1. Birmingham E, Smith Johnston KH, Iarocci G. {{Spontaneous Gaze Selection and Following During Naturalistic Social Interactions in School-Aged Children and Adolescents With Autism Spectrum Disorder}}. {Can J Exp Psychol}. 2017.
Using a novel naturalistic paradigm allowing participants the freedom to spontaneously select and follow gaze cues in their environment, this study extends previous research conducted with younger children to determine whether school-age children with autism spectrum disorder (ASD, n = 17) demonstrate abnormal gaze following relative to typically developing (TD, n = 15) children. The participant and experimenter played a series of games, during which the experimenter pseudorandomly averted her gaze toward a social target (person) or a nonsocial target (object). A significant finding was that, relative to TD children, children with ASD were slower to follow the experimenter’s gaze relative to the start of the trial (social targets d = -.93 [-1.70, -.16], nonsocial targets d = -1.05 [-1.88, -.20]). When we analyzed the duration of glances to the experimenter, we found that the ASD group made longer glances relative to TD children, but only in the nonsocial target condition (social targets d = .01 [-.68, .71], nonsocial targets d = -.81 [-1.53, -.08]). Other analyses revealed patterns of gaze selection and following that may help interpret the main findings. Despite the differences in the timing of gaze selection and following, the most common type of responder in both groups was one who followed the experimenter’s gaze on over half of the trials. This pattern of results argues against a clear deficit in social attention in school-age children with ASD and underscores the importance of measuring both the timing of distinct mechanisms of social attention and the context in which these behaviors occur. (PsycINFO Database Record
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2. Burrows CA, Timpano KR, Uddin LQ. {{Putative Brain Networks Underlying Repetitive Negative Thinking and Comorbid Internalizing Problems in Autism}}. {Clin Psychol Sci}. 2017; 5(3): 522-36.
Many high-functioning individuals with autism spectrum disorder (ASD) also experience depression and anxiety, yet little is known about mechanisms underlying this comorbidity. Repetitive negative thinking (RNT) about self-referential information is a transdiagnostic cognitive vulnerability factor that may account for the relationship between these two classes of symptoms. We propose a model where self-referential processing and cognitive inflexibility interact to increase risk for RNT, leading to internalizing problems in ASD. Examination of interactions within and between two well-characterized large-scale brain networks, the default mode network and the salience network, may provide insights into neurobiological mechanisms underlying RNT in ASD. We summarize previous literature supporting this model, emphasizing moving towards understanding RNT as a factor accounting for the high rates of internalizing problems in ASD. Future research avenues include understanding heterogeneity in clinical presentation, and promise for identifying and treating cognitive flexibility and RNT to reduce comorbid internalizing problems in ASD.
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3. Cheng N, Alshammari F, Hughes E, Khanbabaei M, Rho JM. {{Dendritic overgrowth and elevated ERK signaling during neonatal development in a mouse model of autism}}. {PLoS One}. 2017; 12(6): e0179409.
Autism spectrum disorder (hereafter referred to as « ASD ») is a heterogeneous neurodevelopmental condition characterized by impaired social communication and interactions, and restricted, repetitive activities or interests. Alterations in network connectivity and memory function are frequently observed in autism patients, often involving the hippocampus. However, specific changes during early brain development leading to disrupted functioning remain largely unclear. Here, we investigated the development of dendritic arbor of hippocampal CA1 pyramidal neurons in the BTBR T+tf/J (BTBR) mouse model of autism. BTBR mice display the defining behavioural features of autism, and also exhibit impaired learning and memory. We found that compared to control C57BL/6J (B6) animals, the lengths of both apical and basal dendrites were significantly greater in neonatal BTBR animals. Further, basal dendrites in the BTBR mice had higher branching complexity. In contrast, cross-sectional area of the soma was unchanged. In addition, we observed a similar density of CA1 pyramidal neurons and thickness of the neuronal layer between the two strains. Thus, there was a specific, compartmentalized overgrowth of dendrites during early development in the BTBR animals. Biochemical analysis further showed that the extracellular signal-regulated kinases (ERK) pathway was up-regulated in the hippocampus of neonatal BTBR animals. Since dendritic structure is critical for information integration and relay, our data suggest that altered development of dendrites could potentially contribute to impaired hippocampal function and behavior observed in the BTBR model, and that this might be related to increased activation of the ERK pathway.
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4. Cuevas-Olguin R, Roychowdhury S, Banerjee A, Garcia-Oscos F, Esquivel-Rendon E, Bringas ME, Kilgard MP, Flores G, Atzori M. {{Cerebrolysin prevents deficits in social behavior, repetitive conduct, and synaptic inhibition in a rat model of autism}}. {J Neurosci Res}. 2017.
Autism spectrum disorder (ASD) is a syndrome of diverse neuropsychiatric diseases of growing incidence characterized by repetitive conduct and impaired social behavior and communication for which effective pharmacological treatment is still unavailable. While the mechanisms and etiology of ASD are still unknown, a consensus is emerging about the synaptic nature of the syndrome, suggesting a possible avenue for pharmacological treatment with synaptogenic compounds. The peptidic mixture cerebrolysin (CBL) has been successfully used during the last three decades in the treatment of stroke and neurodegenerative disease. Animal experiments indicate that at least one possible mechanism of action of CBL is through neuroprotection and/or synaptogenesis. In the present study, we tested the effect of CBL treatment (daily injection of 2.5 mL/Kg i.p. during 15 days) on a rat model of ASD. This was based on the offspring (43 male and 51 female pups) of a pregnant female rat injected with valproic acid (VPA, 600 mg/Kg) at the embryonic day 12.5, which previous work has shown to display extensive behavioral, as well as synaptic impairment. Comparison between saline vs. CBL-injected VPA animals shows that CBL treatment improves behavioral as well as synaptic impairments, measured by behavioral performance (social interaction, Y-maze, plus-maze), maximal response of inhibitory gamma-amino butyric acid type A receptor (GABAA R)-mediated synaptic currents, as well as their kinetic properties and adrenergic and muscarinic modulation. We speculate that CBL might be a viable and effective candidate for pharmacological treatment or co-treatment of ASD patients. (c) 2017 Wiley Periodicals, Inc.
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5. Demopoulos C, Yu N, Tripp J, Mota N, Brandes-Aitken AN, Desai SS, Hill SS, Antovich AD, Harris J, Honma S, Mizuiri D, Nagarajan SS, Marco EJ. {{Magnetoencephalographic Imaging of Auditory and Somatosensory Cortical Responses in Children with Autism and Sensory Processing Dysfunction}}. {Front Hum Neurosci}. 2017; 11: 259.
This study compared magnetoencephalographic (MEG) imaging-derived indices of auditory and somatosensory cortical processing in children aged 8-12 years with autism spectrum disorder (ASD; N = 18), those with sensory processing dysfunction (SPD; N = 13) who do not meet ASD criteria, and typically developing control (TDC; N = 19) participants. The magnitude of responses to both auditory and tactile stimulation was comparable across all three groups; however, the M200 latency response from the left auditory cortex was significantly delayed in the ASD group relative to both the TDC and SPD groups, whereas the somatosensory response of the ASD group was only delayed relative to TDC participants. The SPD group did not significantly differ from either group in terms of somatosensory latency, suggesting that participants with SPD may have an intermediate phenotype between ASD and TDC with regard to somatosensory processing. For the ASD group, correlation analyses indicated that the left M200 latency delay was significantly associated with performance on the WISC-IV Verbal Comprehension Index as well as the DSTP Acoustic-Linguistic index. Further, these cortical auditory response delays were not associated with somatosensory cortical response delays or cognitive processing speed in the ASD group, suggesting that auditory delays in ASD are domain specific rather than associated with generalized processing delays. The specificity of these auditory delays to the ASD group, in addition to their correlation with verbal abilities, suggests that auditory sensory dysfunction may be implicated in communication symptoms in ASD, motivating further research aimed at understanding the impact of sensory dysfunction on the developing brain.
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6. Hornig M, Bresnahan MA, Che X, Schultz AF, Ukaigwe JE, Eddy ML, Hirtz D, Gunnes N, Lie KK, Magnus P, Mjaaland S, Reichborn-Kjennerud T, Schjolberg S, Oyen AS, Levin B, Susser ES, Stoltenberg C, Lipkin WI. {{Prenatal fever and autism risk}}. {Mol Psychiatry}. 2017.
Some studies suggest that prenatal infection increases risk of autism spectrum disorders (ASDs). This study was undertaken in a prospective cohort in Norway to examine whether we could find evidence to support an association of the prenatal occurrence of fever, a common manifestation of infection, with ASD risk. Prospective questionnaires provided maternal exposure data; case status was established from clinical assessments and registry linkages. In a large, prospectively ascertained cohort of pregnant mothers and their offspring, we examined infants born 32 weeks for associations between fever exposure in each trimester and ASD risk using logistic regression. Maternal exposure to second-trimester fever was associated with increased ASD risk, adjusting for presence of fever in other trimesters and confounders (adjusted odds ratio (aOR), 1.40; 95% confidence interval, 1.09-1.79), with a similar, but nonsignificant, point estimate in the first trimester. Risk increased markedly with exposure to three or more fever episodes after 12 weeks’ gestation (aOR, 3.12; 1.28-7.63). ASD risk appears to increase with maternal fever, particularly in the second trimester. Risk magnified dose dependently with exposure to multiple fevers after 12 weeks’ gestation. Our findings support a role for gestational maternal infection and innate immune responses to infection in the pathogenesis of at least some cases of ASD.Molecular Psychiatry advance online publication, 13 June 2017; doi:10.1038/mp.2017.119.
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7. Johnson J, Piercy FP. {{Exploring Partner Intimacy Among Couples Raising Children on the Autism Spectrum: A Grounded Theory Investigation}}. {J Marital Fam Ther}. 2017.
In this study, we explored how couples raising children with autism spectrum disorder negotiate intimacy, including what contextual and temporal factors influence these processes. We conducted conjoint interviews with 12 couples, employing grounded theory methodology to collect and analyze the data. Our results indicated that fostering intimacy in these couples’ relationships involves partners working together to make key cognitive and relational shifts. Couples are aided or hindered in making these shifts by the degree to which they experience various contextual and environmental factors as resources or roadblocks. We also found that intimacy is not a fixed point at which couples one day arrive, but is an iterative process taking place over time and requiring work to develop and maintain.
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8. Keogh K. {{Children with autism need better hospital care, says RCN}}. {Nurs Child Young People}. 2017; 29(5): 6.
Nurses have called for improvements to the care of children with autism in hospitals and the community. About 1% of children in the UK have autism spectrum disorder (ASD), which affects social interaction, behaviour and communication. However, as healthcare services are pushed to breaking point, support for such children is dwindling, the RCN warns.
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9. Lawson RP, Aylward J, Roiser JP, Rees G. {{Adaptation of social and non-social cues to direction in adults with autism spectrum disorder and neurotypical adults with autistic traits}}. {Dev Cogn Neurosci}. 2017.
Perceptual constancy strongly relies on adaptive gain control mechanisms, which shift perception as a function of recent sensory history. Here we examined the extent to which individual differences in magnitude of adaptation aftereffects for social and non-social directional cues are related to autistic traits and sensory sensitivity in healthy participants (Experiment 1); and also whether adaptation for social and non-social directional cues is differentially impacted in adults with Autism Spectrum Disorder (ASD) relative to neurotypical (NT) controls (Experiment 2). In Experiment 1, individuals with lower susceptibility to adaptation aftereffects, i.e. more ‘veridical’ perception, showed higher levels of autistic traits across social and non-social stimuli. Furthermore, adaptation aftereffects were predictive of sensory sensitivity. In Experiment 2, only adaptation to eye-gaze was diminished in adults with ASD, and this was related to difficulties categorizing eye-gaze direction at baseline. Autism Diagnostic Observation Schedule (ADOS) scores negatively predicted lower adaptation for social (head and eye-gaze direction) but not non-social (chair) stimuli. These results suggest that the relationship between adaptation and the broad socio-cognitive processing style captured by ‘autistic traits’ may be relatively domain-general, but in adults with ASD diminished adaptation is only apparent where processing is most severely impacted, such as the perception of social attention cues.
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10. Lee CW, Yoon KJ, Ha SS. {{Which approach is advantageous to preventing the development of ASD? A comparative analysis of 3 different lumbar interbody fusion techniques (ALIF, LLIF, and PLIF) in L4-5 spondylolisthesis}}. {World Neurosurg}. 2017.
OBJECTIVE: The purpose of this study was to compare radiological and clinical outcomes in patients with L4-5 lumbar spondylolisthesis who have undergone either instrumented Anterior lumbar interbody fusion (ALIF), Lateral lumbar interbody fusion (LLIF), or Posterior Lumbar interbody fusion (PLIF), especially with regard to the development of Adjacent segment disease (ASD). METHODS: Eighty-two patients with preoperative L4-5 spondylolisthesis and minimal ASD who underwent instrumented L4-5 fusion were divided into three groups according to the surgical approach used for treatment (ALIF: 27 patients, LLIF: 24 patients, PLIF: 31 patients). Radiographic measurements including preoperative and postoperative foraminal and disc height, segmental and lumbar lordosis, percentage of vertebral slippage, and reduction rate were reviewed. The incidence of ASD and clinical outcomes were evaluated and compared between the 3 groups. RESULTS: ASD was found in 37.0% (10/27), 41.7% (10/24), and 64.5% (20/31) of the patients in the ALIF, LLIF, and PLIF groups, respectively (mean follow-up duration : 35.42+/-9.35 months). The ALIF and LLIF groups had significantly increased disc and foraminal height compared to the PLIF group. The ALIF group had significantly improved lordosis compared to the PLIF and LLIF groups. There were no statistically significant intergroup differences in clinical outcomes assessed by Visual analog scale (VAS) and Oswestry disability index (ODI). CONCLUSION: The 3 different fusion techniques investigated can all produce good outcomes in treating lumbar spondylolisthesis in L4-5, but ALIF and LLIF are more advantageous in preventing the development of ASD.
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11. Morimura N, Yasuda H, Yamaguchi K, Katayama KI, Hatayama M, Tomioka NH, Odagawa M, Kamiya A, Iwayama Y, Maekawa M, Nakamura K, Matsuzaki H, Tsujii M, Yamada K, Yoshikawa T, Aruga J. {{Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice}}. {Nat Commun}. 2017; 8: 15800.
Lrfn2/SALM1 is a PSD-95-interacting synapse adhesion molecule, and human LRFN2 is associated with learning disabilities. However its role in higher brain function and underlying mechanisms remain unknown. Here, we show that Lrfn2 knockout mice exhibit autism-like behavioural abnormalities, including social withdrawal, decreased vocal communications, increased stereotyped activities and prepulse inhibition deficits, together with enhanced learning and memory. In the hippocampus, the levels of synaptic PSD-95 and GluA1 are decreased. The synapses are structurally and functionally immature with spindle shaped spines, smaller postsynaptic densities, reduced AMPA/NMDA ratio, and enhanced LTP. In vitro experiments reveal that synaptic surface expression of AMPAR depends on the direct interaction between Lrfn2 and PSD-95. Furthermore, we detect functionally defective LRFN2 missense mutations in autism and schizophrenia patients. Together, these findings indicate that Lrfn2/LRFN2 serve as core components of excitatory synapse maturation and maintenance, and their dysfunction causes immature/silent synapses with pathophysiological state.
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12. Pisansky MT, Young AE, O’Connor MB, Gottesman, II, Bagchi A, Gewirtz JC. {{Mice lacking the chromodomain helicase DNA-binding 5 chromatin remodeler display autism-like characteristics}}. {Transl Psychiatry}. 2017; 7(6): e1152.
Although autism spectrum disorders (ASDs) share a core set of nosological features, they exhibit substantial genetic heterogeneity. A parsimonious hypothesis posits that dysregulated epigenetic mechanisms represent common pathways in the etiology of ASDs. To investigate this hypothesis, we generated a novel mouse model resulting from brain-specific deletion of chromodomain helicase DNA-binding 5 (Chd5), a chromatin remodeling protein known to regulate neuronal differentiation and a member of a gene family strongly implicated in ASDs. RNA sequencing of Chd5-/- mouse forebrain tissue revealed a preponderance of changes in expression of genes important in cellular development and signaling, sociocommunicative behavior and ASDs. Pyramidal neurons cultured from Chd5-/- cortex displayed alterations in dendritic morphology. Paralleling ASD nosology, Chd5-/- mice exhibited abnormal sociocommunicative behavior and a strong preference for familiarity. Chd5-/- mice further showed deficits in responding to the distress of a conspecific, a mouse homolog of empathy. Thus, dysregulated chromatin remodeling produces a pattern of transcriptional, neuronal and behavioral effects consistent with the presentation of ASDs.
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13. Piwowarczyk A, Horvath A, Lukasik J, Pisula E, Szajewska H. {{Gluten- and casein-free diet and autism spectrum disorders in children: a systematic review}}. {Eur J Nutr}. 2017.
PURPOSE: Effective treatments for core symptoms of autism spectrum disorders (ASD) are lacking. We systematically updated evidence on the effectiveness of a gluten-free and casein-free (GFCF) diet as a treatment for ASD in children. METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched up until August 2016, for randomized controlled trials (RCTs); additional references were obtained from reviewed articles. RESULTS: Six RCTs (214 participants) were included. With few exceptions, there were no statistically significant differences in autism spectrum disorder core symptoms between groups, as measured by standardized scales. One trial found that compared with the control group, in the GFCF diet group there were significant improvements in the scores for the ‘communication’ subdomain of the Autism Diagnostic Observation Schedule and for the ‘social interaction’ subdomain of the Gilliam Autism Rating Scale. Another trial found significant differences between groups in the post-intervention scores for the ‘autistic traits’, ‘communication’, and ‘social contact’ subdomains of a standardized Danish scheme. The remaining differences, if present, referred to parent-based assessment tools or other developmental/ASD-related features. No adverse events associated with a GFCF diet were reported. CONCLUSIONS: Overall, there is little evidence that a GFCF diet is beneficial for the symptoms of ASD in children.
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14. Qadir AA, Obringer E, Hageman J, Marcuccilli C. {{Risk of Second Seizure in Pediatric Patients With Idiopathic Autism}}. {J Child Neurol}. 2017: 883073817713906.
PURPOSE: Epilepsy is a comorbidity of idiopathic autism spectrum disorder. The aim was to characterize the risk and time of second seizure in children with idiopathic autism spectrum disorder. METHODS: A retrospective review was performed at the University of Chicago and NorthShore University HealthSystem. Patients with idiopathic autism spectrum disorder, >/=1 seizure, and age 2 to 23 years were included. RESULTS: 153 patients were included; 141 (92%) had a second seizure. The average age at first seizure was 7.14 years (median: 5.08 years) and 8.12 years (median: 7.3 years) at second seizure. Average time between first and second seizure was 7.68 months. DISCUSSION: A high risk of seizure recurrence was found in this population. There was a short time to second seizure, with most having a recurrence within 1 year. These findings may be used to guide therapy in children with autism spectrum disorder and epilepsy.
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15. Saxbe DE, Golan O, Ostfeld-Etzion S, Hirschler-Guttenberg Y, Zagoory-Sharon O, Feldman R. {{HPA axis linkage in parent-child dyads: Effects of parent sex, autism spectrum diagnosis, and dyadic relationship behavior}}. {Dev Psychobiol}. 2017.
Families of preschoolers participated in two dyadic home visits, once with mother (56 dyads) and once with father (59 dyads). Each member of the dyad provided three cortisol samples and participated in several interaction tasks that were behaviorally coded. Approximately half of the children had been diagnosed with autism spectrum disorders (ASD), whereas half were typically developing (TD). In a multilevel model, father’s cortisol level at each timepoint predicted child cortisol. Father-child linkage was stronger in dyads that showed less reciprocity, in which fathers showed less sensitivity, and in which children showed less self-regulation and more withdrawal. Cortisol levels were not significantly correlated in mother-child dyads, and there was a trend toward moderation by ASD diagnosis, such that linkage was greater in TD children. Mother-child linkage was stronger in dyads that showed less behavioral coordination and less sensitivity. HPA axis linkage may be stronger in less behaviorally attuned dyads.
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16. Tint A, Palucka AM, Bradley E, Weiss JA, Lunsky Y. {{Correlates of Police Involvement Among Adolescents and Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
This study aimed to describe police interactions, satisfaction with police engagement, as well as examine correlates of police involvement among 284 adolescents and adults with autism spectrum disorder (ASD) followed over a 12- to 18-month period. Approximately 16% of individuals were reported to have some form of police involvement during the study period. Aggressive behaviors were the primary concern necessitating police involvement. Individuals with police involvement were more likely to be older, have a history of aggression, live outside the family home, and have parents with higher rates of caregiver strain and financial difficulty at baseline. Most parents reported being satisfied to very satisfied with their children’s police encounters. Areas for future research are discussed in relation to prevention planning.
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17. Torrado JC, Gomez J, Montoro G. {{Emotional Self-Regulation of Individuals with Autism Spectrum Disorders: Smartwatches for Monitoring and Interaction}}. {Sensors (Basel)}. 2017; 17(6).
In this paper, we analyze the needs of individuals with Autism Spectrum Disorders (ASD) to have a pervasive, feasible and non-stigmatizing form of assistance in their emotional self-regulation, in order to ease certain behavioral issues that undermine their mental health throughout their life. We argue the potential of recent widespread wearables, and more specifically smartwatches, to achieve this goal. Then, a smartwatch system that implements a wide range of self-regulation strategies and infers outburst patterns from physiological signals and movement is presented, along with an authoring tool for smartphones that is to be used by caregivers or family members to create and edit these strategies, in an adaptive way. We conducted an intensive experiment with two individuals with ASD who showed varied, representative behavioral responses to their emotional dysregulation. Both users were able to employ effective, customized emotional self-regulation strategies by means of the system, recovering from the majority of mild stress episodes and temper tantrums experienced in the nine days of experiment in their classroom.
