1. Asberg Johnels J, Hovey D, Zurcher N, Hippolyte L, Lemonnier E, Gillberg C, Hadjikhani N. {{Autism and emotional face-viewing}}. {Autism Res};2016 (Nov 28)
Atypical patterns of face-scanning in individuals with autism spectrum disorder (ASD) may contribute to difficulties in social interactions, but there is little agreement regarding what exactly characterizes face-viewing in ASD. In addition, little research has examined how face-viewing is modulated by the emotional expression of the stimuli, in individuals with or without ASD. We used eye-tracking to explore viewing patterns during perception of dynamic emotional facial expressions in relatively large groups of individuals with (n = 57) and without ASD (n = 58) and examined diagnostic- and age-related effects, after subgrouping children and adolescents (18 years), on the other. Results showed that children/adolescents with ASD fixated the mouth of happy and angry faces less than their typically developing (TD) peers, and conversely looked more to the eyes of happy faces. Moreover, while all groups fixated the mouth in happy faces more than in other expressions, children/adolescents with ASD did relatively less so. Correlation analysis showed a similar lack of relative orientation toward the mouth of smiling faces in TD children/adolescents with high autistic traits, as measured by the Autism-Spectrum Quotient (AQ). Among adults, participants with ASD attended less to the eyes only for neutral faces. Our study shows that the emotional content of a face influences gaze behavior, and that this effect is not fully developed in children/adolescents with ASD. Interestingly, this lack of differentiation observed in the younger ASD group was also seen in younger TD individuals with higher AQ scores. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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2. Backer van Ommeren T, Koot HM, Scheeren AM, Begeer S. {{Sex differences in the reciprocal behaviour of children with autism}}. {Autism};2016 (Nov 29)
Differences in the social limitations of girls compared to boys on the autism spectrum are still poorly understood. Impaired social-emotional reciprocity is a core diagnostic criterion for an autism spectrum disorder. This study compares sex differences in reciprocal behaviour in children with autism spectrum disorder (32 girls, 114 boys) and in typically developing children (24 girls, 55 boys). While children with autism spectrum disorder showed clear limitations in reciprocal behaviour compared to typically developing children, sex differences were found only in the autism spectrum disorder group: girls with autism spectrum disorder had higher reciprocity scores than boys with autism spectrum disorder. However, compared to typically developing girls, girls with autism spectrum disorder showed subtle differences in reciprocal behaviour. The sex-specific response patterns in autism spectrum disorder can inform and improve the diagnostic assessment of autism in females.
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3. Callow E, Tahir M, Feldman M. {{Judicial Reliance on Parental IQ in Appellate-Level Child Welfare Cases Involving Parents with Intellectual and Developmental Disabilities}}. {J Appl Res Intellect Disabil};2016 (Nov 27)
BACKGROUND: Parents with intellectual and developmental disabilities (IDDs) are over-represented in child welfare cases. Although IQ per se is an invalid indicator of parenting abilities, this study examined the prevalence of judicial consideration of parental IQ test evidence in US appellate cases. METHODS: The present authors conducted Boolean searches of Westlaw Corporation’s case database since 1999. The present authors used a six-question checklist to survey the 42 most recent American appellate cases involving termination of parental rights (TPR) decisions that included evidence of parental intellectual and developmental disabilities based on IQ. RESULTS: In 86% of cases, parental low IQ was presented as a barrier to parenting competence. Higher courts uphold TPR decision in 81% of cases involving parents with intellectual and developmental disabilities. CONCLUSIONS: Parental IQ scores are routinely relied upon to judge parenting capacity in custody cases where parents have intellectual and developmental disabilities. The present authors recommend more comprehensive assessments examining a broader range of contextual variable that may impact on parenting abilities.
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4. Cortelazzo A, de Felice C, Leoncini S, Signorini C, Guerranti R, Leoncini R, Armini A, Bini L, Ciccoli L, Hayek J. {{Inflammatory protein response in CDKL5-Rett syndrome: evidence of a subclinical smouldering inflammation}}. {Inflamm Res};2016 (Nov 29)
BACKGROUND: Mutations in the cyclin-dependent kinase-like 5 gene cause a clinical variant of Rett syndrome (CDKL5-RTT). A role for the acute-phase response (APR) is emerging in typical RTT caused by methyl-CpG-binding protein 2 gene mutations (MECP2-RTT). No information is, to date, available on the inflammatory protein response in CDKL5-RTT. We evaluated, for the first time, the APR protein response in CDKL5-RTT. METHODS: Protein patterns in albumin- and IgG-depleted plasma proteome from CDKL5-RTT patients were evaluated by two-dimensional gel electrophoresis/mass spectrometry. The resulting data were related to circulating cytokines and compared to healthy controls or MECP2-RTT patients. The effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) were evaluated. RESULTS: CDKL5-RTT mutations resulted in a subclinical attenuated inflammation, specifically characterized by an overexpression of the complement component C3 and CD5 antigen-like, both strictly related to the inflammatory response. Cytokine dysregulation featuring a bulk increase of anti-inflammatory cytokines, predominantly IL-10, could explain the unchanged erythrocyte sedimentation rate and atypical features of inflammation in CDKL5-RTT. Omega-3 PUFAs were able to counterbalance the pro-inflammatory status. CONCLUSION: For the first time, we revealed a subclinical smouldering inflammation pattern in CDKL5-RTT consisting in the coexistence of an atypical APR coupled with a dysregulated cytokine response.
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5. Dean M, Harwood R, Kasari C. {{The art of camouflage: Gender differences in the social behaviors of girls and boys with autism spectrum disorder}}. {Autism};2016 (Nov 29)
This study examined the extent to which gender-related social behaviors help girls with autism spectrum disorder to seemingly mask their symptoms. Using concurrent mixed methods, we examined the social behaviors of 96 elementary school children during recess (autism spectrum disorder = 24 girls and 24 boys, typically developing = 24 girls and 24 boys). Children with autism spectrum disorder had average intelligence (IQ 70), a confirmed diagnosis, and were educated in the general education classroom. Typically developing children were matched by sex, age, and city of residence to children with autism spectrum disorder. The results indicate that the female social landscape supports the camouflage hypothesis; girls with autism spectrum disorder used compensatory behaviors, such as staying in close proximately to peers and weaving in and out of activities, which appeared to mask their social challenges. Comparatively, the male landscape made it easier to detect the social challenges of boys with autism spectrum disorder. Typically developing boys tended to play organized games; boys with autism spectrum disorder tended to play alone. The results highlight a male bias in our perception of autism spectrum disorder. If practitioners look for social isolation on the playground when identifying children with social challenges, then our findings suggest that girls with autism spectrum disorder will continue to be left unidentified.
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6. Diab HM, Motlaq SS, Alsharare A, Alshammery A, Alshammery N, Khawja SG, Shah AH. {{Comparison of Gingival Health and Salivary Parameters among Autistic and Non-Autistic School Children in Riyadh}}. {J Clin Diagn Res};2016 (Oct);10(10):Zc110-zc113.
INTRODUCTION: Autism is a neuro-developmental disorder which is manifested as impairment of social interaction, communication and a repetitive behaviour. Autism can obscure dental treatment for the affected patients; furthermore, children with autism commonly have destructive oral habits. AIM: The aims of this study were to evaluate the Modified Gingival Index (MGI), Plaque Index (PI), salivary pH and buffering capacity of the saliva among autistic children compared to normal children in Riyadh City that may provide baseline data to enable comparison and future planning of dental services for autistic children. MATERIALS AND METHODS: A total of 50 children diagnosed with autism (mean age 8.5 years) were selected from Azzam Autism School, Riyadh City. The control group consisted of 50 non-autistic school children (mean age 8.7 years), gender matched, selected from Outpatient Clinic, Riyadh Colleges of Dentistry and Pharmacy. MGI, PI, salivary pH and salivary buffer capacity tests were done for all participants. The buffering capacity of the stimulated saliva was grouped under ‘very low’, ‘low’ and ‘normal’. Pearson’s Chi square and one way ANOVA were used to find statistical significance if any among the autistic and the normal control group. RESULTS: The results of the study showed that the mean +/- standard deviation of MGI, PI and pH of unstimulated resting saliva for autistic group were 1.82 +/- 0.65, 1.92 +/- 0.35 and 6.8 +/- 0.5 respectively. Normal control group had values 1.35 +/- 0.85, 1.44 +/- 0.43 and 7 +/- 0.4 respectively. A statistically significant difference between both groups for all parameters was found. Salivary buffering capacity was found to be normal for the majority among both groups. However, 60% children among the autistic group presented with normal buffering capacity of the stimulated saliva as compared to 70% among the normal control group. However, this difference was not statistically significant (p = 0.544). CONCLUSION: Children with autism appear to have higher gingival inflammation, poor oral hygiene and a slightly lower salivary pH as compared to healthy control group. Special oral health programmes regarding treatment and maintenance of good oral health should be taken in consideration for autistic children.
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7. Edwards A, Brebner C, McCormack P, MacDougall C. {{The early intervention message: perspectives of parents of children with autism spectrum disorder}}. {Child Care Health Dev};2016 (Nov 28)
BACKGROUND: There is strong evidence that early intervention (EI) can improve outcomes for children with autism spectrum disorder (ASD), and consequently, the importance of EI has been widely promoted to families of children with ASD. However, the perspectives of parents of children with ASD regarding the EI message have not been widely examined. METHODS: This study used qualitative methods to explore parental perspectives on the EI message. Semi-structured interviews were undertaken with 14 participants from 12 family units to explore the perspectives of parents of children with ASD on the EI message. Thematic analysis was undertaken on the data. RESULTS: Three central themes were constructed following data analysis: (i) parents’ initial perceptions of EI following their child’s diagnosis with ASD; (ii) the consequences (both positive and negative) of the EI message; and (iii) parents’ perspectives on life after EI. The results of this study indicated that parents were acutely aware of the importance of EI, and although this provided parents with hope immediately post-diagnosis, it also placed pressure on parental decision-making regarding which intervention approaches to access for their children with ASD. CONCLUSIONS: The results of this study highlight the importance of carefully considering how health messages, specifically the importance of EI, are communicated to families of children with ASD. Furthermore, the findings of this study also highlight the need for allied health professionals to communicate openly with parents about the anticipated outcomes of EI programmes.
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8. Erickson SR, Salgado TM, Tan X. {{Issues in the Medication Management Process in People Who Have Intellectual and Developmental Disabilities: A Qualitative Study of the Caregivers’ Perspective}}. {Intellect Dev Disabil};2016 (Dec);54(6):412-426.
People who have intellectual and developmental disabilities (IDD) often rely on caregivers to assist in the medication management process. The aim of this study was to learn from caregivers, who are either family or support staff, what major issues arise throughout the process of managing medication and how these might be addressed. Problems identified by caregivers include (a) prescribers understanding of insurance and agency policies regarding medication utilization; (b) lack of continuity of care and accuracy of the medication record as well as clinical records;
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9. Gedek HM, Pantelis PC, Kennedy DP. {{The influence of presentation modality on the social comprehension of naturalistic scenes in adults with autism spectrum disorder}}. {Autism};2016 (Nov 29)
The comprehension of dynamically unfolding social situations is made possible by the seamless integration of multimodal information merged with rich intuitions about the thoughts and behaviors of others. We examined how high-functioning adults with autism spectrum disorder and neurotypical controls made a complex social judgment (i.e. rating the social awkwardness of scenes from a television sitcom) across three conditions that manipulated presentation modality-visual alone, transcribed text alone, or visual and auditory together. The autism spectrum disorder and control groups collectively assigned similar mean awkwardness ratings to individual scenes. However, individual participants with autism spectrum disorder tended to respond more idiosyncratically than controls, assigning ratings that were less correlated with the ratings of the other participants in the sample. We found no evidence that this group difference was isolated to any specific presentation modality. In a comparison condition, we found no group differences when participants instead rated the happiness of characters (a more basic social judgment) in full audiovisual format. Thus, although we observed differences in the manner with which high-functioning adults with autism spectrum disorder make social judgments compared to controls, these group differences may be dependent on the social dimension being judged, rather than the specific modality of presentation.
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10. Green SA, Hernandez L, Bookheimer SY, Dapretto M. {{Reduced modulation of thalamocortical connectivity during exposure to sensory stimuli in ASD}}. {Autism Res};2016 (Nov 29)
Recent evidence for abnormal thalamic connectivity in autism spectrum disorders (ASD) and sensory processing disorders suggests the thalamus may play a role in sensory over-responsivity (SOR), an extreme negative response to sensory stimuli, which is common in ASD. However, there is yet little understanding of changes in thalamic connectivity during exposure to aversive sensory inputs in individuals with ASD. In particular, the pulvinar nucleus of the thalamus is implicated in atypical sensory processing given its role in selective attention, regulation, and sensory integration. This study aimed to examine the role of pulvinar connectivity in ASD during mildly aversive sensory input. Functional magnetic resonance imaging was used to examine connectivity with the pulvinar during exposure to mildly aversive auditory and tactile stimuli in 38 youth (age 9-17; 19 ASD, 19 IQ-matched typically developing (TD)). Parents rated children’s SOR severity on two standard scales. Compared to TD, ASD participants displayed aberrant modulation of connectivity between pulvinar and cortex (including sensory-motor and prefrontal regions) during sensory stimulation. In ASD participants, pulvinar-amygdala connectivity was correlated with severity of SOR symptoms. Deficits in modulation of thalamocortical connectivity in youth with ASD may reflect reduced thalamo-cortical inhibition in response to sensory stimulation, which could lead to difficulty filtering out and/or integrating sensory information. An increase in amygdala connectivity with the pulvinar might be partially responsible for deficits in selective attention as the amygdala signals the brain to attend to distracting sensory stimuli. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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11. Kalandadze T, Norbury C, Naerland T, Naess KB. {{Figurative language comprehension in individuals with autism spectrum disorder: A meta-analytic review}}. {Autism};2016 (Nov 29)
We present a meta-analysis of studies that compare figurative language comprehension in individuals with autism spectrum disorder and in typically developing controls who were matched based on chronological age or/and language ability. A total of 41 studies and 45 independent effect sizes were included based on predetermined inclusion criteria. Group matching strategy, age, types of figurative language, and cross-linguistic differences were examined as predictors that might explain heterogeneity in effect sizes. Overall, individuals with autism spectrum disorder showed poorer comprehension of figurative language than their typically developing peers (Hedges’ g = -0.57). A meta-regression analysis showed that group matching strategy and types of figurative language were significantly related to differences in effect sizes, whereas chronological age and cross-linguistic differences were not. Differences between the autism spectrum disorder and typically developing groups were small and nonsignificant when the groups were matched based on the language ability. Metaphors were more difficult to comprehend for individuals with autism spectrum disorder compared with typically developing controls than were irony and sarcasm. Our findings highlight the critical role of core language skills in figurative language comprehension. Interventions and educational programmes designed to improve social communication skills in individuals with autism spectrum disorder may beneficially target core language skills in addition to social skills.
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12. Komeda H, Osanai H, Yanaoka K, Okamoto Y, Fujioka T, Arai S, Inohara K, Koyasu M, Kusumi T, Takiguchi S, Kawatani M, Kumazaki H, Hiratani M, Tomoda A, Kosaka H. {{Decision making processes based on social conventional rules in early adolescents with and without autism spectrum disorders}}. {Sci Rep};2016 (Nov 29);6:37875.
Autism spectrum disorder (ASD) is characterized by problems with reciprocal social interaction, repetitive behaviours/narrow interests, and impairments in the social cognition and emotional processing necessary for intention-based moral judgements. The aim of this study was to examine the information used by early adolescents with and without ASD when they judge story protagonists as good or bad. We predicted that adolescents with ASD would use protagonists’ behaviour, while typically developing (TD) adolescents would use protagonists’ characteristics when making the judgements. In Experiment 1, we measured sentence by sentence reading times and percentages for good or bad judgements. In Experiment 2, two story protagonists were presented and the participants determined which protagonist was better or worse. Experiment 1 results showed that the adolescents with ASD used protagonist behaviours and outcomes, whereas the TD adolescents used protagonist characteristics, behaviours, and outcomes. In Experiment 2, TD adolescents used characteristics information when making « bad » judgements. Taken together, in situations in which participants cannot go back and assess (Experiment 1), and in comparable situations in which all information is available (Experiment 2), adolescents with ASD do not rely on information about individual characteristics when making moral judgements.
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13. Kuijper SJ, Hartman CA, Bogaerds-Hazenberg ST, Hendriks P. {{Narrative Production in Children With Autism Spectrum Disorder (ASD) and Children With Attention-Deficit/Hyperactivity Disorder (ADHD): Similarities and Differences}}. {J Abnorm Psychol};2016 (Nov 28)
The present study focuses on the similarities and differences in language production between children with autism spectrum disorder (ASD) and children with attention-deficit/hyperactivity disorder (ADHD). In addition, we investigated whether Theory of Mind (ToM), working memory, and response inhibition are associated with language production. Narratives, produced by 106 Dutch-speaking children (36 with ASD, 34 with ADHD, and 36 typically developing) aged 6 to 12 during ADOS assessment, were examined on several linguistic measures: verbal productivity, speech fluency, syntactic complexity, lexical semantics, and discourse pragmatics. Children were tested on ToM, working memory, and response inhibition and parents filled in the Children’s Communication Checklist (CCC-2). Gold-standard diagnostic measures (Autism Diagnostic Observation Schema [ADOS], Autism Diagnostic Interview Revised [ADI-R], and the Parent Interview for Child Symptoms [PICS]) were administered to all children to confirm diagnosis. Regarding similarities, both clinical groups showed impairments in narrative performance relative to typically developing children. These were confirmed by the CCC-2. These impairments were not only present on pragmatic measures, such as the inability to produce a narrative in a coherent and cohesive way, but also on syntactic complexity and their production of repetitions. As for differences, children with ADHD but not children with ASD showed problems in their choice of referring expressions and speech fluency. ToM and working memory performance but not response inhibition were associated with many narrative skills, suggesting that these cognitive mechanisms explain some of the impairments in language production. We conclude that children with ASD and children with ADHD manifest multiple and diverse language production problems, which may partly relate to their problems in ToM and working memory. (PsycINFO Database Record
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14. Lai MC, Lombardo MV, Ruigrok AN, Chakrabarti B, Auyeung B, Szatmari P, Happe F, Baron-Cohen S. {{Quantifying and exploring camouflaging in men and women with autism}}. {Autism};2016 (Nov 29)
Autobiographical descriptions and clinician observations suggest that some individuals with autism, particularly females, ‘camouflage’ their social communication difficulties, which may require considerable cognitive effort and lead to increased stress, anxiety and depression. Using data from 60 age- and IQ-matched men and women with autism (without intellectual disability), we operationalized camouflaging in adults with autism for the first time as the quantitative discrepancy between the person’s ‘external’ behavioural presentation in social-interpersonal contexts (measured by the Autism Diagnostic Observation Schedule) and the person’s ‘internal’ status (dispositional traits measured by the Autism Spectrum Quotient and social cognitive capability measured by the ‘Reading the Mind in the Eyes’ Test). We found that the operationalized camouflaging measure was not significantly correlated with age or IQ. On average, women with autism had higher camouflaging scores than men with autism (Cohen’s d = 0.98), with substantial variability in both groups. Greater camouflaging was associated with more depressive symptoms in men and better signal-detection sensitivity in women with autism. The neuroanatomical association with camouflaging score was largely sex/gender-dependent and significant only in women: from reverse inference, the most correlated cognitive terms were about emotion and memory. The underlying constructs, measurement, mechanisms, consequences and heterogeneity of camouflaging in autism warrant further investigation.
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15. Liska A, Gozzi A. {{Can Mouse Imaging Studies Bring Order to Autism Connectivity Chaos?}}. {Front Neurosci};2016;10:484.
Functional Magnetic Resonance Imaging (fMRI) has consistently highlighted impaired or aberrant functional connectivity across brain regions of autism spectrum disorder (ASD) patients. However, the manifestation and neural substrates of these alterations are highly heterogeneous and often conflicting. Moreover, their neurobiological underpinnings and etiopathological significance remain largely unknown. A deeper understanding of the complex pathophysiological cascade leading to aberrant connectivity in ASD can greatly benefit from the use of model organisms where individual pathophysiological or phenotypic components of ASD can be recreated and investigated via approaches that are either off limits or confounded by clinical heterogeneity. Despite some obvious limitations in reliably modeling the full phenotypic spectrum of a complex developmental disorder like ASD, mouse models have played a central role in advancing our basic mechanistic and molecular understanding of this syndrome. Recent progress in mouse brain connectivity mapping via resting-state fMRI (rsfMRI) offers the opportunity to generate and test mechanistic hypotheses about the elusive origin and significance of connectional aberrations observed in autism. Here we discuss recent progress toward this goal, and illustrate initial examples of how the approach can be employed to establish causal links between ASD-related mutations, developmental processes, and brain connectional architecture. As the spectrum of genetic and pathophysiological components of ASD modeled in the mouse is rapidly expanding, the use of rsfMRI can advance our mechanistic understanding of the origin and significance of the connectional alterations associated with autism, and their heterogeneous expression across patient cohorts.
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16. Mery DP. {{Does data cleaning disproportionately affect autistics?}}. {Autism};2016 (Nov 29)
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17. Mihaila I, Hartley SL. {{Parental sleep quality and behavior problems of children with autism}}. {Autism};2016 (Nov 29)
This study explored the impact of parental sleep quality on the experience of behavior problems by children with autism spectrum disorder. A 14-day daily diary was used in a sample of 176 mother-father couples. Dyadic multilevel models were conducted to examine the between-person and within-person effects of previous-night sleep quality on parents’ rating of level of behavior problems by the child with autism spectrum disorder and level of positive and negative affect. Results indicated that persistently poor sleep quality was associated with between-person differences in initial rating of level of behavior problems by the child with autism spectrum disorder for mothers. At a within-person level, previous-night sleep quality moderated the association between rating of level of behavior problems by the child with autism spectrum disorder and level of positive and negative affect in fathers. Child-related stressors exerted less influence on fathers’ affect following a day with poor sleep quality. Interventions aimed at enhancing sleep quality in parents of children with autism spectrum disorder may have important effects on parental psychological well-being.
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18. Murray AL, Allison C, Smith PL, Baron-Cohen S, Booth T, Auyeung B. {{Investigating diagnostic bias in autism spectrum conditions: An item response theory analysis of sex bias in the AQ-10}}. {Autism Res};2016 (Nov 28)
Diagnostic bias is a concern in autism spectrum conditions (ASC) where prevalence and presentation differ by sex. To ensure that females with ASC are not under-identified, it is important that ASC screening tools do not systematically underestimate autistic traits in females relative to males. We evaluated whether the AQ-10, a brief screen for ASC recommended by the National Institute of Clinical Excellence in cases of suspected ASC, exhibits such a bias. Using an item response theory approach, we evaluated differential item functioning and differential test functioning. We found that although individual items showed some sex bias, these biases at times favored males and at other times favored females. Thus, at the level of test scores the item-level biases cancelled out to give an unbiased overall score. Results support the continued use of the AQ-10 sum score in its current form; however, suggest that caution should be exercised when interpreting responses to individual items. The nature of the item level biases could serve as a guide for future research into how ASC affects males and females differently. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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19. Pisula E, Pudlo M, Slowinska M, Kawa R, Strzaska M, Banasiak A, Wolanczyk T. {{Behavioral and emotional problems in high-functioning girls and boys with autism spectrum disorders: Parents’ reports and adolescents’ self-reports}}. {Autism};2016 (Nov 29)
The purpose of this study was to investigate sex differences in behavioral and emotional problems in high-functioning girls and boys with autism spectrum disorder. The results obtained by adolescents with autism spectrum disorder were compared with those of typically developing girls and boys. Correlations between parents’ and adolescents’ ratings were also analyzed. Participants were 35 girls and 35 boys with autism spectrum disorder, aged 11-18 years, matched for chronological age and full-scale IQ. The control group consisted of 24 typically developing girls and 24 boys of the same age and IQ. The parents of adolescent participants were also included in the study. The measures used were the Child Behavior Checklist (4-18) completed by parents and Youth Self-Report (11-18) completed by adolescents. The adolescents with autism spectrum disorder presented higher levels of behavioral and emotional problems than the control group, according to both the parents’ reports and the adolescents’ self-reports. No sex differences were found in that respect. More differences between the assessments of adolescents and their parents occurred in the control group, and the effect size was larger.
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20. Santosh PJ, Bell L, Lievesley K, Singh J, Fiori F. {{Paradoxical physiological responses to propranolol in a Rett syndrome patient: a case report}}. {BMC Pediatr};2016 (Nov 29);16(1):194.
BACKGROUND: Rett Syndrome (RTT), caused by a loss-of-function in the epigenetic modulator: X-linked methyl-CpG binding protein 2 (MeCP2), is a pervasive neurological disorder characterized by compromised brain functions, anxiety, severe mental retardation, language and learning disabilities, repetitive stereotyped hand movements and developmental regression. An imbalance in the sympathetic and the parasympathetic nervous system (dysautonomia) and the resulting autonomic storms is a frequent occurrence in patients with RTT. The prototypical beta blocker propranolol has been used to manage sympathetic hyperactivity in patients with RTT. CASE PRESENTATION: A 13 year old girl with RTT was referred to the Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust. Her clinical picture included disordered breathing with concomitant hyperventilation and apnoea, epilepsy, scoliosis, no QT prolongation (QT/QTc [372/467 ms on automated electrocardiogram [ECG], but manually calculated to be 440 ms]), no cardiac abnormalities (PR interval: 104 ms, QRS duration: 78 ms), and generalised anxiety disorder (ICD-10-CM Diagnosis Code F41.1). She was also constipated and was fed via percutaneous endoscopic gastrostomy (PEG). To manage the dysautonomia, propranolol was given (5 mg and 10 mg) and in parallel her physiological parameters, including heart rate, skin temperature and skin transpiration, were monitored continuously for 24 h as she went about her activities of daily living. Whilst her skin temperature increased and skin transpiration decreased, unexpectedly there was a significant paradoxical increase in the patient’s average heart rate following propranolol treatment. CONCLUSION: Here, we present a unique case of a paradoxical increase in heart rate response following propranolol treatment for managing dysautonomia in a child with RTT. Further studies are warranted to better understand the underlying dysautonomia in patients with RTT and the impact this might have on treatment strategies in rare disorders such as RTT.
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21. Scahill L, Bearss K, Sarhangian R, McDougle CJ, Arnold LE, Aman MG, McCracken JT, Tierney E, Gillespie S, Postorino V, Vitiello B. {{Using a Patient-Centered Outcome Measure to Test Methylphenidate Versus Placebo in Children with Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol};2016 (Nov 28)
OBJECTIVES: Parent rating scales are commonly used to evaluate change in clinical trials. Despite advantages, these measures may not capture parental impression of the child’s most salient problems. We examine the use of parent target problems (PTPs) in a randomized trial of methylphenidate (MPH) in children with autism spectrum disorder and symptoms of attention-deficit/hyperactivity disorder. METHODS: This multisite, 4-week, randomized crossover trial compared three dose levels (low, medium, and high) of MPH with placebo. At baseline, the independent evaluator (IE) asked parents to nominate the child’s two biggest problems. For each problem, the IE and parent coconstructed a brief narrative of the behavior and the impact on family life. The IE and parents reviewed and revised the narratives at subsequent visits. A panel of four judges, blind to treatment condition, independently reviewed the narratives to rate change from baseline on a 9-point scale: 1, normal; 2, markedly improved; 3, definitely improved; 4, equivocally improved; 5, no change; 6, possibly worse; 7, definitely worse; 8, markedly worse; 9, disastrously worse. The mean of the four raters was compared with primary and key secondary ratings from the original study. RESULTS: Two PTPs were recorded at baseline for 60 participants. The inter-rater reliability of the four judges across all PTPs and time points was excellent (intraclass correlation = 0.95). On the primary outcome measure (Aberrant Behavior Checklist Hyperactivity subscale), the medium and high-dose levels were superior to placebo. On the mean PTP rating, only the high dose was superior to placebo. We also compared PTP cutoff scores 3.0 (definitely improved), 3.25, and 3.5 with the rate of positive response on the Improvement item of the Clinical Global Impressions scale in the original study. Sensitivities ranged from 68% to 88%. CONCLUSIONS: The parent target problem method offers a systematic way to identify and track patient-centered outcomes.
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22. Shephard E, Milosavljevic B, Pasco G, Jones EJ, Gliga T, Happe F, Johnson MH, Charman T. {{Mid-childhood outcomes of infant siblings at familial high-risk of autism spectrum disorder}}. {Autism Res};2016 (Nov 29)
Almost one-in-five infants at high familial risk for autism spectrum disorder (ASD), due to having an older sibling with an ASD diagnosis, develop ASD themselves by age 3 years. Less is known about the longer-term outcomes of high-risk infants. To address this issue, we examined symptoms of ASD and associated developmental conditions (attention-deficit/hyperactivity disorder (ADHD); anxiety), language, IQ, and adaptive behaviour at age 7 years in high- and low-risk children studied from infancy. We compared outcomes between high-risk children who met criteria for ASD at age 7, high-risk children without ASD, and low-risk control children. Diagnostic stability between 3 and 7 years was moderate. High-risk siblings with ASD showed elevated levels of ADHD and anxiety symptoms and lower adaptive behaviour than low-risk control children. High-risk siblings without ASD had higher repetitive behaviours, lower adaptive functioning, and elevated scores on one anxiety subscale (Separation Anxiety) compared to low-risk controls. The findings indicate that the difficulties experienced by high-risk siblings at school age extend beyond ASD symptoms. Better understanding of these difficulties may improve models of the development of co-occurring problems seen in children with ASD. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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23. Shirama A, Kato N, Kashino M. {{When do individuals with autism spectrum disorder show superiority in visual search?}}. {Autism};2016 (Nov 29)
Although superior visual search skills have been repeatedly reported for individuals with autism spectrum disorder, the underlying mechanisms remain controversial. To specify the locus where individuals with autism spectrum disorder excel in visual search, we compared the performance of autism spectrum disorder adults and healthy controls in briefly presented search tasks, where the search display was replaced by a noise mask at a stimulus-mask asynchrony of 160 ms to interfere with a serial search process while bottom-up visual processing remains intact. We found that participants with autism spectrum disorder show faster overall reaction times regardless of the number of stimuli and the presence of a target with higher accuracy than controls in a luminance and shape conjunction search task as well as a hard feature search task where the target feature information was ineffective in prioritizing likely target stimuli. In addition, the analysis of target eccentricity illustrated that the autism spectrum disorder group has better target discriminability regardless of target eccentricity, suggesting that the autism spectrum disorder advantage does not derive from a reduced crowding effect, which is known to be enhanced with increasing retinal eccentricity. The findings suggest that individuals with autism spectrum disorder excel in non-search processes, especially in the simultaneous discrimination of multiple visual stimuli.
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24. Swatzyna RJ, Tarnow JD, Turner RP, Roark AJ, MacInerney EK, Kozlowski GP. {{Integration of EEG into Psychiatric Practice: A Step Toward Precision Medicine for Autism Spectrum Disorder}}. {J Clin Neurophysiol};2016 (Nov 22)
INTRODUCTION: Data from an EEG is not commonly used by psychiatrists to plan treatment and medication. However, EEG abnormalities such as isolated epileptiform discharges (IEDs) are found to be more prevalent in psychiatric patients, particularly those diagnosed with Autism Spectrum Disorder (ASD). Most medications prescribed for ASD lower seizure threshold and increase side-effects. Therefore, it may be prudent to order an EEG for ASD cases, especially those categorized as refractory. The objective of this study was to explore integrating EEG into a psychiatric practice that treats patients with ASD. METHODS: The dataset was obtained from a multidisciplinary practice that treats a wide variety of neuroatypical children and adolescent refractory patients. This study investigated 140 non-epileptic subjects diagnosed with ASD, ages 4 to 25. Visual inspection of the EEG was performed in order to search for paroxysmal, focal, or lateralizing patterns. RESULTS: Of the 140 subjects, the EEG data identified 36 percent with IEDs. The Chi-square analysis found no significant difference between genders among the three age groups. Findings indicated a high prevalence of IEDs among individuals with ASD. CONCLUSIONS: Our results find that compared to the healthy population, a large number of patients with ASD have IEDs despite never having a seizure. Our findings support the use of EEG in children, adolescents, and young adults with ASD, regardless of gender or age. This is particularly true for those who exhibit aggressive behaviors or those who have failed prior medication attempts with stimulants, antidepressants, and/or antipsychotics.
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25. Tsai PC, Harrington RA, Lung FW, Lee LC. {{Disparity in report of autism-related behaviors by social demographic characteristics: Findings from a community-based study in Taiwan}}. {Autism};2016 (Nov 29)
The Social Communication Questionnaire is one of the most commonly used screening tools for autism spectrum disorder. The Social Communication Questionnaire is a caregiver-reported questionnaire with 40 items based on questions from the Autism Diagnostic Interview-Revised. This study collected Social Communication Questionnaire data from a community-based, multi-stage case identification design epidemiologic study in one socioeconomically disadvantaged county in Taiwan. The Social Communication Questionnaire was distributed to 3034 school children, aged 6-8 years. Item prevalence results indicate males were reported to have more autism-related behaviors than females (higher prevalence on most items), in the whole study sample as well as in children meeting Social Communication Questionnaire clinical cut-offs (15). Children whose biological fathers completed the Social Communication Questionnaire were reported to have more behavioral issues than children whose biological mothers were the respondent. Lower respondent education levels were associated with reports of clinically concerning autism-related behaviors. However, males were not at higher risk of meeting Social Communication Questionnaire clinical cut-offs than females in this study population. Findings from this study help to better understand reporting patterns on children’s autism-related behaviors potentially due to social demographic characteristics and child sex, which may lead to improved identification of these behaviors.
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26. Vinkhuyzen AA, Eyles DW, Burne TH, Blanken LM, Kruithof CJ, Verhulst F, Jaddoe VW, Tiemeier H, McGrath JJ. {{Gestational vitamin D deficiency and autism-related traits: the Generation R Study}}. {Mol Psychiatry};2016 (Nov 29)
There is intense interest in identifying modifiable risk factors associated with autism-spectrum disorders (ASD). Autism-related traits, which can be assessed in a continuous fashion, share risk factors with ASD, and thus can serve as informative phenotypes in population-based cohort studies. Based on the growing body of research linking gestational vitamin D deficiency with altered brain development, this common exposure is a candidate modifiable risk factor for ASD and autism-related traits. The association between gestational vitamin D deficiency and a continuous measure of autism-related traits at ~6 years (Social Responsiveness Scale; SRS) was determined in a large population-based cohort of mothers and their children (n=4229). 25-hydroxyvitamin D (25OHD) was assessed from maternal mid-gestation sera and from neonatal sera (collected from cord blood). Vitamin D deficiency was defined as 25OHD concentrations less than 25 nmol l-1. Compared with the 25OHD sufficient group (25OHD>50 nmol l-1), those who were 25OHD deficient had significantly higher (more abnormal) SRS scores (mid-gestation n=2866, beta=0.06, P<0.001; cord blood n=1712, beta=0.03, P=0.01). The findings persisted (a) when we restricted the models to offspring with European ancestry, (b) when we adjusted for sample structure using genetic data, (c) when 25OHD was entered as a continuous measure in the models and (d) when we corrected for the effect of season of blood sampling. Gestational vitamin D deficiency was associated with autism-related traits in a large population-based sample. Because gestational vitamin D deficiency is readily preventable with safe, cheap and accessible supplements, this candidate risk factor warrants closer scrutiny.Molecular Psychiatry advance online publication, 29 November 2016; doi:10.1038/mp.2016.213. Lien vers le texte intégral (Open Access ou abonnement)
27. Werling DM. {{The role of sex-differential biology in risk for autism spectrum disorder}}. {Biol Sex Differ};2016;7:58.
Autism spectrum disorder (ASD) is a developmental condition that affects approximately four times as many males as females, a strong sex bias that has not yet been fully explained. Understanding the causes of this biased prevalence may highlight novel avenues for treatment development that could benefit patients with diverse genetic backgrounds, and the expertise of sex differences researchers will be invaluable in this endeavor. In this review, I aim to assess current evidence pertaining to the sex difference in ASD prevalence and to identify outstanding questions and remaining gaps in our understanding of how males come to be more frequently affected and/or diagnosed with ASD. Though males consistently outnumber females in ASD prevalence studies, prevalence estimates generated using different approaches report male/female ratios of variable magnitude that suggest that ascertainment or diagnostic biases may contribute to the male skew in ASD. Here, I present the different methods applied and implications of their findings. Additionally, even as prevalence estimations challenge the degree of male bias in ASD, support is growing for the long-proposed female protective effect model of ASD risk, and I review the relevant results from recurrence rate, quantitative trait, and genetic analyses. Lastly, I describe work investigating several sex-differential biological factors and pathways that may be responsible for females’ protection and/or males’ increased risk predicted by the female protective effect model, including sex steroid hormone exposure and regulation and sex-differential activity of certain neural cell types. However, much future work from both the ASD and sex differences research communities will be required to flesh out our understanding of how these factors act to influence the developing brain and modulate ASD risk.
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28. Zerbo O, Qian Y, Yoshida C, Fireman BH, Klein NP, Croen LA. {{Association Between Influenza Infection and Vaccination During Pregnancy and Risk of Autism Spectrum Disorder}}. {JAMA Pediatr};2016 (Nov 28)
Importance: Maternal infections and fever during pregnancy are associated with increased risk for autism spectrum disorders (ASDs). To our knowledge, no study has investigated the association between influenza vaccination during pregnancy and ASD. Objective: To investigate the association between influenza infection and vaccination during pregnancy and ASD risk. Design, Setting, and Participants: This cohort study included 196 929 children born at Kaiser Permanente Northern California from January 1, 2000 to December 31, 2010, at a gestational age of at least 24 weeks. Exposures: Data on maternal influenza infection and vaccination from conception date to delivery date, obtained from Kaiser Permanente Northern California inpatient and outpatient databases. Influenza infection was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification codes or positive influenza laboratory test results. Main Outcomes and Measures: Clinical diagnoses of ASDs identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes 299.0, 299.8, or 299.9 recorded in Kaiser Permanente Northern California electronic medical records on at least 2 occasions any time from birth through June 2015. Results: Within this cohort of 196 929 children, influenza was diagnosed in 1400 (0.7%) mothers and 45 231 (23%) received an influenza vaccination during pregnancy. The mean (SD) ages of vaccinated and unvaccinated women were 31.6 (5.2) and 30.4 (5.6) years, respectively. A total number of 3101 (1.6%) children were diagnosed with ASD. After adjusting for covariates, we found that maternal influenza infection (adjusted hazard ratio, 1.04; 95% CI, 0.68-1.58) or influenza vaccination (adjusted hazard ratio, 1.10; 95% CI, 1.00-1.21) anytime during pregnancy was not associated with increased ASD risk. In trimester-specific analyses, first-trimester influenza vaccination was the only period associated with increased ASD risk (adjusted hazard ratio, 1.20; 95% CI, 1.04-1.39). However, this association could be due to chance (P = 0.1) if Bonferroni corrected for the multiplicity of hypotheses tested (n = 8). Maternal influenza vaccination in the second or third trimester was not associated with increased ASD risk. Conclusions and Relevance: There was no association between maternal influenza infection anytime during pregnancy and increased ASD risk. There was a suggestion of increased ASD risk among children whose mothers received an influenza vaccination in their first trimester, but the association was not statistically significant after adjusting for multiple comparisons, indicating that the finding could be due to chance. These findings do not call for changes in vaccine policy or practice, but do suggest the need for additional studies on maternal influenza vaccination and autism.
