Pubmed du 30/12/09

lundi 4 janvier 2010

1. Anholt GE, Cath DC, van Oppen P, Eikelenboom M, Smit JH, van Megen H, van Balkom AJ. Autism and ADHD Symptoms in Patients with OCD : Are They Associated with Specific OC Symptom Dimensions or OC Symptom Severity ?. J Autism Dev Disord. 2009 Dec 29.

In obsessive-compulsive disorder (OCD), the relationship between autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) symptom, and obsessive-compulsive (OC) symptom dimensions and severity has scarcely been studied. Therefore, 109 adult outpatients with primary OCD were compared to 87 healthy controls on OC, ADHD and ASD symptoms. OCD patients showed increased ADHD and autism symptom frequencies, OCD + ADHD patients reporting more autism symptoms (particularly attention switching and social skills problems) than OCD - ADHD patients. Attention switching problems were most significant predictors of OC symptom dimensions (except hoarding) and of symptom severity. Hoarding was not associated with elevated autism scale scores, but with inattention. In conclusion, attention switching problems may reflect both symptom overlap and a common etiological factor underlying ASD, ADHD and OCD.

2. Bauminger N, Solomon M, Rogers SJ. Predicting Friendship Quality in Autism Spectrum Disorders and Typical Development. J Autism Dev Disord. 2009 Dec 29.

The role played by social relationship variables (attachment security ; mother-child relationship qualities) and social-cognitive capacities (theory of mind) was examined in both observed friendship behaviors and in children’s descriptions of friendships (age 8-12) with high functioning children with autism spectrum disorders (HFASD) (n = 44) and with typical development (TYP) (n = 38). Overall, half of the HFASD sample (54.45%) reported maternal attachment security, corroborating data from younger children with ASD. The hypothesized predictors and their interrelations had both direct and indirect effects on friendship for both groups of children, highlighting the importance of these factors in children’s friendship development and suggesting both compensatory and amplification mechanisms for friendship qualities. Practical and clinical implications are discussed for friendship support in both ASD and TYP.

3. Levav-Rabkin T, Melamed O, Clarke G, Farber M, Cryan JF, Dinan TG, Grossman Y, Golan HM. A Sensitive Period of Mice Inhibitory System to Neonatal GABA Enhancement by Vigabatrin is Brain Region Dependent. Neuropsychopharmacology. 2009 Dec 30.

Neurodevelopmental disorders, such as schizophrenia and autism, have been associated with disturbances of the GABAergic system in the brain. We examined immediate and long-lasting influences of exposure to the GABA-potentiating drug vigabatrin (GVG) on the GABAergic system in the hippocampus and cerebral cortex, before and during the developmental switch in GABA function (postnatal days P1-7 and P4-14). GVG induced a transient elevation of GABA levels. A feedback response to GABA enhancement was evident by a short-term decrease in glutamate decarboxylase (GAD) 65 and 67 levels. However, the number of GAD65/67-immunoreactive (IR) cells was greater in 2-week-old GVG-treated mice. A long-term increase in GAD65 and GAD67 levels was dependent on brain region and treatment period. Vesicular GABA transporter was insensitive to GVG. The overall effect of GVG on the Cl(-) co-transporters NKCC1 and KCC2 was an enhancement of their synthesis, which was dependent on the treatment period and brain region studied. In addition, a short-term increase was followed by a long-term decrease in KCC2 oligomerization in the cell membrane of P4-14 hippocampi and cerebral cortices. Analysis of the Ca(2+) binding proteins expressed in subpopulations of GABAergic cells, parvalbumin and calbindin, showed region-specific effects of GVG during P4-14 on parvalbumin-IR cell density. Moreover, calbindin levels were elevated in GVG mice compared to controls during this period. Cumulatively, these results suggest a particular susceptibility of the hippocampus to GVG when exposed during days P4-14. In conclusion, our studies have identified modifications of key components in the inhibitory system during a critical developmental period. These findings provide novel insights into the deleterious consequences observed in children following prenatal and neonatal exposure to GABA-potentiating drugs.Neuropsychopharmacology advance online publication, 30 December 2009 ; doi:10.1038/npp.2009.219.

4. Smith RG, Kember RL, Mill J, Fernandes C, Schalkwyk LC, Buxbaum JD, Reichenberg A. Advancing paternal age is associated with deficits in social and exploratory behaviors in the offspring : a mouse model. PLoS One. 2009 ;4(12):e8456.

BACKGROUND : Accumulating evidence from epidemiological research has demonstrated an association between advanced paternal age and risk for several psychiatric disorders including autism, schizophrenia and early-onset bipolar disorder. In order to establish causality, this study used an animal model to investigate the effects of advanced paternal age on behavioural deficits in the offspring. METHODS : C57BL/6J offspring (n = 12 per group) were bred from fathers of two different ages, 2 months (young) and 10 months (old), and mothers aged 2 months (n = 6 breeding pairs per group). Social and exploratory behaviors were examined in the offspring. PRINCIPAL FINDINGS : The offspring of older fathers were found to engage in significantly less social (p = 0.02) and exploratory (p = 0.02) behaviors than the offspring of younger fathers. There were no significant differences in measures of motor activity. CONCLUSIONS : Given the well-controlled nature of this study, this provides the strongest evidence for deleterious effects of advancing paternal age on social and exploratory behavior. De-novo chromosomal changes and/or inherited epigenetic changes are the most plausible explanatory factors.

5. Zhang X, Cui N, Wu Z, Su J, Tadepalli JS, Sekizar S, Jiang C. Intrinsic membrane properties of locus coeruleus neuronsin Mecp2-null mice. Am J Physiol Cell Physiol. 2009 Dec 30.

Rett syndrome caused by mutations in Mecp2 gene shows abnormalities in autonomic functions in which brainstem norepinephrinergic systems play an important role. Here we present systematic comparisons of intrinsic membrane properties of locus coeruleus (LC) neurons between Mecp2( horizontal line /Y) and wild-type (WT) mice. Whole-cell current clamp was performed in brain slices of 3-4 week-old mice. Mecp2( horizontal line /Y) neurons showed stronger inward rectification and had shorter time constant than WT cells. The former was likely due to over-expression of Kir4.1 channel, and the latter was attributable to the smaller cell surface area. The action potential duration was prolonged in Mecp2( horizontal line /Y) cells with an extended rise time. This was associated with a significant reduction in the voltage-activated Na(+) current density. Following action potentials, over 60% Mecp2( horizontal line /Y) neurons displayed fast and medium afterhyperpolarizations (fAHP and mAHP), while nearly 90% WT neurons showed only mAHP. The mAHP amplitude was smaller in Mecp2( horizontal line /Y) neurons. The firing frequency was higher in neurons with mAHP, and the frequency variation was greater in cells with both fAHP and mAHP in Mecp2( horizontal line /Y) mice. Small but significant differences in spike frequency adaption and delayed excitation were found in Mecp2( horizontal line /Y) neurons. These results indicate that there are several electrophysiological abnormalities in LC neurons of Mecp2( horizontal line /Y) mice, which may contribute to the dysfunction of norepinephrine system in the central nervous system.


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