1. Araujo DJ, Anderson AG, Berto S, Runnels W, Harper M, Ammanuel S, Rieger MA, Huang HC, Rajkovich K, Loerwald KW, Dekker JD, Tucker HO, Dougherty JD, Gibson JR, Konopka G. {{FoxP1 orchestration of ASD-relevant signaling pathways in the striatum}}. {Genes Dev}. 2015; 29(20): 2081-96.
Mutations in the transcription factor Forkhead box p1 (FOXP1) are causative for neurodevelopmental disorders such as autism. However, the function of FOXP1 within the brain remains largely uncharacterized. Here, we identify the gene expression program regulated by FoxP1 in both human neural cells and patient-relevant heterozygous Foxp1 mouse brains. We demonstrate a role for FoxP1 in the transcriptional regulation of autism-related pathways as well as genes involved in neuronal activity. We show that Foxp1 regulates the excitability of striatal medium spiny neurons and that reduction of Foxp1 correlates with defects in ultrasonic vocalizations. Finally, we demonstrate that FoxP1 has an evolutionarily conserved role in regulating pathways involved in striatal neuron identity through gene expression studies in human neural progenitors with altered FOXP1 levels. These data support an integral role for FoxP1 in regulating signaling pathways vulnerable in autism and the specific regulation of striatal pathways important for vocal communication.
Lien vers le texte intégral (Open Access ou abonnement)
2. Broady TR, Stoyles GJ, Morse C. {{Understanding carers’ lived experience of stigma: the voice of families with a child on the autism spectrum}}. {Health Soc Care Community}. 2015.
Existing research suggests that there are several unique challenges associated with caring for a child on the autism spectrum. Despite a growing evidence base regarding autism spectrum disorders and their increasing prevalence, children on the autism spectrum and their families continue to perceive stigmatisation from various sources throughout the community. These perceptions of stigma can profoundly impact the quality of life of these children and their carers alike. This exploratory study sought to investigate carers’ perceptions of stigma in caring for a child with high functioning autism. Fifteen carers from Sydney and the South Coast regions of New South Wales, Australia, participated in semi-structured interviews regarding their caring experiences and any perceived encounters with stigma. Four domains of stigmatising experiences were identified: (i) lack of knowledge, (ii) judgement, (iii) rejection and (iv) lack of support. These domains were each reported to exist in four main contexts: (i) school, (ii) public, (iii) family and (iv) friends. These domains and contexts established a framework which provided a detailed account of how and where carers felt stigmatised, including the suggestion of a stigmatising pathway through the four domains. The main contexts in which stigma was perceived also appeared to be related, with those carers who experienced stigma in one context being more likely to report similar experiences in other contexts. Any attempts to empower carers in the face of stigmatisation should therefore consider each of these domains, the pathway that connects them and the relationship between different social contexts. Through identifying this pathway, supportive services can be acutely aware of how carers may perceive potentially stigmatising experiences and therefore provide appropriate interventions or support for the relevant stage of the pathway.
Lien vers le texte intégral (Open Access ou abonnement)
3. Careaga M, Rogers S, Hansen RL, Amaral DG, Van de Water J, Ashwood P. {{Immune Endophenotypes in Children with Autism Spectrum Disorder}}. {Biol Psychiatry}. 2015.
BACKGROUND: Autism spectrum disorder (ASD) is characterized by social communication deficits and restricted, repetitive patterns of behavior. Varied immunological findings have been reported in children with ASD. To address the question of heterogeneity in immune responses, we sought to examine the diversity of immune profiles within a representative cohort of boys with ASD. METHODS: Peripheral blood mononuclear cells from male children with ASD (n = 50) and from typically developing age-matched male control subjects (n = 16) were stimulated with either lipopolysaccharide or phytohemagglutinin. Cytokine production was assessed after stimulation. The ASD study population was clustered into subgroups based on immune responses and assessed for behavioral outcomes. RESULTS: Children with ASD who had a proinflammatory profile based on lipopolysaccharide stimulation were more developmentally impaired as assessed by the Mullen Scales of Early Learning. They also had greater impairments in social affect as measured by the Autism Diagnostic Observation Schedule. These children also displayed more frequent sleep disturbances and episodes of aggression. Similarly, children with ASD and a more activated T cell cytokine profile after phytohemagglutinin stimulation were more developmentally impaired as measured by the Mullen Scales of Early Learning. CONCLUSIONS: Children with ASD may be phenotypically characterized based upon their immune profile. Those showing either an innate proinflammatory response or increased T cell activation/skewing display a more impaired behavioral profile than children with noninflamed or non-T cell activated immune profiles. These data suggest that there may be several possible immune subphenotypes within the ASD population that correlate with more severe behavioral impairments.
Lien vers le texte intégral (Open Access ou abonnement)
4. Dyches TT, Christensen R, Harper JM, Mandleco B, Roper SO. {{Respite Care for Single Mothers of Children with Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2015.
Single mothers of children with autism spectrum disorders are rarely studied, yet they may experience unique stressors. Researchers asked 122 single mothers to complete questionnaires concerning respite care, daily hassles/uplifts, depression, and caregiver burden. More than half (59.8 %) accessed respite care, which was provided for 1 h per day, often by multiple sources (41 %), such as grandparents and community agencies; most were satisfied with this care. Most mothers (77 %) were at risk for clinical depression. While uplifts were negatively correlated with depression, hassles and caregiver burden were positively correlated with depression. Respite care was positively related to daily uplifts, and uplifts mediated the relationship between respite care and depression. Recommendations for researchers, policymakers, and school personnel are offered.
Lien vers le texte intégral (Open Access ou abonnement)
5. Floris DL, Lai MC, Auer T, Lombardo MV, Ecker C, Chakrabarti B, Wheelwright SJ, Bullmore ET, Murphy DG, Baron-Cohen S, Suckling J. {{Atypically rightward cerebral asymmetry in male adults with autism stratifies individuals with and without language delay}}. {Hum Brain Mapp}. 2015.
In humans, both language and fine motor skills are associated with left-hemisphere specialization, whereas visuospatial skills are associated with right-hemisphere specialization. Individuals with autism spectrum conditions (ASC) show a profile of deficits and strengths that involves these lateralized cognitive functions. Here we test the hypothesis that regions implicated in these functions are atypically rightward lateralized in individuals with ASC and, that such atypicality is associated with functional performance. Participants included 67 male, right-handed adults with ASC and 69 age- and IQ-matched neurotypical males. We assessed group differences in structural asymmetries in cortical regions of interest with voxel-based analysis of grey matter volumes, followed by correlational analyses with measures of language, motor and visuospatial skills. We found stronger rightward lateralization within the inferior parietal lobule and reduced leftward lateralization extending along the auditory cortex comprising the planum temporale, Heschl’s gyrus, posterior supramarginal gyrus, and parietal operculum, which was more pronounced in ASC individuals with delayed language onset compared to those without. Planned correlational analyses showed that for individuals with ASC, reduced leftward asymmetry in the auditory region was associated with more childhood social reciprocity difficulties. We conclude that atypical cerebral structural asymmetry is a potential candidate neurophenotype of ASC. Hum Brain Mapp, 2015. (c) 2015 Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
6. Grove R, Roth I, Hoekstra RA. {{The motivation for special interests in individuals with autism and controls: Development and validation of the special interest motivation scale}}. {Autism Res}. 2015.
Clinical observations and first person accounts of living with autism suggest that individuals with autism are highly motivated to engage in special interests, and that these interests remain important throughout life. Previous research assessing special interests has mainly focused on parental reports of children with autism spectrum conditions (ASC). To better understand the significance of and motivations for engaging in special interests it is essential to use self-report ratings. This paper aims to systematically explore the motivations for engagement in special interests, and whether these differ in adults with ASC, first-degree relatives and general population controls. The Special Interest Motivation Scale (SIMS) was developed to assess motivation to engage in special interests. The internal structure of this scale was evaluated using factor analysis, and mean scores on the SIMS factors were subsequently compared across individuals with autism, parents and general population controls. Factor analysis indicated a 20-item SIMS containing five factors assessing Personal life values and goals; Intrinsic interest and knowledge; Prestige; Engagement and « flow » and Achievement. Individuals with autism were more motivated by Intrinsic interest and knowledge and by Engagement and flow than controls. The 20-item SIMS is a quick to administer measure that provides a reliable description of motivation to engage in special interests. This study indicates that individuals with ASC are highly motivated to engage in their special interest, and are more motivated than controls by intrinsic motivational factors, some of which are associated with positive affect. This has implications for research and clinical practice. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
7. Lim CK, Essa MM, de Paula Martins R, Lovejoy DB, Bilgin AA, Waly MI, Al-Farsi YM, Al-Sharbati M, Al-Shaffae MA, Guillemin GJ. {{Altered kynurenine pathway metabolism in autism: Implication for immune-induced glutamatergic activity}}. {Autism Res}. 2015.
Dysfunction of the serotoninergic and glutamatergic systems is implicated in the pathogenesis of autism spectrum disorder (ASD) together with various neuroinflammatory mediators. As the kynurenine pathway (KP) of tryptophan degradation is activated in neuroinflammatory states, we hypothesized that there may be a link between inflammation in ASD and enhanced KP activation resulting in reduced serotonin synthesis from tryptophan and production of KP metabolites capable of modulating glutamatergic activity. A cross-sectional study of 15 different Omani families with newly diagnosed children with ASD (n = 15) and their age-matched healthy siblings (n = 12) was designed. Immunological profile and the KP metabolic signature were characterized in the study participants. Our data indicated that there were alterations to the KP in ASD. Specifically, increased production of the downstream metabolite, quinolinic acid, which is capable of enhancing glutamatergic neurotransmission was noted. Correlation studies also demonstrated that the presence of inflammation induced KP activation in ASD. Until now, previous studies have failed to establish a link between inflammation, glutamatergic activity, and the KP. Our findings also suggest that increased quinolinic acid may be linked to 16p11.2 mutations leading to abnormal glutamatergic activity associated with ASD pathogenesis and may help rationalize the efficacy of sulforaphane treatment in ASD. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
8. Maynard DW, McDonald TA, Stickle T. {{Parents as a Team: Mother, Father, a Child with Autism Spectrum Disorder, and a Spinning Toy}}. {J Autism Dev Disord}. 2015.
This paper is a single case study involving a visit to a diagnostic clinic for autism spectrum disorder. A young boy finds a toy that he can hold with one hand and spin with another. In order to retrieve the toy and leave it in the clinic, the parents engage in a team effort. We describe this achievement in terms of two styles of practice or interactional routines with differing participation frameworks. We examine not only how the parents work as a team using these styles, but also how they improvise to extract the spinning toy from their son’s grasp with minimal protest on his part.
Lien vers le texte intégral (Open Access ou abonnement)
9. Nair A, Carper RA, Abbott AE, Chen CP, Solders S, Nakutin S, Datko MC, Fishman I, Muller RA. {{Regional specificity of aberrant thalamocortical connectivity in autism}}. {Hum Brain Mapp}. 2015; 36(11): 4497-511.
Preliminary evidence suggests aberrant (mostly reduced) thalamocortical (TC) connectivity in autism spectrum disorder (ASD), but despite the crucial role of thalamus in sensorimotor functions and its extensive connectivity with cerebral cortex, relevant evidence remains limited. We performed a comprehensive investigation of region-specific TC connectivity in ASD. Resting-state functional MRI and diffusion tensor imaging (DTI) data were acquired for 60 children and adolescents with ASD (ages 7-17 years) and 45 age, sex, and IQ-matched typically developing (TD) participants. We examined intrinsic functional connectivity (iFC) and anatomical connectivity (probabilistic tractography) with thalamus, using 68 unilateral cerebral cortical regions of interest (ROIs). For frontal and parietal lobes, iFC was atypically reduced in the ASD group for supramodal association cortices, but was increased for cingulate gyri and motor cortex. Temporal iFC was characterized by overconnectivity for auditory cortices, but underconnectivity for amygdalae. Occipital iFC was broadly reduced in the ASD group. DTI indices (such as increased radial diffusion) for regions with group differences in iFC further indicated compromised anatomical connectivity, especially for frontal ROIs, in the ASD group. Our findings highlight the regional specificity of aberrant TC connectivity in ASD. Their overall pattern can be largely accounted for by functional overconnectivity with limbic and sensorimotor regions, but underconnectivity with supramodal association cortices. This could be related to comparatively early maturation of limbic and sensorimotor regions in the context of early overgrowth in ASD, at the expense of TC connectivity with later maturing cortical regions. Hum Brain Mapp 36:4497-4511, 2015. (c) 2015 Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
10. Tossebro J, Wendelborg C. {{Marriage, Separation and Beyond: A Longitudinal Study of Families of Children with Intellectual and Developmental Disabilities in a Norwegian Context}}. {J Appl Res Intellect Disabil}. 2015.
BACKGROUND: This study addresses family structure in families raising a child with disabilities in Norway. The aims are to add to the literature on termination of parental relationships and to explore family research topics that are rarely discussed in disability research, such as cohabitation versus marriage and repartnering. METHODS: Longitudinal survey data on families of children with intellectual and developmental disabilities who were born 1993-1995 were compared with register data on all families of same-aged children (five waves 1999-2012). RESULTS: Parents of children with disabilities had slightly lower termination rates and formalized their partnerships earlier. Furthermore, the rate of repartnering among divorced/separated mothers of young children with disabilities was similar to that of other mothers but decreases later in the child’s life course. CONCLUSIONS: Results support the view that findings diverge and are most likely dependent on context.
