1. Alvarez-Mora MI, Rodriguez-Revenga L, Feliu A, Badenas C, Madrigal I, Mila M. {{Skewed X Inactivation in Women Carrying the FMR1 Premutation and Its Relation with Fragile-X-Associated Tremor/Ataxia Syndrome}}. {Neurodegener Dis};2015 (Nov 27)
BACKGROUND: Fragile-X-associated tremor/ataxia syndrome (FXTAS) is a late-onset multisystem neurological disorder characterized by intention tremor and cerebellar ataxia. OBJECTIVE: We hypothesized that in FMR1 premutation females with FXTAS, a normal X chromosome might more frequently be inactivated; therefore, the aim of this study was to determine the relationship between skewed X chromosome inactivation (XCI) and FXTAS. METHODS: We studied the XCI patterns of cases of FMR1 premutation in 10 women with FXTAS and 21 without FXTAS. RESULTS: The distribution of XCI patterns in the FXTAS and no-FXTAS groups showed differences regarding the allele presenting severe skewed XCI. In the FXTAS group, all cases preferentially inactivated the non-expanded X chromosome, whereas in the no-FXTAS group, all inactivated the expanded X chromosome. Nevertheless, no significant differences were found on comparing XCI frequencies among FMR1 premutation carriers with and without FXTAS. As expected, we found statistically significant differences in the skewed XCI on comparing FMR1 premutation women and controls. CONCLUSION: Although the reduced sample size and blood XCI patterns are two limitations of this study, our results suggest that the skewed XCI of the normal FMR1 allele may be a risk factor for the development of FXTAS. Furthermore, our findings also support the protective effect of the expression of a normal FMR1 allele.
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2. Aramaki E, Shikata S, Miyabe M, Usuda Y, Asada K, Ayaya S, Kumagaya S. {{Understanding the Relationship between Social Cognition and Word Difficulty. A Language Based Analysis of Individuals with Autism Spectrum Disorder}}. {Methods Inf Med};2015 (Nov 27);54(6):522-529.
BACKGROUND: Few quantitative studies have been conducted on the relationship between society and its languages. Individuals with autistic spectrum disorder (ASD) are known to experience social hardships, and a wide range of clinical information about their quality of life has been provided through numerous narrative analyses. However, the narratives of ASD patients have thus far been examined mainly through qualitative approaches. OBJECTIVES: In this study, we analyzed adults with ASD to quantitatively examine the relationship between language abilities and ASD severity scores. METHODS: We generated phonetic transcriptions of speeches by 16 ASD adults at an ASD workshop, and divided the participants into 2 groups according to their Social Responsiveness Scale(TM), 2nd Edition (SRS(TM)-2) scores (where higher scores represent more severe ASD): Group A comprised high-scoring ASD adults (SRS(TM)-2 score: >/= 76) and Group B comprised low- and intermediate-scoring ASD adults (SRS(TM)-2 score: < 76). Using natural language processing (NLP)-based analytical methods, the narratives were converted into numerical data according to four language ability indicators, and the relationships between the language ability scores and ASD severity scores were compared. RESULTS AND DISCUSSION: Group A showed a marginally negative correlation with the level of Japanese word difficulty (p < .10), while the "social cognition" subscale of the SRS(TM)-2 score showed a significantly negative correlation (p < .05) with word difficulty. When comparing only male participants, Group A demonstrated a significantly lower correlation with word difficulty level than Group B (p < .10). CONCLUSION: Social communication was found to be strongly associated with the level of word difficulty in speech. The clinical applications of these findings may be available in the near future, and there is a need for further detailed study on language metrics designed for ASD adults. Lien vers le texte intégral (Open Access ou abonnement)
3. Baller JB, Barry CL, Shea K, Walker MM, Ouellette R, Mandell DS. {{Assessing early implementation of state autism insurance mandates}}. {Autism};2015 (Nov 27)
In the United States, health insurance coverage for autism spectrum disorder treatments has been historically limited. In response, as of 2015, 40 states and Washington, DC, have passed state autism insurance mandates requiring many health plans in the private insurance market to cover autism diagnostic and treatment services. This study examined five states’ experiences implementing autism insurance mandates. Semi-structured, key-informant interviews were conducted with 17 participants representing consumer advocacy organizations, provider organizations, and health insurance companies. Overall, participants thought that the mandates substantially affected the delivery of autism services. While access to autism treatment services has increased as a result of implementation of state mandates, states have struggled to keep up with the demand for services. Participants provided specific information about barriers and facilitators to meeting this demand. Understanding of key informants’ perceptions about states’ experiences implementing autism insurance mandates is useful for other states considering adopting or expanding mandates or other policies to expand access to autism treatment services.
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4. Barnard-Brak L, Brewer A, Chesnut S, Richman D, Schaeffer AM. {{The sensitivity and specificity of the social communication questionnaire for autism spectrum with respect to age}}. {Autism Res};2015 (Nov 26)
The age neutrality of the Social Communication Questionnaire (SCQ) was examined as a common screener for ASD. Mixed findings have been reported regarding the recommended cutoff score’s ability to accurately classify an individual as at-risk for autism spectrum disorder (ASD) (sensitivity) versus accurately classifying an individual as not at-risk for ASD (specificity). With a sample from the National Database for Autism Research, this study examined the SCQ’s sensitivity versus specificity. Analyses indicated that the actual sensitivity and specificity scores were lower than initially reported by the creators of the SCQ. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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5. Bhattacharyya A, Zhao X. {{Human pluripotent stem cell models of Fragile X syndrome}}. {Mol Cell Neurosci};2015 (Nov 27)
Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism. The causal mutation in FXS is a trinucleotide CGG repeat expansion in the FMR1 gene that leads to human specific epigenetic silencing and loss of Fragile X Mental Retardation Protein (FMRP) expression. Human pluripotent stem cells (PSCs), including human embryonic stem cells (ESCs) and particularly induced PSCs (iPSCs), offer a model system to reveal cellular and molecular events underlying human neuronal development and function in FXS. Human FXS PSCs have been established and have provided insight into the epigenetic silencing of the FMR1 gene as well as aspects of neuronal development.
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6. Chang AD, Berges VA, Chung SJ, Fridman GY, Baraban JM, Reti IM. {{High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models}}. {Neuropsychopharmacology};2015 (Nov 26)
Approximately one quarter of individuals with an autism spectrum disorder (ASD) display self-injurious behavior (SIB) ranging from head banging to self-directed biting and punching. Sometimes, these behaviors are extreme and unresponsive to pharmacological and behavioral therapies. We have found electroconvulsive therapy (ECT) can produce life-changing results, with more than 90% suppression of SIB frequency. However, these patients typically require frequent maintenance ECT (mECT), as often as every 5 days, to sustain the improvement gained during the acute course. Long-term consequences of such frequent mECT started as early as childhood in some cases are unknown. Accordingly, there is a need for alternative forms of chronic stimulation for these patients. To explore the feasibility of deep brain stimulation (DBS) for intractable SIB seen in some patients with an ASD, we utilized two genetically distinct mouse models demonstrating excessive self-grooming, namely the Viaat-Mecp2-/y and Shank3B-/- lines, and administered high-frequency stimulation (HFS) via implanted electrodes at the subthalamic nucleus (STN-HFS). We found that STN-HFS significantly suppressed excessive self-grooming in both genetic lines. Suppression occurs both acutely when stimulation is switched on, and persists for several days after HFS is stopped. This effect was not explained by a change in locomotor activity, which was unaffected by STN-HFS. Likewise, social interaction deficits were not corrected by STN-HFS. Our data show STN-HFS suppresses excessive self-grooming in two autism-like mouse models, raising the possibility DBS might be used to treat intractable SIB associated with ASDs. Further studies are required to explore the circuitry engaged by STN-HFS, as well as other potential stimulation sites. Such studies might also yield clues about pathways, which could be modulated by non-invasive stimulatory techniques.Neuropsychopharmacology advance online publication, 16 December 2015; doi:10.1038/npp.2015.350.
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7. Farrant K, Uddin LQ. {{Atypical developmental of dorsal and ventral attention networks in autism}}. {Dev Sci};2015 (Nov 27)
Individuals with autism spectrum disorders (ASD) exhibit early and lifelong impairments in attention across multiple domains. While the disorder is known to affect attention processes, very little is currently known about the brain networks underlying attention in ASD, and even less is known about whether these atypicalities persist across the lifespan. We used functional connectivity analysis applied to resting state functional magnetic resonance imaging (fMRI) data to explore the dorsal (DAN) and ventral (VAN) attention networks in two separate age cohorts of children and adults with and without ASD. We find significant developmental differences in functional connectivity of brain regions that are critical for attention in children and adults with ASD. Specifically, children with ASD show hyper-connectivity of regions-of-interest (ROIs) in both attention networks compared with both typically developing (TD) children and adults with ASD. In contrast, adults with ASD show hypo-connectivity of these networks compared with neurotypical adults. These findings are consistent with the notion that consideration of developmental stage is critical in studies of functional connectivity in ASD. This study further illustrates diverging developmental patterns for top-down and bottom-up attention systems in autism.
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8. Gao J, Wang X, Sun H, Cao Y, Liang S, Wang H, Wang Y, Yang F, Zhang F, Wu L. {{Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model}}. {Int J Dev Neurosci};2015 (Nov 27)
Prenatal exposure to valproic acid (VPA) in rat offspring is capable of inducing experimental autism with neurobehavioral aberrations. This study investigated the effect of docosahexaenoic acid (DHA) on hippocampal cell death, learning and memory alteration in an experimental rat autism model. We found that DHA supplementation (75, 150 or 300mg/kg/day, 21 days) rescued the VPA (600mg/kg) induced DHA reduction in plasma and hippocampus in a dose-dependent manner, increased the levels of hippocampal p-CaMKII and p-CREB without affecting total protein level, and altered BDNF-AKT-Bcl-2 signaling pathway, as well as inhibited the activity of caspase-3. DHA also influenced the content of malondialdehyde (MDA) and the activities of antioxidant enzymes in the VPA-treated offspring. Consistent with the previous results, we also observed that 300mg/kg DHA supplementation markedly increased the cell survival, decreased the cell apoptosis, and increased mature neuronal cell in the hippocampus in VPA-treated offspring. Utilizing the Morris water maze test, we found that DHA prevented cognitive impairment in offspring of VPA-treated rats. The data suggested that DHA may play a neuroprotective role in hippocampal neuronal cell and ameliorates dysfunctions in learning and memory in this rat autism model. Thus, DHA could be used as treatment intervention for mitigating behavioral dysfunctions in autism spectrum disorder (ASD).
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9. Grefer M, Flory K, Cornish K, Hatton D, Roberts J. {{The emergence and stability of attention deficit hyperactivity disorder in boys with fragile X syndrome}}. {J Intellect Disabil Res};2015 (Nov 27)
BACKGROUND: Children with fragile X syndrome (FXS) are at high risk for developing a range of behavioural disorders, including attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). However, very few studies have investigated the comorbid profile of FXS and ADHD and the possible dissociation from the FXS and ASD profile. The present study examined the relationship of childhood temperament characteristics of the Surgency facet (activity level, impulsivity, approach, shyness, and smiling and laughter) and the severity of ADHD and ASD features at two measurement time points in childhood, preschool (ages 3-4) and at school entry (ages 5-6). METHODS: The study consisted of males with FXS measured at each time point (preschool and school entry), as well as comparison of typically developing (TD) boys at the preschool measurement time point. Parent reported measures of temperament and behavioural symptoms were collected at each time point. Multiple regression analyses were used to analyse obtained data. RESULTS: Elevated activity level scores are associated with ADHD scores at preschool age and elevated shyness and decreased smiling and laughter are strongly associated with ADHD scores upon school entry. Impulsivity emerges as a strong indicator of elevated ADHD scores around school age, but even preschool impulsivity scores demonstrate some predictive value for higher ADHD scores later in school. Finally, no Surgency characteristic was significantly related to ASD scores at any age. CONCLUSIONS: Impulsivity serves as an indicator of elevated ADHD symptoms across development periods in boys with FXS, while activity level is just indicative of higher ADHD scores at the preschool age. The Surgency facet of temperament at either age does not predict strong relationships of comorbid pathologies of ADHD and ASD in FXS. However, Surgency characteristics may serve as informative discriminative factors when studying behavioural outcomes in boys with FXS.
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10. Guy J, Mottron L, Berthiaume C, Bertone A. {{The developmental trajectory of contrast sensitivity in autism spectrum disorder}}. {Autism Res};2015 (Nov 27)
Autism Spectrum Disorder (ASD) is characterized by a detail-driven visual processing strategy, evidence for which has been based largely on cross-sectional studies in small participant groups of limited age ranges. It is therefore unknown when sensitivity to detailed information emerges and develops in ASD. Contrast sensitivity to sinusoidal gratings of different spatial frequencies (0.5, 1, 2, 4, and 8 cycles per degree (cpd)) was measured for 34 participants with ASD and 55 typically developing participants (aged 6-16 years). Cross-sectional, developmental trajectories were constructed to examine within and between group differences across the range of spatial frequencies tested. Developmental trajectories indicated that sensitivity across low (i.e., 0.5 and 1 cpd) and mid (2 and 4 cpd) spatial frequencies varied by chronological age within each group, with mid frequencies developing at a more significant rate than low frequencies. There was no overall difference between groups in terms of the relationship of sensitivity and age across spatial frequencies, yet the ASD group had an overall lower level of sensitivity. Closer examination revealed that the youngest participants with ASD had a reduced sensitivity for mid frequencies. Moreover, the ASD group showed a statistically significant developmental relationship at 8 cpd, which suggests that a trend for increased sensitivity to early detailed information may manifest beyond the ages tested. These findings demonstrate a differential development of contrast sensitivity for spatial frequencies in ASD and underscore the need to better identify what drives such differences in the « building blocks » of visual perception. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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11. Huynh K. {{Antiplatelet therapy: Clopidogrel plus aspirin reduces migrane attacks after ASD closure}}. {Nat Rev Cardiol};2016 (Jan);13(1):2-3.
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12. Koehne S, Behrends A, Fairhurst MT, Dziobek I. {{Fostering Social Cognition through an Imitation- and Synchronization-Based Dance/Movement Intervention in Adults with Autism Spectrum Disorder: A Controlled Proof-of-Concept Study}}. {Psychother Psychosom};2015 (Nov 27);85(1):27-35.
BACKGROUND: Since social cognition is impaired in individuals with autism spectrum disorder (ASD), this study aimed at establishing the efficacy of a newly developed imitation- and synchronization-based dance/movement intervention (SI-DMI) in fostering emotion inference and empathic feelings (emotional reaction to feelings of others) in adults with high-functioning ASD. METHODS: Fifty-five adults with ASD (IQ >/=85) who were blinded to the aim of the study were assigned to receive either 10 weeks of a dance/movement intervention focusing on interpersonal movement imitation and synchronization (SI-DMI, n = 27) or a control movement intervention (CMI, n = 24) focusing on individual motor coordination (2 participants from each group declined before baseline testing). The primary outcome measure was the objective Multifaceted Empathy Test targeting emotion inference and empathic feelings. Secondary outcomes were scores on the self-rated Interpersonal Reactivity Index. The well-established automatic imitation task and synchronization finger-tapping task were used to quantify effects on imitation and synchronization functions, complemented by the more naturalistic Assessment of Spontaneous Interaction in Movement. RESULTS: Intention-to-treat analyses revealed that from baseline to 3 months, patients treated with SI-DMI showed a significantly larger improvement in emotion inference (d = 0.58), but not empathic feelings, than those treated with CMI (d = -0.04). On the close generalization level, SI-DMI increased synchronization skills and imitation tendencies, as well as whole-body imitation/synchronization and movement reciprocity/dialogue, compared to CMI. CONCLUSIONS: SI-DMI can be successful in promoting emotion inference in adults with ASD and warrants further investigation.
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13. Landry O, Al-Taie S. {{A Meta-analysis of the Wisconsin Card Sort Task in Autism}}. {J Autism Dev Disord};2015 (Nov 27)
We conducted a meta-analysis of 31 studies, spanning 30 years, utilizing the WCST in participants with autism. We calculated Cohen’s d effect sizes for four measures of performance: sets completed, perseveration, failure-to-maintain-set, and non-perseverative errors. The average weighted effect size ranged from 0.30 to 0.74 for each measure, all statistically greater than 0. No evidence was found for reduced impairment when WCST is administered by computer. Age and PIQ predicted perseverative error rates, while VIQ predicted non-perseverative error rates, and both perseverative and non-perseverative error rates in turn predicted number of sets completed. No correlates of failure-to-maintain set errors were found; further research is warranted on this aspect of WCST performance in autism.
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14. Luo SX, Shinall JA, Peterson BS, Gerber AJ. {{Semantic mapping reveals distinct patterns in descriptions of social relations in adults with autism spectrum disorder}}. {Autism Res};2015 (Nov 27)
Adults with autism spectrum disorder (ASD) may describe other individuals differently compared with typical adults. In this study, we first asked participants to describe closely related individuals such as parents and close friends with 10 positive and 10 negative characteristics. We then used standard natural language processing methods to digitize and visualize these descriptions. The complex patterns of these descriptive sentences exhibited a difference in semantic space between individuals with ASD and control participants. Machine learning algorithms were able to automatically detect and discriminate between these two groups. Furthermore, we showed that these descriptive sentences from adults with ASD exhibited fewer connections as defined by word-word co-occurrences in descriptions, and these connections in words formed a less « small-world » like network. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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15. Nuttall JR. {{The plausibility of maternal toxicant exposure and nutritional status as contributing factors to the risk of autism spectrum disorders}}. {Nutr Neurosci};2015 (Nov 27)
Recent research suggests the maternal environment may be especially important for the risk of developing autism spectrum disorders (ASD). In particular maternal infections, micronutrient deficiencies, obesity, and toxicant exposures are likely to interact with genetic risk factors to disrupt fetal brain development. Objectives The goal of this paper is to investigate the plausibility of maternal toxicant exposure and nutritional status as causal factors in the development of ASD. Methods This paper reviews current research investigating the hypothesis that maternal toxicant exposure and prenatal micronutrient intake are important modifiable risk factors for ASD. Results Zinc, copper, iron, and vitamin B9 are identified as specific micronutrients with relevance to the etiology of ASD. Specific toxicants induce a maternal inflammatory response leading to fetal micronutrient deficiencies that disrupt early brain development. Importantly, maternal micronutrient supplementation is associated with reduced risk of ASD. Furthermore, animal studies show that micronutrient supplementation can prevent the teratogenicity and developmental neurotoxicity of specific toxicants. Discussion These findings lead to the hypothesis that maternal infection, obesity, and toxicant exposures (e.g. valproic acid, endocrine disrupting plasticizers, ethanol, and heavy metals) are all environmental risk factors for ASD that lead to fetal micronutrient deficiencies resulting from a maternal inflammatory response. It could be possible to use markers of inflammation and micronutrient status to identify women that would benefit from micronutrient supplementation or dietary interventions to reduce the risk of ASD. However, more research is needed to demonstrate a causal role of fetal micronutrient deficiencies and clarify the underlying mechanisms that contribute to ASD.
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16. Pamphlett R, Kum Jew S. {{Locus ceruleus neurons in people with autism contain no histochemically-detectable mercury}}. {Biometals};2015 (Nov 27)
Exposure to environmental mercury has been proposed to play a part in autism. Mercury is selectively taken up by the human locus ceruleus, a region of the brain that has been implicated in autism. We therefore looked for the presence of mercury in the locus ceruleus of people who had autism, using the histochemical technique of autometallography which can detect nanogram amounts of mercury in tissues. In addition, we sought evidence of damage to locus ceruleus neurons in autism by immunostaining for hyperphosphorylated tau. No mercury was found in any neurons of the locus ceruleus of 6 individuals with autism (5 male, 1 female, age range 16-48 years). Mercury was present in locus ceruleus neurons in 7 of 11 (64 %) age-matched control individuals who did not have autism, which is significantly more than in individuals with autism. No increase in numbers of locus ceruleus neurons containing hyperphosphorylated tau was detected in people with autism. In conclusion, most people with autism have not been exposed early in life to quantities of mercury large enough to be found later in adult locus ceruleus neurons. Human locus ceruleus neurons are sensitive indicators of mercury exposure, and mercury appears to remain in these neurons indefinitely, so these findings do not support the hypothesis that mercury neurotoxicity plays a role in autism.
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17. Parsons TD, Carlew AR. {{Bimodal Virtual Reality Stroop for Assessing Distractor Inhibition in Autism Spectrum Disorders}}. {J Autism Dev Disord};2015 (Nov 27)
Executive functioning deficits found in college students with ASD may have debilitating effects on their everyday activities. Although laboratory studies tend to report unimpaired inhibition in autism, studies of resistance to distractor inhibition reveal difficulties. In two studies, we compared a Virtual Classroom task with paper-and-pencil and computerized Stroop modalities in typically developing individuals and individuals with ASD. While significant differences were not observed between ASD and neurotypical groups on the paper-and-pencil and computerized task, individuals with ASD performed significantly worse on the virtual task with distractors. Findings suggest the potential of the Virtual Classroom Bimodal Stroop task to distinguish between prepotent response inhibition (non-distraction condition) and resistance to distractor inhibition (distraction condition) in adults with high functioning autism.
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18. Petkovic ZB, Marsanic VB, Divcic B, Ercegovic N. {{Late diagnosis of Asperger syndrome in Croatia – a low-income country}}. {Psychiatr Danub};2015 (Dec);27(4):426-428.
19. Picci G, Scherf KS. {{A Two-Hit Model of Autism: Adolescence as the Second Hit}}. {Clin Psychol Sci};2015 (May);3(3):349-371.
Adolescence brings dramatic changes in behavior and neural organization. Unfortunately, for some 30% of individuals with autism, there is marked decline in adaptive functioning during adolescence. We propose a two-hit model of autism. First, early perturbations in neural development function as a « first hit » that sets up a neural system that is « built to fail » in the face of a second hit. Second, the confluence of pubertal hormones, neural reorganization, and increasing social demands during adolescence provides the « second hit » that interferes with the ability to transition into adult social roles and levels of adaptive functioning. In support of this model, we review evidence about adolescent-specific neural and behavioral development in autism. We conclude with predictions and recommendations for empirical investigation about several domains in which developmental trajectories for individuals with autism may be uniquely deterred in adolescence.
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20. Woodman AC, Mailick MR, Greenberg JS. {{Trajectories of internalizing and externalizing symptoms among adults with autism spectrum disorders}}. {Dev Psychopathol};2015 (Nov 27):1-17.
Individuals with autism spectrum disorder (ASD) experience higher rates of psychopathology than their typically developing peers or peers with other intellectual or developmental disabilities. Little is known about the developmental course of psychiatric symptoms such as internalizing and externalizing behaviors in this population. Individual characteristics and aspects of the family environment may explain variability in outcomes for adults with ASD. The present study extends our current understanding of psychopathology among individuals with ASD by examining group-based trajectories of internalizing and externalizing symptoms in adulthood. Overall, the results showed that symptoms became less severe over time. Distinct patterns of change in psychopathology were observed and associated with differential profiles of psychotropic medication use, comorbid mental health diagnoses, and residential placement. The likelihood of following each developmental trajectory was estimated based on characteristics of the adults with ASD (gender, adaptive behavior, and autistic symptoms) and maternal expressed emotion (criticism and warmth). Maternal criticism and warmth were identified as key risk and protective factors, respectively, with important implications for future research and intervention for individuals with ASD.
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21. Zwaigenbaum L, Bryson SE, Brian J, Smith IM, Roberts W, Szatmari P, Roncadin C, Garon N, Vaillancourt T. {{Stability of diagnostic assessment for autism spectrum disorder between 18 and 36 months in a high-risk cohort}}. {Autism Res};2015 (Nov 27)
Children with autism spectrum disorder (ASD) are diagnosed, on average, around the age of 4 years. However, previous research has shown that the diagnosis can be made as early as 2 years, and that if the child is seen a year or more later, it is highly likely that the diagnosis will be confirmed. In this study, to examine whether diagnoses made as early as 18 months of age are also « stable, » we followed a group of younger siblings of children with ASD (who are known to be at higher risk). We also examined whether the age of ASD diagnosis within this high-risk group was related to the severity of children’s ASD symptoms or developmental delays. Participants (n = 381) were seen at three ages: 18 months, 24 months, and 3 years. ASD symptoms, general development, and adaptive functioning were assessed at each time point. Twenty-three children were diagnosed with ASD at 18 months and a total of 61 at 24 months. Of these diagnoses, 19/23 (82.6%) and 56/61 (91.8%), respectively, were confirmed independently at 3 years. However, 45 children were diagnosed with ASD at 3 years who had not been identified at earlier visits. Children diagnosed at 18 months, in comparison to those diagnosed at 24 months, had less advanced language and adaptive skills at 18 months. Children not diagnosed with ASD until 3 years, compared with those diagnosed earlier, had more advanced language and adaptive skills, and milder ASD symptoms. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.