1. Zhang W, Xu C, Tu H, Wang Y, Sun Q, Hu P, Hu Y, Rondard P, Liu J. {{GABAB receptor upregulates fragile X mental retardation protein expression in neurons}}. {Sci Rep};2015;5:10468.
Fragile X mental retardation protein (FMRP) is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome (FXS), which leads to intellectual disability and social impairment. gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, but the signaling events linking the GABAB receptor and FMRP are unknown. In this study, we found that GABAB receptor activation upregulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms: the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. These results suggest a role for GABAB receptor in Fmrp regulation and a potential interest of GABAB receptor signaling in FXS improvement.
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2. Gdalyahu A, Lazaro M, Penagarikano O, Golshani P, Trachtenberg JT, Geschwind DH. {{Correction: The Autism Related Protein Contactin-Associated Protein-Like 2 (CNTNAP2) Stabilizes New Spines: An In Vivo Mouse Study}}. {PLoS One};2015;10(5):e0129638.
[This corrects the article DOI: 10.1371/journal.pone.0125633.].
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3. Mari-Bauset S, Llopis-Gonzalez A, Zazpe I, Mari-Sanchis A, Suarez-Varela MM. {{Fat intake in children with autism spectrum disorder in the Mediterranean region (Valencia, Spain)}}. {Nutr Neurosci};2015 (May 28)
Objective Children with autism spectrum disorder (ASD) have been found to have alterations in dietary fat intake and fat quality. The fat intakes of the foods consumed by children with and without ASD were compared, and the deficiency and excess of these nutrients were examined. Methods In a matched case-control study, 3-day food diaries were completed by 105 children with ASD and 495 typically developing (TD) 6- to 9-year-old children in Valencia (Spain). We used the probabilistic approach and estimated average requirement cut-point to evaluate the risk of inadequate nutrients intakes. These were compared between groups and with Spanish recommendations using linear and logistic regression, respectively. Results Groups did not differ significantly in age, total dietary intake, Healthy Eating Index, or food variety score. Children with ASD had lower saturated fatty acids (SFAs) and omega-3 polyunsaturated fatty acids (PUFAs) intakes, but their total PUFAs and (PUFAs + monounsaturated fatty acids (MUFAs)/SFAs, PUFAs/SFAs intakes and omega-6/omega-3 ratios were higher than TD children. The total fat and cholesterol intakes of both groups were slightly above Spanish recommendations. Both groups had low omega-6 intakes, very low omega-3 intakes, and high omega-6/omega-3 ratios. Conclusion Further research is required to clarify associations between ASD symptomatology, fat-eating patterns and health status.
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4. MacFabe DF. {{Enteric short-chain fatty acids: microbial messengers of metabolism, mitochondria, and mind: implications in autism spectrum disorders}}. {Microb Ecol Health Dis};2015;26:28177.
Clinical observations suggest that gut and dietary factors transiently worsen and, in some cases, appear to improve behavioral symptoms in a subset of persons with autism spectrum disorders (ASDs), but the reason for this is unclear. Emerging evidence suggests ASDs are a family of systemic disorders of altered immunity, metabolism, and gene expression. Pre- or perinatal infection, hospitalization, or early antibiotic exposure, which may alter gut microbiota, have been suggested as potential risk factors for ASD. Can a common environmental agent link these disparate findings? This review outlines basic science and clinical evidence that enteric short-chain fatty acids (SCFAs), present in diet and also produced by opportunistic gut bacteria following fermentation of dietary carbohydrates, may be environmental triggers in ASD. Of note, propionic acid, a major SCFA produced by ASD-associated gastrointestinal bacteria (clostridia, bacteroides, desulfovibrio) and also a common food preservative, can produce reversible behavioral, electrographic, neuroinflammatory, metabolic, and epigenetic changes closely resembling those found in ASD when administered to rodents. Major effects of these SCFAs may be through the alteration of mitochondrial function via the citric acid cycle and carnitine metabolism, or the epigenetic modulation of ASD-associated genes, which may be useful clinical biomarkers. It discusses the hypothesis that ASDs are produced by pre- or post-natal alterations in intestinal microbiota in sensitive sub-populations, which may have major implications in ASD cause, diagnosis, prevention, and treatment.
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5. Geretsegger M, Holck U, J AC, Elefant C, Kim J, Gold C. {{Common Characteristics of Improvisational Approaches in Music Therapy for Children with Autism Spectrum Disorder: Developing Treatment Guidelines}}. {J Music Ther};2015 (May 26)
BACKGROUND: Improvisational methods of music therapy have been increasingly applied in the treatment of individuals with autism spectrum disorder (ASD) over the past decades in many countries worldwide. OBJECTIVE: This study aimed at developing treatment guidelines based on the most important common characteristics of improvisational music therapy (IMT) with children affected by ASD as applied across various countries and theoretical backgrounds. METHODS: After initial development of treatment principle items, a survey among music therapy professionals in 10 countries and focus group workshops with experienced clinicians in three countries were conducted to evaluate the items and formulate revised treatment guidelines. To check usability, a treatment fidelity assessment tool was subsequently used to rate therapy excerpts. RESULTS: Survey findings and feedback from the focus groups corroborated most of the initial principles for IMT in the context of children with ASD. Unique and essential principles include facilitating musical and emotional attunement, musically scaffolding the flow of interaction, and tapping into the shared history of musical interaction between child and therapist. Raters successfully used the tool to evaluate treatment adherence and competence. CONCLUSIONS: Summarizing an international consensus about core principles of improvisational approaches in music therapy for children with ASD, these treatment guidelines may be applied in diverse theoretical models of music therapy. They can be used to assess treatment fidelity, and may be applied to facilitate future research, clinical practice, and training.
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6. Kaufmann M, Schuffenhauer A, Fruh I, Klein J, Thiemeyer A, Rigo P, Gomez-Mancilla B, Heidinger-Millot V, Bouwmeester T, Schopfer U, Mueller M, Fodor BD, Cobos-Correa A. {{High-Throughput Screening Using iPSC-Derived Neuronal Progenitors to Identify Compounds Counteracting Epigenetic Gene Silencing in Fragile X Syndrome}}. {J Biomol Screen};2015 (May 29)
Fragile X syndrome (FXS) is the most common form of inherited mental retardation, and it is caused in most of cases by epigenetic silencing of the Fmr1 gene. Today, no specific therapy exists for FXS, and current treatments are only directed to improve behavioral symptoms. Neuronal progenitors derived from FXS patient induced pluripotent stem cells (iPSCs) represent a unique model to study the disease and develop assays for large-scale drug discovery screens since they conserve the Fmr1 gene silenced within the disease context. We have established a high-content imaging assay to run a large-scale phenotypic screen aimed to identify compounds that reactivate the silenced Fmr1 gene. A set of 50,000 compounds was tested, including modulators of several epigenetic targets. We describe an integrated drug discovery model comprising iPSC generation, culture scale-up, and quality control and screening with a very sensitive high-content imaging assay assisted by single-cell image analysis and multiparametric data analysis based on machine learning algorithms. The screening identified several compounds that induced a weak expression of fragile X mental retardation protein (FMRP) and thus sets the basis for further large-scale screens to find candidate drugs or targets tackling the underlying mechanism of FXS with potential for therapeutic intervention.
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7. Roy M, Wolfgang D. {{[Eye contact in adult patients with asperger syndrome]}}. {Fortschr Neurol Psychiatr};2015 (May);83(5):269-275.
INTRODUCTION: It is unclear if individuals with autism spectrum disorders rarely hold direct eye contact because eyes are unimportant for them, or if it is actively avoided. The aim of the current investigation was to gain a better understanding for their views on direct eye contact by exploring adult patients with Asperger syndrome. METHOD: 63 adult patients with Asperger syndrome (28 females, 35 males, 21 – 62 years old) were explored about using and sensing direct eye contact by means of a standardised questionnaire. RESULT: 87 % of investigated patients depict direct eye contact as being disagreeable. They describe it as arduous and distracting. Therefore they mostly actively avoid direct eye contact. DISCUSSION: The here gained knowledge about aversion towards direct eye contact in individuals with autism should lead to a stronger understanding and acceptance of this problem in the non-autistic population.
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8. Stendal K, Balandin S. {{Virtual worlds for people with autism spectrum disorder: a case study in Second Life}}. {Disabil Rehabil};2015 (May 29):1-8.
PURPOSE: The purpose of this study is to explore the use of virtual worlds by people with autism spectrum disorder (ASD), with a particular focus on the virtual world Second Life. METHOD: Case study methodology was selected to explore the experiences of Wolf, a participant with ASD, in Second Life. Wolf participated in three in-depth interviews. The interviews were analyzed using a content analysis to identify themes and sub-themes. RESULTS: Analysis identified four main themes: social factors and communication, empowerment, virtual world versus physical world, and social cues and body language. CONCLUSION: Anecdotally Wolf’s experiences suggest that people with ASD enjoy using a virtual world and may feel more comfortable communicating in the virtual world context than the physical world. Virtual worlds offer a venue for people with ASD to be a part of a virtual society, lowers communication barriers experienced in the physical world, and gives the participant a unique opportunity to create and maintain friendships. Virtual worlds offer an arena for people with ASD to meet their peers on equal terms, not being dependent on social cues, which in the physical world can be a barrier for communication for this group. Further research in this area is required. Implications for Rehabiliation People with autism spectrum disorder enjoy using a virtual world and may feel more comfortable communicating in the virtual world context than the physical world. Virtual worlds offer a venue for people with autism spectrum disorder to be a part of a virtual society. Virtual worlds offer an arena for people with autism spectrum disorder to meet their peers on equal terms, not being dependent on social cues, which in the physical world can be a barrier for this group.
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9. Kondo MA, Gray LJ, Pelka GJ, Leang SK, Christodoulou J, Tam PP, Hannan AJ. {{Affective dysfunction in a mouse model of Rett syndrome: Therapeutic effects of environmental stimulation and physical activity}}. {Dev Neurobiol};2015 (May 27)
Rett syndrome is a neurodevelopmental disorder associated with mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2) and consequent dysregulation of brain maturation. Patients suffer from a range of debilitating physical symptoms, however behavioural and emotional symptoms also severely affect their quality of life. Here we present previously unreported and clinically relevant affective dysfunction in the female heterozygous Mecp2tm1Tam mouse model of Rett syndrome (129sv and C57BL6 mixed background). The affective dysfunction and aberrant anxiety-related behaviour of the Mecp2+/- mice were found to be reversible with environmental enrichment from 4 weeks of age. The effect of exercise alone (via wheel running) was also explored, providing the first evidence that increased voluntary physical activity in an animal model of Rett syndrome is beneficial for some phenotypes. Mecp2+/- mutants displayed elevated corticosterone despite decreased Crh expression, demonstrating HPA-axis dysregulation. Environmental enrichment of Mecp2+/- mice normalised basal serum corticosterone and hippocampal BDNF protein levels. The enrichment-induced rescue appears independent of the transcriptional regulation of the MeCP2 targets Bdnf exon 4 and Crh. These findings provide new insight into the neurodevelopmental role of MeCP2 and pathogenesis of Rett syndrome, in particular the affective dysfunction. The positive outcomes of environmental stimulation and physical exercise have implications for the development of therapies targeting the affective symptoms, as well as behavioural and cognitive dimensions, of this devastating neurodevelopmental disorder. This article is protected by copyright. All rights reserved.
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10. Curtin C, Humphrey K, Vronsky K, Mattern K, Nicastro S, Perrin EC. {{Expanding Horizons: A Pilot Mentoring Program Linking College/Graduate Students and Teens With ASD}}. {Clin Pediatr (Phila)};2015 (May 27)
A small pilot program of 9 youth 13 to 18 years old with high-functioning autism spectrum disorder (ASD) or Asperger’s syndrome assessed the feasibility, acceptability, and potential efficacy of an individualized mentoring program. Youth met weekly for 6 months with trained young adult mentors at a local boys and girls club. Participants reported improvements in self-esteem, social anxiety, and quality of life. Participants, parents, mentors, and staff reported that the program improved participants’ social connectedness. Although the pilot study was small, it provides preliminary data that mentoring for youth with ASD has promise for increasing self-esteem, social skills, and quality of life.
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11. Lederman VR, Alves Bdos S, Maria JN, Schwartzman JS, D’Antino ME, Brunoni D. {{Divorce in families of children with Down Syndrome or Rett Syndrome}}. {Cien Saude Colet};2015 (May);20(5):1363-1369.
This study evaluates the impact in the stability and management of the marriage of parents of a child with Down or Rett Syndrome. Morbidity of the syndromes and the marital status of the couples before and after the birth of the affected children were considered variables. The divorce rate in families with Down syndrome was 10%, similar to the Brazilian rate population. In Rett Syndrome, the divorce rate was significantly higher, 23.5%. The higher morbidity of Rett Syndrome, and the moment of diagnosis could be relevant factors for the increased divorce rate related to this syndrome.
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12. Salomone E, Charman T, McConachie H, Warreyn P. {{Child’s verbal ability and gender are associated with age at diagnosis in a sample of young children with ASD in Europe}}. {Child Care Health Dev};2015 (May 28)
BACKGROUND: Autism spectrum disorder can in some cases be reliably diagnosed by age 2 years, but in community settings, the mean age at diagnosis is often considerably higher. Later diagnosis has been found to be associated with lower symptom severity, lower parental socioeconomic status and fewer parental concerns. Gender differences in age at diagnosis have been examined, with mixed evidence. METHODS: We examined the association of child’s verbal ability and gender, and parental education, with age at diagnosis in a large sample of young children with autism spectrum disorder in 18 European countries (n = 1410). RESULTS: There was considerable variation in age at diagnosis across countries. Children with better communication skills were diagnosed significantly later than non-verbal and minimally verbal children. There was also a significant interaction of gender with verbal ability on age at diagnosis, in that female children with complex phrase speech were diagnosed later than male children with the same level of verbal ability. CONCLUSIONS: Our findings highlight the need to implement public awareness initiatives and training for professionals to promote early detection and, consequently, early intervention for autism spectrum disorder in Europe.
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13. Cascio CJ, Gu C, Schauder KB, Key AP, Yoder P. {{Somatosensory Event-Related Potentials and Association with Tactile Behavioral Responsiveness Patterns in Children with ASD}}. {Brain Topogr};2015 (May 28)
The goal of this study was to explore neural response to touch in children with and without autism spectrum disorder (ASD). Patterns of reduced (hypo-responsiveness) and enhanced (hyper-responsiveness) behavioral reaction to sensory input are prevalent in ASD, but their neural mechanisms are poorly understood. We measured event-related potentials (ERP) to a puff of air on the fingertip and collected parent report of tactile hypo- and hyper-responsiveness in children with ASD (n = 21, mean (SD) age 11.25 (3.09), 2 female), and an age-matched typically developing comparison group (n = 28, mean (SD) age 10.1 (3.08, 2 female). A global measure of ERP response strength approximately 220-270 ms post-stimulus was associated with tactile hypo-responsiveness in ASD, while tactile hyper-responsiveness was associated with earlier neural response (approximately 120-220 ms post-stimulus) in both groups. These neural responses also related to autism severity. These results suggest that, in ASD, tactile hypo- and hyper-responsiveness may reflect different waypoints in the neural processing stream of sensory input. The timing of the relationship for hyper-responsiveness is consistent with somatosensory association cortical response, while that for hypo-responsiveness is more consistent with later processes that may involve allocation of attention or emotional valence to the stimulus.
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14. Murdaugh DL, Deshpande HD, Kana RK. {{The Impact of Reading Intervention on Brain Responses Underlying Language in Children With Autism}}. {Autism Res};2015 (May 25)
Deficits in language comprehension have been widely reported in children with autism spectrum disorders (ASD), with behavioral and neuroimaging studies finding increased reliance on visuospatial processing to aid in language comprehension. However, no study to date, has taken advantage of this strength in visuospatial processing to improve language comprehension difficulties in ASD. This study used a translational neuroimaging approach to test the role of a visual imagery-based reading intervention in improving the brain circuitry underlying language processing in children with ASD. Functional magnetic resonance imaging (MRI), in a longitudinal study design, was used to investigate intervention-related change in sentence comprehension, brain activation, and functional connectivity in three groups of participants (age 8-13 years): an experimental group of ASD children (ASD-EXP), a wait-list control group of ASD children (ASD-WLC), and a group of typically developing control children. After intervention, the ASD-EXP group showed significant increase in activity in visual and language areas and right-hemisphere language area homologues, putamen, and thalamus, suggestive of compensatory routes to increase proficiency in reading comprehension. Additionally, ASD children who had the most improvement in reading comprehension after intervention showed greater functional connectivity between left-hemisphere language areas, the middle temporal gyrus and inferior frontal gyrus while reading high imagery sentences. Thus, the findings of this study, which support the principles of dual coding theory [Paivio 2007], suggest the potential of a strength-based reading intervention in changing brain responses and facilitating better reading comprehension in ASD children. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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15. Williams DL, Minshew NJ, Goldstein G. {{Further understanding of complex information processing in verbal adolescents and adults with autism spectrum disorders}}. {Autism};2015 (May 27)
More than 20 years ago, Minshew and colleagues proposed the Complex Information Processing model of autism in which the impairment is characterized as a generalized deficit involving multiple modalities and cognitive domains that depend on distributed cortical systems responsible for higher order abilities. Subsequent behavioral work revealed a related dissociation between concept formation and concept identification in autism suggesting the lack of an underlying organizational structure to manage increases in processing loads. The results of a recent study supported the impact of this relative weakness in conceptual reasoning on adaptive functioning in children and adults with autism. In this study, we provide further evidence of the difficulty relatively able older adolescents and adults with autism have with conceptual reasoning and provide evidence that this characterizes their difference from age- and ability-matched controls with typical development better than their differences in language. For verbal adults with autism, language may serve as a bootstrap or compensatory mechanism for learning but cannot overcome an inherent weakness in concept formation that makes information processing challenging as task demands increase.
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16. Weiss JA, Tint A, Paquette-Smith M, Lunsky Y. {{Perceived self-efficacy in parents of adolescents and adults with autism spectrum disorder}}. {Autism};2015 (May 27)
Many parents of adolescents and adults with autism spectrum disorder experience difficulty accessing appropriate services for their children, and may report low levels of parent self-efficacy. In an effort to identify the factors that contribute to the difficulties these families face, this study examined the role of demographic, systemic, and clinical need variables as they relate to parents’ experience of self-efficacy. Participants included 324 parents of individuals with autism spectrum disorder, 12-25 years of age. Results suggest that parent self-efficacy is related to a number of variables and not simply a child’s clinical situation, including child age, parent immigrant status, barriers to service access, and caregiver burden. Given the crucial role that parents often play in the lives of individuals with autism spectrum disorder across the lifespan, it is important that service providers support the efforts of parents who provide and access care for their children.
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17. Taylor JL, Henninger NA, Mailick MR. {{Longitudinal patterns of employment and postsecondary education for adults with autism and average-range IQ}}. {Autism};2015 (May 27)
This study examined correlates of participation in postsecondary education and employment over 12 years for 73 adults with autism spectrum disorders and average-range IQ whose families were part of a larger, longitudinal study. Correlates included demographic (sex, maternal education, paternal education), behavioral (activities of daily living, maladaptive behaviors, autism symptoms), and family (size of maternal social network; maternal depressive symptoms, anxiety, and pessimism) factors. Although two-thirds of adults with autism spectrum disorder participated in competitive employment/postsecondary education during the study, fewer than 25% maintained these activities over the study period. Behavioral characteristics distinguished those who never had competitive employment/postsecondary education from those who sometimes or consistently participated in these activities. Women were considerably less likely than men to maintain employment/postsecondary education over time.
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18. Fisher MH, Taylor JL. {{Let’s talk about it: Peer victimization experiences as reported by adolescents with autism spectrum disorder}}. {Autism};2015 (May 27)
Individuals with autism spectrum disorder experience high rates of peer victimization; yet, their personal experiences and perceptions of such victimization are not well understood. In this qualitative investigation, responses to questions about bullying and teasing were examined to gain insight into the perception of peer victimization as reported by adolescents with autism spectrum disorder. While the majority of participants provided examples of peer victimization, their situations differed from items typically assessed on bullying questionnaires. Participants were also able to provide explanations for why they believe they are targets and descriptions of their reactions to bullying. Findings from the interviews are used to provide suggestions for the development of more informative bullying assessments and prevention programs for students with autism spectrum disorder.
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19. Schwartzman JS, Velloso Rde L, D’Antino ME, Santos S. {{The eye-tracking of social stimuli in patients with Rett syndrome and autism spectrum disorders: a pilot study}}. {Arq Neuropsiquiatr};2015 (May);73(5):402-407.
Objective To compare visual fixation at social stimuli in Rett syndrome (RT) and autism spectrum disorders (ASD) patients. Method Visual fixation at social stimuli was analyzed in 14 RS female patients (age range 4-30 years), 11 ASD male patients (age range 4-20 years), and 17 children with typical development (TD). Patients were exposed to three different pictures (two of human faces and one with social and non-social stimuli) presented for 8 seconds each on the screen of a computer attached to an eye-tracker equipment. Results Percentage of visual fixation at social stimuli was significantly higher in the RS group compared to ASD and even to TD groups. Conclusion Visual fixation at social stimuli seems to be one more endophenotype making RS to be very different from ASD.
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20. Tonhajzerova I, Ondrejka I, Mestanik M, Mikolka P, Hrtanek I, Mestanikova A, Bujnakova I, Mokra D. {{Inflammatory Activity in Autism Spectrum Disorder}}. {Adv Exp Med Biol};2015 (May 29)
Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder in early childhood characterized by impairment in communication and behavior. Recent research is focused on the immune dysregulation as a potential pathomechanism leading to ASD. Thus, we addressed the hypothesis that inflammatory activity might be enhanced in children suffering from ASD. We examined 15 children with ASD (13 boys/2 girls, mean age of 9.3 +/- 0.7 years) and 20 age/gender-matched healthy subjects as a control group. All children were medication free and in good health. Hematological parameters in venous blood and plasma levels of pro-inflammatory cytokines – tumor necrosis factor alpha (TNF-alpha), interleukin 1ss (IL-1ss), and interleukin 8 (IL-8) – were assessed in each subject using human ultra-sensitive ELISA kits. In addition, TBARS as a marker of oxidative stress was evaluated. We found that the level of IL-8 was significantly increased in the ASD children, whereas the other markers remained unappreciably changed compared to controls (p = 0.003). In conclusion, the study demonstrates a discrete immune dysfunction in ASD of pro-inflammatory character.
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21. Wachtel L, Commins E, Park M, Rolider N, Stephens R, Reti I. {{Neuroleptic malignant syndrome and delirious mania as malignant catatonia in autism: prompt relief with electroconvulsive therapy}}. {Acta Psychiatr Scand};2015 (May 28)
