1. Azmitia EC, Saccomano ZT, Alzoobaee MF, Boldrini M, Whitaker-Azmitia PM. {{Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum}}. {Journal of autism and developmental disorders}. 2015 Dec 14.
In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was seen throughout superior temporal cortex (primary auditory cortex), fusiform cortex (face recognition center), pons/midbrain and cerebellum in postmortem brains from ASD patients but not control brains. We found significant increases in both nestin and CD34, which are markers of angiogenesis localized to pericyte cells and endothelial cells, respectively. This labeling profile is indicative of splitting (intussusceptive), rather than sprouting, angiogenesis indicating the blood vessels are in constant flux rather than continually expanding.
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2. Bennett M. {{The Importance of Interviewing Adults on the Autism Spectrum About Their Depression and Suicidal Ideation Experiences}}. {Journal of autism and developmental disorders}. 2015 Dec 14.
This letter will summarise the current body of literature on adults with Asperger syndrome and their depression and suicidal ideation experiences. The purpose of this summary is to highlight the lack of published research on adults with Asperger syndrome or autism describing these experiences.
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3. Casartelli L, Chiamulera C. {{The motor way: Clinical implications of understanding and shaping actions with the motor system in autism and drug addiction}}. {Cognitive, affective & behavioral neuroscience}. 2015 Dec 17.
To understand others’ minds is crucial for survival; however, it is quite puzzling how access to others’ minds can be-to some extent-direct and not necessarily mediated by conceptual reasoning. Recent advances in neuroscience have led to hypothesize a role for motor circuits not only in controlling the elementary physical features of movement (e.g., force, direction, and amplitude), but also in understanding and shaping human behavior. The concept of « motor cognition » refers to these aspects, and neurophysiological, neuroimaging, and behavioral studies in human and nonhuman primates support this view. From a clinical perspective, motor cognition represents a challenge in several domains. A thorough investigation of the neural mechanisms mediating motor action/intention understanding and automatized/compulsive behaviors seems to be a promising way to tackle a range of neurodevelopmental and drug-related disorders. On the one hand, anomalies in motor cognition may have cascade effects on social functioning in individuals with autism spectrum disorder (ASD); on the other, motor cognition may help explain the pathophysiology of drug-seeking and drug-taking behaviors in the most severe phase of drug addiction (i.e., see drug dependence, motor low-order cue reactivity). This may represent a promising approach that could improve the efficacy of rehabilitative interventions. The only way to shed light on multifactorial disorders such as ASD and drug addiction is through the investigation of their multiple factors. This motor way can promote new theoretical and experimental perspectives that would help bridge the gap between the basic neuroscience approach and clinical practice.
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4. Famula J, Basuta K, Gane LW, Hagerman RJ, Tassone F. {{Identification of a male with fragile X syndrome through newborn screening}}. {Intractable & rare diseases research}. 2015 Nov;4(4):198-202.
A pilot newborn screening (NBS) study for fragile X syndrome was recently conducted at the University of California, Davis Medical Center. The screening study identified a case of a male with the full mutation completely methylated and no detectable expression of the fragile X mental retardation-1 (FMR1) gene. The patient was initially seen in clinic at the MIND Institute, for medical follow-up and a genetic counseling session at the chronological age of 3 months. Since then, he has been seen in clinic every six months for follow up, medical examination and developmental assessments. Longitudinally administered developmental testing of the infant has revealed persistent delays in development, consistent with fragile X syndrome. Cascade testing revealed that the patient’s mother and two siblings also have the full mutation. The patient has been receiving speech and language therapy, combined with physical and occupational therapies on a weekly basis since the age of one year. He is currently being treated with 2.5 mg of sertraline, which has been demonstrated to be helpful for improving language in young children with the syndrome.
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5. Field C, Allen ML, Lewis C. {{Are Children with Autism Spectrum Disorder Initially Attuned to Object Function Rather Than Shape for Word Learning?}}. {Journal of autism and developmental disorders}. 2015 Dec 14.
We investigate the function bias-generalising words to objects with the same function-in typically developing (TD) children, children with autism spectrum disorder (ASD) and children with other developmental disorders. Across four trials, a novel object was named and its function was described and demonstrated. Children then selected the other referent from a shape match (same shape, different function) and function match (same function, different shape) object. TD children and children with ASD were ‘function biased’, although further investigation established that having a higher VMA facilitated function bias understanding in TD children, but having a lower VMA facilitated function bias understanding in children with ASD. This suggests that children with ASD are initially attuned to object function, not shape.
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6. Guo W, Ceolin L, Collins KA, Perroy J, Huber KM. {{Elevated CaMKIIalpha and Hyperphosphorylation of Homer Mediate Circuit Dysfunction in a Fragile X Syndrome Mouse Model}}. {Cell reports}. 2015 Dec 15;13(10):2297-311.
Abnormal metabotropic glutamate receptor 5 (mGluR5) function, as a result of disrupted scaffolding with its binding partner Homer, contributes to the pathophysiology of fragile X syndrome, a common inherited form of intellectual disability and autism caused by mutations in Fmr1. How loss of Fmr1 disrupts mGluR5-Homer scaffolds is unknown, and little is known about the dynamic regulation of mGluR5-Homer scaffolds in wild-type neurons. Here, we demonstrate that brief (minutes-long) elevations in neural activity cause CaMKIIalpha-mediated phosphorylation of long Homer proteins and dissociation from mGluR5 at synapses. In Fmr1 knockout (KO) cortex, Homers are hyperphosphorylated as a result of elevated CaMKIIalpha protein. Genetic or pharmacological inhibition of CaMKIIalpha or replacement of Homers with dephosphomimetics restores mGluR5-Homer scaffolds and multiple Fmr1 KO phenotypes, including circuit hyperexcitability and/or seizures. This work links translational control of an FMRP target mRNA, CaMKIIalpha, to the molecular-, cellular-, and circuit-level brain dysfunction in a complex neurodevelopmental disorder.
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7. Jones KB, Wilson B, Weedon D, Bilder D. {{Care of Adults With Intellectual and Developmental Disabilities: Traumatic Brain Injury}}. {FP essentials}. 2015 Dec;439:31-41.
Traumatic brain injuries (TBIs) manifest in various forms and severities, and patients with TBIs can have multiple physical and psychological comorbidities. The physician should be prepared to assess effects of the injury and associated comorbidities, and provide needed social support. Common comorbidities include cognitive changes; epilepsy; chronic pain; headache; sleep disorders; neuroendocrine disorders; dizziness and balance issues; substance abuse; depression and anxiety; dementia; and behavioral disturbances, such as aggression. Early severity and cognitive assessment after TBI is key. For patients with mild TBIs, short-term management focuses on cognitive rest, symptom management, and gradual return to regular activities. Short-term management of patients with moderate to severe TBI often requires intensive care unit admission, early psychological consultation, and use of mannitol and probiotics. Long-term care includes monitoring and managing of the physical, behavioral, emotional, and psychological comorbidities that commonly occur in patients with TBIs. Assisting patients in accessing community and government resources can be crucial for improving their independence and quality of life.
8. Jones KB, Wilson B, Weedon D, Bilder D. {{Care of Adults With Intellectual and Developmental Disabilities: Cerebral Palsy}}. {FP essentials}. 2015 Dec;439:26-30.
Cerebral palsy (CP) is a group of disorders that primarily affect motor function. This developmental disability is becoming more common in adults as life expectancy increases for individuals with CP. Many physical, medical, mental, and behavioral health conditions are associated with CP, and assistance should be provided to patients with CP to optimize function, when available. These comorbidities include intellectual disabilities, seizures, muscle contractures, abnormal gait, osteoporosis, communication disorders, malnutrition, sleep disorders, and mental health disorders, such as depression and anxiety. The physician should be familiar with screening for and assisting patients with these issues. Optimizing quality of life requires individualized care plans that may include physical therapy, muscle relaxants, surgery, and nutritional support. Other issues to be addressed include methods to facilitate employment; sexual concerns; and support through local and national organizations for patients, families, and caregivers.
9. Klapwijk ET, Aghajani M, Colins OF, Marijnissen GM, Popma A, van Lang ND, van der Wee NJ, Vermeiren RR. {{Different brain responses during empathy in autism spectrum disorders versus conduct disorder and callous-unemotional traits}}. {Journal of child psychology and psychiatry, and allied disciplines}. 2015 Dec 17.
BACKGROUND: Deficits in empathy are reported in autism spectrum disorders (ASD) and also underlie antisocial behavior of individuals with conduct disorder and callous-unemotional traits (CD/CU+). Many studies suggest that individuals with ASD are typically impaired in cognitive aspects of empathy, and individuals with CD/CU+ typically in affective aspects. In the current study, we compared the neural correlates of cognitive and affective aspects of empathy between youth with ASD and youth with CD/CU+. METHODS: Functional magnetic resonance imaging (fMRI) was used to assess boys with ASD (N = 23), boys with CD/CU+ (N = 23), and typically developing (TD) boys (N = 33), aged 15-19 years. Angry and fearful faces were presented and participants were asked to either infer the emotional state from the face (other-task; emotion recognition) or to judge their own emotional response to the face (self-task; emotional resonance). RESULTS: During emotion recognition, boys with ASD showed reduced responses compared to the other groups in the ventromedial prefrontal cortex (vmPFC). During emotional resonance, the CD/CU+ and ASD groups showed reduced amygdala responses compared to the TD controls, boys with ASD showed reduced responses in bilateral hippocampus, and the CD/CU+ boys showed reduced responses in the inferior frontal gyrus (IFG) and anterior insula (AI). CONCLUSION: Results suggest differential abnormal brain responses associated with specific aspects of empathic functioning in ASD and CD/CU+. Decreased amygdala responses in ASD and CD/CU+ might point to impaired emotion processing in both disorders, whereas reduced vmPFC responses suggest problems in processing cognitive aspects of empathy in ASD. Reduced IFG/AI responses, finally, suggest decreased emotional resonance in CD/CU+.
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10. Kleinhans NM, Reiter MA, Neuhaus E, Pauley G, Martin N, Dager S, Estes A. {{Subregional differences in intrinsic amygdala hyperconnectivity and hypoconnectivity in autism spectrum disorder}}. {Autism research : official journal of the International Society for Autism Research}. 2015 Dec 15.
The amygdala is a complex structure with distinct subregions and dissociable functional networks. The laterobasal subregion of the amygdala is hypothesized to mediate the presentation and severity of autism symptoms, although very little data are available regarding amygdala dysfunction at the subregional level. In this study, we investigated the relationship between abnormal amygdalar intrinsic connectivity, autism symptom severity, and anxiety and depressive symptoms. We collected resting state fMRI data on 31 high functioning adolescents and adults with autism spectrum disorder and 38 typically developing (TD) controls aged 14-45. Twenty-five participants with ASD and 28 TD participants were included in the final analyses. ASD participants were administered the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule. Adult participants were administered the Beck Depression Inventory II and the Beck Anxiety Inventory. Functional connectivity analyses were conducted from three amygdalar subregions: centromedial (CM), laterobasal (LB) and superficial (SF). In addition, correlations with the behavioral measures were tested in the adult participants. In general, the ASD group showed significantly decreased connectivity from the LB subregion and increased connectivity from the CM and SF subregions compared to the TD group. We found evidence that social symptoms are primarily associated with under-connectivity from the LB subregion whereas over-connectivity and under-connectivity from the CM, SF and LB subregions are related to co-morbid depression and anxiety in ASD, in brain regions that were distinct from those associated with social dysfunction, and in different patterns than were observed in mildly symptomatic TD participants. Our findings provide new evidence for functional subregional differences in amygdala pathophysiology in ASD. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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11. Oh S, Ji H, Barzman D, Lin PI, Hutton J. {{Pediatric asthma and autism-genomic perspectives}}. {Clinical and translational medicine}. 2015 Dec;4(1):37.
High-throughput technologies, ranging from microarrays to NexGen sequencing of RNA and genomic DNA, have opened new avenues for exploration of the pathobiology of human disease. Comparisons of the architecture of the genome, identification of mutated or modified sequences, and pre-and post- transcriptional regulation of gene expression as disease specific biomarkers are revolutionizing our understanding of the causes of disease and are guiding the development of new therapies. There is enormous heterogeneity in types of genomic variation that occur in human disease. Some are inherited, while others are the result of new somatic or germline mutations or errors in chromosomal replication. In this review, we provide examples of changes that occur in the human genome in two of the most common chronic pediatric disorders, autism and asthma. The incidence and economic burden of both of these disorders are increasing worldwide. Genomic variations have the potential to serve as biomarkers for personalization of therapy and prediction of outcomes.
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12. Pramparo T, Lombardo MV, Campbell K, Barnes CC, Marinero S, Solso S, Young J, Mayo M, Dale A, Ahrens-Barbeau C, Murray SS, Lopez L, Lewis N, Pierce K, Courchesne E. {{Cell cycle networks link gene expression dysregulation, mutation, and brain maldevelopment in autistic toddlers}}. {Molecular systems biology}. 2015;11(12):841.
Genetic mechanisms underlying abnormal early neural development in toddlers with Autism Spectrum Disorder (ASD) remain uncertain due to the impossibility of direct brain gene expression measurement during critical periods of early development. Recent findings from a multi-tissue study demonstrated high expression of many of the same gene networks between blood and brain tissues, in particular with cell cycle functions. We explored relationships between blood gene expression and total brain volume (TBV) in 142 ASD and control male toddlers. In control toddlers, TBV variation significantly correlated with cell cycle and protein folding gene networks, potentially impacting neuron number and synapse development. In ASD toddlers, their correlations with brain size were lost as a result of considerable changes in network organization, while cell adhesion gene networks significantly correlated with TBV variation. Cell cycle networks detected in blood are highly preserved in the human brain and are upregulated during prenatal states of development. Overall, alterations were more pronounced in bigger brains. We identified 23 candidate genes for brain maldevelopment linked to 32 genes frequently mutated in ASD. The integrated network includes genes that are dysregulated in leukocyte and/or postmortem brain tissue of ASD subjects and belong to signaling pathways regulating cell cycle G1/S and G2/M phase transition. Finally, analyses of the CHD8 subnetwork and altered transcript levels from an independent study of CHD8 suppression further confirmed the central role of genes regulating neurogenesis and cell adhesion processes in ASD brain maldevelopment.
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13. Searles Quick VB, Davis JM, Olincy A, Sikela JM. {{DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases}}. {Translational psychiatry}. 2015;5:e697.
The copy number of DUF1220, a protein domain implicated in human brain evolution, has been linearly associated with autism severity. Given the possibility that autism and schizophrenia are related disorders, the present study examined DUF1220 copy number variation in schizophrenia severity. There are notable similarities between autism symptoms and schizophrenia negative symptoms, and divergence between autism symptoms and schizophrenia positive symptoms. We therefore also examined DUF1220 copy number in schizophrenia subgroups defined by negative and positive symptom features, versus autistic individuals and controls. In the schizophrenic population (N=609), decreased DUF1220 copy number was linearly associated with increasing positive symptom severity (CON1 P=0.013, HLS1 P=0.0227), an association greatest in adult-onset schizophrenia (CON1 P=0.00155, HLS1 P=0.00361). In schizophrenic males, DUF1220 CON1 subtype copy number increase was associated with increased negative symptom severity (P=0.0327), a finding similar to that seen in autistic populations. Subgroup analyses demonstrated that schizophrenic individuals with predominantly positive symptoms exhibited reduced CON1 copy number compared with both controls (P=0.0237) and schizophrenic individuals with predominantly negative symptoms (P=0.0068). These findings support the view that (1) autism and schizophrenia exhibit both opposing and partially overlapping phenotypes and may represent a disease continuum, (2) variation in DUF1220 copy number contributes to schizophrenia disease risk and to the severity of both disorders, and (3) schizophrenia and autism may be, in part, a harmful by-product of the rapid and extreme evolutionary increase in DUF1220 copy number in the human species.
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14. Smith MA. {{Care of Adults With Intellectual and Developmental Disabilities: Foreword}}. {FP essentials}. 2015 Dec;439:2.
15. Takahashi T, Okabe S, Broin PO, Nishi A, Ye K, Beckert MV, Izumi T, Machida A, Kang G, Abe S, Pena JL, Golden A, Kikusui T, Hiroi N. {{Structure and function of neonatal social communication in a genetic mouse model of autism}}. {Molecular psychiatry}. 2015 Dec 15.
A critical step toward understanding autism spectrum disorder (ASD) is to identify both genetic and environmental risk factors. A number of rare copy number variants (CNVs) have emerged as robust genetic risk factors for ASD, but not all CNV carriers exhibit ASD and the severity of ASD symptoms varies among CNV carriers. Although evidence exists that various environmental factors modulate symptomatic severity, the precise mechanisms by which these factors determine the ultimate severity of ASD are still poorly understood. Here, using a mouse heterozygous for Tbx1 (a gene encoded in 22q11.2 CNV), we demonstrate that a genetically triggered neonatal phenotype in vocalization generates a negative environmental loop in pup-mother social communication. Wild-type pups used individually diverse sequences of simple and complicated call types, but heterozygous pups used individually invariable call sequences with less complicated call types. When played back, representative wild-type call sequences elicited maternal approach, but heterozygous call sequences were ineffective. When the representative wild-type call sequences were randomized, they were ineffective in eliciting vigorous maternal approach behavior. These data demonstrate that an ASD risk gene alters the neonatal call sequence of its carriers and this pup phenotype in turn diminishes maternal care through atypical social communication. Thus, an ASD risk gene induces, through atypical neonatal call sequences, less than optimal maternal care as a negative neonatal environmental factor.Molecular Psychiatry advance online publication, 15 December 2015; doi:10.1038/mp.2015.190.
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16. Weedon D, Wilson B, Jones KB, Bilder D. {{Care of Adults With Intellectual and Developmental Disabilities: Developmental Disabilities}}. {FP essentials}. 2015 Dec;439:11-9.
Approximately 4.8% of individuals in the United States are affected by developmental disabilities (DDs). These individuals have a spectrum of abilities in terms of communication, mobility, and activities of daily living (ADLs). Because there typically is no specific treatment for the underlying disability, the focus of care should be on diagnosing and managing co-occurring medical and mental or behavioral health conditions and improving function and quality of life. Care of patients with DDs is similar to care of patients without DDs, although adjustments may be needed in the physician’s interactive approach, engagement of caregivers, and sensitivity to symptoms. Health care can be enhanced by obtaining information about caregivers and guardians, living and work situations, support services received, and functional and instrumental ADL levels. In managing acute conditions, physicians should assess change from baseline and identify and manage maladaptive behaviors that interfere with care. An individualized preventive care plan should be created that may include additional or adapted screening. Needs for consent/medical decision-making support should be identified and addressed, and consent obtained as appropriate. Providing caregiver support and becoming familiar with community resources are other aspects of caring for this population.
17. Wilson B, Jones KB, Weedon D, Bilder D. {{Care of Adults With Intellectual and Developmental Disabilities: Down Syndrome}}. {FP essentials}. 2015 Dec;439:20-5.
Down syndrome (DS) is a genetic disorder involving excess genetic material from chromosome 21. The incidence of DS is increasing, and the life expectancy for individuals with DS has increased to a median age of 55 years. Adults with DS are at increased risk of several conditions, including significant neurologic, cardiovascular, pulmonary, gastrointestinal, musculoskeletal, endocrine, psychiatric, hematologic, and social comorbidities, and additional screening or monitoring may be needed. Additional preventive measures for patients with DS include regular screening for thyroid dysfunction, hearing loss, eye disorders, heart disease, osteoporosis, and dementia, and one-time vaccination with the polyvalent pneumococcal polysaccharide vaccine (PPV23). Quality of life should be the main focus of treatment, with patients being involved in medical decisions as much as possible.
18. Yang W, Xia H, Wen G, Liu L, Fu X, Lu J, Li H. {{Epidemiological investigation of suspected autism in children and implications for healthcare system: a mainstream kindergarten-based population study in Longhua District, Shenzhen}}. {BMC pediatrics}. 2015;15(1):207.
BACKGROUND: Individuals with autism put a heavy demand on medical services, and prevalence estimates are needed for the planning of such services. Screening for autism in children has important implications for individuals and policy makers. This study aimed to estimate prevalence of suspected autism in children in Longhua District, Shenzhen, and to investigate risk factors for autism. METHODS: A cross-sectional study was conducted in Longhua District, Shenzhen in October 2014. A total of 141 kindergartens were approached and consented to participate in the current study. All children who met the inclusion criteria were screened for autism by using the Autism Behavior Checklist (ABC). RESULTS: 15,200 children in total completed the survey and were included in the final analysis. 2.6 % (95 % CI 2.3-2.9) respondents had a high probability of autism, while 4.0 % (95 % CI 3.7-4.3) respondents had questionable autism. Male children were more likely to develop autism when compared with their female counterparts (P < 0.001). Children of mothers with a lower education level and younger age tended to develop autism (P < 0.001). CONCLUSIONS: Our study shows a high prevalence rate of suspected autism in children which suggests an urgent need of early detection of autism with ABC across the Shenzhen city, or even around China. Further studies with diagnostic procedure are warranted. Maternal age and education level, and gender of children are possible factors related to autism. Lien vers le texte intégral (Open Access ou abonnement)
19. Yusuf A, Elsabbagh M. {{At the cross-roads of participatory research and biomarker discovery in autism: the need for empirical data}}. {BMC medical ethics}. 2015;16(1):88.
BACKGROUND: Identifying biomarkers for autism can improve outcomes for those affected by autism. Engaging the diverse stakeholders in the research process using community-based participatory research (CBPR) can accelerate biomarker discovery into clinical applications. However, there are limited examples of stakeholder involvement in autism research, possibly due to conceptual and practical concerns. We evaluate the applicability of CBPR principles to biomarker discovery in autism and critically review empirical studies adopting these principles. METHODS: Using a scoping review methodology, we identified and evaluated seven studies using CBPR principles in biomarker discovery. RESULTS AND CONCLUSIONS: The limited number of studies in biomarker discovery adopting CBPR principles coupled with their methodological limitations suggests that such applications are feasible but challenging. These studies illustrate three CBPR themes: community assessment, setting global priorities, and collaboration in research design. We propose that further research using participatory principles would be useful in accelerating the pace of discovery and the development of clinically meaningful biomarkers. For this goal to be successful we advocate for increased attention to previously identified conceptual and methodological challenges to participatory approaches in health research, including improving scientific rigor and developing long-term partnerships among stakeholders.
