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Decreased Left Caudate Volume Is Associated with Increased Severity of Autistic-Like Symptoms in a Cohort of ADHD Patients and Their Unaffected Siblings.
Catégorie PLoS One
Description:

Decreased Left Caudate Volume Is Associated with Increased Severity of Autistic-Like Symptoms in a Cohort of ADHD Patients and Their Unaffected Siblings.

PLoS One. 2016;11(11):e0165620

Authors: O'Dwyer L, Tanner C, van Dongen EV, Greven CU, Bralten J, Zwiers MP, Franke B, Heslenfeld D, Oosterlaan J, Hoekstra PJ, Hartman CA, Groen W, Rommelse N, Buitelaar JK

Abstract
Autism spectrum disorder (ASD) symptoms frequently occur in individuals with attention-deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural brain correlates, knowledge of the structural brain profile of individuals with ADHD with raised ASD symptoms is limited. The presence of ASD-like symptoms was measured by the Children's Social Behavior Questionnaire (CSBQ) in a sample of typically developing controls (n = 154), participants with ADHD (n = 239), and their unaffected siblings (n = 144) between the ages of 8 and 29. Structural magnetic resonance imaging (MRI) correlates of ASD ratings were analysed by studying the relationship between ASD ratings and grey matter volumes using mixed effects models which controlled for ADHD symptom count and total brain volume. ASD ratings were significantly elevated in participants with ADHD relative to controls and unaffected siblings. For the entire group (participants with ADHD, unaffected siblings and TD controls), mixed effect models revealed that the left caudate nucleus volume was negatively correlated with ASD ratings (t = 2.83; P = 0.005). The current findings are consistent with the role of the caudate nucleus in executive function, including the selection of goals based on the evaluation of action outcomes and the use of social reward to update reward representations. There is a specific volumetric profile associated with subclinical ASD-like symptoms in participants with ADHD, unaffected siblings and controls with the caudate nucleus and globus pallidus being of critical importance in predicting the level of ASD-like symptoms in all three groups.

PMID: 27806078 [PubMed - in process]

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Distinct roles for extracellular and intracellular domains in neuroligin function at inhibitory synapses.
Catégorie Elife
Description:

Distinct roles for extracellular and intracellular domains in neuroligin function at inhibitory synapses.

Elife. 2016 Nov 02;5:

Authors: Nguyen QA, Horn ME, Nicoll RA

Abstract
Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that interact trans-synaptically with neurexins to mediate synapse development and function. NLGN2 is only at inhibitory synapses while NLGN3 is at both excitatory and inhibitory synapses. We found that NLGN3 function at inhibitory synapses in rat CA1 depends on the presence of NLGN2 and identified a domain in the extracellular region that accounted for this functional difference between NLGN2 and 3 specifically at inhibitory synapses. We further show that the presence of a cytoplasmic tail (c-tail) is indispensible, and identified two domains in the c-tail that are necessary for NLGN function at inhibitory synapses. These domains point to a gephyrin-dependent mechanism that is disrupted by an autism-associated mutation at R705 and a gephyrin-independent mechanism reliant on a putative phosphorylation site at S714. Our work highlights unique and separate roles for the extracellular and intracellular regions in specifying and carrying out NLGN function respectively.

PMID: 27805570 [PubMed - as supplied by publisher]

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Mental states and activities in Danish narratives: children with autism and children with language impairment.
Catégorie J Child Lang
Description:

Mental states and activities in Danish narratives: children with autism and children with language impairment.

J Child Lang. 2016 Nov 2;:1-26

Authors: Engberg-Pedersen E, Christensen RV

Abstract
This study focuses on the relationship between content elements and mental-state language in narratives from twenty-seven children with autism (ASD), twelve children with language impairment (LI), and thirty typically developing children (TD). The groups did not differ on chronological age (10;6-14;0) and non-verbal cognitive skills, and the groups with ASD and TD did not differ on language measures. The children with ASD and LI had fewer content elements of the storyline than the TD children. Compared with the TD children, the children with ASD used fewer subordinate clauses about the characters' thoughts, and preferred talking about mental states as reported speech, especially in the form of direct speech. The children with LI did not differ from the TD children on these measures. The results are discussed in the context of difficulties with socio-cognition in children with ASD and of language difficulties in children with LI.

PMID: 27804897 [PubMed - as supplied by publisher]

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Siblings of children with life-limiting conditions: psychological adjustment and sibling relationships.
Catégorie Child Care Health Dev
Description:
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Siblings of children with life-limiting conditions: psychological adjustment and sibling relationships.

Child Care Health Dev. 2016 Nov 1;:

Authors: Fullerton JM, Totsika V, Hain R, Hastings RP

Abstract
BACKGROUND: This study explored psychological adjustment and sibling relationships of siblings of children with life-limiting conditions (LLCs), expanding on previous research by defining LLCs using a systematic classification of these conditions.
METHODS: Thirty-nine siblings participated, aged 3-16?years. Parents completed measures of siblings' emotional and behavioural difficulties, quality of life, sibling relationships and impact on families and siblings. Sibling and family adjustment and relationships were compared with population norms, where available, and to a matched comparison group of siblings of children with autistic spectrum disorder (ASD), as a comparable 'high risk' group.
RESULTS: LLC siblings presented significantly higher levels of emotional and behavioural difficulties, and lower quality of life than population norms. Their difficulties were at levels comparable to siblings of children with ASD. A wider impact on the family was confirmed. Family socio-economic position, time since diagnosis, employment and accessing hospice care were factors associated with better psychological adjustment.
CONCLUSIONS: Using a systematic classification of LLCs, the study supported earlier findings of increased levels of psychological difficulties in siblings of children with a LLC. The evidence is (i) highlighting the need to provide support to these siblings and their families, and (ii) that intervention approaches could be drawn from the ASD field.

PMID: 27804151 [PubMed - as supplied by publisher]

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Executive functioning and local-global visual processing: candidate endophenotypes for autism spectrum disorder?
Catégorie J Child Psychol Psychiatry
Description:
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Executive functioning and local-global visual processing: candidate endophenotypes for autism spectrum disorder?

J Child Psychol Psychiatry. 2016 Nov 2;:

Authors: Van Eylen L, Boets B, Cosemans N, Peeters H, Steyaert J, Wagemans J, Noens I

Abstract
BACKGROUND: Heterogeneity within autism spectrum disorder (ASD) hampers insight in the etiology and stimulates the search for endophenotypes. Endophenotypes should meet several criteria, the most important being the association with ASD and the higher occurrence rate in unaffected ASD relatives than in the general population. We evaluated these criteria for executive functioning (EF) and local-global (L-G) visual processing.
METHODS: By administering an extensive cognitive battery which increases the validity of the measures, we examined which of the cognitive anomalies shown by ASD probands also occur in their unaffected relatives (n = 113) compared to typically developing (TD) controls (n = 100). Microarrays were performed, so we could exclude relatives from probands with a de novo mutation in a known ASD susceptibility copy number variant, thus increasing the probability that genetic risk variants are shared by the ASD relatives. An overview of studies investigating EF and L-G processing in ASD relatives was also provided.
RESULTS: For EF, ASD relatives - like ASD probands - showed impairments in response inhibition, cognitive flexibility and generativity (specifically, ideational fluency), and EF impairments in daily life. For L-G visual processing, the ASD relatives showed no anomalies on the tasks, but they reported more attention to detail in daily life. Group differences were similar for siblings and for parents of ASD probands, and yielded larger effect sizes in a multiplex subsample. The group effect sizes for the comparison between ASD probands and TD individuals were generally larger than those of the ASD relatives compared to TD individuals.
CONCLUSIONS: Impaired cognitive flexibility, ideational fluency and response inhibition are strong candidate endophenotypes for ASD. They could help to delineate etiologically more homogeneous subgroups, which is clinically important to allow assigning ASD probands to different, more targeted, interventions.

PMID: 27804132 [PubMed - as supplied by publisher]

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Reelin and Neuropsychiatric Disorders.
Catégorie Front Cell Neurosci
Description:
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Reelin and Neuropsychiatric Disorders.

Front Cell Neurosci. 2016;10:229

Authors: Ishii K, Kubo KI, Nakajima K

Abstract
Proper neuronal migration and laminar formation during corticogenesis is essential for normal brain function. Disruption of these developmental processes is thought to be involved in the pathogenesis of some neuropsychiatric conditions. Especially, Reelin, a glycoprotein mainly secreted by the Cajal-Retzius cells and a subpopulation of GABAergic interneurons, has been shown to play a critical role, both during embryonic and postnatal periods. Indeed, animal studies have clearly revealed that Reelin is an essential molecule for proper migration of cortical neurons and finally regulates the cell positioning in the cortex during embryonic and early postnatal stages; by contrast, Reelin signaling is closely involved in synaptic function in adulthood. In humans, genetic studies have shown that the reelin gene (RELN) is associated with a number of psychiatric diseases, including Schizophrenia (SZ), bipolar disorder (BP) and autistic spectrum disorder. Indeed, Reln haploinsufficiency has been shown to cause cognitive impairment in rodents, suggesting the expression level of the Reelin protein is closely related to the higher brain functions. However, the molecular abnormalities in the Reelin pathway involved in the pathogenesis of psychiatric disorders are not yet fully understood. In this article, we review the current progress in the understanding of the Reelin functions that could be related to the pathogenesis of psychiatric disorders. Furthermore, we discuss the basis for selecting Reelin and molecules in its downstream signaling pathway as potential therapeutic targets for psychiatric illnesses.

PMID: 27803648 [PubMed - in process]

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Correction for Patel et al., Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism.
Catégorie Proc Natl Acad Sci U S A
Description:
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Correction for Patel et al., Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism.

Proc Natl Acad Sci U S A. 2016 Nov 1;:

Authors:

PMID: 27803332 [PubMed - as supplied by publisher]

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N-acetylcysteine in the treatment of psychiatric disorders: current status and future prospects.
Catégorie Expert Opin Drug Metab Toxicol
Description:
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N-acetylcysteine in the treatment of psychiatric disorders: current status and future prospects.

Expert Opin Drug Metab Toxicol. 2016 Nov 2;:1-14

Authors: Minarini A, Ferrari S, Galletti M, Giambalvo N, Perrone D, Rioli G, Galeazzi GM

Abstract
INTRODUCTION: N-acetylcysteine (NAC) is widely known for its role as a mucolytic and as an antidote to paracetamol overdose. There is increasing interest in the use of NAC in the treatment of several psychiatric disorders. The rationale for the administration of NAC in psychiatric conditions is based on its role as a precursor to the antioxidant glutathione, and its action as a modulating agent of glutamatergic, dopaminergic, neurotropic and inflammatory pathways. Areas covered: This study reviews the available data regarding the use of NAC in different psychiatric disorders including substance use disorders, autism, obsessive-compulsive spectrum disorders, schizophrenia, depression, bipolar disorder. Promising results were found in trials testing the use of NAC, mainly as an add-on treatment, in cannabis use disorder in young people, depression in bipolar disorder, negative symptoms in schizophrenia, and excoriation (skin-picking) disorder. Despite initial optimism, recent findings regarding NAC efficacy in autism have been disappointing. Expert opinion: These preliminary positive results require further confirmation in larger samples and with longer follow-ups. Given its high tolerability and wide availability, NAC represents an important target to investigate in the field of new adjunctive treatments for psychiatric conditions.

PMID: 27766914 [PubMed - as supplied by publisher]

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Carboxyethylpyrroles: From Hypothesis to the Discovery of Biologically Active Natural Products.
Catégorie Chem Res Toxicol
Description:
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Carboxyethylpyrroles: From Hypothesis to the Discovery of Biologically Active Natural Products.

Chem Res Toxicol. 2016 Nov 2;

Authors: Salomon RG

Abstract
Our research on the roles of lipid oxidation in human disease is guided by chemical intuition. For example, we postulated that 2-(?-carboxyethyl)pyrrole (CEP) derivatives of primary amines would be produced through covalent adduction of a ?-hydroxyalkenal generated, in turn, through oxidative fragmentation of docosahexaenoates. Our studies confirmed the natural occurrence of this chemistry, and the biological activities of these natural products and their extensive involvements in human physiology (wound healing) and pathology (age-related macular degeneration, autism, atherosclerosis, sickle cell disease, and tumor growth) continue to emerge. This perspective recounts these discoveries and proposes new frontiers where further developments are likely. Perhaps more significantly, it depicts an effective chemistry-based approach to the discovery of novel biochemistry.

PMID: 27750413 [PubMed - as supplied by publisher]

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Exploring Boundaries for the Genetic Consequences of Assortative Mating for Psychiatric Traits.
Catégorie JAMA Psychiatry
Description:
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Exploring Boundaries for the Genetic Consequences of Assortative Mating for Psychiatric Traits.

JAMA Psychiatry. 2016 Nov 1;73(11):1189-1195

Authors: Peyrot WJ, Robinson MR, Penninx BW, Wray NR

Abstract
Importance: Considerable partner resemblances have been found for a wide range of psychiatric disorders, meaning that partners of affected individuals have an increased risk of being affected compared with partners of unaffected individuals. If this resemblance is reflected in genetic similarity between partners, genetic risk is anticipated to accumulate in offspring, but these potential consequences have not been quantified and have been left implicit.
Observations: The anticipated consequences of partner resemblance on prevalence and heritability of psychiatric traits in the offspring generation were modeled for disorders with varying heritabilities, population prevalence (lifetime risk), and magnitudes of partner resemblance. These models facilitate interpretation for a wide range of psychiatric disorders, such as autism, schizophrenia, and depression. The genetic consequences of partner resemblance are most pronounced when attributable to phenotypic assortment (driven by the psychiatric trait). Phenotypic assortment results in increased genetic variance in the offspring generation, which may result in increased heritability and population prevalence. These consequences add generation after generation to a limit, but assortative mating is unlikely to balance the impact of reduced fecundity of patients with psychiatric disorders in the long term. This modeling suggests that the heritabilities of psychiatric disorders are unlikely to increase by more than 5% from 1 generation of assortative mating (maximally 13% across multiple generations). The population prevalence will increase most for less common disorders with high heritability; for example, the prevalence of autism might increase by 1.5-fold after 1 generation of assortative mating (?2.4-fold in the long term) depending on several assumptions.
Conclusions and Relevance: The considerable partner resemblances found for psychiatric disorders deserve more detailed interpretation than has been provided thus far. Although the limitations of modeling are emphasized, the anticipated consequences are at most modest for the heritability but may be considerable for the population prevalence of rare disorders with a high heritability.

PMID: 27732705 [PubMed - in process]

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