1. Aldridge K, George ID, Cole KK, Austin JR, Takahashi TN, Duan Y, Miles JH. {{Facial phenotypes in subgroups of pre-pubertal boys with autism spectrum disorders are correlated with clinical phenotypes}}. {Mol Autism};2011 (Oct 14);2(1):15.
ABSTRACT: BACKGROUND: The brain develops in concert and in coordination with the developing facial tissues, with each influencing the development of the other and sharing genetic signaling pathways. Autism spectrum disorders (ASDs) result from alterations in the embryological brain, suggesting that the development of the faces of children with ASD may result in subtle facial differences compared to typically developing children. In this study, we tested two hypotheses. First, we asked whether children with ASD display a subtle but distinct facial phenotype compared to typically developing children. Second, we sought to determine whether there are subgroups of facial phenotypes within the population of children with ASD that denote biologically discrete subgroups. METHODS: The 3dMD cranial System was used to acquire three dimensional stereophotogrammetric images for our study sample of 8- to 12-year-old boys diagnosed with essential ASD (n = 65) and typically developing boys (n = 41) following approved Institutional Review Board protocols. Three dimensional coordinates were recorded for 17 facial anthropometric landmarks using the 3dMD Patient software . Statistical comparisons of facial phenotypes were completed using Euclidean Distance Matrix Analysis and Principal Coordinates Analysis. Data representing clinical and behavioral traits were statistically compared among groups by using chi2 tests, Fisher’s exact tests, Kolmogorov-Smirnov tests and Student’s t-tests where appropriate. RESULTS: First, we found that there are significant differences in facial morphology in boys with ASD compared to typically developing boys. Second, we also found two subgroups of boys with ASD with facial morphology that differed from the majority of the boys with ASD and the typically developing boys. Furthermore, membership in each of these distinct subgroups was correlated with particular clinical and behavioral traits. CONCLUSIONS: Boys with ASD display a facial phenotype distinct from that of typically developing boys, which may reflect alterations in the prenatal development of the brain. Subgroups of boys with ASD defined by distinct facial morphologies correlated with clinical and behavioral traits, suggesting potentially different etiologies and genetic differences compared to the larger group of boys with ASD. Further investigations into genes involved in neurodevelopment and craniofacial development of these subgroups will help to elucidate the causes and significance of these subtle facial differences. KEYWORDS: autism, neurodevelopment, anthropometry, facial phenotype, biomarker, craniofacial genetics.
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2. Anagnostou E, Hansen R. {{Medical treatment overview: traditional and novel psycho-pharmacological and complementary and alternative medications}}. {Curr Opin Pediatr};2011 (Oct 13)
PURPOSE OF REVIEW: Up to 35% of children and youth with autism spectrum disorder (ASD) receive at least one psychotropic medication. 50-70% of this population also receives biologically based complementary and alternative medicine (CAM). The data evaluating such practices are being reviewed. RECENT FINDINGS: There are accumulating data to suggest that atypical antipsychotics and stimulants may be useful for the treatment of irritability and hyperactivity in children and youth with ASD. The data for the use of selective serotonin reuptake inhibitors are less promising. New avenues of pharmacologic research targeting molecular targets identified by genomics, animal models and neuropathology are being evaluated. Areas of interest include glutamate/gamma-aminobutyric acid systems, neuropeptides such as oxytocin, and immune dysfunction, among others. In the case of biologically based CAM, a few compounds have been shown to be well tolerated, although efficacy is still being evaluated, such as melatonin, certain vitamins, and omega 3 fatty acids. Others have safety concerns without demonstrated efficacy, such as chelation therapies. SUMMARY: Accumulating data suggest a series of existing medications may be useful in ASD and large randomized clinical trials are necessary to evaluate safety and efficacy of both pharmaceuticals and alternative treatments.
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3. Buchbinder M. {{« Sticky » Brains and Sticky Encounters in a U.S. Pediatric Pain Clinic}}. {Cult Med Psychiatry};2011 (Oct 18)
In the U.S. multidisciplinary pediatric pain clinic where I conducted 18 months of fieldwork, a widely held explanatory model tied the neurobiology of intractable pain to certain features of pervasive developmental disorders (PDD) such as concrete thinking, an interest in details, and hyper-attentiveness. Clinicians used terms such as « sticky brains » and « sticky neurons » to describe the perseverative thoughts and quirky behavior that characterized a sizable subset of the program’s chronic pain patients who were believed to show signs of PDD, and consequently, did not respond well to treatment. Drawing on observations of clinical consultations, team meetings, and interviews with clinicians and families, I examine the meta-discursive processes by which clinical difficulties were inscribed onto difficult patients. Specifically, I demonstrate how discourse on sticky brains worked to re-classify challenging patients as psychologically abnormal, rationalizing their failed response to standard treatment. I argue that ‘stickiness’ provides an appropriate metaphor not only for a particular neurobiological configuration, but also for challenging clinical encounters. By illuminating the interactional processes through which clinical difficulties are managed, interpreted, and explained, the paper advances anthropological theorizing on the performative work of diagnosis and institutionalized misrecognition.
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4. Chonchaiya W, Au J, Schneider A, Hessl D, Harris SW, Laird M, Mu Y, Tassone F, Nguyen DV, Hagerman RJ. {{Increased prevalence of seizures in boys who were probands with the FMR1 premutation and co-morbid autism spectrum disorder}}. {Hum Genet};2011 (Oct 15)
Seizures are a common co-occurring condition in those with fragile X syndrome (FXS), and in those with idiopathic autism spectrum disorder (ASD). Seizures are also associated with ASD in those with FXS. However, little is known about the rate of seizures and how commonly these problems co-occur with ASD in boys with the FMR1 premutation. We, therefore, determined the prevalence of seizures and ASD in boys with the FMR1 premutation compared with their sibling counterparts and population prevalence estimates. Fifty premutation boys who presented as clinical probands (N = 25), or non-probands (identified by cascade testing after the proband was found) (N = 25), and 32 non-carrier controls were enrolled. History of seizures was documented and ASD was diagnosed by standardized measures followed by a team consensus of ASD diagnosis. Seizures (28%) and ASD (68%) were more prevalent in probands compared with non-probands (0 and 28%), controls (0 and 0%), and population estimates (1 and 1.7%). Seizures occurred more frequently in those with the premutation and co-morbid ASD particularly in probands compared with those with the premutation alone (25 vs. 3.85%, p = 0.045). Although cognitive and adaptive functioning in non-probands were similar to controls, non-probands were more likely to meet the diagnosis of ASD than controls (28 vs. 0%, p < 0.0001). In conclusion, seizures were relatively more common in premutation carriers who presented clinically as probands of the family and seizures were commonly associated with ASD in these boys. Therefore, boys with the premutation, particularly if they are probands should be assessed carefully for both ASD and seizures.
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5. El-Ansary AK, Ben Bacha AG, Al-Ayadhi LY. {{Proinflammatory and proapoptotic markers in relation to mono and di-cations in plasma of autistic patients from Saudi Arabia}}. {J Neuroinflammation};2011 (Oct 15);8(1):142.
ABSTRACT: Objectives: Autism is a developmental disorder characterized by social and emotional deficits, language impairments and stereotyped behaviors that manifest in early postnatal life. This study aims to clarify the relationship amongst absolute and relative concentrations of K+, Na+, Ca2+, Mg2+ and/or proinflammatory and proapoptotic biomarkers. Materials and methods: Na+, K+, Ca2+, Mg2+, Na+/K+, Ca2+/Mg2+ together with IL6, TNFalpha as proinflammatory cytokines and caspase3 as proapoptotic biomarker were determined in plasma of 25 Saudi autistic male patients and compared to 16 age and gender matching control samples. RESULTS: The obtained data recorded that Saudi autistic patients have a remarkable lower plasma caspase3, IL6, TNFalpha, Ca2+ and a significantly higher K+ compared to age and gender matching controls. On the other hand both Mg2+ and Na+ were non-significantly altered in autistic patients. Pearson correlations revealed that plasma concentrations of the measured cytokines and caspase-3 were positively correlated with Ca2+ and Ca2+/K+ ratio. Reciever Operating Characteristics analysis (ROC) analysis proved that the measured parameters recorded satisfactory levels of specificity and sensitivity. CONCLUSION: Alteration of the selected measured ions confirms that oxidative stress and defective mitochondrial energy production could be contributed in the pathogenesis of autism. Moreover, it highlights the relationship between the measured ions, IL6, TNFalpha and caspase3 as a set of signalling pathways that might have a role in generating this increasingly prevalent disorder. Ions and the possible proinflammation and proapoptic mechanisms of autistics’ brains were hypothesized and explained.
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6. Hattori K, Tanaka H, Yamamoto N, Teraishi T, Hori H, Kinoshita Y, Matsuo J, Kawamoto Y, Kunugi H. {{Blood CADPS2DeltaExon3 expression is associated with intelligence and memory in healthy adults}}. {Biol Psychol};2011 (Oct 12)
Ca(2+)-dependent activator protein for secretion 2 (CADPS2), a secretory granule associate protein, mediates monoamine transmission and neurotrophin release. Both monoamines and neurotrophins play a crucial role in cognition, learning and memory. An aberrant splice variant of CADPS2, CADPS2DeltaExon3, was reported to be associated with autism. Therefore, we examined the possible association between the expression of CADPS2/CADPS2DeltaExon3 in peripheral blood and brain functions such as intelligence and memory. Quantitative polymerase chain reaction analysis was performed in 271 healthy adults (age range 20-74 years, mean+/-SD 43.3+/-15.3). Data on intelligence quotient (IQ) and memory were obtained by using full versions of the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the Wechsler Memory Scale-Revised (WMS-R), respectively. CADPS2 expression levels were not significantly associated with any scores/sub-scores of these scales. However, CADPS2DeltaExon3 expression was significantly associated with lower IQ (p=0.022; effect size: eta(p)(2)=0.031), particularly verbal IQ of WAIS-R (p=0.019; eta(p)(2)=0.032), lower verbal memory (p=0.026; eta(p)(2)=0.026) and delayed recall (p=0.042; eta(p)(2)=0.021) of WMS-R. Our results suggest that CADPS2DeltaExon3 affects intelligence and memory in the non-clinical population.
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7. Kirkland A. {{The Legitimacy of Vaccine Critics: What Is Left after the Autism Hypothesis?}}. {J Health Polit Policy Law};2011 (Oct 14)
The last dozen years have seen a massive transnational mobilization of the legal, political, and research communities in response to the worrisome hypothesis that vaccines could have a link to childhood autism and other developmental conditions. Vaccine critics, some already organized and some composed of newly galvanized parents, developed an alternate world of internally legitimating studies, blogs, conferences, publications, and spokespeople to affirm a connection. When the consensus turned against the autism hypothesis, these structures and a committed membership base unified all the organizations in resistance. This article examines the relationship between mobilization based on science and the trajectory of legitimacy vaccine criticism has taken. I argue that vaccine critics have run up against the limits of legitimate scientific argument and are now in the curious position of both doubling down on credibility-depleting stances and innovating new and possibly resonant formulations.
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8. Kroger A, Hanig S, Seitz C, Palmason H, Meyer J, Freitag CM. {{Risk factors of autistic symptoms in children with ADHD}}. {Eur Child Adolesc Psychiatry};2011 (Oct 16)
Autistic symptoms are frequently observed in children with attention-deficit/hyperactivity disorder (ADHD), but their etiology remains unclear. The main aim of this study was to describe risk factors for increased autistic symptoms in children with ADHD without an autism or autism-spectrum diagnosis. Comorbid psychiatric disorders, developmental delay, current medication, prenatal biological and postnatal psychosocial risk factors as well as parental autistic traits were assessed in 205 children with ADHD. Linear regression models identified maternal autistic traits, current familial risk factors and hyperactive symptoms as predictors of autistic symptoms in children with ADHD. Findings are indicative of possible genetic as well as environmental risk factors mediating autistic symptoms in children with ADHD. An additional validity analysis by ROC, area under the curve (AUC), suggested a cut-off of 11 to differentiate between ADHD and high-functioning ASD by the Social Communication Questionnaire (SCQ).
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9. Mashal N, Kasirer A. {{Principal component analysis study of visual and verbal metaphoric comprehension in children with autism and learning disabilities}}. {Res Dev Disabil};2011 (Oct 14);33(1):274-282.
This research extends previous studies regarding the metaphoric competence of autistic and learning disable children on different measures of visual and verbal non-literal language comprehension, as well as cognitive abilities that include semantic knowledge, executive functions, similarities, and reading fluency. Thirty seven children with autism (ASD), 20 children with learning disabilities (LD), and 21 typically developed (TD) children participated in the study. Principal components analysis was used to examine the interrelationship among the various tests in each group. Results showed different patterns in the data according to group. In particular, the results revealed that there is no dichotomy between visual and verbal metaphors in TD children but rather metaphor are classified according to their familiarity level. In the LD group visual metaphors were classified independently of the verbal metaphors. Verbal metaphoric understanding in the ASD group resembled the LD group. In addition, our results revealed the relative weakness of the ASD and LD children in suppressing irrelevant information.
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10. Patterson PH. {{Maternal infection and autism}}. {Brain Behav Immun};2011 (Oct 7)
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11. Rooms L, Kooy RF. {{Advances in understanding fragile X syndrome and related disorders}}. {Curr Opin Pediatr};2011 (Oct 13)
PURPOSE OF REVIEW: Fragile X syndrome is the most common form of inherited intellectual disability. Over the past 2 decades, insights into the cause of this disease have increased tremendously. This review will highlight recent discoveries with an emphasis on biochemical pathways affected in the disorder that are potentially amenable to treatment. RECENT FINDINGS: Recent work in the field demonstrated that multiple pathways are deregulated as a consequence of the FMR1 gene inactivation in patients with fragile X syndrome. In fragile X patients, no fragile X mental retardation protein is formed and thereby protein translation is compromised. As a consequence, a variety of biological pathways are disturbed. These pathways include mainly the metabotropic glutamate receptor and gamma-aminobutyric acid (GABA)ergic pathways, but recently potassium channels and the muscarinic cholinergic receptor have also been implied in fragile X syndrome. An overview is given of the potential therapeutic targets and clinical studies that have been performed. SUMMARY: The gene defect underlying fragile X syndrome was discovered back in 1991. Since then, there has been enormous progress in our understanding of the molecular basis of the disease. Excitingly, our insights have now reached a next phase in which therapy specifically targeting the underlying molecular defect becomes feasible.
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12. Schieve LA, Rice C, Devine O, Maenner MJ, Lee LC, Fitzgerald R, Wingate MS, Schendel D, Pettygrove S, Naarden Braun KV, Durkin M. {{Have Secular Changes in Perinatal Risk Factors Contributed to the Recent Autism Prevalence Increase? Development and Application of a Mathematical Assessment Model}}. {Ann Epidemiol};2011 (Oct 12)
BACKGROUND: A 57% increase in the U.S. prevalence of autism spectrum disorders (ASD) for 8-year-old children born in 1994 versus 1998 was recently reported. METHODS: To quantify the possible contributions of given risk/predictive factors on the recent ASD prevalence increase, we formulated a mathematical model based on the baseline risk factor prevalence (RFP), the proportionate change in RFP (cRFP), and the magnitude of the association between the risk factor and ASD [estimated relative risk (RR)]. We applied this model to several pregnancy-related factors (preterm, very preterm, low and very low birth weight, multiple birth, cesarean delivery, breech presentation, and assisted reproductive technology use). RFP and cRFP estimates for each factor were obtained from U.S. population-based surveillance datasets. Estimated RRs were obtained from a series of systematic literature reviews. RESULTS: We estimate that each risk factor examined, alone or in various combinations, accounted for a very small proportion (<1%) of the ASD increase. Additionally, hypothetical scenarios indicate RFP, cRFP, and RR all need to be sizable for a risk factor to appreciably influence ASD prevalence. CONCLUSIONS: Thus, although various pregnancy factors have been found to be associated with ASDs, the contribution of many of these factors to the recently observed ASD increase is likely minimal.
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13. Song Y, Kawabe T, Hakoda Y, Du X. {{Do the eyes have it? Extraction of identity and positive expression from another’s eyes in autism, probed using « Bubbles »}}. {Brain Dev};2011 (Oct 13)
Background: It has been debated whether attending to a particular facial region, such as the eyes, is impaired in children with autism. The purpose of this study was to verify the poor eye gaze hypothesis postulating that children with High-Functioning Autism (HFA)/AS are impaired in their ability to attend to another’s eyes. Methods: Our study used the « Bubbles » method. A group with ASD (n=15) and a paired non-ASD group (n=18) completed an identity judgment task requiring a binary judgment of the identity of a person in an image, and an emotion judgment task requiring perception of expressed happiness in a facial image. Results: Results indicated that similar to non-ASD individuals, ASD individuals used information from other people’s eyes to judge identity as well as emotion, and performed as successfully as the non-ASD group both in identity and emotion judgment tasks. The results challenge the conventional hypothesis that individuals with ASD cannot attend to or derive information from another’s eyes. Conclusion: Our findings combined with the results of poor eye gaze to expressions of fear in previous studies suggest that ASD individuals can derive information pertaining to positive emotion, but cannot sufficiently extract information pertaining to negative emotion from another’s eyes.
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14. Tavassoli T, Baron-Cohen S. {{Taste Identification in Adults with Autism Spectrum Conditions}}. {J Autism Dev Disord};2011 (Oct 18)
Sensory issues are widely reported in Autism Spectrum Conditions (ASC). Since taste perception is one of the least studied senses in ASC we explored taste identification in adults with ASC (12 males, 11 females) compared to control participants (14 males, 12 females). ‘Taste strips’ were used to measure taste identification overall, as well as bitter, sour, sweet and salty tastes. Results revealed lower taste scores overall in the ASC group, as well as for bitter, sour and sweet tastes. Salty taste scores did not differ between the groups. Examining error types showed that adults with ASC more often misidentified a taste as salty or as no taste. Future studies should investigate underlying mechanisms of taste identification difficulties in ASC.
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15. Willemsen MH, Valles A, Kirkels LA, Mastebroek M, Olde Loohuis N, Kos A, Wissink-Lindhout WM, de Brouwer AP, Nillesen WM, Pfundt R, Holder-Espinasse M, Vallee L, Andrieux J, Coppens-Hofman MC, Rensen H, Hamel BC, van Bokhoven H, Aschrafi A, Kleefstra T. {{Chromosome 1p21.3 microdeletions comprising DPYD and MIR137 are associated with intellectual disability}}. {J Med Genet};2011 (Oct 15)
BackgroundMicroRNAs (miRNAs) are non-coding gene transcripts involved in post-transcriptional regulation of genes. Recent studies identified miRNAs as important regulators of learning and memory in model organisms. So far, no mutations in specific miRNA genes have been associated with impaired cognitive functions.Methods and resultsIn three sibs and two unrelated patients with intellectual disability (ID), overlapping 1p21.3 deletions were detected by genome-wide array analysis. The shortest region of overlap included dihydropyrimidine dehydrogenase (DPYD) and microRNA 137 (MIR137). DPYD is involved in autosomal recessive dihydropyrimidine dehydrogenase deficiency. Hemizygous DPYD deletions were previously suggested to contribute to a phenotype with autism spectrum disorder and speech delay. Interestingly, the mature microRNA transcript microRNA-137 (miR-137) was recently shown to be involved in modulating neurogenesis in adult murine neuronal stem cells. Therefore, this study investigated the possible involvement of MIR137 in the 1p21.3-deletion phenotype. The patients displayed a significantly decreased expression of both precursor and mature miR-137 levels, as well as significantly increased expression of the validated downstream targets microphthalmia-associated transcription factor (MITF) and Enhancer of Zeste, Drosophila, Homologue 2 (EZH2), and the newly identified target Kruppel-like factor 4 (KLF4). The study also demonstrated significant enrichment of miR-137 at the synapses of cortical and hippocampal neurons, suggesting a role of miR-137 in regulating local synaptic protein synthesis machinery.ConclusionsThis study showed that dosage effects of MIR137 are associated with 1p21.3 microdeletions and may therefore contribute to the ID phenotype in patients with deletions harbouring this miRNA. A local effect at the synapse might be responsible.
