1. Ashwood KL, Tye C, Azadi B, Cartwright S, Asherson P, Bolton P. {{Brief Report: Adaptive Functioning in Children with ASD, ADHD and ASD + ADHD}}. {J Autism Dev Disord}. 2015.
Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) often co-occur. Children with ASD and ADHD demonstrate deficits in adaptive functioning, yet pure and comorbid groups have not been directly compared. Vineland Adaptive Behaviour Scales (VABS-II) data were examined in boys with ASD (n = 17), ADHD (n = 31) and ASD + ADHD (n = 38). Results demonstrated lower socialisation and composite scores and greater discrepancy between cognitive and adaptive abilities in the ASD + ADHD group compared to the ADHD-only group. Significant associations were shown between reduced adaptive functioning and autism symptoms, but not ADHD symptoms. Children with ASD + ADHD present with exacerbated impairments in adaptive functioning relative to children with ADHD, associated with ASD symptoms. Disentangling variation in adaptive skills may aid the assessment of complex cases.
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2. Assadi F. {{Renal dysfunction in fetal alcohol syndrome: a potential contributor on developmental disabilities of offspring}}. {J Renal Inj Prev}. 2014; 3(4): 83-6.
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3. Calderoni S, Fantozzi P, Balboni G, Pagni V, Franzoni E, Apicella F, Narzisi A, Maestro S, Muratori F. {{The impact of internalizing symptoms on autistic traits in adolescents with restrictive anorexia nervosa}}. {Neuropsychiatr Dis Treat}. 2015; 11: 75-85.
BACKGROUND: Although previous studies indicated a positive association between restrictive anorexia-nervosa (AN-R) and autistic traits, the potential interference of psychiatric internalizing comorbidity on this association is not yet fully investigated. MATERIALS AND METHODS: The aim of this study was to explore autistic traits and internalizing psychopathology in adolescents (age range: 11.7-17.2 years) with AN-R. Twenty-five patients referred to two tertiary-care hospitals were compared to a large control group (N=170) with no differences in age and sex. AN-R patients and controls filled out instruments assessing autistic traits (autism spectrum quotient [AQ]), psychopathology (youth self-report [YSR] 11-18), and eating patterns (eating attitude test [EAT]). In order to disentangle the possible mediating role of internalizing symptoms on autistic traits, two separate control groups (called True and False healthy control, both composed of 25 eating-problem-free participants) were derived from the whole control group on the basis of the presence or absence of internalizing problems in the YSR. RESULTS: AN-R patients scored significantly higher on AQ compared to the whole control group and to controls without internalizing problems (True HC), but these differences disappeared when only controls with internalizing problems (False HC) were considered. CONCLUSION: Autistic traits in AN-R individuals may have been overestimated and may partly be due to comorbid internalizing symptoms in investigated patients.
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4. Deacon RM, Glass L, Snape M, Hurley MJ, Altimiras FJ, Biekofsky RR, Cogram P. {{NNZ-2566, a Novel Analog of (1-3) IGF-1, as a Potential Therapeutic Agent for Fragile X Syndrome}}. {Neuromolecular Med}. 2015.
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. Previous studies have implicated mGlu5 in the pathogenesis of the disease, and many agents that target the underlying pathophysiology of FXS have focused on mGluR5 modulation. In the present work, a novel pharmacological approach for FXS is investigated. NNZ-2566, a synthetic analog of a naturally occurring neurotrophic peptide derived from insulin-like growth factor-1 (IGF-1), was administered to fmr1 knockout mice correcting learning and memory deficits, abnormal hyperactivity and social interaction, normalizing aberrant dendritic spine density, overactive ERK and Akt signaling, and macroorchidism. Altogether, our results indicate a unique disease-modifying potential for NNZ-2566 in FXS. Most importantly, the present data implicate the IGF-1 molecular pathway in the pathogenesis of FXS. A clinical trial is under way to ascertain whether these findings translate into clinical effects in FXS patients.
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5. Erickson SR, LeRoy B. {{Health literacy and medication administration performance by caregivers of adults with developmental disabilities}}. {J Am Pharm Assoc (2003)}. 2015: e52-e60.
Objectives: To measure health literacy (HL) of caregivers of adults with intellectual/developmental disabilities (IDDs); to determine the association between HL and a medication administration task (MAT) assessment; and to identify caregiver characteristics associated with higher HL and MAT scores. Design: Cross-sectional study. Setting: Southeastern Michigan. Participants: Caregivers, aged 18 years or older, who provided supportive care of adults with IDDs. Interventions: Survey and demonstration. Main Outcome Measures: Short Test of Functional Health Literacy in Adults (STOFHLA); a MAT assessment consisting of interpretation of five sets of medication instructions followed by demonstration of understanding using a pill box; and a survey of caregivers’ demographics, medication-related experiences, education, characteristics of persons for whom they provide care, and care-related activities performed. Results: A total of 47 caregivers provided data. Caregivers had a mean age of 45.7 +/- 14.6 years; 41 (87.2%) were women and 38 (80.9%) had education beyond high school. Caregivers were involved in obtaining medication from pharmacies, reminded the person with IDD to take medications and/or administered them to the person, documented medication and health information, and accompanied persons with IDD to physician offices. Most did not conduct monitoring procedures. The STOFHLA mean score was 34.5 +/- 2.5 (median, 35; range, 22-36), while the MAT mean score was 12.0 +/- 2.2 (median, 12; range, 6-15). Compared with family caregivers, direct support staff more frequently had undergone some medication training and had other people with whom they could discuss medication questions, but they had worked with the person with IDD a significantly shorter amount of time. No significant differences in STOFHLA and MAT scores between the family caregivers and direct support staff were observed. Caregiver education was significantly correlated with the STOFHLA score. MAT scores were not significantly correlated with caregiver characteristics. Conclusion: Caregivers are involved in the medication use process for people who have IDD. Ensuring caregiver understanding of medication regimens and/or improving medication-related HL may be an important step to ensure safe and effective use of medications by people with IDD.
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6. Flevaris AV, Murray SO. {{Orientation-specific surround suppression in the primary visual cortex varies as a function of autistic tendency}}. {Front Hum Neurosci}. 2014; 8: 1017.
Individuals with autism spectrum disorder (ASD) exhibit superior performance on tasks that rely on local details in an image, and they exhibit deficits in tasks that require integration of local elements into a unified whole. These perceptual abnormalities have been proposed to underlie many of the characteristic features of ASD, but the underlying neural mechanisms are poorly understood. Here, we investigated the degree to which orientation-specific surround suppression, a well-known form of contextual modulation in visual cortex, is associated with autistic tendency in neurotypical (NT) individuals. Surround suppression refers to the phenomenon that the response to a stimulus in the receptive field of a neuron is suppressed when it is surrounded by stimuli just outside the receptive field. The suppression is greatest when the center and surrounding stimuli share perceptual features such as orientation. Surround suppression underlies a number of fundamental perceptual processes that are known to be atypical in individuals with ASD, including perceptual grouping and perceptual pop-out. However, whether surround suppression in the primary visual cortex (V1) is related to autistic traits has not been directly tested before. We used fMRI to measure the neural response to a center Gabor when it was surrounded by Gabors having the same or orthogonal orientation, and calculated a suppression index (SI) for each participant that denoted the magnitude of suppression in the same vs. orthogonal conditions. SI was positively correlated with degree of autistic tendency in each individual, as measured by the Autism Quotient (AQ) scale, a questionnaire designed to assess autistic traits in the general population. Age also correlated with SI and with autistic tendency in our sample, but did not account for the correlation between SI and autistic tendency. These results suggest a reduction in orientation-specific surround suppression in V1 with increasing autistic tendency.
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7. Itahashi T, Yamada T, Nakamura M, Watanabe H, Yamagata B, Jimbo D, Shioda S, Kuroda M, Toriizuka K, Kato N, Hashimoto R. {{Linked alterations in gray and white matter morphology in adults with high-functioning autism spectrum disorder: A multimodal brain imaging study}}. {Neuroimage Clin}. 2015; 7: 155-69.
Growing evidence suggests that a broad range of behavioral anomalies in people with autism spectrum disorder (ASD) can be linked with morphological and functional alterations in the brain. However, the neuroanatomical underpinnings of ASD have been investigated using either structural magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI), and the relationships between abnormalities revealed by these two modalities remain unclear. This study applied a multimodal data-fusion method, known as linked independent component analysis (ICA), to a set of structural MRI and DTI data acquired from 46 adult males with ASD and 46 matched controls in order to elucidate associations between different aspects of atypical neuroanatomy of ASD. Linked ICA identified two composite components that showed significant between-group differences, one of which was significantly correlated with age. In the other component, participants with ASD showed decreased gray matter (GM) volumes in multiple regions, including the bilateral fusiform gyri, bilateral orbitofrontal cortices, and bilateral pre- and post-central gyri. These GM changes were linked with a pattern of decreased fractional anisotropy (FA) in several white matter tracts, such as the bilateral inferior longitudinal fasciculi, bilateral inferior fronto-occipital fasciculi, and bilateral corticospinal tracts. Furthermore, unimodal analysis for DTI data revealed significant reductions of FA along with increased mean diffusivity in those tracts for ASD, providing further evidence of disrupted anatomical connectivity. Taken together, our findings suggest that, in ASD, alterations in different aspects of brain morphology may co-occur in specific brain networks, providing a comprehensive view for understanding the neuroanatomy of this disorder.
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8. Lartseva A, Dijkstra T, Buitelaar JK. {{Emotional language processing in autism spectrum disorders: a systematic review}}. {Front Hum Neurosci}. 2014; 8: 991.
In his first description of Autism Spectrum Disorders (ASD), Kanner emphasized emotional impairments by characterizing children with ASD as indifferent to other people, self-absorbed, emotionally cold, distanced, and retracted. Thereafter, emotional impairments became regarded as part of the social impairments of ASD, and research mostly focused on understanding how individuals with ASD recognize visual expressions of emotions from faces and body postures. However, it still remains unclear how emotions are processed outside of the visual domain. This systematic review aims to fill this gap by focusing on impairments of emotional language processing in ASD. We systematically searched PubMed for papers published between 1990 and 2013 using standardized search terms. Studies show that people with ASD are able to correctly classify emotional language stimuli as emotionally positive or negative. However, processing of emotional language stimuli in ASD is associated with atypical patterns of attention and memory performance, as well as abnormal physiological and neural activity. Particularly, younger children with ASD have difficulties in acquiring and developing emotional concepts, and avoid using these in discourse. These emotional language impairments were not consistently associated with age, IQ, or level of development of language skills. We discuss how emotional language impairments fit with existing cognitive theories of ASD, such as central coherence, executive dysfunction, and weak Theory of Mind. We conclude that emotional impairments in ASD may be broader than just a mere consequence of social impairments, and should receive more attention in future research.
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9. Leung RC, Pang EW, Cassel D, Brian JA, Smith ML, Taylor MJ. {{Early neural activation during facial affect processing in adolescents with Autism Spectrum Disorder}}. {Neuroimage Clin}. 2015; 7: 203-12.
Impaired social interaction is one of the hallmarks of Autism Spectrum Disorder (ASD). Emotional faces are arguably the most critical visual social stimuli and the ability to perceive, recognize, and interpret emotions is central to social interaction and communication, and subsequently healthy social development. However, our understanding of the neural and cognitive mechanisms underlying emotional face processing in adolescents with ASD is limited. We recruited 48 adolescents, 24 with high functioning ASD and 24 typically developing controls. Participants completed an implicit emotional face processing task in the MEG. We examined spatiotemporal differences in neural activation between the groups during implicit angry and happy face processing. While there were no differences in response latencies between groups across emotions, adolescents with ASD had lower accuracy on the implicit emotional face processing task when the trials included angry faces. MEG data showed atypical neural activity in adolescents with ASD during angry and happy face processing, which included atypical activity in the insula, anterior and posterior cingulate and temporal and orbitofrontal regions. Our findings demonstrate differences in neural activity during happy and angry face processing between adolescents with and without ASD. These differences in activation in social cognitive regions may index the difficulties in face processing and in comprehension of social reward and punishment in the ASD group. Thus, our results suggest that atypical neural activation contributes to impaired affect processing, and thus social cognition, in adolescents with ASD.
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10. Marko MK, Crocetti D, Hulst T, Donchin O, Shadmehr R, Mostofsky SH. {{Behavioural and neural basis of anomalous motor learning in children with autism}}. {Brain}. 2015.
Autism spectrum disorder is a developmental disorder characterized by deficits in social and communication skills and repetitive and stereotyped interests and behaviours. Although not part of the diagnostic criteria, individuals with autism experience a host of motor impairments, potentially due to abnormalities in how they learn motor control throughout development. Here, we used behavioural techniques to quantify motor learning in autism spectrum disorder, and structural brain imaging to investigate the neural basis of that learning in the cerebellum. Twenty children with autism spectrum disorder and 20 typically developing control subjects, aged 8-12, made reaching movements while holding the handle of a robotic manipulandum. In random trials the reach was perturbed, resulting in errors that were sensed through vision and proprioception. The brain learned from these errors and altered the motor commands on the subsequent reach. We measured learning from error as a function of the sensory modality of that error, and found that children with autism spectrum disorder outperformed typically developing children when learning from errors that were sensed through proprioception, but underperformed typically developing children when learning from errors that were sensed through vision. Previous work had shown that this learning depends on the integrity of a region in the anterior cerebellum. Here we found that the anterior cerebellum, extending into lobule VI, and parts of lobule VIII were smaller than normal in children with autism spectrum disorder, with a volume that was predicted by the pattern of learning from visual and proprioceptive errors. We suggest that the abnormal patterns of motor learning in children with autism spectrum disorder, showing an increased sensitivity to proprioceptive error and a decreased sensitivity to visual error, may be associated with abnormalities in the cerebellum.
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11. Nowell KP, Schanding GT, Jr., Kanne SM, Goin-Kochel RP. {{Cognitive Profiles in Youth with Autism Spectrum Disorder: An Investigation of Base Rate Discrepancies using the Differential Ability Scales-Second Edition}}. {J Autism Dev Disord}. 2015.
Extant data suggest that the cognitive profiles of individuals with ASD may be characterized by variability, particularly in terms of verbal intellectual functioning (VIQ) and non-verbal intellectual functioning (NVIQ) discrepancies. The Differential Ability Scales, Second Edition (DAS-II) has limited data available on its use with youth with ASD. The current study examined data from 2,110 youth with ASD in order to characterize performance on the DAS-II and to investigate potential discrepancies between VIQ and NVIQ. A larger proportion of individuals in the ASD sample had significant discrepancies between VIQ and NVIQ when compared to the normative sample [early years sample chi2 (2) = 38.36; p < .001; school age sample chi2 (2) = 13.48; p < .01]. Clinical and research implications are discussed.
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12. Ou JJ, Shi LJ, Xun GL, Chen C, Wu RR, Luo XR, Zhang FY, Zhao JP. {{Employment and financial burden of families with preschool children diagnosed with autism spectrum disorders in urban China: results from a descriptive study}}. {BMC Psychiatry}. 2015; 15(1): 3.
BackgroundAutism spectrum disorder (ASD) affects many aspects of family life, such as social and economic burden. Little investigation of this phenomenon has been carried out in China. We designed this study to evaluate the employment and financial burdens of families with ASD-diagnosed preschoolers.MethodsFour hundred and fifty-nine nuclear families of children with ASD, 418 with some other disability (OD) and 424 with typically developing (TD) children were recruited for this study. Employment and financial burdens of families were evaluated using a structured questionnaire; logistic regression was used to examine differences in job change measures by group, and ordinal logistic regression was used to investigate the association between household income and group.ResultsFifty-eight percent of families with ASD children and 19% of families with OD children reported that childcare problems had greatly affected their employment decisions, compared with 9% of families with TD children (p inverted question mark< inverted question mark0.001). Age of child, parental education and parental age notwithstanding, having a child with ASD and having a child with OD were both associated with increased odds of reporting that childcare greatly interfered with employment (ASD, OR: 15.936; OD, OR: 2.502; all p inverted question mark< inverted question mark0.001) and decreased the odds of living in a higher-income household (ASD, estimate inverted question mark= inverted question mark-1.271; OD, estimate inverted question mark= inverted question mark-0.569; all p inverted question mark< inverted question mark0.001). The average loss of annual income associated with having a child with ASD was Chinese RenMinBi (RMB) 44,077 ($7,226), compared with RMB 20,788 ($3,408) for families of OD children.ConclusionsASD is associated with severe employment and financial burdens, much more than for OD, in families with preschool children.
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13. Penagarikano O, Lazaro MT, Lu XH, Gordon A, Dong H, Lam HA, Peles E, Maidment NT, Murphy NP, Yang XW, Golshani P, Geschwind DH. {{Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism}}. {Sci Transl Med}. 2015; 7(271): 271ra8.
Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homolog of CNTNAP2 (contactin-associated protein-like 2), in which mutations cause cortical dysplasia and focal epilepsy (CDFE) syndrome, displays many features that parallel those of the human disorder. Because CDFE has high penetrance for autism spectrum disorder (ASD), we performed an in vivo screen for drugs that ameliorate abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment to rectify this deficit.
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14. Scherf KS, Elbich D, Minshew N, Behrmann M. {{Individual differences in symptom severity and behavior predict neural activation during face processing in adolescents with autism}}. {Neuroimage Clin}. 2015; 7: 53-67.
Despite the impressive literature describing atypical neural activation in visuoperceptual face processing regions in autism, almost nothing is known about whether these perturbations extend to more affective regions in the circuitry and whether they bear any relationship to symptom severity or atypical behavior. Using fMRI, we compared face-, object-, and house-related activation in adolescent males with high-functioning autism (HFA) and typically developing (TD) matched controls. HFA adolescents exhibited hypo-activation throughout the core visuoperceptual regions, particularly in the right hemisphere, as well as in some of the affective/motivational face-processing regions, including the posterior cingulate cortex and right anterior temporal lobe. Conclusions about the relative hyper- or hypo-activation of the amygdala depended on the nature of the contrast that was used to define the activation. Individual differences in symptom severity predicted the magnitude of face activation, particularly in the right fusiform gyrus. Also, among the HFA adolescents, face recognition performance predicted the magnitude of face activation in the right anterior temporal lobe, a region that supports face individuation in TD adults. Our findings reveal a systematic relation between the magnitude of neural dysfunction, severity of autism symptoms, and variation in face recognition behavior in adolescents with autism. In so doing, we uncover brain-behavior relations that underlie one of the most prominent social deficits in autism and help resolve discrepancies in the literature.
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15. Yang Q, Yang L, Zhang K, Guo YY, Liu SB, Wu Y, Li XQ, Song Q, Zhuo M, Zhao MG. {{Increased coupling of caveolin-1 and ERalpha contributes to the Fragile X syndrome}}. {Ann Neurol}. 2015.
Objective: Fragile X syndrome (FXS) is a form of inherited mental retardation in humans that results from expansion of a CGG repeat in the Fmr1 gene. Interaction between estrogen receptor (ER) and lipid raft caveolae is critical for the estrogen signaling. Here, we tested the hypothesis that impaired ER-caveolae coupling contributes to the mental retardation of Fragile X syndrome. Methods: Fmr1 knockout (KO) mouse was used as the model of Fragile X syndrome. Multiple techniques were performed including primary neuronal culture, shRNA interference, western blot, electrophysiological recording, RNA-binding protein immunoprecipitation, RT-PCR, and behavioral tests. Results: In this study, we reported that GluA1 surface expression and phosphorylation induced by 17beta-estradiol (E2) were impaired in the Fmr1 KO neurons. The E2-mediated facilitation of long-term potentiation and fear memory was impaired in the anterior cingulate cortex of Fmr1 KO mice. The increased coupling of caveolin-1 (CAV1) and the membrane estrogen receptor ERalpha under basal conditions contributed to the impairment of ER signaling in Fmr1 KO neurons. FMRP interacted with CAV1 mRNA, and knockdown of CAV1 with shRNA rescued the synaptic GluA1 delivery, plasticity, and memory in Fmr1 KO mice. Interpretation: This is the first demonstration that the coupling between ERalpha and lipid raft CAV1 is critical for the membrane estrogen receptor signaling in synaptic plasticity. Therefore, increased coupling of CAV1 and ERalpha may elucidate one of the critical abnormal mechanisms for fragile X syndrome. This article is protected by copyright. All rights reserved.