1. Baum SH, Stevenson RA, Wallace MT. {{Behavioral, Perceptual, and Neural Alterations in Sensory and Multisensory Function in Autism Spectrum Disorder}}. {Prog Neurobiol};2015 (Oct 6)
Although sensory processing challenges have been noted since the first clinical descriptions of autism, it has taken until the release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013 for sensory problems to be included as part of the core symptoms of autism spectrum disorder (ASD) in the diagnostic profile. Because sensory information forms the building blocks for higher-order social and cognitive functions, we argue that sensory processing is not only an additional piece of the puzzle, but rather a critical cornerstone for characterizing and understanding ASD. In this review we discuss what is currently known about sensory processing in ASD, how sensory function fits within contemporary models of ASD, and what is understood about the differences in the underlying neural processing of sensory and social communication observed between individuals with and without ASD. In addition to highlighting the sensory features associated with ASD, we also emphasize the importance of multisensory processing in building perceptual and cognitive representations, and how deficits in multisensory integration may also be a core characteristic of ASD.
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2. 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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3. De Giacomo A, Craig F, Cristella A, Terenzio V, Buttiglione M, Margari L. {{Can PEP-3 Provide a Cognitive Profile in Children with ASD? A Comparison Between the Developmental Ages of PEP-3 and IQ of Leiter-R}}. {J Appl Res Intellect Disabil};2015 (Oct 6)
BACKGROUND: The assessment of the intelligence quotient (IQ) in children with autism spectrum disorder (ASD) is important to plan a detailed therapeutic-educative programme. The aim of the study was to evaluate the usefulness of the Psychoeducational Profile-third edition (PEP-3) to estimate the general cognitive development of children with ASD. METHOD: We recruited 30 children with ASD assessed with the Leiter International Performance Scale-Revised (Leiter-R) and the PEP-3. We compared the IQ of the Leiter-R with the developmental level (DL) of PEP-3. RESULTS: The findings showed a significant positive correlation between IQ with DL of the cognitive verbal/pre-verbal (P = 0.0005), DL of the area of expressive language (P = 0.0004), DL of the area of receptive language (P = 0.0001), DL of fine motor (P = 0.0066), DL of gross motor (P = 0.0217), DL of visuo-motor imitation (P = 0.02), DL of communication (P = 0.0001) and DL of motor (P = 0.0063). CONCLUSIONS: These findings show that the DLs could be considered as indicators of cognitive functioning in ASD.
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4. Durkin MS, Elsabbagh M, Barbaro J, Gladstone M, Happe F, Hoekstra RA, Lee LC, Rattazzi A, Stapel-Wax J, Stone WL, Tager-Flusberg H, Thurm A, Tomlinson M, Shih A. {{Autism screening and diagnosis in low resource settings: Challenges and opportunities to enhance research and services worldwide}}. {Autism Res};2015 (Oct 6)
Most research into the epidemiology, etiology, clinical manifestations, diagnosis and treatment of autism is based on studies in high income countries. Moreover, within high income countries, individuals of high socioeconomic status are disproportionately represented among participants in autism research. Corresponding disparities in access to autism screening, diagnosis, and treatment exist globally. One of the barriers perpetuating this imbalance is the high cost of proprietary tools for diagnosing autism and for delivering evidence-based therapies. Another barrier is the high cost of training of professionals and para-professionals to use the tools. Open-source and open access models provide a way to facilitate global collaboration and training. Using these models and technologies, the autism scientific community and clinicians worldwide should be able to work more effectively and efficiently than they have to date to address the global imbalance in autism knowledge and at the same time advance our understanding of autism and our ability to deliver cost-effective services to everyone in need. 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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5. Eisenberg IW, Wallace GL, Kenworthy L, Gotts SJ, Martin A. {{Insistence on sameness relates to increased covariance of gray matter structure in autism spectrum disorder}}. {Mol Autism};2015;6:54.
BACKGROUND: Autism spectrum disorder (ASD) is characterized by atypical development of cortical and subcortical gray matter volume. Subcortical structural changes have been associated with restricted and repetitive behavior (RRB), a core component of ASD. Behavioral studies have identified insistence on sameness (IS) as a separable RRB dimension prominent in high-functioning ASD, though no simple brain-behavior relationship has emerged. Structural covariance, a measure of morphological coupling among brain regions using magnetic resonance imaging (MRI), has proven an informative measure of anatomical relationships in typical development and neurodevelopmental disorders. In this study, we use this measure to characterize the relationship between brain structure and IS. METHODS: We quantified the structural covariance of cortical and subcortical gray matter volume in 55 individuals with high-functioning ASD using 3T MRI. We then related these structural metrics to individual IS scores, as assessed by the Repetitive Behavior Scale-Revised (RBS-R). RESULTS: We found that increased coupling among subcortical regions and between subcortical and cortical regions related to greater IS symptom severity. Most pronounced, the striatum and amygdala participated in a plurality of identified relationships, indicating a central role for these structures in IS symptomatology. These structural associations were specific to IS and did not relate to any of the other RRB subcomponents measured by the RBS-R. CONCLUSIONS: This study indicates that behavioral dimensions in ASD can relate to the coordination of development across multiple brain regions, which might be otherwise obscured using typical brain-behavior correlations. It also expands the structures traditionally related to RRB in ASD and provides neuroanatomical evidence supportive of IS as a separate RRB dimension. TRIAL REGISTRATION: ClinicalTrials.gov NCT01031407.
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6. Gabriele S, Sacco R, Altieri L, Neri C, Urbani A, Bravaccio C, Riccio MP, Iovene MR, Bombace F, De Magistris L, Persico AM. {{Slow intestinal transit contributes to elevate urinary p-cresol level in Italian autistic children}}. {Autism Res};2015 (Oct 6)
The uremic toxin p-cresol (4-methylphenol) is either of environmental origin or can be synthetized from tyrosine by cresol-producing bacteria present in the gut lumen. Elevated p-cresol amounts have been previously found in the urines of Italian and French autism spectrum disorder (ASD) children up until 8 years of age, and may be associated with autism severity or with the intensity of abnormal behaviors. This study aims to investigate the mechanism producing elevated urinary p-cresol in ASD. Urinary p-cresol levels were thus measured by High Performance Liquid Chromatography in a sample of 53 Italian ASD children assessed for (a) presence of Clostridium spp. strains in the gut by means of an in vitro fecal stool test and of Clostridium difficile-derived toxin A/B in the feces, (b) intestinal permeability using the lactulose/mannitol (LA/MA) test, (c) frequent use of antibiotics due to recurrent infections during the first 2 years of postnatal life, and (d) stool habits with the Bristol Stool Form Scale. Chronic constipation was the only variable significantly associated with total urinary p-cresol concentration (P < 0.05). No association was found with presence of Clostridium spp. in the gut flora (P = 0.92), augmented intestinal permeability (P = 0.18), or frequent use of antibiotics in early infancy (P = 0.47). No ASD child was found to carry C. difficile in the gut or to release toxin A/B in the feces. In conclusion, urinary p-cresol levels are elevated in young ASD children with increased intestinal transit time and chronic constipation. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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7. Gadad BS, Li W, Yazdani U, Grady S, Johnson T, Hammond J, Gunn H, Curtis B, English C, Yutuc V, Ferrier C, Sackett GP, Marti CN, Young K, Hewitson L, German DC. {{Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology}}. {Proc Natl Acad Sci U S A};2015 (Oct 6);112(40):12498-12503.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD.
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8. Goldenthal MJ, Damle S, Sheth S, Shah N, Melvin J, Jethva R, Hardison H, Marks H, Legido A. {{Mitochondrial enzyme dysfunction in autism spectrum disorders; a novel biomarker revealed from buccal swab analysis}}. {Biomark Med};2015 (Oct 6)
AIM: Mitochondrial function studies in autism spectrum disorders (ASD) have detected skeletal muscle mitochondrial enzyme deficiencies in respiratory complex (RC) activities. As a muscle biopsy is expensive and invasive, we assessed RC-I and RC-IV activities in buccal swabs. METHODS: 92 children with ASD and 68 controls were studied with immunocapture for RC-I and microspectrophotometry for RC-IV. RESULTS: Significant RC activity deficiencies were found in 39 (42%) ASD patients (p < 0.01) and more prevalent in more severe cases. Aberrant RC overactivity was seen in 9 children. RC-I/RC-IV activity ratio was significantly increased in 64% of the entire ASD cohort including 76% of those more severely affected (p < 0.05). CONCLUSION: Buccal swab analysis revealed extensive RC abnormalities in ASD providing a noninvasive biomarker to assess mitochondrial function in ASD patients.
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9. Harris H, Israeli D, Minshew N, Bonneh Y, Heeger DJ, Behrmann M, Sagi D. {{Perceptual learning in autism: over-specificity and possible remedies}}. {Nat Neurosci};2015 (Oct 5)
Inflexible behavior is a core characteristic of autism spectrum disorder (ASD), but its underlying cause is unknown. Using a perceptual learning protocol, we observed initially efficient learning in ASD that was followed by anomalously poor learning when the location of the target was changed (over-specificity). Reducing stimulus repetition eliminated over-specificity. Our results indicate that inflexible behavior may be evident ubiquitously in ASD, even in sensory learning, but can be circumvented by specifically designed stimulation protocols.
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10. Higuchi Y, Uchitomi Y, Fujimori M, Koyama T, Kataoka H, Kitamura Y, Sendo T, Inagaki M. {{Exploring autistic-like traits relating to empathic attitude and psychological distress in hospital pharmacists}}. {Int J Clin Pharm};2015 (Oct 6)
Background Pharmacists are expected to play a key role in modern cancer care. Research suggests that an empathic approach and attitude in medical staff improves the quality of patient care. An empathic attitude and psychological distress are thought to be associated with autistic-like traits, but little is known about such traits. Objective In this study, we aimed to clarify the associations among autistic-like traits, empathic attitude in a medical context, and psychological health in hospital pharmacists. Setting Eligibility criteria for inclusion were certified pharmacists working at hospitals for patient care who returned their questionnaires. Method Eight hundred and twenty-three hospital pharmacists completed a number of self-administered questionnaires anonymously by mail. Main outcome measures Scores were obtained on the Autism-Spectrum Quotient, the Jefferson Scale of Empathy, the General Health Questionnaire-12, and subscales of the Interpersonal Reactivity Index (Perspective Taking, IRI-Empathic Concern, IRIPersonal Distress). We performed correlation and mediation analyses to confirm that the empathy and general health questionnaires were associated with autism-spectrum quotient scores, and with each IRI subscale. Results Complete responses were obtained from 379 pharmacists comprising 151 males (39.8 %) with a mean age of 37.7 +/- 10.8 years (missing data, n = 13) and a median of 11 years after qualification as a pharmacist. Autism-Spectrum Quotient scores were inversely correlated with empathy (r = -0.22, p < 0.001) and positively correlated with general health scores (r = 0.40, p < 0.001). In the models with mediation, the inverse correlation between autism-spectrum quotient and empathy scores was mediated indirectly by IRI-Perspective Taking and IRI-Empathic Concern, and the positive correlation between autism-spectrum quotient and general health was mediated indirectly by IRI-Personal Distress. There were also direct effects, with significant effects of autism-spectrum quotient on empathy and general health scores. Conclusion Our findings suggest that autistic-like traits affect both empathic attitude in a medical context and the psychological health of pharmacists. We recommend that to improve empathy in those with high levels of autistic-like traits, we may need to develop specialized interventions, such as improving communication skills training.
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11. 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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12. 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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13. Offit PA. {{Vaccines and autism in primate model}}. {Proc Natl Acad Sci U S A};2015 (Oct 6);112(40):12236-12237.
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14. Ratto AB, Anthony BJ, Kenworthy L, Armour AC, Dudley K, Anthony LG. {{Are Non-intellectually Disabled Black Youth with ASD Less Impaired on Parent Report than Their White Peers?}}. {J Autism Dev Disord};2015 (Oct 6)
There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social-emotional functioning. White and Black youth (n = 64; ages 6-17) with ASD without ID were compared on each of these domains. Black youth had significantly lower levels of impairment on all three domains. Findings may reflect better daily functioning among Black youth with ASD and/or cultural differences in parent response to questionnaires. Regardless, these findings raise concern about the sensitivity of commonly used measures for Black children with ASD and the impact of culture on daily functioning and symptom manifestation.
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15. 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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16. Talbott EO, Marshall LP, Rager JR, Arena VC, Sharma RK, Stacy SL. {{Air toxics and the risk of autism spectrum disorder: the results of a population based case-control study in southwestern Pennsylvania}}. {Environ Health};2015;14:80.
BACKGROUND: Autism spectrum disorders (ASD) constitute a major public health problem affecting one in 68 children. There is little understanding of the causes of ASD despite its serious social impact. Air pollution contains many toxicants known to have adverse effects on the fetus. We conducted a population based case-control study in southwestern Pennsylvania to estimate the association between ASD and 2005 US EPA modeled NATA (National Air Toxics Assessment) levels for 30 neurotoxicants. METHODS: A total of 217 ASD cases born between 2005 and 2009 were recruited from local ASD diagnostic and treatment centers. There were two different control groups: 1) interviewed controls (N = 224) frequency matched by child’s year of birth, sex and race with complete residential histories from prior to pregnancy through the child’s second birthday, and 2) 5,007 controls generated from a random sample of birth certificates (BC controls) using residence at birth. We used logistic regression analysis comparing higher to first quartile of exposure to estimate odds ratios (ORs) and 95% confidence intervals (CI), adjusting for mother’s age, education, race, smoking status, child’s year of birth and sex. RESULTS: Comparing fourth to first quartile exposures for all births, the adjusted OR for styrene was 2.04 (95% CI = 1.17-3.58, p = 0.013) for the interviewed case-control analysis and 1.61 (95% CI = 1.08-2.40, p = 0.018) for the BC analysis. In the BC comparison, chromium also exhibited an elevated OR of 1.60 (95% CI = 1.08-2.38, p = 0.020), which was similarly elevated in the interviewed analysis (OR = 1.52, 95% CI = 0.87-2.66). There were borderline significant ORs for the BC comparison for methylene chloride (OR = 1.41, 95% CI = 0.96-2.07, p = 0.082) and PAHs (OR = 1.44, 95% CI = 0.98-2.11, p = 0.064). CONCLUSIONS: Living in areas with higher levels of styrene and chromium during pregnancy was associated with increased risk of ASD, with borderline effects for PAHs and methylene chloride. These results are consistent with other studies. It is unclear, however, whether these chemicals are risk factors themselves or if they reflect the effect of a mixture of pollutants. Future work should include improved spatiotemporal estimates of exposure to air toxics, taking into account the dynamic movement of individuals during daily life.
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17. Walsh JA, Creighton SE, Rutherford MD. {{Emotion Perception or Social Cognitive Complexity: What Drives Face Processing Deficits in Autism Spectrum Disorder?}}. {J Autism Dev Disord};2015 (Oct 6)
Some, but not all, relevant studies have revealed face processing deficits among those with autism spectrum disorder (ASD). In particular, deficits are revealed in face processing tasks that involve emotion perception. The current study examined whether either deficits in processing emotional expression or deficits in processing social cognitive complexity drive face processing deficits in ASD. We tested adults with and without ASD on a battery of face processing tasks that varied with respect to emotional expression processing and social cognitive complexity. Results revealed significant group differences on tasks involving emotional expression processing, but typical performance on a non-emotional but socially complex task. These results support an emotion processing rather than a social complexity explanation for face processing deficits in ASD.
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18. 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.
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19. Yi L, Quinn PC, Fan Y, Huang D, Feng C, Joseph L, Li J, Lee K. {{Children with Autism Spectrum Disorder scan own-race faces differently from other-race faces}}. {J Exp Child Psychol};2015 (Oct 1);141:177-186.
It has been well documented that people recognize and scan other-race faces differently from faces of their own race. The current study examined whether this cross-racial difference in face processing found in the typical population also exists in individuals with Autism Spectrum Disorder (ASD). Participants included 5- to 10-year-old children with ASD (n=29), typically developing (TD) children matched on chronological age (n=29), and TD children matched on nonverbal IQ (n=29). Children completed a face recognition task in which they were asked to memorize and recognize both own- and other-race faces while their eye movements were tracked. We found no recognition advantage for own-race faces relative to other-race faces in any of the three groups. However, eye-tracking results indicated that, similar to TD children, children with ASD exhibited a cross-racial face-scanning pattern: they looked at the eyes of other-race faces longer than at those of own-race faces, whereas they looked at the mouth of own-race faces longer than at that of other-race faces. The findings suggest that although children with ASD have difficulty with processing some aspects of faces, their ability to process face race information is relatively spared.
