1. Brondino N, Fusar-Poli L, Panisi C, Damiani S, Barale F, Politi P. {{Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A Systematic Review of Human Studies}}. {J Autism Dev Disord};2015 (Oct 6)
Autism spectrum disorders are an emerging health problem worldwide, but little is known about their pathogenesis. It has been hypothesized that autism may result from an imbalance between excitatory glutamatergic and inhibitory GABAergic pathways. Commonly used medications such as valproate, acamprosate, and arbaclofen may act on the GABAergic system and be a potential treatment for people with ASD. The present systematic review aimed at evaluating the state-of-the-art of clinical trials of GABA modulators in autism. To date there is insufficient evidence to suggest the use of these drugs in autistic subjects, even if data are promising. Of note, short-term use of all the reviewed medications appears to be safe. Future well designed trials are needed to elucidate these preliminary findings.
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2. Brown HK, Kirkham YA, Cobigo V, Lunsky Y, Vigod SN. {{Labour and delivery interventions in women with intellectual and developmental disabilities: a population-based cohort study}}. {J Epidemiol Community Health};2015 (Oct 8)
BACKGROUND: Our objectives were to: (1) examine the occurrence of labour induction, caesarean section, and operative vaginal delivery in women with intellectual and developmental disabilities compared to those without and (2) determine whether pre-pregnancy health conditions and pregnancy complications explain any elevated occurrence of these interventions. METHODS: We conducted a population-based study using linked Ontario (Canada) administrative data. We identified deliveries to women with (N=3932) and without (N=382 774) intellectual and developmental disabilities (2002-2011). Modified Poisson regression was used to estimate adjusted relative risks (aRR) and 95% CIs for interventions, controlling for sociodemographic characteristics. We used generalised estimating equations to determine whether pre-pregnancy health conditions and pregnancy complications explained any statistically significantly elevated aRRs. RESULTS: After controlling for socio-demographic characteristics, women with intellectual and developmental disabilities were more likely to have labour inductions (aRR, 1.13; 95% CI 1.06 to 1.20) and caesarean sections (aRR, 1.09; 95% CI 1.03 to 1.16) but not operative vaginal deliveries, compared to the referent group. Pre-pregnancy health conditions explained 12.9% of their elevated aRR for labour induction. Pre-pregnancy health conditions and maternal complications explained 27.8% and 13.3%, respectively, of their elevated aRR for caesarean section. CONCLUSIONS: Women with intellectual and developmental disabilities are slightly more likely to have labour inductions and caesarean sections than women without intellectual and developmental disabilities. The elevated occurrence of these interventions is not fully explained by their pre-pregnancy health conditions or pregnancy complications. Non-medical issues should be evaluated for their influence on the timing of labour and delivery in this population.
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3. Bultas MW, McMillin SE, Zand DH. {{Reducing Barriers to Care in the Office-Based Health Care Setting for Children With Autism}}. {J Pediatr Health Care};2015 (Oct 8)
The purpose of this survey-design research study was to evaluate the usefulness of a researcher-developed tool designed to improve office-based health care services and to assess the barriers and resources affecting office-based health care services for children with autism spectrum disorder. Fifty-four health care providers (HCPs) and 59 parents participated in the study. HCPs reported child behaviors, communication, and fears as barriers to providing care, whereas parents reported child behavior, sensory issues, and feelings of a disconnect with the HCP as barriers. HCPs identified the parent as a key resource. Parent-identified resources included provider adaptations to the patient, including slowing down the delivery of care and environmental adaptations to the office. In addition, both HCPs and parents indicated that the researcher-developed tool would be useful in reducing barriers during the HCE. Reducing barriers and improving health care interactions during delivery of care for children with autism spectrum disorder has the potential to improve health outcomes.
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4. Habibe RC, Ortega AO, Guare RO, Diniz MB, Santos MT. {{Risk factors for anterior traumatic dental injury in children and adolescents with autism spectrum disorders: a case-control study}}. {Eur Arch Paediatr Dent};2015 (Oct 8)
AIM: This was to assess and compare risk factors for traumatic dental injury (TDI) among children/adolescents with and without autism spectrum disorders (ASD). METHODS: The study consisted of 122 children and adolescents (98 males, 24 females), 61 with ASD (study group) and 61 without ASD (control group, CG). Dental injuries were determined according to Andreasen ss classification. The cause, location and type of activity at the time of trauma were recorded from patient/carer recollection. RESULTS: Subjects with ASD presented higher percentages of TDI in routine activities (P = 0.003), falling while walking and episodes of self-harm (P = 0.007) in the individual’s own residence (P = 0.036). TDI prevalence in the ASD group was higher (39.3 %) than in the CG (26.2 %) though not significant, (P = 0.123). Girls with ASD presented a significantly higher TDI percentage (50.0 %) compared with girls from the CG (8.3 %) (P = 0.024). Enamel fracture was the most frequent type of TDI for both groups (P = 0.292). The teeth most commonly affected were #11 and #21 for both groups. CONCLUSIONS: Children and adolescents with ASD exhibit different risk factors for TDI compared with those without ASD, and girls with ASD are more prone than boys.
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5. Ingersoll B, Berger NI. {{Parent Engagement With a Telehealth-Based Parent-Mediated Intervention Program for Children With Autism Spectrum Disorders: Predictors of Program Use and Parent Outcomes}}. {J Med Internet Res};2015;17(10):e227.
BACKGROUND: There has been growing interest in using telehealth to increase access to parent-mediated interventions for children with ASD. However, little is known about how parents engage with such programs. OBJECTIVE: This paper presents program engagement data from a pilot study comparing self-directed and therapist-assisted versions of a novel telehealth-based parent-mediated intervention for young children with autism spectrum disorders (ASD). METHODS: Parents of young children with ASD were randomly assigned to receive a self-directed or therapist-assisted version of ImPACT Online. Parent engagement and satisfaction with the different components of the program website were examined using the program’s automated data collection and a post-treatment evaluation survey. We examined the relationship between program engagement and changes in parent knowledge and implementation and participant characteristics associated with program engagement. RESULTS: Of the 27 parent participants, the majority were female (26/27, 96%), married (22/27, 81%), with a college degree or higher (18/27, 66%), and less than half were employed outside of the home (10/27, 37%). The mean chronological age of the child participants was 43.26 months, and the majority were male (19/27, 70%) and white (21/27, 78%). Most of the families (19/27, 70%) resided in a rural or medically underserved area. Parents logged into the website an average of 46.85 times, spent an average of 964.70 minutes on the site, and completed an average of 90.17% of the lesson learning activities. Participants in the therapist-assisted group were more likely to engage with the website than those in the self-directed group: F2,24=17.65, P<.001. In total, 85% of participants completed the program, with a significantly greater completion rate in the therapist-assisted group (N=27): chi(2) 1=5.06, P=.03. Lesson learning activities were visited significantly more often than the supplemental activities (all Ps<.05). Multiple regression controlling for pretreatment performance indicated that program completion (beta=.51, P=.02) predicted post-treatment intervention knowledge, and program completion (beta=.43, P=.03) and group assignment (beta=-.37, P=.045) predicted post-treatment intervention fidelity. Partial correlations indicated that parent depressive symptoms at pretreatment were negatively associated with program completion (r=-.40, P=.04), but other key parent and child demographic factors were not. Post-treatment measures of website usability (r=.65, P<.001), treatment acceptability (r=.58, P=.002), and overall satisfaction (r=.58, P=.002) were all related to program completion. CONCLUSIONS: Parent engagement and satisfaction with ImPACT Online was high for both self-directed and therapist-assisted versions of the program, although therapist assistance increased engagement. Program completion was associated with parent outcomes, providing support for the role of the website in parent learning. This program has the potential to increase access to parent-mediated intervention for families of children with ASD.
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6. Kantarcioglu AS, Kiraz N, Aydin A. {{Microbiota-Gut-Brain Axis: Yeast Species Isolated from Stool Samples of Children with Suspected or Diagnosed Autism Spectrum Disorders and In Vitro Susceptibility Against Nystatin and Fluconazole}}. {Mycopathologia};2015 (Oct 6)
Autism spectrum disorder (ASD) is a general term for a group of complex neurodevelopmental disorders of brain development that limits a person’s ability to function normally. Etiology has not been clearly defined up to date. However, gut microbiota and the bidirectional communication between the gastrointestinal tract and brain, the so-called microbiota-gut-brain axis, are hypothesized, which may be involved in the etiology of several mental disorders. Recent reports suggest that Candida, particularly Candida albicans, growth in intestines may cause lower absorption of carbohydrates and minerals and higher toxin levels which are thought to contribute autistic behaviors. The aim of this study was to identify the 3-year deposited yeasts isolated from stool samples of children with diagnosed or suspected ASD and to determine in vitro activity of nystatin and fluconazole against these isolates using Clinical Laboratory Standards Institute M27-A3 guidelines. A 17-year retrospective assessment was also done using our laboratory records. Among the species identified, intrinsically fluconazole-resistent Candida krusei (19.8 %) and Candida glabrata (14.8 %) with elevated MICs were remarkable. Overall, C. albicans (57.4 %) was the most commonly isolated species in 17 years. The species identification and/or antifungal susceptibility tests have to be performed using the strain isolated from stool sample, to select the appropriate antifungal agent, if antimycotic therapy is needed.
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7. Kardas F, Bayram AK, Demirci E, Akin L, Ozmen S, Kendirci M, Canpolat M, Oztop DB, Narin F, Gumus H, Kumandas S, Per H. {{Increased Serum Phthalates (MEHP, DEHP) and Bisphenol A Concentrations in Children With Autism Spectrum Disorder: The Role of Endocrine Disruptors in Autism Etiopathogenesis}}. {J Child Neurol};2015 (Oct 8)
The aim of this study was to investigate the relationship between autism spectrum disorders development and exposure to mono-(2-ethylhexyl)-phthalate (MEHP), di-(2-ethylhexyl)-phthalate (DEHP), and bisphenol A (BPA), 1 of the endocrine disruptors, among phthalates. The study included 48 children with autism spectrum disorder (27 boys, 21 girls) and 41 healthy subjects (24 boys, 17 girls) as controls. Serum MEHP, DEHP, and BPA levels were measured by using high-performance liquid chromatography. Children with autism spectrum disorder had significantly increased serum MEHP, DEHP, and BPA concentrations (0.47 +/- 0.14 microg/ml, 2.70 +/- 0.90 microg/ml, 1.25 +/- 0.30 ng/ml) compared to healthy control subjects (0.29 +/- 0.05 microg/ml, 1.62 +/- 0.56 microg/ml, 0.88 +/- 0.18 ng/ml) respectively (P = .000). The fact that higher serum MEHP, DEHP, and BPA were found levels in the autism spectrum disorder group compared to healthy controls suggests that endocrine disruptors may have a role in the pathogenesis of autism spectrum disorders.
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8. Neufeld J, Ioannou C, Korb S, Schilbach L, Chakrabarti B. {{Spontaneous Facial Mimicry is Modulated by Joint Attention and Autistic Traits}}. {Autism Res};2015 (Oct 7)
Joint attention (JA) and spontaneous facial mimicry (SFM) are fundamental processes in social interactions, and they are closely related to empathic abilities. When tested independently, both of these processes have been usually observed to be atypical in individuals with autism spectrum conditions (ASC). However, it is not known how these processes interact with each other in relation to autistic traits. This study addresses this question by testing the impact of JA on SFM of happy faces using a truly interactive paradigm. Sixty-two neurotypical participants engaged in gaze-based social interaction with an anthropomorphic, gaze-contingent virtual agent. The agent either established JA by initiating eye contact or looked away, before looking at an object and expressing happiness or disgust. Eye tracking was used to make the agent’s gaze behavior and facial actions contingent to the participants’ gaze. SFM of happy expressions was measured by Electromyography (EMG) recording over the Zygomaticus Major muscle. Results showed that JA augments SFM in individuals with low compared with high autistic traits. These findings are in line with reports of reduced impact of JA on action imitation in individuals with ASC. Moreover, they suggest that investigating atypical interactions between empathic processes, instead of testing these processes individually, might be crucial to understanding the nature of social deficits in autism. Autism Res 2015. (c) 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
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9. Oakes A, Thurman AJ, McDuffie A, Bullard LM, Hagerman RJ, Abbeduto L. {{Characterising repetitive behaviours in young boys with fragile X syndrome}}. {J Intellect Disabil Res};2015 (Oct 8)
BACKGROUND: Repetitive behaviours are frequently observed in individuals with intellectual disability (ID). The present study examined the profile, inter-correlations and predictive correlates of repetitive behaviours in boys with fragile X syndrome (FXS), the leading inherited cause of ID. Specific child characteristics examined as predictors included anxiety, nonverbal cognition and autism social-affective symptomatology. METHOD: Participants were 39 boys with FXS (aged 6-10 years). Repetitive behaviours were measured using the Repetitive Behavior Scale – Revised (RBS-R) – a 43-item caregiver-report measure normed on individuals with ID. RESULTS: Restricted Interests and Sensory Motor behaviours were reported as most problematic for this sample of boys, whereas Self-injurious behaviours were less problematic. All subscales of the RBS-R were significantly inter-correlated. Nonverbal IQ was negatively related, whereas anxiety and social affective symptoms of autism spectrum disorder were positively related, to scores for Restricted Interests. Anxiety was also positively related to scores for Compulsive behaviours and Ritualistic Sameness behaviours. CONCLUSIONS: This study provides a preliminary description of repetitive behaviours in boys with FXS, which may form the groundwork for future research.
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10. Ochiai M, Ichiyama M, Iwayama M, Sakai Y, Yoshida K, Hara T. {{Longitudinal study of very low birth weight infants until 9years of age; attention deficit hyperactivity and autistic features are correlated with their cognitive functions}}. {Early Hum Dev};2015 (Oct 3)
BACKGROUND: Increasing attention has been given to neuro-developmental problems of very low birth weight infants (VLBWIs) at school age. However, it remains unknown whether their neuro-cognitive function and psychiatric symptoms are mutually associated. AIM: The aim of this study was to investigate the characteristics of neuro-cognitive functions in VLBWIs and their relationship with psychiatric symptoms. METHODS: A total of 160 VLBWIs who were born at our institute between 2001 and 2005 were recruited consecutively and followed up until nine years of age. The developmental profiles were obtained from 77 children (45 males and 32 females) at six to nine years of age using the ADHD Rating Scale-Fourth edition (ADHD-RS), Autism Screening Questionnaire-Japanese version (ASQ-J) and the Wechsler Intelligence Scale for Children-Third edition (WISC-III). RESULTS: The full-scale intelligence quotient did not significantly differ between the male and female VLBWIs (median: 91 vs. 99, p=0.17). The males had higher total scores (median: 13 vs. 4, p<0.01) and higher scores on the subscales of Inattention (8 vs. 2, p<0.01) and Hyperactivity-Impulsivity (5 vs. 1, p<0.01) of the ADHD-RS compared with the females. The Verbal Comprehension Index (VCI) of the WISC-III was inversely correlated with the total scores of the ASQ-J for all VLBWIs (n=77, rc: -0.32, 95% CI: -0.19 to -0.01, p=0.04). We also observed that the Freedom from Distractibility Index (FDI) of the WISC-III was significantly correlated with the Inattentive scores of the ADHD-RS (n=45, rc: -0.18, 95% CI: -0.35 to -0.02, p=0.03) in male, but not female VLBWIs. CONCLUSIONS: We herein report that the VCI and FDI of the WISC-III were correlated with the autism spectrum disorder and attention deficit hyperactivity disorder symptoms, respectively, in male VLBWIs.
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11. Roberts AL, Nguyen VT. {{Growing evidence that maternal gestational diabetes increases risk of autism in offspring}}. {Evid Based Ment Health};2015 (Oct 6)
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12. Sharer EA, Mostofsky SH, Pascual-Leone A, Oberman LM. {{Isolating Visual and Proprioceptive Components of Motor Sequence Learning in ASD}}. {Autism Res};2015 (Oct 7)
In addition to defining impairments in social communication skills, individuals with autism spectrum disorder (ASD) also show impairments in more basic sensory and motor skills. Development of new skills involves integrating information from multiple sensory modalities. This input is then used to form internal models of action that can be accessed when both performing skilled movements, as well as understanding those actions performed by others. Learning skilled gestures is particularly reliant on integration of visual and proprioceptive input. We used a modified serial reaction time task (SRTT) to decompose proprioceptive and visual components and examine whether patterns of implicit motor skill learning differ in ASD participants as compared with healthy controls. While both groups learned the implicit motor sequence during training, healthy controls showed robust generalization whereas ASD participants demonstrated little generalization when visual input was constant. In contrast, no group differences in generalization were observed when proprioceptive input was constant, with both groups showing limited degrees of generalization. The findings suggest, when learning a motor sequence, individuals with ASD tend to rely less on visual feedback than do healthy controls. Visuomotor representations are considered to underlie imitative learning and action understanding and are thereby crucial to social skill and cognitive development. Thus, anomalous patterns of implicit motor learning, with a tendency to discount visual feedback, may be an important contributor in core social communication deficits that characterize ASD. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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13. Unterrainer JM, Rauh R, Rahm B, Hardt J, Kaller CP, Klein C, Paschke-Muller M, Biscaldi M. {{Development of Planning in Children with High-Functioning Autism Spectrum Disorders and/or Attention Deficit/Hyperactivity Disorder}}. {Autism Res};2015 (Oct 7)
Planning impairment is often observed in children with high-functioning autism spectrum disorders (ASD), but attempts to differentiate planning in ASD from children with attention deficit hyperactivity disorder (ADHD) and typically developing children (TD) have yielded inconsistent results. This study examined differences between these groups by focusing on development and analyzing performance in searching ahead several steps (« search depth ») in addition to commonly used global performance measures in planning. A cross-sectional consecutive sample of 83 male patients (6-13 years), subgrouped as ASD without (ASD-, n = 18) or with comorbid ADHD (ASD+, n = 23), ADHD only (n = 42) and n = 42 TD children (6-13 years) were tested with the Tower-of-London-task. For global performance, ASD+ showed the lowest accuracy in younger children, but similar performance as TD at older ages, suggesting delayed development. Typically, a prolongation of planning time with increasing problem difficulty is observed in older children as compared to younger children. Here, this was most pronounced in ASD-, but under-expressed in ADHD. In contrast to global performance, effects of search depth were independent of age. ASD-, but not ASD+, showed increased susceptibility to raised demands on mentally searching ahead, along with the longest planning times. Thus, examining both global and search depth performance across ages revealed discernible patterns of planning between groups. Notably, the potentially detrimental impact of two diagnosed disorders does not add up in ASD+ in this task. Rather, our results suggest paradoxical enhancement of performance, ostensibly attributable to disruption of behavioral rigidity through increased impulsivity, which did not take place in ASD-. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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14. Ure AM, Treyvaud K, Thompson DK, Pascoe L, Roberts G, Lee KJ, Seal ML, Northam E, Cheong JL, Hunt RW, Inder T, Doyle LW, Anderson PJ. {{Neonatal brain abnormalities associated with autism spectrum disorder in children born very preterm}}. {Autism Res};2015 (Oct 7)
Very preterm (VP) survivors are at increased risk of autism spectrum disorder (ASD) compared with term-born children. This study explored whether neonatal magnetic resonance (MR) brain features differed in VP children with and without ASD at 7 years. One hundred and seventy-two VP children (<30 weeks’ gestation or <1250 g birth weight) underwent structural brain MR scans at term equivalent age (TEA; 40 weeks’ gestation +/-2 weeks) and were assessed for ASD at 7 years of age. The presence and severity of white matter, cortical gray matter, deep nuclear gray matter, and cerebellar abnormalities were assessed, and total and regional brain volumes were measured. ASD was diagnosed using a standardized parent report diagnostic interview and confirmed via an independent assessment. Eight VP children (4.7%) were diagnosed with ASD. Children with ASD had more cystic lesions in the cortical white matter at TEA compared with those without ASD (odds ratio [OR] 8.7, 95% confidence interval [CI] 1.5, 51.3, P = 0.02). There was also some evidence for smaller cerebellar volumes in children with ASD compared with those without ASD (OR = 0.82, CI = 0.66, 1.00, P = 0.06). Overall, the results suggest that VP children with ASD have different brain structure in the neonatal period compared with those who do not have ASD. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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15. Wolfe FH, Auzias G, Deruelle C, Chaminade T. {{Focal atrophy of the hypothalamus associated with third ventricle enlargement in autism spectrum disorder}}. {Neuroreport};2015 (Oct 6)
The hypothalamus is a brain structure containing multiple nuclei that mediate essential behavioral, autonomic, and endocrine functions including oxytocin synthesis. Oxytocin is a neuropeptide linked to complex social cognition and behaviors necessary for an effective social interaction. Oxytocinergic system dysfunction has been linked to social deficits in autism spectrum disorders (ASD). Limited studies have been carried out on the hypothalamus because of its small size and methodological constraints in current technologies. This neuroimaging study examines hypothalamic atrophy in ASD in comparison with a typically developing population (a) by directly measuring gray matter (GM) density with a region-of-interest analysis using voxel-based morphometry in a homogenous sample of participants controlled for age and intelligence quotient; (b) for generalization, by measuring third ventricular volume, on the basis of its position bilaterally surrounded by the hypothalamus, using Freesurfer in a heterogeneous sample of participants. A voxel-based morphometry analysis of cerebrospinal fluid density on the first sample provides a link between GM density and third ventricle volume. Our results show decreased hypothalamic GM density and increased third ventricle volume in ASD compared with typically developing patients. Our findings provide neuroanatomical insights into social deficits in ASD within the hypothalamus that might be relevant for other psychiatric conditions.
