1. Brien A, Hutchins T. Development of a Manualized Intervention to Support Episodic Memory in Autistic Children: Elaborative Reminiscing Is Key. Semin Speech Lang;2022 (Aug);43(4):299-315.

Episodic memory (EM) is memory for past personal experiences. EM and social development are inextricably linked, and both are impacted in autistic persons. Parents of autistic children can be taught to engage in a unique conversational style (i.e., elaborative reminiscing) to support a child’s memory and social development. This article discusses the importance of EM in autism and describes a new manualized caregiver training to support EM in autistic children. An uncontrolled pre-post study design was employed to test proof of concept. Results affirmed the potential of this intervention for increasing caregivers’ elaborateness and improving children’s EM in a family-centered, naturalistic way. Results suggest that further treatment development and examination of effectiveness are needed. We argue that these kinds of intervention are important: not only is EM theoretically potent for social cognitive development, it is essential for a sense of self-determination, social connection, and psychological well-being.

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2. Cervantes PE, Conlon GR, Seag DE, Feder M, Lang Q, Meril S, Baroni A, Li A, Hoagwood KE, Horwitz SM. Mental health service availability for autistic youth in New York City: An examination of the developmental disability and mental health service systems. Autism;2022 (Jul 27):13623613221112202.

Autistic children and adolescents experience high rates of co-occurring mental health conditions, including depression and suicidality, which are frequently identified by stakeholders as treatment priorities. Unfortunately, accessing community-based mental health care is often difficult for autistic youth and their families. The first obstacle families confront is finding a provider that offers mental health treatment to autistic youth within the many service systems involved in supporting the autism community. The mental health and developmental disability systems are two of the most commonly accessed, and previous work has shown there is often confusion over which of these systems is responsible for providing mental health care to autistic individuals. In this study, we conducted a telephone survey to determine the availability of outpatient mental health services for autistic youth with depressive symptoms or suicidal thoughts or behaviors in New York City across the state’s mental health and developmental disability systems. Results showed that while a greater percentage of clinics in the mental health system compared with in the developmental disability system offered outpatient mental health services to autistic youth (47.1% vs 25.0%), many more did not offer care to autistic youth and there were very few options overall. Therefore, it is important that changes to policy are made to increase the availability of services and that mental health care providers’ knowledge and confidence in working with autistic youth are improved.

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3. Coorey B, Haase F, Ellaway C, Clarke A, Lisowski L, Gold WA. Gene Editing and Rett Syndrome: Does It Make the Cut?. CRISPR J;2022 (Jul 26)

Rett syndrome (RTT) is a rare neurogenetic disorder caused by pathogenic variants of the Methyl CpG binding protein 2 (MECP2) gene. The RTT is characterized by apparent normal early development followed by regression of communicative and fine motor skills. Comorbidities include epilepsy, severe cognitive impairment, and autonomic and motor dysfunction. Despite almost 60 clinical trials and the promise of a gene therapy, no cure has yet emerged with treatment remaining symptomatic. Advances in understanding RTT has provided insight into the complexity and exquisite control of MECP2 expression, where loss of expression leads to RTT and overexpression leads to MECP2 duplication syndrome. Therapy development requires regulated expression that matches the spatiotemporal endogenous expression of MECP2 in the brain. Gene editing has revolutionized gene therapy and promises an exciting strategy for many incurable monogenic disorders, including RTT, by editing the native locus and retaining endogenous gene expression. Here, we review the literature on the currently available editing technologies and discuss their limitations and applicability to the treatment of RTT.

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4. Crooke PJ, Winner MG. Social Thinking Metacognitive Strategies to Support Self-Determined Social Goals in Autistic Youth. Semin Speech Lang;2022 (Aug);43(4):277-298.

On any given day, the social mind is taxed with attending to and making sense of a myriad of social events. The social mind is at work when trying to imagine the experiences of others and their inner mental worlds, and is equally active when people seek to approach, connect with, and sometimes avoid one another. Ultimately, the social mind is responsible for thinking about (social) thinking, or social metacognition. Social metacognitive teaching strategies can be helpful for supporting social learners as they observe social landscapes, interpret what is observed to problem solve, or decide whether and how to produce social responses. This article describes how social metacognitive strategies from the Social Thinking Methodology have been used to support the self-determined social goals of two autistic students. Visual frameworks and their underlying theories are provided as evidence-aligned tools for supporting clinical journeys.

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5. Del Casale A, Ferracuti S, Alcibiade A, Simone S, Modesti MN, Pompili M. Neuroanatomical correlates of autism spectrum disorders: A meta-analysis of structural magnetic resonance imaging (MRI) studies. Psychiatry Res Neuroimaging;2022 (Jul 20);325:111516.

Autism spectrum disorders (ASD) are neurodevelopmental disorders correlated to various neuroanatomical modifications. We aimed to identify neuroanatomical changes assessed in magnetic resonance imaging (MRI) studies of autism spectrum disorder (ASD) through Activation Likelihood Estimate (ALE) meta-analysis. We included 19 peer-reviewed magnetic resonance imaging (MRI) studies that analyzed cortical volume in patients with ASD compared to healthy control subjects (HCs). The between-group analyses comparing subjects with ASD to HCs showed a volumetric reduction of a large cluster in the right brain, including the uncus/amygdala, parahippocampal gyrus, and entorhinal cortex, and putamen. The anomalies are primarily found in the right hemisphere, involved in social cognitive function, particularly impaired in ASD. These results correlate with several clinical aspects of ASD. These volumetric alterations can be considered a major correlate of disease in the context of multifactorial etiology. Further studies on brain lateralization in ASD are needed, considering the clinical phenotype variability of these disorders.

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6. Feng H, Mahoor MH, Dino F. Corrigendum: A Music-Therapy Robotic Platform for Children With Autism: A Pilot Study. Front Robot AI;2022;9:965369.

[This corrects the article DOI: 10.3389/frobt.2022.855819.].

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7. Fremion E, Cowley R, Berens J, Staggers KA, Kemere KJ, Kim JL, Acosta E, Peacock C. Improved health care transition for young adults with developmental disabilities referred from designated transition clinics. J Pediatr Nurs;2022 (Jul 23);67:27-33.

PURPOSE: Young adults with intellectual/developmental disabilities (YAIDD) are a vulnerable population during HCT due to their complex care coordination and adaptive needs, yet factors associated with transition preparedness are not well defined. We aimed to determine factors associated with health care transition (HCT) preparation satisfaction for YAIDD establishing care with an adult medical home. DESIGN AND METHODS: 408 YAIDD or their families completed the HCT Feedback Survey 2.0 upon establishing adult care. Logistic regression models were used to determine associations between a composite of six HCT Feedback Survey questions that most correlated with the 2019 National Survey of Children’s Health transition questions. RESULTS: YADD who had HCT preparation visits with a designated HCT clinic were 9 times more likely to have met all six composite HCT criteria after controlling for the number of technologies required and race/ethnicity (adj OR 9.04, 95% CI: 4.35, 18.76) compared to those referred from the community. Compared to patients who were referred from the community, the odds of feeling very prepared versus somewhat or not prepared were 3.7 times higher (adj OR 3.73, 95% CI: 1.90, 7.32) among patients referred from a designated HCT program. CONCLUSIONS: YAIDD who participated in a structured HCT program prior to transfer to adult care experienced higher transition preparation satisfaction. PRACTICAL IMPLICATIONS: A structured HCT clinic model to prepare adolescents with DD for transition to adult care may improve HCT preparation satisfaction for this population.

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8. Hutchins TL. A Review of the Nature and Development of Humor Appreciation and Considerations for Teaching Humor to Autistic Persons. Semin Speech Lang;2022 (Aug);43(4):347-360.

The development of humor is complex and heterogeneous within and across neurotypical and neurodivergent groups. Some autistics develop differences (not deficits) in humor appreciation, whereas others report difficulties « getting the joke » and identify this as in need of support. This is important because humor appreciation and comprehension are linked to psychological well-being and social success. This article describes the therapeutic potential for teaching humor comprehension to autistic persons and the benefit of broader education efforts to forge an understanding of the value of « different senses of humor. » The nature and development of humor comprehension in neurotypical development and autism are reviewed. Considerations for whether and how to teach humor comprehension are offered that maximize goodness-of-fit, prioritize autistic autonomy, and promote the sharing and appreciation of different kinds of « funny. »

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9. Hutchins TL. A Review of the Nature and Development of Lying and Deception and Considerations for Teaching Prosocial Lying to Autistic Persons. Semin Speech Lang;2022 (Aug);43(4):316-330.

Compared with their neurotypical (NT) counterparts, persons with autism appear to be less inclined to tell lies and less skilled in delivering sophisticated forms of deception. At the same time, some forms of deception like white lies and prosocial lies are frequent in human interaction because they are important for social success. This article challenges the reader to evaluate the therapeutic potential for prosocial deception and teaching white-lie telling to autistic persons. The nature and development of antisocial and prosocial lying in NT development and autism are reviewed. Considerations for when to (and when not to) teach the skill of empathic lying are discussed and recommendations for how to teach the comprehension and production of prosocial lies are offered.

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10. Jenabi E, Bashirian S, Salehi AM, Khazaei S. Not breastfeeding and risk of autism spectrum disorders among children: a meta-analysis. Clin Exp Pediatr;2022 (Jul 19)

To our knowledge, this is the first meta-analysis of the association of not breastfeeding and the risk of autism spectrum disorder (ASD) based on observational studies. Three databases (PubMed, Web of Science, and Scopus) were systematically searched until December 2021. Heterogeneity was determined using the chi-square test and its quantity was measured using the I2 statistic. The Begg’s line regression test was used to assess publication bias. A random-effects model was used to analyze the data. Seven studies were included in this meta-analysis. The total study population included 3,270 individuals. According to the random-effects model, the estimated odds ratio of the risk of ASD associated with not breastfeeding was 1.81 (95% confidence interval, 1.35-2.27; I2=0.0%). The results of the included studies were homogeneous. Our findings showed that not breastfeeding is a risk factor for ASD. These results suggest the importance of breastfeeding in decreasing the risk of ASD in children.

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11. Kim I, Dababnah S, Wang Y, Reyes C. Diagnostic Process and Barriers Among Chinese-American and Korean-American Parents of Children with Autism. J Dev Behav Pediatr;2022 (Aug 1);43(6):327-334.

OBJECTIVE: We sought to understand the experiences of Chinese-American and Korean-American parents of children with autism, including their initial concerns regarding their child’s development, reported health professionals’ responses to these concerns, diagnostic barriers, and factors associated with early autism diagnosis. METHOD: We designed a survey with support from an expert advisory group and Asian-American parents of children with autism. We measured 3 time points of diagnostic history, areas of parents’ concerns, professionals’ responses to their concerns, 15 types of diagnostic barriers, and professionals’ helpfulness. We used descriptive and independent t tests to analyze data from 28 parents of children with autism. RESULTS: Most of the parents (86%) had early concerns about their children’s developmental delays and expressed their concerns to health professionals. However, approximately 60% of the parents reported that the professionals did not conduct developmental screenings or make referrals to specialists. The most common diagnostic barrier was the stress of the diagnostic process, followed by navigating health care systems. Parents who required interpreters noted poor quality and unavailability. Early child developmental concerns were associated with early autism diagnoses. CONCLUSION: Although many Chinese-American and Korean-American parents had early concerns regarding their child’s development and shared their concerns with health care professionals, parents encountered many barriers, including the stress of the diagnostic process. Chinese-American and Korean-American parents with limited English proficiency required additional support. Health care professionals’ active listening and responses to parents’ concerns can promote early diagnosis.

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12. MacKenzie KT, Mazefsky CA, Eack SM. Obtaining a First Diagnosis of Autism Spectrum Disorder: Descriptions of the Diagnostic Process and Correlates of Parent Satisfaction from a National Sample. J Autism Dev Disord;2022 (Jul 27)

Obtaining an autism spectrum disorder (ASD) diagnosis is often challenging for parents. The purpose of this study was to better understand this process and examine how elements of the process may influence parent satisfaction. A total of 406 parents of autistic children participated. Participants were administered a survey covering the ASD diagnostic process. Parents had developmental concerns early but experienced long wait times and usually attended many appointments. Mean diagnostic age was 3.26 years and overall delay was 1.20 years. Stress and being told there was « no problem » were significantly associated with parental satisfaction with the process. Findings provide insight into challenges experienced by families of autistic children and can help pinpoint areas where the diagnostic process may be improved.

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13. McDonald RG, Khawar S, Yacoub N, Cargill MI, Lerner MD, Kang E. Performance- and Theater-Based Interventions for Supporting Social Cognition and Social Communication in Autistic Youth: A Review and Theoretical Synthesis. Semin Speech Lang;2022 (Aug);43(4):255-276.

Social skills interventions (SSIs) are commonly used to improve social functioning in youth with autism spectrum disorder (ASD), which is a condition characterized by differences in social cognition and social communication. Although more traditional SSIs have used knowledge-based, didactic instruction, recent research has explored the utility of performance-based SSIs, which use various activities to support implicit learning of social skills in supportive, enriched environments. This article reviews the extant literature evaluating the effectiveness or efficacy of five performance-based SSIs using theater-based approaches on social cognition and social communication. Overall, this body of literature suggests social communication gains that include increased peer interactions, peer liking, and reciprocal friendships, as well as social cognitive gains in theory of mind and affect recognition. This review also discusses theoretical models that may help explain the emerging strengths of performance- and theater-based SSIs with underlying hypotheses related to the social communication and social cognitive differences in ASD. Limitations of performance-based SSIs in the evidence-base include several approaches in initial stages of research with small sample sizes and limited maintenance of effects. Future research should aim to bridge the research-to-practice gap and use more rigorous designs and more diverse samples, including those with cooccurring intellectual disability.

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14. Narzisi A. Haste Makes Waste: There Is No Solid Evidence to Translate the Use of Stem Cells into Clinical Practice for Children with Autism Spectrum Disorder. Brain Sci;2022 (Jul 27);12(8)

Increasingly, private clinics around the world offer stem cell therapy as a therapeutic approach for autism spectrum disorder (ASD) […].

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15. Panzenhagen AC, Cavalcanti A, Stein DJ, de Castro LL, Vasconcelos M, Abreu MB, Almeida RF, Bertoglio LJ, Herrmann AP. Behavioral manifestations in rodent models of autism spectrum disorder: protocol for a systematic review and network meta-analysis. Syst Rev;2022 (Jul 26);11(1):150.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with severe social communication, interaction, and sensory processing impairments. Efforts to understand its etiology and pathophysiology are crucial for improving treatment and prevention measures. Preclinical models of ASD are essential for investigating the biological mechanisms and should present translatability potential. We aim to evaluate the consistency of the most commonly used rodent models of ASD in displaying autistic-like behavior through a systematic review and meta-analysis. METHODS: This review will focus on the most frequently used autism models, surveying studies of six genetic (Ube3a, Pten, Nlgn3, Shank3, Mecp2, and Fmr1), three chemically induced (valproic acid (VPA), lipopolysaccharide (LPS), and polyinosinic:polycytidylic acid (poly(I:C))), and one inbred model (BTBR T+ Itpr3tf/J mouse strain). Two independent reviewers will screen the records. Data extraction of behavioral outcomes and risk of bias evaluation will be performed. We will conduct a meta-analysis whenever at least five studies investigate the same model and behavioral outcome. We will also explore the heterogeneity and publication bias. Network meta-analyses are planned to compare different models. DISCUSSION: By shortening the gap between animal behavior and human endophenotypes or specific clinical symptoms, we expect to help researchers on which rodent models are adequate for research of specific behavioral manifestations of autism, which potentially require a combination of them depending on the research interest. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021226299 .

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16. Pietropaolo S, Provenzano G. Editorial: Targeting Excitation-Inhibition Imbalance in Neurodevelopmental and Autism Spectrum Disorders. Front Neurosci;2022;16:968115.

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17. Smith E, Stogios N, Au E, Maksyutynska K, De R, Ji A, Sørensen ME, John LS, Lin HY, Desarkar P, Lunsky Y, Remington G, Hahn M, Agarwal SM. The Metabolic Adverse Effects of Antipsychotic Use in Individuals with Intellectual and/or Developmental Disability (IDD): A Systematic Review and Meta-Analysis. Acta Psychiatr Scand;2022 (Jul 27)

OBJECTIVE: Individuals with intellectual and/or developmental disability (IDD) are often prescribed antipsychotics (APs). However, despite their known propensity to cause metabolic adverse effects, including weight gain, diabetes, and increased risk of cardiovascular events, there is currently a limited body of literature describing the metabolic consequences of AP use in this population. METHODS: We searched MEDLINE, EMBASE, PsychINFO, CENTRAL and CINAHL databases to identify all randomized trials that reported on the metabolic effects of APs in individuals with IDD. Random effects meta-analyses were used to examine weight gain as both a continuous and dichotomous outcome. RESULTS: Eighteen randomized trials met our inclusion criteria with a total of 1376 patients across a variety of IDDs. AP use was associated with significantly greater weight gain compared to placebo (Continuous: mean difference = 1.10 kg, [0.79, 1.40], p<0.00001, I(2) =54%; Dichotomous: odds ratio = 3.94, [2.15, 7.23], p<0.00001, I(2) =0). Sub-group analysis revealed no significant effect of AP type. Data regarding the effects of APs on other metabolic outcomes were limited. CONCLUSION: This review (PROSPERO # CRD42021255558) demonstrates that AP use is associated with significant weight gain among patients with IDD. Concerningly, most reported studies were in children and adolescents, which sets up an already vulnerable population for adverse medical sequalae at an early age. There was also a lack of long-term studies in adults with IDD. Further studies are required to better understand how AP use affects metabolic parameters in this group of individuals.

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18. Song C, Broadie K. Dysregulation of BMP, Wnt, and Insulin Signaling in Fragile X Syndrome. Front Cell Dev Biol;2022;10:934662.

Drosophila models of neurological disease contribute tremendously to research progress due to the high conservation of human disease genes, the powerful and sophisticated genetic toolkit, and the rapid generation time. Fragile X syndrome (FXS) is the most prevalent heritable cause of intellectual disability and autism spectrum disorders, and the Drosophila FXS disease model has been critical for the genetic screening discovery of new intercellular secretion mechanisms. Here, we focus on the roles of three major signaling pathways: BMP, Wnt, and insulin-like peptides. We present Drosophila FXS model defects compared to mouse models in stem cells/embryos, the glutamatergic neuromuscular junction (NMJ) synapse model, and the developing adult brain. All three of these secreted signaling pathways are strikingly altered in FXS disease models, giving new mechanistic insights into impaired cellular outcomes and neurological phenotypes. Drosophila provides a powerful genetic screening platform to expand understanding of these secretory mechanisms and to test cellular roles in both peripheral and central nervous systems. The studies demonstrate the importance of exploring broad genetic interactions and unexpected regulatory mechanisms. We discuss a number of research avenues to pursue BMP, Wnt, and insulin signaling in future FXS investigations and the development of potential therapeutics.

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19. Starry R, Stokes TF, Longerbeam M, Richardson E. Incorporating merged treatment procedures for children with autism: A case report. J Interprof Care;2022 (Jul 26):1-9.

We examined interprofessional collaboration in a pre-service training model which incorporated the merging of three treatments: Occupational Therapy, Speech-Language Pathology, and Applied Behavior Analysis. We examined the effects of changes in the clinician interprofessional skill repertoire on therapeutic outcomes for children with Autism Spectrum Disorder. Three licensed professionals modeled core techniques from their respective professions to establish benchmark standards for skill demonstration in the treatment of children with autism. Treatment phases were implemented sequentially targeting multiple therapist and child behaviors within a multiple-baseline across participants’ single case experimental design. Therapist skills improved to show a diverse repertoire of intervention techniques to match supervisor proficiencies. These interprofessional skills were delivered simultaneously in a timely and efficient manner. Assessed outcomes for children with autism included increased frequency of verbalizations, engagement during adult-directed interactions, visual-motor task productivity, and improved postural alignment. The study suggests that integrated training across interprofessional techniques enhanced a diverse repertoire of clinician skills, while systematically demonstrating child improvement on many interprofessional treatment goals.

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20. Stokreef S, Lemos M, Quintas S. Importance of an echocardiogram in the evaluation of ataxia. BMJ Case Rep;2022 (Jul 27);15(7)

We present the case of a boy in his middle childhood with gait ataxia and loss of reflexes with a 1-year onset. He had a background of an autism spectrum disorder but was otherwise healthy. A paediatric cardiology assessment was requested to investigate possible cardiac involvement associated to his neurological symptoms. Even though he had no cardiac symptoms and a normal electrocardiography, the echocardiogram revealed severe asymmetric left ventricle hypertrophy consistent with hypertrophic cardiomyopathy. This prompted genetic testing and the diagnosis of Friedreich’s ataxia was confirmed.

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21. Tassanakijpanich N, Wright R, Tassone F, Shankar SP, Hagerman R. Fragile X syndrome in a girl with variant Turner syndrome and an isodicentric X chromosome. BMJ Case Rep;2022 (Jul 26);15(7)

Fragile X (FXS) and Turner (TS) syndromes are X-chromosome-associated disorders. Herein, we report the case of a girl in middle childhood with bicuspid aortic valve in infancy, growth failure, global developmental delay (GDD), visual problems, and coexisting attention-deficit/hyperactivity and anxiety disorders. A high-resolution karyotype in 20 cells revealed 46,X,Idic(X)(p11.21)[19]/45,X[1], suggestive of variant TS. Given her atypical phenotype, subsequent DNA testing was performed. Four FMR1 cytosine-guanine-guanine repeats (30, 410, 580 and 800) were identified, confirming the additional FXS diagnosis. This case study highlights the importance of additional genetic testing in individuals with atypical variant TS, such as unexplained GDD and distinct facial characteristics. The additional FXS diagnosis prompted new therapeutic development for the patient to advance precision healthcare.

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22. Waldman J, McPaul A, Jahoda A. A comparison of the content and nature of worries of autistic and neurotypical young people as they transition from school. Autism;2022 (Jul 27):13623613221111313.

Autistic young people experience higher levels of anxiety than neurotypical young people. Having worries is part of feeling anxious. This makes it surprising that very little research has looked at the kind of worries autistic young people have. Leaving school, in particular, can be a worrying time for young people. Twenty-two autistic young people and 22 neurotypical young people who were at mainstream secondary schools agreed to take part in the study. They were between 16 and 18 years of age. They were asked to sort through a series of pictures, showing the different types of worries that young people might experience. They were then asked to pick out their four main worries and say how much they thought about each worry and how upset the worry made them. They also completed a questionnaire about their level of anxiety. There were similarities and differences between the autistic and neurotypical young people’s worries. Both groups worried about failing and how they might get on in further education. The autistic young people were more worried about change and friendships. Work and money were particular concerns for the neurotypical young people. The autistic young people said that they found their worries more upsetting than the neurotypical young people. Having a better understanding of autistic young people’s worries at important points in their lives might mean that more timely help and support can be given to them. Simply knowing what to ask young autistic school leavers about may help them to express unspoken concerns.

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23. Westby C. Playing to Pretend or « Pretending » to Play: Play in Children with Autism Spectrum Disorder. Semin Speech Lang;2022 (Aug);43(4):331-346.

Children diagnosed with autism spectrum disorder (ASD) exhibit early delays and deficits in play. In infancy, they engage in unusual exploratory behaviors with toys. As toddlers, they are slow to develop functional play, and in preschool some children with ASD fail to develop symbolic play despite having the necessary cognitive and language skills. Furthermore, when children with ASD are engaged in play, they demonstrate less playfulness. This article reviews the literature on the characteristics of exploratory, functional, and symbolic/pretend play in children with ASD and possible reasons for their unusual patterns of play development. Increased quantity and quality of play are frequent therapeutic goals for children with ASD. If play interventions are to be successful, it is critical that speech-language pathologists have an adequate assessment of children’s play skills. Several frameworks and tools appropriate for assessing play in typical children and children with ASD are described.

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24. Yamazaki M, Arai T, Yarimizu J, Matsumoto M. The 5-HT5A receptor antagonist ASP5736 ameliorates several abnormal behaviors in an Fmr1-targeted transgenic male rat model of fragile X syndrome. Int J Neuropsychopharmacol;2022 (Jul 26)

BACKGROUND: Fragile X syndrome (FXS) is a genetic condition that causes a range of developmental problems including intellectual disability, aggressive behavior, anxiety, abnormal sensory processing and cognitive impairment. Despite intensive preclinical research in Fmr1-targeted transgenic mice, an effective treatment for FXS has yet to be developed. We previously demonstrated that ASP5736, a 5-HT5A receptor antagonist, ameliorated scopolamine-induced working memory deficits in mice, reference memory impairment in aged rats and methamphetamine-induced positive symptoms and phencyclidine-induced cognitive impairment in animal models of schizophrenia. We hypothesized that ASP5736 may be effective for ameliorating similar behavior deficits in male Fmr1-targeted transgenic rats as a preclinical model of FXS. METHODS: We evaluated the effect of acute oral administration of ASP5736 on the abnormal behavior of hyperactivity (0.01, 0.1 mg/kg), prepulse inhibition (PPI; 0.01, 0.03, 0.1 mg/kg), and the novel object recognition task (NORT; 0.1 mg/kg) in Frmr1-knockout (KO) rats. RESULTS: Fmr1-KO rats showed body weight gain, hyperactivity, abnormal sensory motor gating and cognitive impairment. ASP5736 (0.1 mg/kg) reversed the hyperactivity and ameliorated the sensory motor gating deficits (0.03-0.1 mg/kg). ASP5736 (0.01 mg/kg) also improved cognitive impairment. CONCLUSIONS: ASP5736 is a potential drug candidate for FXS. Further studies are needed to confirm its clinical efficacy.

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