The Intersection of Faith and Neurodiversity: Unraveling Religiosity in Autistic Adolescents-A Critical Review Analysis.

This literature review aims to explore religiosity, faith, and related beliefs in autistic adolescents. The term religiosity was used interchangeably with various related concepts such as faith, spirituality, and religious beliefs, and a broader, multifaceted approach encompassing the cognitive, subjective, social, cultural, and emotional domains of religiosity is analyzed in this population subgroup. In alignment with the neurodiversity paradigm, this review endeavors to adopt an inclusive lens toward autism spectrum conditions, appreciating the spectrum of cognitive and behavioral differences and highlighting the importance of recognizing strengths and challenges alike, reflecting the nuanced discourse surrounding neurodiversity and autism spectrum conditions. However, terms such as "high-functioning autism" and "disorder" were used where needed to reflect the journals included in the review. A systematic search was conducted by accessing academic search engines such as APA PsycInfo, APA PsycArticles, APA PsycTests, and PubMed. Only peer-reviewed articles written in English and performed on human subjects were included using strict inclusion and exclusion criteria. Several recurring themes were identified from the 13 articles selected after review for relevance and quality. The most important finding was the association of different terminologies and features while exploring "religiosity in autism." Thirty-nine key themes were identified, which were grouped into six major themes. These were religious faith, spirituality, and its expression in autistic adolescents; religious behaviors and practices of autistic adolescents; cognition and religion in autistic teens; social and cultural influences on religiosity in autistic young ones; parents' and carers' influence, perspectives, and experiences about faith and spirituality on autistic adolescents; and perceived benefits of faith to autistic teens: parents and adolescent perspectives. Looking at the concept of religiosity and spirituality as a whole, it can be inferred from the available research included in this review that religiosity (cognitive abilities, behaviors, and experiences) in a subset of autistic adolescents (high-functioning autism) might not be significantly subdued as compared to neurotypical adolescents. However, there is not enough research to conclude the same or the opposite for autistic adolescents in general. When found, reserved religiosity could be attributed to a plethora of factors, and decreased mental ability or mentalization, empathy, or imagination did not seem to be the sole or primary predictors or contributors to religiosity. The role of culture, parents, carers, and religious affiliations was significant and might be a stronger contributor to religiosity and its expression than other previously argued predictors like mentalization. Many autistic teens and their carers regard religiosity and spirituality as essential domains in their and their children's lives, want their children to be given opportunities to be a part of religious groups and affiliations, and look forward to government, religious, and healthcare authorities actively supporting them in this domain. The findings call for policymakers, religious leaders, and stakeholders to devise strategies for inclusion and support for autistic adolescents. The possible role of religion as a resource and coping strategy for these children and their families is worth exploring.

Racial Differences in the Prevalence of Autism Spectrum Disorder: A Systematic Review.

PURPOSE: Racial differences in prevalence rates of autism spectrum disorder (ASD) have shifted in the United States (US) since the 1990s. This review addresses the nature and context of this shift and discusses potential contributing factors and areas for future research. METHODS: Seventeen population-based epidemiological birth cohort studies on ASD prevalence in the US that included race as a variable are included in the review. Studies were identified via a keyword search on PubMed. To be included, studies were required to include race or ethnicity as a variable in the prevalence estimates, include at least 1000 cases with autism, and be published in English by June 3rd, 2023. RESULTS: Results suggest that in nearly all birth cohorts prior to 2010, ASD prevalence rates were highest among White children. ASD prevalence rates among Black, Hispanic, and Asian/Pacific Islander (API) children (22.3, 22.5, and 22.2 per 1000, respectively) surpassed prevalence rates among White children (21.2 per 1000) in the 2010 birth cohort and continued to increase in the 2012 birth cohorts. CONCLUSIONS: There are persistent racial differences in ASD prevalence in the US, and these differences were inverted after 2010, when ASD prevalence among Black, Hispanic, & API children surpassed ASD prevalence among White children. Possible drivers of this racial repatterning of ASD prevalence include changes in ASD screening and diagnosis, changes to health insurance policy, changes to immigration policy, and increased education attainment by minority groups.

Investigating the borders of autism spectrum disorder: lessons from the former diagnosis of pervasive developmental disorder not otherwise specified.

Introduction: Autism Spectrum Disorder (ASD) diagnosis is relatively consensual in typical forms. The margins of the spectrum and their degree of extension, however, are controversial. This has far-reaching implications, which extend beyond theoretical considerations: first, peripheral forms of autism are more prevalent than central forms; second, we do not know how relevant typical-targeted recommendations are for atypical forms. In DSM-IV-TR, these margins of autism were studied within the category of Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS). In spite of its low reliability, this former diagnosis was of particular interest to shed light on the gray area of margins. The aim of this systematic is therefore to investigate the clinical characteristics of PDD-NOS in comparison with Autistic Disorder. Method: A stepwise systematic PRISMA literature review was conducted by searching PubMed and Web Of Science databases to select corresponding studies. Results: The systematic review included 81 studies comprising 6,644 children with PDD-NOS. Cross-sectional and longitudinal studies comparing PDD-NOS and AD showed that PDD-NOS corresponds to milder form of autism with less impact and less associated disorder, with the exception of schizophrenia and mood disorder. Discussion: Our review challenges initial views of PDD-NOS, and shows the clinical relevance of this diagnosis when dealing with the margins of autism, and the de facto diversity included in the spectrum. However, in view of the many limitations of PDD-NOS (low reliability, instability through time, low acceptability), we suggest taxonomic changes in DSM-5: we introduce a new category based on three main dimensions related to socialization impairment, emotional lability and psychotic symptoms. Conclusion: Our review argues for a distinction between AD and PDD-NOS on clinical characteristics and thus highlights the need to study the margins of autism. While the limitations of the PDD-NOS category made it irrelevant to investigate these margins from a research perspective, we believe that a multidimensional approach for mental health professionals taping socialization, emotion lability and psychotic symptoms would be interesting. Our review therefore encourage future studies to test relevant criteria for a new category and possibly identify developmental trajectories, specific interventions and treatments.

Trastornos generalizados del desarrollo: programa de seguimiento post-CDIAP / Trastorns generalitzats del desenvolupament: programa de seguiment post CDIAP / Pervasive developmental disorders: post-CDIAP follow-up programme

Desde el Centro de Desarrollo Infantil y Atención Precoz (CDIAP) del Maresme (Barcelona), organizamos un seguimiento longitudinal una vez finalizada nuestra intervención. En este seguimiento han participado niños con diagnósticos distintos, centrados en el abanico de los trastornos generalizados del desarrollo que se ubican en la órbita de los trastornos del espectro del autismo (TEA). Este seguimiento se realizó entre los años 2016 y 2020, y consistió en visitas presenciales anuales en nuestro servicio, y la aplicación de distintos cuestionarios para progenitores, maestros y terapeutas. En el presente artículo mostramos una parte de los resultados y las conclusiones obtenidas.(AU)

From the Child Development and Early Care Center (CDIAP) of Maresme (Barcelona), we organized a longitudinal follow-up once our intervention has finished. This follow-up has involved children with different diagnoses, focused on the range of pervasive developmental disorders that are located in the orbit of autism spectrum disorders (ASD). This follow-up was carried out between 2016 and 2020 and consisted of annual face-to-face visits to our service, and the application of different questionnaires for parents, teachers, and therapists. In this article, we show part of the results and the conclusions obtained.(AU)

Des del Centre de Desenvolupament Infantil i Atenció Precoç (CDIAP) del Maresme (Barcelona), vam organitzar un seguiment longitudinal un cop finalitzada la nostra intervenció. En aquest seguiment, hi van participar nens amb diagnòstics diferents, centrats en el ventall dels trastorns generalitzats del desenvolupament que s'ubiquen a l'òrbita dels trastorns de l'espectre de l'autisme (TEA). Aquest seguiment es va realitzar entre els anys 2016 i 2020, i va consistir en visites presencials anuals al nostre servei, i en l'aplicació de diferents qüestionaris per a progenitors, mestres i terapeutes. En aquest article, mostrem una part de dels resultats i les conclusions obtingudes.(AU)

Autism in a Child With X-linked Agammaglobulinemia.

A growing evidence base has implicated immune dysfunction in the etiology of some cases of autism spectrum disorder. The precise relationship between immune disorders and autism spectrum disorder remains unclear. Herein we report a 14-year-old-male with agammaglobulinemia, who was diagnosed with autism spectrum disorder, and who has received exogenous immunoglobulins regularly for most of his life. This case study supports current theories implicating antibody deficiencies in some individuals with an autism spectrum disorder. Our case will add to the growing literature of understanding the connection between immune deficiencies in the pathogenesis of autism.

Utilizing Genomically Targeted Molecular Data to Improve Patient-Specific Outcomes in Autism Spectrum Disorder.

Molecular biology combined with genomics can be a powerful tool for developing potential intervention strategies for improving outcomes in children with autism spectrum disorders (ASD). Monogenic etiologies rarely cause autism. Instead, ASD is more frequently due to many polygenic contributing factors interacting with each other, combined with the epigenetic effects of diet, lifestyle, and environment. One limitation of genomics has been identifying ways of responding to each identified gene variant to translate the information to something clinically useful. This paper will illustrate how understanding the function of a gene and the effects of a reported variant on a molecular level can be used to develop actionable and targeted potential interventions for a gene variant or combinations of variants. For illustrative purposes, this communication highlights a specific genomic variant, SHANK3. The steps involved in developing molecularly genomically targeted actionable interventions will be demonstrated. Cases will be shared to support the efficacy of this strategy and to show how clinicians utilized these targeted interventions to improve ASD-related symptoms significantly. The presented approach demonstrates the utility of genomics as a part of clinical decision-making.

Use of selective serotonin and norepinephrine reuptake inhibitors (SNRIs) in the treatment of autism spectrum disorder (ASD), comorbid psychiatric disorders and ASD-associated symptoms: a clinical review.

It is challenging to treat symptoms of autism spectrum disorder (ASD), comorbid psychiatric disorders and ASD-associated symptoms. Some of the commonly used medications to treat these can, and frequently do have serious adverse side effects. Therefore, it is important to identify medications that are effective and with fewer side effects and negative outcomes. In this review, we looked at current evidence available for using the serotonin and norepinephrine reuptake inhibitors (SNRIs) class of medications in treating some of these often difficult to treat symptoms and behaviors. An extensive literature search was conducted using EBSCO.host. Our search algorithm identified 130 articles, 6 of which were deemed to meet criteria for the purpose of this review. Each of these six articles was independently reviewed and critically appraised. As a prototype of the SNRIs family, venlafaxine was found to be a useful adjuvant in children and adults with ASD for the treatment of self-injurious behaviors, aggression, and ADHD symptoms when used in doses lower than its antidepressant dosage. However, duloxetine was not found to show any added benefit in treatment of any of the comorbid symptoms and behaviors in ASD when compared to other antidepressants. On the other hand, milnacipran was reported to produce improvements in impulsivity, hyperactivity symptoms, and social functioning through reduction of inattention of ADHD when comorbid with ASD. Overall, SNRIs were shown variable effectiveness in treatment of these comorbid symptoms and behaviors in ASD.

Rehabilitation Treatment of Medulloblastoma in a Patient with Pervasive Developmental Disorder（Autism Spectrum Disorder） / The Japanese Journal of Rehabilitation Medicine

We provided inpatient rehabilitation treatment and return-to-school guidance to a junior high school student with medulloblastoma and pervasive developmental disorder (autism spectrum disorder). Here we describe the rehabilitation treatment for patients with physical and developmental disabilities. A 13-year-old boy who was diagnosed with pervasive developmental disorder at 4 years of age was able to perform activities of daily living independently and attend junior high school. However, he was admitted to our hospital with new-onset ataxia. Magnetic resonance imaging revealed a cerebellar tumor. After total tumor excision was performed, pathological analysis revealed medulloblastoma, which was treated initially with radiation therapy and then chemotherapy for 1 year. Rehabilitation was initiated 2 days post-surgery. We evaluated his communication abilities. He showed stereotypical behavior owing to the autism spectrum disorder；therefore, we performed low-intensity repetitive exercises. The functional independence measure score at discharge was 67/126 (motor 44/91, cognitive 23/35). We taught his teachers how to properly assist him, and he successfully returned to school post-discharge. Although this was a case in which the child had multiple disabilities, ataxia caused by the medulloblastoma aggravated his developmental disability. Thus, understanding the characteristics of communication and its strengths was vital in determining a treatment plan that enabled his return to school.

Rehabilitation Treatment of Medulloblastoma in a Patient with Pervasive Developmental Disorder（Autism Spectrum Disorder） / The Japanese Journal of Rehabilitation Medicine

We provided inpatient rehabilitation treatment and return-to-school guidance to a junior high school student with medulloblastoma and pervasive developmental disorder (autism spectrum disorder). Here we describe the rehabilitation treatment for patients with physical and developmental disabilities. A 13-year-old boy who was diagnosed with pervasive developmental disorder at 4 years of age was able to perform activities of daily living independently and attend junior high school. However, he was admitted to our hospital with new-onset ataxia. Magnetic resonance imaging revealed a cerebellar tumor. After total tumor excision was performed, pathological analysis revealed medulloblastoma, which was treated initially with radiation therapy and then chemotherapy for 1 year. Rehabilitation was initiated 2 days post-surgery. We evaluated his communication abilities. He showed stereotypical behavior owing to the autism spectrum disorder；therefore, we performed low-intensity repetitive exercises. The functional independence measure score at discharge was 67/126 (motor 44/91, cognitive 23/35). We taught his teachers how to properly assist him, and he successfully returned to school post-discharge. Although this was a case in which the child had multiple disabilities, ataxia caused by the medulloblastoma aggravated his developmental disability. Thus, understanding the characteristics of communication and its strengths was vital in determining a treatment plan that enabled his return to school.

Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence.

Autism spectrum disorder (ASD) pathophysiology is not completely understood; however, altered inflammatory response and glutamate signaling have been reported, leading to the investigation of molecules targeting the immune-glutamatergic system in ASD treatment. Palmitoylethanolamide (PEA) is a naturally occurring saturated N-acylethanolamine that has proven to be effective in controlling inflammation, depression, epilepsy, and pain, possibly through a neuroprotective role against glutamate toxicity. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in ASD. Studies indicate altered serum/brain levels of PEA and other endocannabinoids (ECBs)/acylethanolamines (AEs) in ASD. Altered PEA signaling response to social exposure and altered expression/activity of enzymes responsible for the synthesis and catalysis of ECBs/AEs, as well as downregulation of the peroxisome proliferator activated receptor-α (PPAR-α) and cannabinoid receptor target GPR55 mRNA brain expression, have been reported. Stress and exposure to exogenous cannabinoids may modulate ECBs/AEs levels and expression of candidate genes for neuropsychiatric disorders, with implications for ASD. Limited research suggests that PEA supplementation reduces overall autism severity by improving language and social and nonsocial behaviors. Potential neurobiological underpinnings include modulation of immune response, neuroinflammation, neurotrophy, apoptosis, neurogenesis, neuroplasticity, neurodegeneration, mitochondrial function, and microbiota activity, possibly through peroxisome proliferator-activated receptor-α (PPAR-α) activation.

The Efficacy of Early Start Denver Model Intervention in Young Children with Autism Spectrum Disorder Within Japan: A Preliminary Study.

OBJECTIVES: Among the many intervention programs for children with autism spectrum disorder (ASD), the Early Start Denver Model (ESDM) is one of the few approaches that has succeeded in demonstrating clinical efficacy in randomized control trials. Here, we inves-tigate the clinical efficacy of ESDM intervention in young children with ASD in a community setting within Japan. METHODS: All subjects were children with ASD who received ESDM intervention during the study period. Each ESDM session lasted 75 min and occurred once per week for at least 12 weeks. The outcome measures consisted of the Kyoto Scale of Psychological Develop-ment (K-test), Aberrant Behavior Checklist-Japanese version (ABC-J), and the Clinical Global Impression-Severity scale (CGI-S). RESULTS: Twenty-seven subjects (29.4±6.4 months old) received ESDM intervention that lasted for 8.0±2.6 months on average. The score on Language and Social developmental quotient on the K-test increased significantly after the intervention. The total scores on the ABC-J and CGI-S significantly decreased after completion of the ESDM intervention. CONCLUSION: Our results suggest that ESDM intervention could reduce the severity of distinct clinical features of ASD, such as impair-ments in social interaction and communication assessed by the K-test, and maladaptive behavior rated by the ABC-J and CGI-S. We be-lieve that the ESDM adapted to each institution might become one of the standard options for children with ASD in Japan.

Quantifying Therapists' Activities during Sensory Integration Treatment for Young Children with Autism.

AIMS: There is limited research on the type and quantity of actions (activities) occupational therapy practitioners utilize when providing sensory integration treatment to children with Autism Spectrum Disorders (ASD). METHODS: A coding scheme identifying specific aspects of sensory integration treatment was developed and used to analyze 34 videos of 9 children with ASD, aged between 18 and 56 months, treated by 8 occupational therapists. Occupational therapists providing sensory integration treatment to children with ASD were behaviorally coded and rated using Observer XT, a software package designed for analysis of behavioral processes. RESULTS: Verbal communications, including offers, positive commands, and feedback, to facilitate engagement were the most frequent actions enacted by therapists. Proprioceptive activities were the most frequent sensory opportunities presented. Therapists received high ratings for sensitivity qualities. CONCLUSIONS: The number of sensory opportunities and interactions the therapists provided suggest concordance with sensory integration treatment components in the clinical setting. General impression ratings indicate engagement between child and therapist may be an important aspect of sensory integration treatment for young children with ASD. Quantification of therapists' actions can provide insight into the moment-to-moment decision-making and relationships between therapist and child during daily practice of sensory integration treatment.

Practitioner Review: Pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis.

BACKGROUND: Clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta-analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the treatment of ADHD symptoms in ASD and (b) distil findings for clinical translation. METHODS: We searched electronic databases and clinical trial registries (1992 onwards). We selected randomized controlled trials conducted in participants <25 years of age, diagnosed with ASD that evaluated ADHD outcomes (hyperactivity/impulsivity and inattention) following treatment with stimulants (methylphenidate or amphetamines), atomoxetine, alpha-2 adrenergic receptor agonists, antipsychotics, tricyclic antidepressants, bupropion, modafinil, venlafaxine, or a combination, in comparison with placebo, any of the listed medications, or behavioral therapies. Data were pooled using a random-effects model. RESULTS: Twenty-five studies (4 methylphenidate, 4 atomoxetine, 1 guanfacine, 14 antipsychotic, 1 venlafaxine, and 1 tianeptine) were included. Methylphenidate reduced hyperactivity (parent-rated: standardized mean difference [SMD] = -.63, 95%CI = -.95,-.30; teacher-rated: SMD = -.81, 95%CI = -1.43,-.19) and inattention (parent-rated: SMD = -.36, 95%CI = -.64,-.07; teacher-rated: SMD = -.30, 95%CI = -.49,-.11). Atomoxetine reduced inattention (parent-rated: SMD = -.54, 95%CI = -.98,-.09; teacher/investigator-rated: SMD = -0.38, 95%CI = -0.75, -0.01) and parent-rated hyperactivity (parent-rated: SMD = -.49, 95%CI = -.76,-.23; teacher-rated: SMD = -.43, 95%CI = -.92, .06). Indirect evidence for significant reductions in hyperactivity with second-generation antipsychotics was also found. Quality of evidence for all interventions was low/very low. Methylphenidate was associated with a nonsignificant elevated risk of dropout due to adverse events. CONCLUSIONS: Direct pooled evidence supports the efficacy and tolerability of methylphenidate or atomoxetine for treatment of ADHD symptoms in children and youth with ASD. The current review highlights the efficacy of standard ADHD pharmacotherapy for treatment of ADHD symptoms in children and youth with ASD. Consideration of the benefits weighed against the limitations of safety/efficacy data and lack of data evaluating long-term continuation is undertaken to help guide clinical decision-making regarding treatment of co-occurring ADHD symptoms in children and youth with ASD.

Common and unique multimodal covarying patterns in autism spectrum disorder subtypes.

BACKGROUND: The heterogeneity inherent in autism spectrum disorder (ASD) presents a substantial challenge to diagnosis and precision treatment. Heterogeneity across biological etiologies, genetics, neural systems, neurocognitive attributes and clinical subtypes or phenotypes has been observed across individuals with ASD. METHODS: In this study, we aim to investigate the heterogeneity in ASD from a multimodal brain imaging perspective. The Autism Diagnostic Observation Schedule (ADOS) was used as a reference to guide functional and structural MRI fusion. DSM-IV-TR diagnosed Asperger's disorder (n = 79), pervasive developmental disorder-not otherwise specified [PDD-NOS] (n = 58) and Autistic disorder (n = 92) from ABIDE II were used as discovery cohort, and ABIDE I (n = 400) was used for replication. RESULTS: Dorsolateral prefrontal cortex and superior/middle temporal cortex are the primary common functional-structural covarying cortical brain areas shared among Asperger's, PDD-NOS and Autistic subgroups. Key differences among the three subtypes are negative functional features within subcortical brain areas, including negative putamen-parahippocampus fractional amplitude of low-frequency fluctuations (fALFF) unique to the Asperger's subtype; negative fALFF in anterior cingulate cortex unique to PDD-NOS subtype; and negative thalamus-amygdala-caudate fALFF unique to the Autistic subtype. Furthermore, each subtype-specific brain pattern is correlated with different ADOS subdomains, with social interaction as the common subdomain. The identified subtype-specific patterns are only predictive for ASD symptoms manifested in the corresponding subtypes, but not the other subtypes. CONCLUSIONS: Although ASD has a common neural basis with core deficits linked to social interaction, each ASD subtype is strongly linked to unique brain systems and subdomain symptoms, which may help to better understand the underlying mechanisms of ASD heterogeneity from a multimodal neuroimaging perspective. LIMITATIONS: This study is male based, which cannot be generalized to the female or the general ASD population.

An Overview of the Main Genetic, Epigenetic and Environmental Factors Involved in Autism Spectrum Disorder Focusing on Synaptic Activity.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects social interaction and communication, with restricted interests, activity and behaviors. ASD is highly familial, indicating that genetic background strongly contributes to the development of this condition. However, only a fraction of the total number of genes thought to be associated with the condition have been discovered. Moreover, other factors may play an important role in ASD onset. In fact, it has been shown that parental conditions and in utero and perinatal factors may contribute to ASD etiology. More recently, epigenetic changes, including DNA methylation and micro RNA alterations, have been associated with ASD and proposed as potential biomarkers. This review aims to provide a summary of the literature regarding ASD candidate genes, mainly focusing on synapse formation and functionality and relevant epigenetic and environmental aspects acting in concert to determine ASD onset.

[Autism spectrum disorder in childhood and adults: diagnosis and differential diagnoses]. / Autismus-Spektrum-Störungen im Kindes- und Erwachsenenalter: Diagnose und Differenzialdiagnosen.

Autistic disorders are summarized in DSM­5 under the term autism spectrum disorder (ASD) and are severe, lifelong, pervasive neurodevelopmental disorders. Core features manifested even in childhood are impairments in social interaction and communication as well as restricted and repetitive behavior. The intensity of symptoms, language and cognitive impairments vary but the majority of affected individuals have below average intelligence and 80% have at least one comorbid disorder. The diverse pathology and heterogeneity in phenotypes are caused by a complex genetic etiology, which is associated with a reduced synaptic plasticity of neural networks. The disorder is associated with a clearly reduced quality of life as well as a high familial burden. The differential diagnostics have a high relevance and the diagnosis should be carried out by specialized institutions. Behavioral therapeutic interventions are indicated.

Commentary: Demand Avoidance Phenomena, a manifold issue? Intolerance of uncertainty and anxiety as explanatory frameworks for extreme demand avoidance in children and adolescents - a commentary on Stuart et al. (2020).

Demand Avoidance Phenomena (DAP) is a neutral term for Pathological Demand Avoidance, which is sometimes conceptualised as an autism subtype. There is much ongoing controversy around the construct. In this commentary, I attempt to contextualise the recent article, Intolerance of Uncertainty and anxiety (Stuart et al., 2019) within wider discourses. This discussion provides tentative support for monotropism autism theory and the growing body of research indicating that DAP may not be developmentally persistent (a high rate of persons not meeting clinical threshold into adulthood). Going forward I would suggest that Stuart and colleagues' research should be replicated, in order to add to the DAP literature.

Down syndrome as a genetic model to evaluate the role of oxidative stress and transsulfuration abnormalities in autism spectrum disorder: A 10-year longitudinal cohort study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which evidence reveals oxidative stress and transsulfuration pathway abnormalities. Down syndrome (DS) is a genetic disorder characterized by similar oxidative stress and transsulfuration pathway abnormalities. This hypothesis-testing longitudinal cohort study determined whether transsulfuration abnormalities and oxidative stress are important susceptibility factors in ASD etiology by evaluating the rate of ASD diagnoses in DS as compared to the general population. The Independent Healthcare Research Database was analyzed for healthcare records prospectively generated in Florida Medicaid. A cohort of 101,736 persons (born: 1990-1999) with ≥10 outpatient office visits and continuously followed for 120 months after birth was examined. There were 942 children in the DS cohort (ICD-9 code: 758.0) and 100,749 children in the undiagnosed cohort (no DS diagnosis). ASD diagnoses were defined as autistic disorder (ICD-9 code: 299.00) or Asperger's disorder/pervasive developmental disorder-not otherwise specified (ICD-9 code: 299.80). ASDs were diagnosed in 5.31% of the DS cohort and 1.34% of the undiagnosed cohort. The risk ratio of being diagnosed with an ASD in the DS cohort as compared to the undiagnosed cohort was 3.97-fold significantly increased with a risk difference of 3.97%. Among children diagnosed with DS, less than 6% were also diagnosed with an ASD. Among children diagnosed with an ASD, less than 5% were also diagnosed with DS. Children diagnosed with DS are apparently more susceptible to ASD diagnosis relative to the general population suggesting oxidative stress and transsulfuration pathway abnormalities are important susceptibility factors in ASD.

Quantitative facial expression analysis revealed the efficacy and time course of oxytocin in autism.

Discrepancies in efficacy between single-dose and repeated administration of oxytocin for autism spectrum disorder have led researchers to hypothesize that time-course changes in efficacy are induced by repeated administrations of the peptide hormone. However, repeatable, objective, and quantitative measurement of autism spectrum disorder's core symptoms are lacking, making it difficult to examine potential time-course changes in efficacy. We tested this hypothesis using repeatable, objective, and quantitative measurement of the core symptoms of autism spectrum disorder. We examined videos recorded during semi-structured social interaction administered as the primary outcome in single-site exploratory (n = 18, crossover within-subjects design) and multisite confirmatory (n = 106, parallel-group design), double-blind, placebo-controlled 6-week trials of repeated intranasal administrations of oxytocin (48 IU/day) in adult males with autism spectrum disorder. The main outcomes were statistical representative values of objectively quantified facial expression intensity in a repeatable part of the Autism Diagnostic Observation Schedule: the maximum probability (i.e. mode) and the natural logarithm of mode on the probability density function of neutral facial expression and the natural logarithm of mode on the probability density function of happy expression. Our recent study revealed that increases in these indices characterize autistic facial expression, compared with neurotypical individuals. The current results revealed that oxytocin consistently and significantly decreased the increased natural logarithm of mode on the probability density function of neutral facial expression compared with placebo in exploratory (effect-size, -0.57; 95% CI, -1.27 to 0.13; P = 0.023) and confirmatory trials (-0.41; -0.62 to -0.20; P < 0.001). A significant interaction between time-course (at baseline, 2, 4, 6, and 8 weeks) and the efficacy of oxytocin on the natural logarithm of mode on the probability density function of neutral facial expression was found in confirmatory trial (P < 0.001). Post hoc analyses revealed maximum efficacy at 2 weeks (P < 0.001, Cohen's d = -0.78; 95% CI, -1.21 to -0.35) and deterioration of efficacy at 4 weeks (P = 0.042, Cohen's d = -0.46; 95% CI, -0.90 to -0.01) and 6 weeks (P = 0.10, Cohen's d = -0.35; 95% CI, -0.77 to 0.08), while efficacy was preserved at 2 weeks post-treatment (i.e. 8 weeks) (P < 0.001, Cohen's d = -1.24; 95% CI, -1.71 to -0.78). Quantitative facial expression analyses successfully verified the positive effects of repeated oxytocin on autistic individuals' facial expressions and demonstrated a time-course change in efficacy. The current findings support further development of an optimized regimen of oxytocin treatment.

Efficacy and safety of memantine in children with autism spectrum disorder: Results from three phase 2 multicenter studies.

Three phase 2 trials were conducted to assess the efficacy and long-term safety of weight-based memantine extended release (ER) treatment in children with autism spectrum disorder. MEM-MD-91, a 50-week open-label trial, identified memantine extended-release treatment responders for enrollment into MEM-MD-68, a 12-week randomized, double-blind, placebo-controlled withdrawal trial. MEM-MD-69 was an open-label extension trial in which participants from MEM-MD-68, MEM-MD-91, and open-label trial MEM-MD-67 were treated ⩽48 weeks with memantine extended release. In MEM-MD-91, 517 (59.6%) participants were confirmed Social Responsiveness Scale responders at week 12; mean Social Responsiveness Scale total raw scores improved two to three times a minimal clinically important difference of 10 points. In MEM-MD-68, there was no difference between memantine and placebo on the primary efficacy parameter, the proportion of patients with a loss of therapeutic response (defined as ⩾10-point increase from baseline in Social Responsiveness Scale total raw score). MEM-MD-69 exploratory analyses revealed mean standard deviation improvement in Social Responsiveness Scale total raw score of 32.4 (26.4) from baseline of the first lead-in study. No new safety concerns were evident. While the a priori-defined efficacy results of the double-blind trial were not achieved, the considerable improvements in mean Social Responsiveness Scale scores from baseline in the open-label trials were presumed to be clinically important.