1. Barrie ES, Pinsonneault JK, Sadee W, Hollway JA, Handen BL, Smith T, Arnold LE, Butter E, Hansen-Kiss E, Herman GE, Aman MG. {{Testing genetic modifiers of behavior and response to atomoxetine in autism spectrum disorder with ADHD}}. {J Dev Phys Disabil};2018 (Jun);30(3):355-371.
Background: Frequent non-pathogenic genetic variants may act as moderators of phenotypic severity for complex disorders such as autism spectrum disorder (ASD). We previously identified polymorphisms affecting mRNA expression of candidate genes, including tryptophan hydroxylase 2 (TPH2), dopamine beta hydroxylase (DBH), and dopamine transporter (DAT, SLC6A3). Method: We compare genotypes and (1) clinical response to atomoxetine, (2) scores from the Autism Diagnostic Interview-Revised (ADI-R), and (3) severity of Attention Deficit Hyperactivity Disorder (ADHD) symptoms in a cohort of patients with ASD from multiple study sites. Results: There was no association between CYP2D6 metabolizer status and atomoxetine response. TPH2 rs7305115 genotype was associated with ADI-R Restrictive/Repetitive Behavior score (p=0.03). DBH rs1611115 genotype was associated with ADI-R Social score (p=0.002) and Restrictive/Repetitive Behavior score (p=0.04). The DAT intron 8 5/6 repeat was associated with ADHD symptoms (ABC Hyperactivity p=0.01 and SNAP ADHD p=0.03), replicating a previous finding. Conclusions: We find associations between ASD phenotypes and regulatory variants in catecholamine biosynthesis genes. This work may help guide future genetics studies related to ASD.
Lien vers le texte intégral (Open Access ou abonnement)
2. Buchanan CB, Stallworth JL, Scott AE, Glaze DG, Lane JB, Skinner SA, Tierney AE, Percy AK, Neul JL, Kaufmann WE. {{Behavioral profiles in Rett syndrome: Data from the natural history study}}. {Brain Dev};2018 (Sep 11)
INTRODUCTION: Rett syndrome (RTT) is a complex neurodevelopmental disorder with known behavioral abnormalities, both internalizing (e.g., anxiety, social withdrawal) and externalizing (e.g., aggression, self-abuse). However, a broad evaluation of behavioral abnormalities in a large cohort is lacking. OBJECTIVE: In this report, we describe profiles of internalizing and externalizing behaviors in individuals evaluated in the multi-center U.S. Rett Natural History Study. METHODS: Cross-sectional and longitudinal data were collected from 861 females with RTT and from 48 females who have MECP2 mutations without meeting criteria for RTT. Standard statistical methods including linear regression evaluated internalizing behavioral components from the Child Health Questionnaire (CHQ-PF50) and externalizing components from the Motor Behavioral Assessment (MBA). RESULTS: We found mildly to moderately severe internalizing behaviors in nearly all individuals with RTT, while externalizing behaviors were mild and uncommon. Internalizing behavior in RTT was comparable to groups with psychiatric disorders. Participants with mixed (internalizing and externalizing) behaviors were younger and less affected overall, but showed prominent self-injury and worsening internalizing behaviors over time. CONCLUSIONS: This study revealed that internalizing behaviors are common at a clinically significant level in RTT. Understanding clinical features associated with behavioral profiles could guide treatment strategies.
Lien vers le texte intégral (Open Access ou abonnement)
3. Caselli RJ, Langlais BT, Dueck AC, Locke DEC, Woodruff BK. {{Subjective Cognitive Impairment and the Broad Autism Phenotype}}. {Alzheimer Dis Assoc Disord};2018 (Sep 11)
INTRODUCTION: Roughly 4% to 23% of the population embody stress prone personality and other traits characterizing a subclinical « broad autism phenotype » (BAP). Subjective cognitive impairment (SCI) among healthy elderly is associated with psychological distress leading us to predict BAP would be associated with SCI. METHODS: The Autism Spectrum Quotient, a self-administered 50 item questionnaire, was completed by 419 consecutive members of the Arizona APOE Cohort who underwent neuropsychological testing every 2 years. SCI was assessed with self and informant versions of the Multidimensional Assessment of Neurodegenerative Symptoms (MANS) Questionnaire. RESULTS: A total of 45 individuals scored in the BAP range, designated BAP+, and the rest were BAP-. At entry, both Multidimensional Assessment of Neurodegenerative Symptoms Questionnaire Self and Informant scores were higher in the BAP+ group (P<0.0001). After age 60, the BAP+ group had greater annual increases in Multidimensional Assessment of Neurodegenerative Symptoms Questionnaire Self scores (0.05 vs. 0.02; difference=0.03; 95% confidence interval, 0.004-0.05; P=0.02) yet there was no difference between groups in memory decline. Over ~10 years 33 individuals developed mild cognitive impairment: 4 in the BAP+ group (8.9%) and 29 in the BAP- group (7.8%), P=0.77. DISCUSSION: Individuals who meet criteria for the BAP have escalating SCI with age, but no greater rate of memory decline or clinical progression to mild cognitive impairment. Lien vers le texte intégral (Open Access ou abonnement)
4. Coderre EL, Cohn N, Slipher SK, Chernenok M, Ledoux K, Gordon B. {{Visual and linguistic narrative comprehension in autism spectrum disorders: Neural evidence for modality-independent impairments}}. {Brain Lang};2018 (Sep 11);186:44-59.
Individuals with autism spectrum disorders (ASD) have notable language difficulties, including with understanding narratives. However, most narrative comprehension studies have used written or spoken narratives, making it unclear whether narrative difficulties stem from language impairments or more global impairments in the kinds of general cognitive processes (such as understanding meaning and structural sequencing) that are involved in narrative comprehension. Using event-related potentials (ERPs), we directly compared semantic comprehension of linguistic narratives (short sentences) and visual narratives (comic panels) in adults with ASD and typically-developing (TD) adults. Compared to the TD group, the ASD group showed reduced N400 effects for both linguistic and visual narratives, suggesting comprehension impairments for both types of narratives and thereby implicating a more domain-general impairment. Based on these results, we propose that individuals with ASD use a more bottom-up style of processing during narrative comprehension.
Lien vers le texte intégral (Open Access ou abonnement)
5. Frantz MC, Pellissier L, Pflimlin E, Loison S, Gandia J, Marsol C, Durroux T, Mouillac B, Becker J, Le Merrer J, Valencia C, Villa P, Bonnet D, Hibert M. {{LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism}}. {J Med Chem};2018 (Sep 10)
Oxytocin (OT) and its receptor (OT-R) are implicated in the aetiology of autism spectrum disorders (ASD) and OT-R is a potential target for therapeutic intervention. Very few nonpeptide oxytocin agonists have currently been reported. Their molecular and in vivo pharmacology remain to be clarified and none of them has been shown efficient in improving social interaction in animal models relevant to ASD. In an attempt to rationalize the design of centrally active nonpeptide full agonists, we studied in a systematic way the structural determinants of the affinity and efficacy of representative ligands of the V1a and V2 vasopressin receptor subtypes (V1a-R and V2-R) and of the oxytocin receptor. Our results confirm the subtlety of the structure-affinity and structure-efficacy relationships around vasopressin/oxytocin receptor ligands and lead however to the first nonpeptide OT receptor agonist active in a mouse model of ASD after peripheral i.p. administration.
Lien vers le texte intégral (Open Access ou abonnement)
6. Kushima I, Aleksic B, Nakatochi M, Shimamura T, Okada T, Uno Y, Morikawa M, Ishizuka K, Shiino T, Kimura H, Arioka Y, Yoshimi A, Takasaki Y, Yu Y, Nakamura Y, Yamamoto M, Iidaka T, Iritani S, Inada T, Ogawa N, Shishido E, Torii Y, Kawano N, Omura Y, Yoshikawa T, Uchiyama T, Yamamoto T, Ikeda M, Hashimoto R, Yamamori H, Yasuda Y, Someya T, Watanabe Y, Egawa J, Nunokawa A, Itokawa M, Arai M, Miyashita M, Kobori A, Suzuki M, Takahashi T, Usami M, Kodaira M, Watanabe K, Sasaki T, Kuwabara H, Tochigi M, Nishimura F, Yamasue H, Eriguchi Y, Benner S, Kojima M, Yassin W, Munesue T, Yokoyama S, Kimura R, Funabiki Y, Kosaka H, Ishitobi M, Ohmori T, Numata S, Yoshikawa T, Toyota T, Yamakawa K, Suzuki T, Inoue Y, Nakaoka K, Goto YI, Inagaki M, Hashimoto N, Kusumi I, Son S, Murai T, Ikegame T, Okada N, Kasai K, Kunimoto S, Mori D, Iwata N, Ozaki N. {{Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights}}. {Cell Rep};2018 (Sep 11);24(11):2838-2856.
Compelling evidence in Caucasian populations suggests a role for copy-number variations (CNVs) in autism spectrum disorder (ASD) and schizophrenia (SCZ). We analyzed 1,108 ASD cases, 2,458 SCZ cases, and 2,095 controls in a Japanese population and confirmed an increased burden of rare exonic CNVs in both disorders. Clinically significant (or pathogenic) CNVs, including those at 29 loci common to both disorders, were found in about 8% of ASD and SCZ cases, which was significantly higher than in controls. Phenotypic analysis revealed an association between clinically significant CNVs and intellectual disability. Gene set analysis showed significant overlap of biological pathways in both disorders including oxidative stress response, lipid metabolism/modification, and genomic integrity. Finally, based on bioinformatics analysis, we identified multiple disease-relevant genes in eight well-known ASD/SCZ-associated CNV loci (e.g., 22q11.2, 3q29). Our findings suggest an etiological overlap of ASD and SCZ and provide biological insights into these disorders.
Lien vers le texte intégral (Open Access ou abonnement)
7. Mitra M, Parish SL, Clements KM, Zhang J, Simas TAM. {{Antenatal Hospitalization Among U.S. Women With Intellectual and Developmental Disabilities: A Retrospective Cohort Study}}. {Am J Intellect Dev Disabil};2018 (Sep);123(5):399-411.
This population-based retrospective cohort study examines the prevalence of hospital utilization during pregnancy and the primary reason for antenatal hospital utilization among women with intellectual and developmental disabilities (IDD). Massachusetts residents with in-state deliveries that were >/= 20 weeks gestational age were included via data from the 2002-2009 Massachusetts Pregnancy to Early Life Longitudinal Data System. Among women with IDD, 54.8% had at least one emergency department (ED) visit during pregnancy, compared to 23% of women without IDD. Women with IDD were more likely to have an antenatal ED visit, observational stays, and non-delivery hospital stays. This study highlights the need for further understanding of the health care needs of women with IDD during pregnancy.
Lien vers le texte intégral (Open Access ou abonnement)
8. Mulas F, Rojas M. {{[Intellectual developmental disability overlapping with autism spectrum disorder and attention deficit-hyperactivity disorder]}}. {Medicina (B Aires)};2018;78 Suppl 2:63-68.
The subject of disabilities that include cognition and adaptability will never cease to be interesting and relevant. The genetic etiology has more weight every day. The relationship with other neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) is of clinical, diagnostic and therapeutic importance. The objective was to conduct a review of intellectual development disorder and its implication with ASD and ADHD. From Hippocrates to the present the disorders that affect learning, behavior and socialization skills have been the subject of studies and have varied, above all, in the denomination as an entity and its perception from the human and social point of view. The etiology of intellectual development disorders in most cases is an enigma and genetic advances are the cornerstone to elucidate the origin of this neurodevelopmental disorder, as well as its relationship with others such as ASD and ADHD. The disorder of intellectual development, the oldest one with respect to definition, study and approach, still presents mysteries above all of etiological origin. Its relationship with other neurodevelopmental disorders such as ASD and ADHD is evident by having common areas of involvement, which may be coincident diagnoses.
9. Ruggieri V, Cuesta Gomez JL. {{[Aging in people with autism spectrum disorder]}}. {Medicina (B Aires)};2018;78 Suppl 2:69-74.
Autism spectrum disorder is characterized by a qualitative alteration in social interaction and communication associated with restricted interests and stereotyped behaviors. This condition will accompany people throughout their lives, with variations in their evolution. Our objectives were to know the evolutionary characteristics of people with autistic spectrum disorder, analyzing cognitive, behavioral, health, mortality and their needs in the aging stage, which will guide the planning of specific support resources. We analyze studies related to the evolution in adult life in people with this disorder, with or without identified entities, and socio-health conditions that should be considered in the aging process. The knowledge about aging in people with autism is still scarce and it is difficult to define a specific pattern because this will depend, among other factors, on the etiology, the degree, the presence of intellectual disability and/or epilepsy, and the scope in where live, which can even condition the life expectancy. Aging has been associated with mood disorders, depression, deterioration in executive functions and episodic memory, although it is difficult to differentiate it from natural aging in people with typical development. The identification of a specific entity will allow to know the possible evolution and prevent complications in syndromes that may be associated with autism: fragile X, Down, Angelman, Rett and Williams, for that reason we rank the genetic and neurological consultation.
10. Swatt AJ, Schwartz AE, Kramer JM. {{Youth’s Perspective of Responsibility: Exploration of a Construct for Measurement with Youth with Developmental Disabilities}}. {Phys Occup Ther Pediatr};2018 (Sep 11):1-13.
AIMS: There is a need to develop self-reports that measure youth’s responsibility for major life tasks. We examined if the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test’s (PEDI-CAT) operationalization of responsibility is salient to youth with developmental disabilities (DD). The PEDI-CAT defines responsibility as, « the extent to which the young person…take[s] control over organizing and managing major life tasks. » METHODS: During six focus groups (n = 43), youth generated examples of behaviors and actions that demonstrated responsibility. Data were coded as « responsibility » or « discrete skills » per PEDI-CAT definitions. We reviewed examples in both categories and compared and contrasted how youth described responsibility. RESULTS: Youth’s descriptions of responsibility aligned with the PEDI-CAT’s responsibility construct 42.75% of the time. In these instances, youth perceived themselves as causal agents who had to make decisions and self-regulate to manage and organize major life tasks. Otherwise, youth described themselves as causal agents who adhered to rules, social norms, and expectations of others during the execution of discrete skills. CONCLUSIONS: Youth perceive themselves as responsible, causal agents during both the coordination and management of major life tasks and during the execution of discrete skills. As this is not aligned with the PEDI-CAT’s operationalization of responsibility, there is a need to further explore youth’s perceptions of responsibility prior to developing a self-report.
Lien vers le texte intégral (Open Access ou abonnement)
11. Thal LB, Tomlinson ID, Quinlan MA, Kovtun O, Blakely RD, Rosenthal SJ. {{Single Quantum Dot Imaging Reveals PKCbeta-Dependent Alterations in Membrane Diffusion and Clustering of an Attention-Deficit Hyperactivity Disorder/Autism/Bipolar Disorder-Associated Dopamine Transporter Variant}}. {ACS Chem Neurosci};2018 (Sep 11)
The dopamine transporter (DAT) is a transmembrane protein that terminates dopamine signaling in the brain by driving rapid dopamine reuptake into presynaptic nerve terminals. Several lines of evidence indicate that DAT dysfunction is linked to neuropsychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD), bipolar disorder (BPD), and autism spectrum disorder (ASD). Indeed, individuals with these disorders have been found to express the rare, functional DAT coding variant Val559, which confers anomalous dopamine efflux (ADE) in vitro and in vivo. To elucidate the impact of the DAT Val559 variant on membrane diffusion dynamics, we implemented our antagonist-conjugated quantum dot (QD) labeling approach to monitor the lateral mobility of single particle-labeled transporters in transfected HEK-293 and SK-N-MC cells. Our results demonstrate significantly higher diffusion coefficients of DAT Val559 compared to those of DAT Ala559, effects likely determined by elevated N-terminal transporter phosphorylation. We also provide pharmacological evidence that PKCbeta-mediated signaling supports enhanced DAT Val559 membrane diffusion rates. Additionally, our results are complimented with diffusion rates of phosphomimicked and phosphorylation-occluded DAT variants. Furthermore, we show DAT Val559 has a lower propensity for membrane clustering, which may be caused by a mutation-derived shift out of membrane microdomains leading to faster lateral membrane diffusion rates. These findings further demonstrate a functional impact of DAT Val559 and suggest that changes in transporter localization and lateral mobility may sustain ADE and contribute to alterations in dopamine signaling underlying multiple neuropsychiatric disorders.
Lien vers le texte intégral (Open Access ou abonnement)
12. Tromans S, Chester V, Kiani R, Alexander R, Brugha T. {{The Prevalence of Autism Spectrum Disorders in Adult Psychiatric Inpatients: A Systematic Review}}. {Clin Pract Epidemiol Ment Health};2018;14:177-187.
Background: Whilst the prevalence of autism spectrum disorders in adults within the community setting is well-established, less is known about the prevalence among adults based within a psychiatric inpatient setting. Objective: To conduct a systematic literature review pertaining to the prevalence of autism spectrum disorders among the adult psychiatric inpatient population. Method: Eligibility criteria included: (a) investigation of the prevalence of autism spectrum disorders (b) adult psychiatric inpatient study population (c) published in English language. Electronic databases accessed included PubMed, Medline, CINAHL, PsycINFO and EMBASE. Additionally, the ancestry method was utilised for the references of eligible papers, as well as grey literature searches and consultation with experts in the field. Results: From the search, 4 studies were identified which satisfied the inclusion criteria, conducted in a variety of inpatient psychiatric settings, including secure forensic and intellectual disability units and a state psychiatric hospital. There were significant differences in methodological approaches, including the screening tests, diagnostic instruments and diagnostic criteria utilised. Autism spectrum disorder prevalence estimates varied considerably, from 2.4-9.9%. Conclusion: From the limited research data currently available, it appears that the prevalence of autism spectrum disorders is increased in inpatient psychiatric settings relative to the general population. There is a need for further high quality research in this patient group, to add to this limited evidence base, as well as in developing effective strategies to identify patients with a high likelihood of autism spectrum disorders within this setting.
Lien vers le texte intégral (Open Access ou abonnement)
13. Valagussa G, Trentin L, Signori A, Grossi E. {{Toe Walking Assessment in Autism Spectrum Disorder Subjects: A Systematic Review}}. {Autism Res};2018 (Sep 10)
There is increasing evidence that autism spectrum disorder (ASD) subjects have also motor impairments. Toe walking (TW) is a phenomenon that can be found in ASD subjects during gait, even if this condition was found not to be necessarily related only to walking, since these children often also stand and run on their tiptoes. Since persistent TW in ASD subjects may contribute to secondary shortening of the Achilles’s tendon, it becomes important to have an assessment tool and/or outcome measure for both the clinical and rehabilitative settings. The aim of this systematic review is to critically evaluate and describe the methods employed to assess toe walking in ASD subjects. The systematic review protocol was previously registered on PROSPERO. We conducted an extensive literature search in PubMed, CINAHL, PsycINFO, The Cochrane Library, and Scopus databases. There were no restrictions on the types of study design eligible for inclusion. Ten studies were included in the systematic review. Risk of bias of the included studies was conducted using the following instruments depending on the study types: STROBE Statement, Cochrane risk of bias tool, and CARE checklist. Almost all the included studies (8/10) proposed a tip-toe behavior (TTB) assessment only during walking. Nine out of ten of the included studies assessed TTB using a qualitative methodology. The results evidenced the heterogeneity of qualitative methods and a lack of a structured quantitative test to assess toe walking in ASD subjects. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY ABSTRACT: Toe walking (TW) is a phenomenon that can be found during ASD subject’s gait. The persistence of this behavior may contribute to secondary Achilles’s tendon shortening. In this perspective it becomes important to have an assessment tool and/or outcome measure for both the clinical and rehabilitative settings. The current systematic review aimed to describe the methods employed to assess TW. The results evidenced the lack and the need of a structured quantitative test to assess TW in ASD subjects.
