1. Doyle CA, McDougle CJ. {{Pharmacotherapy to control behavioral symptoms in children with autism}}. {Expert Opin Pharmacother}. 2012.
Introduction: Autistic disorder, Asperger’s disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS) are pervasive developmental disorders (PDDs) frequently associated with behavioral symptoms that may require pharmacotherapy to manage. Areas covered: Behavioral symptoms in children with autism include interfering repetitive behaviors, irritability, and hyperactivity and inattention, among others. The psychotropic medications examined in this review include: serotonin reuptake inhibitors, typical and atypical antipsychotics, medications used to treat attention-deficit/hyperactivity disorder, naltrexone, buspirone, divalproex sodium, lamotrigine, levetiracetam, memantine, mirtazapine, riluzole, pioglitazone, and topiramate. Expert opinion: For the treatment of interfering repetitive behaviors, serotonin reuptake inhibitors demonstrate less efficacy and are more poorly tolerated in children with autism compared to adults. Antipsychotics are the most efficacious drugs for the treatment of irritability in children with autism and other PDDs. For the treatment of hyperactivity and inattention, psychostimulants demonstrate some benefit. However, they are overall less efficacious and cause more side effects in children with PDDs compared to typically developing children with attention-deficit/hyperactivity disorder. Results from double-blind, placebo-controlled trials of these agents and others for the treatment of the behavioral symptom domains described above will be discussed in this review.
Lien vers le texte intégral (Open Access ou abonnement)
2. Holt R, Sykes NH, Conceicao IC, Cazier JB, Anney RJ, Oliveira G, Gallagher L, Vicente A, Monaco AP, Pagnamenta AT. {{CNVs leading to fusion transcripts in individuals with autism spectrum disorder}}. {Eur J Hum Genet}. 2012.
There is strong evidence that rare copy number variants (CNVs) have a role in susceptibility to autism spectrum disorders (ASDs). Much research has focused on how CNVs mediate a phenotypic effect by altering gene expression levels. We investigated an alternative mechanism whereby CNVs combine the 5′ and 3′ ends of two genes, creating a ‘fusion gene’. Any resulting mRNA with an open reading frame could potentially alter the phenotype via a gain-of-function mechanism. We examined 2382 and 3096 rare CNVs from 996 individuals with ASD and 1287 controls, respectively, for potential to generate fusion transcripts. There was no increased burden in individuals with ASD; 122/996 cases harbored at least one rare CNV of this type, compared with 179/1287 controls (P=0.89). There was also no difference in the overall frequency distribution between cases and controls. We examined specific examples of such CNVs nominated by case-control analysis and a candidate approach. Accordingly, a duplication involving REEP1-POLR1A (found in 3/996 cases and 0/1287 controls) and a single occurrence CNV involving KIAA0319-TDP2 were tested. However, no fusion transcripts were detected by RT-PCR. Analysis of additional samples based on cell line availability resulted in validation of a MAPKAPK5-ACAD10 fusion transcript in two probands. However, this variant was present in controls at a similar rate and is unlikely to influence ASD susceptibility. In summary, although we find no evidence that fusion-gene generating CNVs lead to ASD susceptibility, discovery of a MAPKAPK5-ACAD10 transcript with an estimated frequency of approximately 1/200 suggests that gain-of-function mechanisms should be considered in future CNVs studies.European Journal of Human Genetics advance online publication, 2 May 2012; doi:10.1038/ejhg.2012.73.
Lien vers le texte intégral (Open Access ou abonnement)
3. Kana RK, Wadsworth HM. {{« The archeologist’s career ended in ruins »: Hemispheric differences in pun comprehension in autism}}. {Neuroimage}. 2012.
Appropriate interpretation of figurative language involves inferring the speaker’s intent by integrating word meaning with context. In disorders like autism, understanding intended and contextual meanings in language may pose a challenge. Such difficulties are prevalent even when individuals exhibit otherwise fluent language ability (Szatmari et al., 1990). A pun is a rhetorical technique in which a speaker deliberately invokes multiple meanings through a word or phrase likely resulting in a joke. Comprehending puns may involve identifying multiple meanings of a word, embedding it in right contexts, and understanding the underlying humor. This fMRI study investigated the brain responses associated with figures of speech like puns. In the fMRI scanner, participants read sentences containing puns (e.g. To write with a broken pencil is pointless) and control sentences (literal meaning) presented in a blocked design format. The participants’ task was to silently read and understand one meaning (in the literal condition) or two meanings (in the pun condition). Participants with autism, relative to typical controls, showed an increase in overall activation while comprehending sentences containing puns, particularly within the right hemisphere as well as in relatively posterior brain areas. Overall, there was reduced response in left hemisphere areas, reduced response to humor, and more distributed recruitment of regions in autism relative to control participants. We also examined the relationship between symptom severity in autism and verbal ability with brain responses to pun comprehension finding negative and positive correlations respectively. Overall, the results from the present study suggest that individuals with autism resort to altered neural routes in comprehending language in general, and figurative language in particular.
Lien vers le texte intégral (Open Access ou abonnement)
4. Parellada M. {{Textbook of autism spectrum disorders}}. {Am J Psychiatry}. 2012; 169(5): 554-5.
Lien vers le texte intégral (Open Access ou abonnement)
5. Spitalnik DM, Coffield CN, Gabry K, White-Scott S. {{A lesson in humanism: educating medical students about family-centered care and developmental disabilities}}. {MD Advis}. 2012; 5(2): 32-4.
6. Stigler KA, Mullett JE, Erickson CA, Posey DJ, McDougle CJ. {{Paliperidone for irritability in adolescents and young adults with autistic disorder}}. {Psychopharmacology (Berl)}. 2012.
RATIONALE: Individuals with autistic disorder (autism) frequently exhibit significant irritability marked by severe tantrums, aggression, and self-injury. Despite advances in the treatment of this symptom domain in autism, there remains an ongoing need for more effective and better tolerated pharmacotherapies. OBJECTIVES: The aim of this study is to determine the effectiveness and tolerability of paliperidone for irritability in autism. METHODS: This is a prospective, 8-week open-label study of paliperidone in 25 adolescents and young adults with autism. Primary outcome measures included the Clinical Global Impressions-Improvement (CGI-I) Scale and the Irritability subscale of the Aberrant Behavior Checklist (ABC-I). Concomitant medications (except antipsychotics) were permitted if dosages were stable for >/=2 months. RESULTS: Twenty-one (84 %) of 25 subjects ages 12-21 years (mean 15.3 years) responded to paliperidone, based on a CGI-I Scale score of 1 or 2 (very much or much improved) and >/=25 % improvement on the ABC-I. The mean final dosage of paliperidone was 7.1 mg/day (range 3-12 mg/day). Two subjects discontinued paliperidone prior to study completion (moderate sedation, n = 1; nonresponse, n = 1). Mild-to-moderate extrapyramidal symptoms were recorded in four subjects. A mean weight gain of 2.2 +/- 2.6 kg (range -3.6 to +7.9 kg) was recorded. Mean age- and sex-normed body mass index increased from 23.6 to 24.2 (p </= 0.001). Mean serum prolactin increased from 5.3 to 41.4 ng/mL (p </= 0.0001). CONCLUSIONS: Paliperidone treatment was associated with significant improvement in irritability and was generally well tolerated. Larger scale, placebo-controlled studies are needed to elucidate the efficacy and tolerability of paliperidone in this population.
Lien vers le texte intégral (Open Access ou abonnement)
7. Whalley K. {{Neurodevelopmental disorders: Reversing the fragile X phenotype}}. {Nat Rev Neurosci}. 2012.
