 2019.
Impairments in social interaction and verbal and non verbal communication are among the main features of Autism Spectrum Disorder (ASD). The causes of ASD are still unknown but the research efforts of the last decade have identified a number of factors (rare gene mutations, gene variations and adverse environmental events) that, interacting in complex ways, affect early brain development. The clinical evidence that prenatal exposure to the antiepileptic drug valproate (VPA) is associated with increased risk of neurodevelopmental delay, cognitive deficits and autism in children, has drawn the attention of scientists on VPA as a tool to unravel the environment contribution to ASD risk in children. In agreement with the clinical evidence, rodents prenatally exposed to VPA display behavioral anomalies resembling ASD symptoms. The mechanisms by which administration of VPA in pregnancy increases the risk of autism are still far to be clear as are still undetermined the specific targets of VPA in the developing brain both in humans and rodents. However, the robustness of the behavioral alterations, mainly in the social domain, and the neural/molecular changes revealed so far support the VPA model as a reliable instrument to investigate the neural underpinnings of social impairment. Here we provide an update of preclinical studies on prenatal exposure to VPA in rodents with a focus on the social and communication deficits induced by VPA, discussing potential pitfalls and future directions in this research field and corroborating the potential of the VPA model to identify new pharmacological targets for ASD.
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18. Veddum L, Pedersen HL, Landert AL, Bliksted V. {{Do patients with high-functioning autism have similar social cognitive deficits as patients with a chronic cause of schizophrenia?}}. {Nord J Psychiatry}. 2019: 1-7.
OBJECTIVE: There is substantial evidence that both patients with schizophrenia and patients with autism spectrum disorders (ASD) have impaired social cognition including theory of mind (ToM) deficits. However, it remains unclear if both verbal (explicit) and non-verbal (implicit) ToM as well as social perception are similarly affected in both disorders. METHODS: Twenty-one patients diagnosed with schizophrenia and 11 patients diagnosed with ASD were matched one-to-one to healthy controls based on gender, age, and educational level. Social functioning was measured by Personal and Social Performance (PSP) scale. Neurocognition was measured using Brief Assessment of Cognition in Schizophrenia (BACS-DK), and four subtests from Wechsler Adult Intelligence (WAIS-IV) scale were applied to estimate IQ. The Animated Triangles Task was used to measure implicit ToM, while explicit ToM and social perception were measured by The Awareness and Social Inference Test (TASIT). RESULTS: Patients with schizophrenia had deficits in implicit ToM and complex social perception compared to their matched controls, but no problems with explicit ToM. Surprisingly, patients with ASD solely had deficits with regard to complex social perception compared to their matched controls. The two patient groups were similar regarding estimated IQ, social functioning and years of education, but differed in age and neurocognition. When adjusting the p-values for age and neurocognitive deficits, both patients groups had similar social cognitive deficits. CONCLUSIONS: Results imply that we compared schizophrenia patients with substantial neurocognitive deficits to a group of high-functioning patients with ASD. However, these two subgroups may have the same level of social cognitive deficits.
