1. Butler MG, Rafi SK, Hossain W, Stephan DA, Manzardo AM. {{Whole exome sequencing in females with autism implicates novel and candidate genes}}. {International journal of molecular sciences}. 2015;16(1):1312-35.
Classical autism or autistic disorder belongs to a group of genetically heterogeneous conditions known as Autism Spectrum Disorders (ASD). Heritability is estimated as high as 90% for ASD with a recently reported compilation of 629 clinically relevant candidate and known genes. We chose to undertake a descriptive next generation whole exome sequencing case study of 30 well-characterized Caucasian females with autism (average age, 7.7 +/- 2.6 years; age range, 5 to 16 years) from multiplex families. Genomic DNA was used for whole exome sequencing via paired-end next generation sequencing approach and X chromosome inactivation status. The list of putative disease causing genes was developed from primary selection criteria using machine learning-derived classification score and other predictive parameters (GERP2, PolyPhen2, and SIFT). We narrowed the variant list to 10 to 20 genes and screened for biological significance including neural development, function and known neurological disorders. Seventy-eight genes identified met selection criteria ranging from 1 to 9 filtered variants per female. Five females presented with functional variants of X-linked genes (IL1RAPL1, PIR, GABRQ, GPRASP2, SYTL4) with cadherin, protocadherin and ankyrin repeat gene families most commonly altered (e.g., CDH6, FAT2, PCDH8, CTNNA3, ANKRD11). Other genes related to neurogenesis and neuronal migration (e.g., SEMA3F, MIDN), were also identified.
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2. Fernandez-Andres MI, Pastor-Cerezuela G, Sanz-Cervera P, Tarraga-Minguez R. {{A comparative study of sensory processing in children with and without Autism Spectrum Disorder in the home and classroom environments}}. {Research in developmental disabilities}. 2015 Jan 6;38C:202-12.
Sensory processing and higher integrative functions impairments are highly prevalent in children with ASD. Context should be considered in analyzing the sensory profile and higher integrative functions. The main objective of this study is to compare sensory processing, social participation and praxis in a group of 79 children (65 males and 14 females) from 5 to 8 years of age (M=6.09) divided into two groups: ASD Group (n=41) and Comparison Group (n=38). The Sensory Processing Measure (SPM) was used to evaluate the sensory profile of the children: parents reported information about their children’s characteristics in the home environment, and teachers reported information about the same characteristics in the classroom environment. The ASD Group obtained scores that indicate higher levels of dysfunction on all the assessed measures in both environments, with the greatest differences obtained on the social participation and praxis variables. The most affected sensory modalities in the ASD Group were hearing and touch. Only in the ASD Group were significant differences found between the information reported by parents and what was reported by teachers: specifically, the teachers reported greater dysfunction than the parents in social participation (p=.000), touch (p=.003) and praxis (p=.010). These results suggest that the context-specific qualities found in children with ASD point out the need to receive information from both parents and teachers during the sensory profile assessment process, and use context-specific assessments.
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3. Frisch M, Simonsen J. {{Ritual circumcision and risk of autism spectrum disorder in 0- to 9-year-old boys: national cohort study in Denmark}}. {Journal of the Royal Society of Medicine}. 2015 Jan 8.
OBJECTIVE: Based on converging observations in animal, clinical and ecological studies, we hypothesised a possible impact of ritual circumcision on the subsequent risk of autism spectrum disorder (ASD) in young boys. DESIGN: National, register-based cohort study. SETTING: Denmark. PARTICIPANTS: A total of 342,877 boys born between 1994 and 2003 and followed in the age span 0-9 years between 1994 and 2013. MAIN OUTCOME MEASURES: Information about cohort members’ ritual circumcisions, confounders and ASD outcomes, as well as two supplementary outcomes, hyperkinetic disorder and asthma, was obtained from national registers. Hazard ratios (HRs) with 95% confidence intervals (CIs) associated with foreskin status were obtained using Cox proportional hazards regression analyses. RESULTS: With a total of 4986 ASD cases, our study showed that regardless of cultural background circumcised boys were more likely than intact boys to develop ASD before age 10 years (HR = 1.46; 95% CI: 1.11-1.93). Risk was particularly high for infantile autism before age five years (HR = 2.06; 95% CI: 1.36-3.13). Circumcised boys in non-Muslim families were also more likely to develop hyperkinetic disorder (HR = 1.81; 95% CI: 1.11-2.96). Associations with asthma were consistently inconspicuous (HR = 0.96; 95% CI: 0.84-1.10). CONCLUSIONS: We confirmed our hypothesis that boys who undergo ritual circumcision may run a greater risk of developing ASD. This finding, and the unexpected observation of an increased risk of hyperactivity disorder among circumcised boys in non-Muslim families, need attention, particularly because data limitations most likely rendered our HR estimates conservative. Considering the widespread practice of non-therapeutic circumcision in infancy and childhood around the world, confirmatory studies should be given priority.
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4. Guinchat V, Cravero C, Diaz L, Perisse D, Xavier J, Amiet C, Gourfinkel-An I, Bodeau N, Wachtel L, Cohen D, Consoli A. {{Acute behavioral crises in psychiatric inpatients with autism spectrum disorder (ASD): Recognition of concomitant medical or non-ASD psychiatric conditions predicts enhanced improvement}}. {Research in developmental disabilities}. 2015 Jan 6;38C:242-55.
During adolescence, some individuals with autism spectrum disorder (ASD) engage in severe challenging behaviors, such as aggression, self-injury, disruption, agitation and tantrums. We aimed to assess risk factors associated with very acute behavioral crises in adolescents with ASD admitted to a dedicated neurobehavioral unit. We included retrospectively in 2008 and 2009 29 adolescents and young adults with ASD hospitalized for severe challenging behaviors and proposed a guideline (Perisse et al., 2010) that we applied prospectively for 29 patients recruited for the same indications between 2010 and 2012. In total, 58 patients were admitted (n=70 hospitalizations, mean age=15.66 (+/-4.07) years, 76% male). We systematically collected data describing socio-demographic characteristics, clinical variables (severity, presence of language, cognitive level), comorbid organic conditions, etiologic diagnosis of the episode, and treatments. We explored predictors of Global Assessment Functioning Scale (GAFS) score and duration of hospitalization at discharge. All but 2 patients exhibited severe autistic symptoms and intellectual disability (ID), and two-thirds had no functional verbal language. During the inpatient stay (mean=84.3 (+/-94.9) days), patients doubled on average their GAFS scores (mean=17.66 (+/-9.05) at admission vs. mean=31.4 (+/-9.48) at discharge). Most common etiologies for acute behavioral crises were organic causes [n=20 (28%), including epilepsy: n=10 (14%) and painful medical conditions: n=10 (14%)], environmental causes [n=17 (25%) including lack of treatment: n=11 (16%) and adjustment disorder: n=6 (9%)], and non-ASD psychiatric condition [n=33 (48%) including catatonia: n=5 (7%), major depressive episode: n=6 (9%), bipolar disorder: n=4 (6%), schizophrenia: n=6 (9%), other/unknown diagnosis: n=12 (17%)]. We found no influence of age, gender, socio-economic status, migration, level of ID, or history of seizure on improvement of GAFS score at discharge. Severity of autism at admission was the only negative predictor (p<.001). Painful medical conditions (p=.04), non-ASD psychiatric diagnoses (p=.001), prior usage of specialized ASD care programs (p=.004), functional language (p=.007), as well as a higher number of challenging behaviors upon admission (p=.001) were associated with higher GAFS scores at discharge. Clinical severity at admission, based on the number of challenging behaviors (r=.35, p=.003) and GAFS score (r=-.32, p=.008) was correlated with a longer inpatient stay. Longer hospitalization was however correlated (r=.27, p=.03) with higher GAFS score at discharge even after adjustment for confounding factors. Challenging behaviors among adolescents with ASD may stem from diverse risk factors, including environmental problems, comorbid acute psychiatric conditions, or somatic illness such as epilepsy or acute pain. The management of these behavioral challenges requires a unified, multidisciplinary approach.
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5. Lord C, Bishop SL. {{Recent Advances in Autism Research as Reflected in DSM-5 Criteria for Autism Spectrum Disorder}}. {Annual review of clinical psychology}. 2015 Jan 2.
This article provides a selective review of advances in scientific knowledge about autism spectrum disorder (ASD), using DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) diagnostic criteria as a framework for the discussion. We review literature that prompted changes to the organization of ASD symptoms and diagnostic subtypes in DSM-IV, and we examine the rationale for new DSM-5 specifiers, modifiers, and severity ratings as well as the introduction of the diagnosis of social (pragmatic) communication disorder. Our goal is to summarize and critically consider the contribution of clinical psychology research, along with that of other disciplines, to the current conceptualization of ASD. Expected final online publication date for the Annual Review of Clinical Psychology Volume 11 is March 28, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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6. Mandy W, Murin M, Baykaner O, Staunton S, Hellriegel J, Anderson S, Skuse D. {{The transition from primary to secondary school in mainstream education for children with autism spectrum disorder}}. {Autism}. 2015 Jan 9.
The transition from primary to secondary education (hereafter ‘school transition’) is a major ecological shift that poses considerable social, emotional, academic and organisational challenges. It is commonly assumed that this school transition is especially difficult for children with autism spectrum disorder, but that idea is mainly based on anecdotal evidence and requires systematic investigation. We describe change and continuity for children with autism spectrum disorder (N = 28, mean age = 11.29 years, mean full-scale IQ = 87.86) transitioning in mainstream education from primary to secondary school. Levels of psychopathology, adaptive functioning and peer victimisation were measured by parent, self and teacher report in the last year of primary school, and again after one term of secondary school. At follow-up, all participants were still in their secondary school, and there was no evidence for a marked escalation of difficulties during the transition. Instead, we observed high levels of psychopathology and maladaption at baseline which persisted across the transition and were in some cases under-recognised. By parent report, levels of bullying fell from primary to secondary school. Future research should investigate factors, such as school characteristics, that influence the move to secondary education in autism spectrum disorder, to inform the development of interventions to promote successful school transition.
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7. Moskowitz LJ, Jones EA. {{Uncovering the evidence for behavioral interventions with individuals with fragile X syndrome: A systematic review}}. {Research in developmental disabilities}. 2015 Jan 6;38C:223-41.
Fragile X syndrome (FXS) is associated with a wide range of cognitive, emotional, and behavioral difficulties. Although there is considerable research on the behavioral phenotype of FXS, few empirical studies of behavioral interventions with this population have been identified. Through a hand search of 34 behavioral journals, we examined the evidence base for behavioral interventions with individuals with FXS and in light of the current state of knowledge regarding the FXS behavioral phenotype. Systematic review procedures were used to identify behavioral intervention studies that included at least one participant with FXS, extract and summarize the data on several relevant dimensions, and rate the methodological quality of the studies. Results revealed 31 intervention studies with a small number of participants with FXS. Overall, results suggest a behavioral approach to intervention with individuals with FXS shows promise. Future research focused on individuals with FXS will be necessary to continue to examine differences in response to intervention and interventions that specifically address phenotypic characteristics.
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8. Nikoo M, Radnia H, Farokhnia M, Mohammadi MR, Akhondzadeh S. {{N-Acetylcysteine as an Adjunctive Therapy to Risperidone for Treatment of Irritability in Autism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Efficacy and Safety}}. {Clinical neuropharmacology}. 2015 Jan 9.
OBJECTIVES: According to the proposed interference of N-acetylcysteine (NAC) with pathophysiologic processes of autistic disorders (ADs), we aimed to assess the effectiveness and safety of NAC as an adjunct to risperidone in the treatment of ADs in a randomized, double-blind, clinical trial. METHODS: The participants were referred outpatients between 4 and 12 years of age with the diagnosis of ADs and a score of more than 12 on Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale score. The participants were randomized into 2 groups. One group received risperidone plus NAC, and the other group received risperidone plus placebo. The dose of risperidone was titrated between 1 and 2.0 mg/d, and the dose of NAC was 600 to 900 mg/d. The main outcome was mean decrease in the ABC-C irritability subscale score from baseline at 5 and 10 weeks. Changes in other subscales were considered as secondary outcome measures. RESULTS: Forty patients completed the 10-week trial. Baseline characteristics including age, sex and body weight, as well as baseline scores in 5 subscales did not demonstrate statistically significant difference between the 2 groups. Repeated-measures analysis showed significant effect for time x treatment interaction in irritability (P = 0.01) and hyperactivity/noncompliance (P = 0.02) subscales. By week 10, the NAC group showed significantly more reduction in irritability (P = 0.02) and hyperactivity/noncompliance (P = 0.01) subscales scores. CONCLUSIONS: N-acetylcysteine can be considered as an adjuvant therapy for ADs with beneficial therapeutic outcomes.
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9. Phillips M, Pozzo-Miller L. {{Dendritic spine dysgenesis in autism related disorders}}. {Neuroscience letters}. 2015 Jan 8.
The activity-dependent structural and functional plasticity of dendritic spines has led to the long-standing belief that these neuronal compartments are the subcellular sites of learning and memory. Of relevance to human health, central neurons in several neuropsychiatric illnesses, including autism related disorders, have atypical numbers and morphologies of dendritic spines. These so-called dendritic spine dysgeneses found in individuals with autism related disorders are consistently replicated in experimental mouse models. Dendritic spine dysgenesis reflects the underlying synaptopathology that drives clinically relevant behavioral deficits in experimental mouse models, providing a platform for testing new therapeutic approaches. By examining molecular signaling pathways, synaptic deficits, and spine dysgenesis in experimental mouse models of autism related disorders we find strong evidence for mTOR to be a critical point of convergence and promising therapeutic target.
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10. Saad K, Elserogy Y, Abdel Rahman AA, Al-Atram AA, Mohamad IL, ElMelegy TT, Bjorklund G, El-Houfy AA. {{ADHD, autism and neuroradiological complications among phenylketonuric children in Upper Egypt}}. {Acta neurologica Belgica}. 2015 Jan 10.
The aim of this study is to evaluate the neuropsychological status in a cohort of children with early and continuously treated phenylketonuria in Assiut, Upper Egypt. The study was implemented in seventy-eight phenylketonuria (PKU) children. Only 34 patients met the inclusion criteria. Investigated patients were evaluated according to detailed history, neurological examination, Childhood Autism Rating Scale, full scale Intelligence Quotient, attention deficit hyperactivity disorder, electroencephalography and magnetic resonance imaging (MRI). This study concluded that the prognosis for early diagnosed children with PKU treated from the first weeks of life is generally good. However, they are at increased risk for neurological complications and behavioral problems. So, neonatal screening for PKU is highly recommended in Egypt, for early detection and management. In addition, neuropsychological and MRI assessments in PKU children should be done.
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11. Sarajlija A, Kisic-Tepavcevic D, Nikolic Z, Savic Pavicevic D, Obradovic S, Djuric M, Pekmezovic T. {{Epidemiology of Rett Syndrome in Serbia: Prevalence, Incidence and Survival}}. {Neuroepidemiology}. 2015 Jan 7;44(1):1-5.
Background: Rett syndrome (RTT) is a severe neurodevelopmental disorder that represents the second most common cause of mental retardation in females. However, incidence and prevalence of RTT are scarcely reported. Methods: A retrospective study included all patients with RTT diagnosed between 1981 and 2012 in Serbia. Estimation of incidence and prevalence was calculated on the basis of vital statistics reported by Statistical Office of Republic of Serbia. Results: From 1981 to 2012, RTT has been diagnosed in 102 girls in Serbia. Incidence of RTT in Serbia is estimated at 0.586:10,000 female live births. We estimated the prevalence of RTT in population of females younger than 19 years at 1:8,439. Death occurred in 19 patients (18.63%), with pneumonia as the most common cause. The lethal outcome by the age of 12 years could be expected for 11% of patients. The mean age at diagnosis was 3.5 years and we have confirmed a significant trend towards earlier dianosis during studied period. Conclusions: Rett syndrome incidence in Serbia is in accordance with reports from other countries. Serbian RTT patients have increased risk for early death when compared to patients in more developed countries, most commonly due to pneumonia. There was significant trend towards early diagnosis of RTT in Serbia over recent decades. (c) 2015 S. Karger AG, Basel.
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12. Saunders BS, Tilford JM, Fussell JJ, Schulz EG, Casey PH, Kuo DZ. {{Financial and Employment Impact of Intellectual Disability on Families of Children With Autism}}. {Families, systems & health : the journal of collaborative family healthcare}. 2015 Jan 12.
Families of children with autism spectrum disorder (ASD) endure significant financial and employment burden because of their children’s numerous needed services. The study objective is to describe additional impact on families of children with intellectual disability (ID) in addition to ASD. The study is a secondary data analysis of the 2009-2010 National Survey of Children with Special Health Care Needs. Children whose parents answered « yes » when asked whether their child had ASD or ID were classified as having ASD alone (unweighted n = 2,406), ID alone (unweighted n = 1,363), or both ASD/ID (unweighted n = 620). Bivariate and multivariate analyses compared study outcomes of family financial and caregiver burden using ASD as the reference group. All analyses were weighted using person-level estimates. Of children with ASD, 24% also had ID. More than half of caregivers of children with ASD/ID reported financial difficulty (52%) and having to stop work to care for their child (51%). Compared with ASD alone, caregivers of children with both ASD/ID were more likely to report financial difficulty (aOR 1.65, 95% CI 1.10-2.46), cutting work hours (aOR 1.43, 95% CI .98-2.08), and stop working (aOR 2.32, 95% CI 1.57-3.43). No differences were found between caregivers of children with ASD only and ID only. We conclude that having ID in addition to ASD may be associated with greater negative impact on family financial and employment burden. Recognition of ID in addition to ASD is important to tailor the clinical approach and sufficiently support families. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
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13. Skotarczak L, Lee GK. {{Effects of parent management training programs on disruptive behavior for children with a developmental disability: A meta-analysis}}. {Research in developmental disabilities}. 2015 Jan 8;38C:272-87.
This meta-analysis determined the effects of parent management training (PMT) on disruptive behaviors in children with a developmental disability. Parent management training programs, based on behavioral theories of psychology, are commonly used in addressing disruptive behavior in children. Eleven studies met inclusion criteria with a total of 540 participants, with 275 in experimental groups and 265 in control groups. The effect of PMT on the disruptive behavior in children with a developmental disability was significant (g=0.39). The moderator effects of type of PMT, delivery type and setting, and administrator level of education were also significant. The moderator effects of child age, and session number and duration were not significant in this meta-analysis.
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14. Su YE, Su LY. {{Interpretation of Logical Words in Mandarin-Speaking Children with Autism Spectrum Disorders: Uncovering Knowledge of Semantics and Pragmatics}}. {Journal of autism and developmental disorders}. 2015 Jan 11.
This study investigated the interpretation of the logical words ‘some’ and ‘every…or…’ in 4-15-year-old high-functioning Mandarin-speaking children with autism spectrum disorders (ASD). Children with ASD performed similarly to typical controls in demonstrating semantic knowledge of simple sentences with ‘some’, and they had delayed knowledge of the complex sentences with ‘every…or…’. Interestingly, the children with ASD had pragmatic knowledge of the scalar implicatures of these logical words, parallel to those of the typical controls. Taken together, the interpretation of logical words may be a relative strength in children with ASD. It is possible that some aspects of semantics and pragmatics may be selectively spared in ASD, due to the contribution the language faculty makes to language acquisition in the ASD population.
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15. Walsh JA, Maurer D, Vida MD, Rhodes G, Jeffery L, Rutherford MD. {{Norm-based coding of facial identity in adults with autism spectrum disorder}}. {Vision research}. 2015 Jan 6.
It is unclear whether reported deficits in face processing in individuals with autism spectrum disorders (ASD) can be explained by deficits in perceptual face coding mechanisms. In the current study, we examined whether adults with ASD showed evidence of norm-based opponent coding of facial identity, a perceptual process underlying the recognition of facial identity in typical adults. We began with an original face and an averaged face and then created an anti-face that differed from the averaged face in the opposite direction from the original face by a small amount (near adaptor) or a large amount (far adaptor). To test for norm-based coding, we adapted participants on different trials to the near versus far adaptor, then asked them to judge the identity of the averaged face. We varied the size of the test and adapting faces in order to reduce any contribution of low-level adaptation. Consistent with the predictions of norm-based coding, high functioning adults with ASD (n=27) and matched typical participants (n=28) showed identity aftereffects that were larger for the far than near adaptor. Unlike results with children with ASD, the strength of the aftereffects were similar in the two groups. This is the first study to demonstrate norm-based coding of facial identity in adults with ASD.
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16. Weiss D, Mielke C, Wachter T, Bender B, Liscic RM, Scholten M, Naros G, Plewnia C, Gharabaghi A, Kruger R. {{Long-term outcome of deep brain stimulation in fragile X-associated tremor/ataxia syndrome}}. {Parkinsonism & related disorders}. 2014 Dec 27.
INTRODUCTION: Fragile X-associated tremor/ataxia syndrome (FXTAS) presents as complex movement disorder including tremor and cerebellar ataxia. The efficacy and safety of deep brain stimulation of the nucleus ventralis intermedius of the thalamus in atypical tremor syndromes like FXTAS remains to be determined. METHODS: Here, we report the long-term outcome of three male genetically confirmed FXTAS patients treated with bilateral neurostimulation of the nucleus ventralis intermedius for up to four years. RESULTS: All patients demonstrated sustained improvement of both tremor and ataxia – the latter included improvement of intention tremor and axial tremor. Kinematic gait analyses further demonstrated a regularization of the gait cycle. Initial improvements of hand functional disability were not sustained and reached the preoperative level of impairment within one to two years from surgery. CONCLUSION: Our data on patients with a genetic cause of tremor show favorable outcome and may contribute to improved patient stratification for neurostimulation therapy in the future.
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17. White SW, Maddox BB, Panneton RK. {{Fear of Negative Evaluation Influences Eye Gaze in Adolescents with Autism Spectrum Disorder: A Pilot Study}}. {Journal of autism and developmental disorders}. 2015 Jan 13.
Social anxiety is common among adolescents with Autism Spectrum Disorder (ASD). In this modest-sized pilot study, we examined the relationship between social worries and gaze patterns to static social stimuli in adolescents with ASD (n = 15) and gender-matched adolescents without ASD (control; n = 18). Among cognitively unimpaired adolescents with ASD, self-reported fear of negative evaluation predicted greater gaze duration to social threat cues (i.e., faces depicting disgust and anger). By comparison, there was no relationship between self-reported social fears and gaze duration in the controls. These findings call attention to the potential import of the impact of co-occurring psychopathology such as social anxiety, and particularly fear of negative evaluation, on social attention and cognition with adolescents who have ASD.
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18. Wong C, Odom SL, Hume KA, Cox AW, Fettig A, Kucharczyk S, Brock ME, Plavnick JB, Fleury VP, Schultz TR. {{Evidence-Based Practices for Children, Youth, and Young Adults with Autism Spectrum Disorder: A Comprehensive Review}}. {Journal of autism and developmental disorders}. 2015 Jan 13.
The purpose of this study was to identify evidenced-based, focused intervention practices for children and youth with autism spectrum disorder. This study was an extension and elaboration of a previous evidence-based practice review reported by Odom et al. (Prev Sch Fail 54:275-282, 2010b, doi: 10.1080/10459881003785506 ). In the current study, a computer search initially yielded 29,105 articles, and the subsequent screening and evaluation process found 456 studies to meet inclusion and methodological criteria. From this set of research studies, the authors found 27 focused intervention practices that met the criteria for evidence-based practice (EBP). Six new EBPs were identified in this review, and one EBP from the previous review was removed. The authors discuss implications for current practices and future research.
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19. Zamora I, Harley EK, Green SA, Smith K, Kipke MD. {{How sex of children with autism spectrum disorders and access to treatment services relates to parental stress}}. {Autism research and treatment}. 2014;2014:721418.
Parents of children with autism spectrum disorders (ASD) experience higher levels of stress in comparison to parents of neurotypical children and consequently are more susceptible to negative health and social outcomes (Dunn et al., 2001). However, less is known about how individual child characteristics impact stress levels in parents of children with ASD. In this study, we examined the relationship between individual characteristics (i.e., sex) of children with ASD and parental stress. Access to comprehensive treatment services was also examined as a contributing factor to parental stress. Parenting stress was higher for parents of girls than for parents of boys, and for parents of girls (but not boys) fewer services predicted higher parental distress. Findings highlight the importance of providing parents of girls with ASD with more tailored support.
