1. Edmiston EK, Merkle K, Corbett BA. {{Neural and Cortisol Responses during Play with Human and Computer Partners in Children with Autism}}. {Social cognitive and affective neuroscience}. 2014 Dec 30.
Background: Children with autism spectrum disorder (ASD) exhibit impairment in reciprocal social interactions, including play, which can manifest as failure to show social preference or discrimination between social and nonsocial stimuli. Methods: To explore mechanisms underlying these deficits, we collected salivary cortisol from forty-two children 8-to-12 years with ASD or typical development during a playground interaction with a confederate child. Participants underwent functional MRI during a Prisoner’s Dilemma game requiring cooperation or defection with a human (confederate) or computer partner. Search region of interest analyses were based on previous research (e.g., insula, amygdala, temporal parietal junction). Results: There were significant group differences in neural activation based on partner and response pattern. When playing with a human partner, children with ASD showed limited engagement of a social salience brain circuit during defection. Reduced insula activation during defection in the ASD children relative to TD children, regardless of partner type, was also a prominent finding. Insula and temporal parietal junction BOLD during defection was also associated with stress responsivity and behavior in the ASD group under playground conditions. Discussion: Children with ASD engage social salience networks less than TD children during conditions of social salience, supporting a fundamental disturbance of social engagement.
Lien vers le texte intégral (Open Access ou abonnement)
2. Jaiswal P, Guhathakurta S, Singh AS, Verma D, Pandey M, Varghese M, Sinha S, Ghosh S, Mohanakumar KP, Rajamma U. {{SLC6A4 markers modulate platelet 5-HT level and specific behaviors of autism: A study from an Indian population}}. {Progress in neuro-psychopharmacology & biological psychiatry}. 2015 Jan 2;56:196-206.
Presence of platelet hyperserotonemia and effective amelioration of behavioral dysfunctions by selective serotonin reuptake inhibitors (SSRI) in autism spectrum disorders (ASD) indicate that irregularities in serotonin (5-HT) reuptake and its homeostasis could be the basis of behavioral impairments in ASD patients. SLC6A4, the gene encoding serotonin transporter (SERT) is considered as a potential susceptibility gene for ASD, since it is a quantitative trait locus for blood 5-HT levels. Three functional polymorphisms, 5-HTTLPR, STin2 and 3’UTR-SNP of SLC6A4 are extensively studied for possible association with the disorder, with inconclusive outcome. In the present study, we investigated association of these polymorphisms with platelet 5-HT content and symptoms severity as revealed by childhood autism rating scale in ASD children from an Indian population. Higher 5-HT level observed in ASD was highly significant in children with heterozygous and homozygous genotypes comprising of minor alleles of the markers. Quantitative transmission disequilibrium test demonstrated significant genetic effect of STin2 allele as well as STin2/3’UTR-SNP and 5-HTTLPR/3’UTR-SNP haplotypes on 5-HT levels, but no direct association with overall CARS score and ASD phenotype. Significant genetic effect of the markers on specific behavioral phenotypes was observed for various sub-phenotypes of CARS in quantitative trait analysis. Even though the 5-HT level was not associated with severity of behavioral CARS score, a significant negative relationship was observed for 5-HT levels and level and consistency of intellectual response and general impression in ASD children. Population-based study revealed higher distribution of the haplotype 10/G of STin2/3’UTR-SNP in male controls, suggesting protective effect of this haplotype in male cases. Overall results of the study suggest that SLC6A4 markers have specific genetic effect on individual ASD behavioral attributes, might be through the modulation of 5-HT content.
Lien vers le texte intégral (Open Access ou abonnement)
3. Lumaban JG, Nelson DL. {{The Fragile X proteins Fmrp and Fxr2p cooperate to regulate glucose metabolism in mice}}. {Human molecular genetics}. 2014 Dec 30.
Fragile X syndrome results from loss of FMR1 expression. Individuals with the disorder exhibit not only intellectual disability, but also an array of physical and behavioral abnormalities, including sleep difficulties. Studies in mice demonstrated that Fmr1, along with its paralog Fxr2, regulate circadian behavior, and that their absence disrupts expression and cycling of essential clock mRNAs in the liver. Recent reports have identified circadian genes to be essential for normal metabolism. Here we describe the metabolic defects that arise in mice mutated for both Fmr1 and Fxr2. These mice have reduced fat deposits compared with age- and weight-matched controls. Several metabolic markers show either low levels in plasma or abnormal circadian cycling (or both). Insulin levels are consistently low regardless of light exposure and feeding conditions and the animals are extremely sensitive to injected insulin. Glucose production from introduced pyruvate and glucagon is impaired and the mice quickly clear injected glucose. These mice also have higher food intake and higher VO2 and VCO2 levels. We analyzed liver expression of genes involved in glucose homeostasis and found several that are expressed differentially in the mutant mice. These results point to the involvement of Fmr1 and Fxr2 in maintaining the normal metabolic state in mice.
Lien vers le texte intégral (Open Access ou abonnement)
4. Rhind C, Bonfioli E, Hibbs R, Goddard E, Macdonald P, Gowers S, Schmidt U, Tchanturia K, Micali N, Treasure J. {{An examination of autism spectrum traits in adolescents with anorexia nervosa and their parents}}. {Molecular autism}. 2014;5(1):56.
BACKGROUND: There may be a link between anorexia nervosa and autism spectrum disorders. The aims of this study were to examine whether adolescents with anorexia nervosa have autism spectrum and/or obsessive-compulsive traits, how many would meet diagnostic criteria for autism spectrum disorder, and whether these traits are shared by parents. METHODS: A total of 150 adolescents receiving outpatient treatment for anorexia nervosa or subthreshold anorexia nervosa and their parents completed the autism spectrum disorder and eating disorder sections of the Development and Well-being Assessment. Patients also completed the Children Yale-Brown Obsessive-Compulsive Scale and other measures of psychiatric morbidity, and parents completed the short Autism Quotient and Obsessive-Compulsive Inventory Revised. RESULTS: Adolescents with anorexia nervosa had a below average social aptitude (19% below cut-off) and high levels of peer relationship problems (39% above cut-off) and obsessive-compulsive symptoms (56% above cut-off). Six cases (4%, all females) were assigned a possible (n = 5) or definite (n = 1) diagnosis of autism spectrum disorder. Parental levels of autism spectrum and obsessive-compulsive traits were within the normal range. CONCLUSIONS: This study suggests that adolescents with anorexia nervosa have elevated levels of autism spectrum traits, obsessive-compulsive symptoms, and a small proportion fulfil diagnostic criteria for a probable autism spectrum disorder. These traits did not appear to be familial. This comorbidity has been associated with a poorer prognosis. Therefore, adaptation of treatment for this subgroup may be warranted. TRIAL REGISTRATION: Controlled-trials.com: ISRCTN83003225. Registered on 29 September 2011.
Lien vers le texte intégral (Open Access ou abonnement)
5. Richter J, Poustka L, Vomstein K, Haffner J, Parzer P, Stieltjes B, Henze R. {{Volumetric alterations in the heteromodal association cortex in children with autism spectrum disorder}}. {European psychiatry : the journal of the Association of European Psychiatrists}. 2015 Jan 2.
BACKGROUND: We investigated if alterations in higher-order association areas related to schizophrenia, namely the heteromodal association cortex (HASC), are also observable in subjects with autism spectrum disorder (ASD). METHODS: A group of 18 children with ASD and 18 healthy controls (HC) underwent magnetic resonance imaging (MRI). The examination comprised an analysis of group differences in gray matter (GM) volume, surface area (SA) and hemispheric lateralization. RESULTS: Differences in GM volumes in children with ASD and HC were detected in frontal and parietal areas related to the HASC. No HASC structure that showed changes in GM volume exhibited differences in SA. Alterations in hemispheric lateralization between ASD and HC are seen in a frontal area of the HASC. CONCLUSIONS: Our results indicate that changes in HASC areas are not restricted to schizophrenia, but extend to other psychiatric disorders, namely ASD. The lacking group differences in SA indicate that changes in GM volume are possibly evoked by other variables than SA in children with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
6. Wang Z, Magnon G, White SP, Greene R, Vaillancourt DE, Mosconi M. {{Individuals with autism spectrum disorder (ASD) show abnormalities during initial and subsequent phases of precision gripping}}. {Journal of neurophysiology}. 2014 Dec 30:jn 00661 2014.
Sensorimotor impairments are common in ASD, but they are not well understood. Here, we examined force control during initial pulses and the subsequent rise, sustained, and relaxation phases of precision gripping in 34 individuals with ASD and 25 healthy controls. Participants pressed on opposing load cells with their thumb and index finger while receiving visual feedback regarding their performance. They completed 2 and 8 sec trials during which they pressed at 15, 45 or 85% of their maximum force. Initial pulses guided by feedforward control mechanisms, sustained force output controlled by visual feedback processes, and force relaxation rates all were examined. Controls favored an initial pulse strategy characterized by a rapid increase in and then relaxation of force when the target force was low (Type 1). When the target force level or duration of trials was increased, controls transitioned to a strategy in which they more gradually increased their force, paused, and then increased their force again. Individuals with ASD showed a more persistent bias towards the Type 1 strategy at higher force levels and during longer trials and their initial force output was less accurate than that of controls. Patients showed increased force variability compared to controls when attempting to sustain a constant force level. During the relaxation phase, they showed reduced rates of force decrease. These findings suggest that both feedforward and feedback motor control mechanisms are compromised in ASD and these deficits may contribute to the dyspraxia and sensorimotor abnormalities often seen in this disorder.
