1. Aiello TP, Whitaker-Azmitia PM. {{Sexual Differentiation and the Neuroendocrine Hypothesis of Autism}}. {Anat Rec (Hoboken)}. 2011 Sep 8.
The phenotypic expression of autism spectrum disorders varies widely in severity and characteristics and it is, therefore, likely that a number of etiological factors are involved. However, one finding which has been found consistently is that there is a greater incidence of autism in boys than girls. Recently, attention has been given to the extreme male hypothesis-that is that autism behaviors are an extreme form of typical male behaviors, including lack of empathy and language deficits but an increase in so-called systemizing behaviors, such as attention to detail and collecting. This points to the possibility that an alteration during sexual differentiation of the brain may occur in autism. During sexual differentiation of the brain, two brain regions are highly sexually dimorphic-the amygdala and the hypothalamus. Both of these regions are also implicated in the neuroendocrine hypothesis of autism, wherein a balance between oxytocin and cortisol may contribute to the disorder. We are thus proposing that the extreme male hypothesis and the neuroendocrine hypothesis are in fact compatible in that sexual differentiation of the brain towards an extreme male phenotype would result in the neuroendocrine changes proposed in autism. We have preliminary data, treating developing rat pups with the differentiating hormone 17-beta estradiol during a critical time and showing changes in social behaviors and oxytocin, to support this hypothesis. Further studies should be undertaken to confirm the role of extremes of normal sexual differentiation in producing the neuroendocrine changes associated with autism. Anat Rec, 2011. (c) 2011 Wiley-Liss, Inc.
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2. Alderson-Day B. {{Verbal problem-solving in autism spectrum disorders: A problem of plan construction?}}. {Autism Res}. 2011 Sep 8.
Children with autism spectrum disorders (ASD) adopt less efficient strategies than typically developing controls (TD) on verbal problem-solving tests such as the Twenty Questions Task. This study examined the hypotheses that this can be explained by differences in (i) planning processes or (ii) selective attention. Twenty-two children with ASD and 21 TD controls matched for age (M(age) = 13:7) and cognitive ability (M(FSIQ) = 96.42) were tested on an adapted version of Twenty Questions and two planning tasks. ASD participants could recognize effective questions as well as TD participants on a forced-choice question discrimination task, but were observed to construct plans that were significantly less efficient. ASD performance was also specifically reduced when items could not be physically removed from the testing array, although this effect could be ameliorated by keeping a written record of participant questions during search. These findings indicate that ASD participants are sensitive to the within-task executive demands of Twenty Questions, but that their inefficiency in strategy relates to planning processes and question selection pretask. The implications for understanding ASD problem-solving skills and their impact on everyday functioning are discussed. Autism Res 2011,4:xxx-xxx. (c) 2011 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Azmitia EC, Singh JS, Hou XP, Wegiel J. {{Dystrophic Serotonin Axons in Postmortem Brains from Young Autism Patients}}. {Anat Rec (Hoboken)}. 2011 Sep 8.
Autism causes neuropathological changes in varied anatomical loci. A coherent neural mechanism to explain the spectrum of autistic symptomatology has not been proposed because most anatomical researchers focus on point-to-point functional neural systems (e.g., auditory and social networks) rather than considering global chemical neural systems. Serotonergic neurons have a global innervation pattern. Disorders Research Program, AS073234, Program Project (JW). Their cell bodies are found in the midbrain but they project their axons throughout the neural axis beginning in the fetal brain. This global system is implicated in autism by animal models and by biochemical, imaging, pharmacological, and genetics studies. However, no anatomical studies of the 5-HT innervation of autistic donors have been reported. Our review presents immunocytochemical evidence of an increase in 5-HT axons in postmortem brain tissue from autism donors aged 2.8-29 years relative to controls. This increase is observed in the principle ascending fiber bundles of the medial and lateral forebrain bundles, and in the innervation density of the amygdala and the piriform, superior temporal, and parahippocampal cortices. In autistic donors 8 years of age and up, several types of dystrophic 5-HT axons were seen in the termination fields. One class of these dystrophic axons, the thick heavily stained axons, was not seen in the brains of patients with neurodegenerative diseases. These findings provide morphological evidence for the involvement of serotonin neurons in the early etiology of autism, and suggest new therapies may be effective to blunt serotonin’s trophic actions during early brain development in children. Anat Rec, 2011. (c) 2011 Wiley-Liss, Inc.
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4. Bernier R, Gerdts J, Munson J, Dawson G, Estes A. {{Evidence for broader autism phenotype characteristics in parents from multiple-incidence autism families}}. {Autism Res}. 2011 Sep 8.
The broader autism phenotype (BAP) was assessed in parents who have two or more children with autism spectrum disorder (ASD) (multiplex (MPX) autism), parents who have no more than one child with ASD (simplex autism), parents who have a child with developmental delay without ASD, and parents who have typically developing children. Clinicians, naive to parent group membership status, rated BAP characteristics from videotaped administration of the Broader Autism Phenotype Symptom Scale (BPASS). Differences among groups in BPASS scores in the four assessed domains (social motivation, conversational skills, expressiveness, and restricted interests) were examined using multivariate ANOVA and post hoc comparisons. Further, ratings of videotapes by observers naive to family status were compared with live, non-naive ratings by observers who were aware of family status (non-naive). Findings demonstrate that the BPASS is an instrument resistant to rater bias. Parents from MPX autism families showed significantly more autism phenotype characteristics than the parents in the other groups. Moreover, the parents from simplex autism families did not differ from the parents of children with developmental delay or typical development. Finally, no differences between live, non-naive ratings and videotaped, naive ratings were observed. These findings suggest that characteristics of the BAP, specifically in the social and communication domains, are present in MPX autism parents to a greater degree than simplex autism and control parents. Further, the results provide support for the notion that genetic transmission mechanisms may differ between families with more than one child with autism and families with only one child with autism. Autism Res 2011,4:xxx-xxx. (c) 2011 International Society for Autism Research, Wiley Periodicals, Inc.
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5. Blatt GJ, Fatemi SH. {{Alterations in GABAergic Biomarkers in the Autism Brain: Research Findings and Clinical Implications}}. {Anat Rec (Hoboken)}. 2011 Sep 8.
Autism is a pervasive developmental disorder characterized by repetitive stereotyped behavior, social-emotional deficits, and delayed or absent language abilities. There are known neuropathologies in the autism brain affecting limbic, cerebellar, and cortical structures but the neurochemical profile of affected individuals, revealed in postmortem tissue studies, is only recently emerging. One major component that appears highly impacted in autism is the GABAergic system. It is now apparent that there are widespread significant effects in many distributed regions in the autism brain revealed by histochemical, autoradiographic, and biochemical studies. The key synthesizing enzymes for GABA, glutamic acid decarboxylase type 65 and 67 (GAD65 and GAD67), are decreased in the cerebellum and closer examination of mRNA levels revealed that it is largely due to decreases in Purkinje cells and a subpopulation of larger dentate neurons as measured by in situ hybridization studies. Other cell types had either normal GAD levels (Golgi cells, smaller dentate interneurons, and stellate cells) or increased levels (basket cells). GABA receptor density, number, and protein expression are all decreased in the cerebellum and in select cortical areas. GABA(A) and GABA(B) subunit protein expression was significantly reduced in cerebellum, BA 9 and BA 40. Benzodiazepine binding sites were significantly reduced in the hippocampus and anterior cingulate cortex (BA 24). Taken together, data from these studies suggest that there is a marked dysregulation of the inhibitory GABA system in the autism brain affecting particular biomarkers localized to specific cell types and lamina likely influencing circuitry and behavior. Anat Rec, 2011. (c) 2011 Wiley-Liss, Inc.
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6. Calderoni S, Retico A, Biagi L, Tancredi R, Muratori F, Tosetti M. {{Female children with autism spectrum disorder: An insight from mass-univariate and pattern classification analyses}}. {Neuroimage}. 2011 Aug 27.
Several studies on structural MRI in children with autism spectrum disorders (ASD) have mainly focused on samples prevailingly consisting of males. Sex differences in brain structure are observable since infancy and therefore caution is required in transferring to females the results obtained for males. The neuroanatomical phenotype of female children with ASD (ASDf) represents indeed a neglected area of research. In this study, we investigated for the first time the anatomic brain structures of a sample entirely composed of ASDf (n=38; 2-7years of age; mean=53months; SD=18) with respect to 38 female age and non verbal IQ matched controls, using both mass-univariate and pattern classification approaches. The whole brain volumes of each group were compared using voxel-based morphometry (VBM) with diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure, allowing us to build a study-specific template. Significantly more gray matter (GM) was found in the left superior frontal gyrus (SFG) in ASDf subjects compared to controls. The GM segments obtained in the VBM-DARTEL preprocessing are also classified with a support vector machine (SVM), using the leave-pair-out cross-validation protocol. Then, the recursive feature elimination (SVM-RFE) approach allows for the identification of the most discriminating voxels in the GM segments and these prove extremely consistent with the SFG region identified by the VBM analysis. Furthermore, the SVM-RFE map obtained with the most discriminating set of voxels corresponding to the maximum Area Under the Receiver Operating Characteristic Curve (AUC(max)=0.80) highlighted a more complex circuitry of increased cortical volume in ASDf, involving bilaterally the SFG and the right temporo-parietal junction (TPJ). The SFG and TPJ abnormalities may be relevant to the pathophysiology of ASDf, since these structures participate in some core atypical features of autism.
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7. Chown N. {{Modified hermeneutic phenomenological approach toward individuals who have autism: A response to newman, cashin and waters}}. {Res Nurs Health}. 2011 Sep 6.
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8. Fairless AH, Shah RY, Guthrie AJ, Li H, Brodkin ES. {{Deconstructing Sociability, An Autism-Relevant Phenotype, in Mouse Models}}. {Anat Rec (Hoboken)}. 2011 Sep 8.
Reduced sociability is a core feature of autism spectrum disorders (ASD) and is highly disabling, poorly understood, and treatment refractory. To elucidate the biological basis of reduced sociability, multiple laboratories are developing ASD-relevant mouse models in which sociability is commonly assessed using the Social Choice Test. However, various measurements included in that test sometimes support different conclusions. Specifically, measurements of time the « test » mouse spends near a confined « stimulus » mouse (chamber scores) sometimes support different conclusions from measurements of time the test mouse sniffs the cylinder containing the stimulus mouse (cylinder scores). This raises the question of which type of measurements are best for assessing sociability. We assessed the test-retest reliability and ecological validity of chamber and cylinder scores. Compared with chamber scores, cylinder scores showed higher correlations between test and retest measurements, and cylinder scores showed higher correlations with time spent in social interaction in a more naturalistic phase of the test. This suggests that cylinder scores are more reliable and valid measures of sociability in mouse models. Cylinder scores are reported less commonly than chamber scores, perhaps because little work has been done to establish automated software systems for measuring the former. In this study, we found that a particular automated software system performed at least as well as human raters at measuring cylinder scores. Our data indicate that cylinder scores are more reliable and valid than chamber scores, and that the former can be measured very accurately using an automated video analysis system in ASD-relevant models. Anat Rec, 2011. (c) 2011 Wiley-Liss, Inc.
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9. Fatemi SH, Folsom TD, Kneeland RE, Liesch SB. {{Metabotropic Glutamate Receptor 5 Upregulation in Children with Autism is Associated with Underexpression of Both Fragile X Mental Retardation Protein and GABA(A) Receptor Beta 3 in Adults with Autism}}. {Anat Rec (Hoboken)}. 2011 Sep 8.
Recent work has demonstrated the impact of dysfunction of the GABAergic signaling system in brain and the resultant behavioral pathologies in subjects with autism. In animal models, altered expression of Fragile X mental retardation protein (FMRP) has been linked to downregulation of GABA receptors. Interestingly, the autistic phenotype is also observed in individuals with Fragile X syndrome. This study was undertaken to test previous theories relating abnormalities in levels of FMRP to GABA(A) receptor underexpression. We observed a significant reduction in levels of FMRP in the vermis of adults with autism. Additionally, we found that levels of metabotropic glutamate receptor 5 (mGluR5) protein were significantly increased in vermis of children with autism versus age and postmortem interval matched controls. There was also a significant decrease in level of GABA(A) receptor beta 3 (GABRbeta3) protein in vermis of adult subjects with autism. Finally, we found significant increases in glial fibrillary acidic protein in vermis of both children and adults with autism when compared with controls. Taken together, our results provide further evidence that altered FMRP expression and increased mGluR5 protein production potentially lead to altered expression of GABA(A) receptors. Anat Rec,, 2011. (c) 2011 Wiley-Liss, Inc.
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10. Li N, Jin BX, Li JL, Liu ZH. {{[Treatment of autism with scalp acupunctur]}}. {Zhongguo Zhen Jiu}. 2011 Aug;31(8):692-6.
OBJECTIVE: To verify the efficacy on autism treated with scalp acupuncture for regaining the consciousness and opening the orifice in children. METHODS: Seventy cases of child autism were divided into an observation group (30 cases) and a control group (40 cases). In observation group, the cases were treated with scalp acupuncture for regaining the consciousness and opening the orifice, in combination with music therapy and structure education method. Scalp acupuncture was applied to intelligent nine needles (frontal five needles, Sishencong (EX-HN 1)), affection area, heart and liver area, once a day, at the interval once every one week. Totally, 60 treatments made one session. In control group, music therapy and structure education method were applied simply. Clancy Autism Behavior Scale, Childhood Autism Behavior Scale (CARS), Autism Behavior Checklist (ABC) and Gesell Developmental Scale (social adaptive behaviors and language development) were adopted to assess the scores before treatment and after 1 session of treatment. RESULTS: After treatment, the scores in Clancy Autism Behavior Scale, CARS and ABC were lower apparently in observation group as compared with those before treatment (all P < 0.01), and the scores in Clancy Autism Behavior Scale and ABC were lower than those in control group (both P < 0.01). In observation group, the scores of social adaptive behavior scale and language development scale were improved obviously after treatment (both P < 0.01), which were all higher than those in control group (both P < 0.01). In observation, between the group aged from 4 to 6 years and the group aged from 2 to 3 years, the value differences in Clancy Autism Behavior Scale, ABC and social adaptive development scale did not present statistical significance in group comparison before and after treatment (all P > 0.05). CONCLUSION: Scalp acupuncture for regaining the consciousness and opening the orifice can significantly improve the efficacy on autism, effectively relieve child autism symptoms and enhance the intelligence, language ability and social adaptive ability. Moreover, the efficacy cannot be impacted by child’s age.
11. Lin RC. {{Special Issue: New Concepts in Developing Brain Disorders-Autism}}. {Anat Rec (Hoboken)}. 2011 Sep 8.
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12. Pinborough-Zimmerman J, Bilder D, Bakian A, Satterfield R, Carbone PS, Nangle BE, et al. {{Sociodemographic risk factors associated with autism spectrum disorders and intellectual disability}}. {Autism Res}. 2011 Sep 8.
This study examined the hypotheses that (1) sociodemographic risk factors in young children with autism spectrum disorders (ASD) and/or intellectual disability (ID) significantly vary by disability type, and (2) measures of income (mean adjusted gross income, mean federal taxes paid, and mean tax exemptions) significantly increase between 1994 and 2002, and are lower in families with a child with ASD and/or ID compared with the general population. A multiple source surveillance system utilizing a retrospective record review was used to identify ASD and ID cases from a population of 26,108 eight-year-old children born in 1994 and living in Utah in 2002. ASD without ID (ASD-only, n = 99) cases were significantly more likely to be male (P<0.01) and have mothers of White non-Hispanic ethnicity (P = 0.02). ASD with ID (ASD/ID, n = 33) cases were significantly more likely to be male (P<0.01) and have mothers older than 34 years (P = 0.03). ID without ASD (ID-only, n = 113) cases were significantly more likely to have fathers older than 34 years (P<0.01) and were significantly less likely to have mothers with >13 years education (P<0.01). Measures of income for cases at birth and at 8 years of age were not significantly lower than the general population and mean adjusted income of cases significantly increased from birth to 8 years of age. Investigations focused on defining early sociodemographic risk factors by different endophenotypes of ASD may assist in identifying risk factors for this complex group of neurodevelopmental disorders. Aggregate tax information may be a unique resource to utilize for population-based analysis. Autism Res 2011,4:xxx-xxx. (c) 2011 International Society for Autism Research, Wiley Periodicals, Inc.
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13. Rodriguez-Porcel F, Green D, Khatri N, Harris SS, May WL, Lin RC, et al. {{Neonatal Exposure of Rats to Antidepressants Affects Behavioral Reactions to Novelty and Social Interactions in a Manner Analogous to Autistic Spectrum Disorders}}. {Anat Rec (Hoboken)}. 2011 Sep 8.
We have demonstrated that neonatal exposure to selective serotonin reuptake inhibitors has lasting effects on behavior and serotonergic neurons in Long Evans rats. Hyperserotoninemia and altered sensory processing are reported in autistic spectrum disorders (ASD). We hypothesized that early life exposure to SSRIs alters sensory processing, disrupts responses to novelty, and impairs social interactions in a manner similar to that observed in ASD. Male and female Long-Evans rat pups were administered citalopram, buproprion, fluoxetine, or saline from postnatal day (P) 8-21. Rats were tested for response to a novel tone before weaning (P25). Later, rats were tested 2x for response to a novel object (P39), and to a novel conspecific (P78, P101). In addition, rats were assessed for juvenile play behaviors (P32-P34) and later, we assessed sexual response to an estrus female in male rats (P153-184). Antidepressant exposure increased freezing after tone, diminished novel object exploration, and reduced conspecific interaction up to 3x compared to saline exposed rats. Juvenile play was profoundly reduced in antidepressant-exposed males when compared to saline exposed groups. Exposure to the SSRIs, but not bupropion disrupted male sexual behaviors. Moreover, specific male responses to female proceptive behaviors were disrupted in SSRI, but not bupropion exposed rats. We conclude that neonatal exposure to antidepressants in rats results in sensory and social abnormalities that parallel many of those reported in ASD. Anat Rec,, 2011. (c) 2011 Wiley-Liss, Inc.
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14. South M, Larson MJ, White SE, Dana J, Crowley MJ. {{Better fear conditioning is associated with reduced symptom severity in autism spectrum disorders}}. {Autism Res}. 2011 Sep 8.
Evidence from behavioral and neuroimaging studies suggest that atypical amygdala function plays a critical role in the development of autism spectrum disorders (ASD). The handful of psychophysiological studies examining amygdala function in ASD using classical fear conditioning paradigms have yielded discordant results. We recorded skin conductance response (SCR) during a simple discrimination conditioning task in 30 children and adolescents (ages 8-18) diagnosed with high-functioning ASD and 30 age- and IQ-matched, typically developing controls. SCR response in the ASD group was uniquely and positively associated with social anxiety; and negatively correlated with autism symptom severity, in particular with social functioning. Fear conditioning studies have tremendous potential to aid understanding regarding the amygdale’s role in the varied symptom profile of ASD. Our data demonstrate that such studies require careful attention to task-specific factors, including task complexity; and also to contributions of dimensional, within-group factors that contribute to ASD heterogeneity. Autism Res 2011,4:xxx-xxx. (c) 2011 International Society for Autism Research, Wiley Periodicals, Inc.
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15. Wilson CE, Palermo R, Burton AM, Brock J. {{Recognition of own- and other-race faces in autism spectrum disorders}}. {Q J Exp Psychol (Colchester)}. 2011 Jul 14.
Empirical data regarding the extent of face recognition abnormalities in autism spectrum disorder (ASD) is inconsistent. Here, 27 ASD and 47 typically developing (TD) children completed an immediate two-alternative forced-choice identity matching task. We contrasted recognition of own- and other-race faces, and, counter to prediction, we found a typical advantage for recognizing own- over other-race faces in both the ASD and TD groups. In addition, ASD and TD groups responded similarly to stimulus manipulations (use of identical or different photographs for identity matching and cropping stimuli to remove hair information). However, age-standardized scores varied widely within the ASD sample, and a subgroup of ASD participants with impaired face recognition did not exhibit a significant own-race recognition advantage. An explanation regarding early experience with faces is considered, and implications for research of individual variation within ASD are discussed.
