1. Brendel C, Klahold E, Gartner J, Huppke P. {{Suppression of nonsense mutations in Rett syndrome by aminoglycoside antibiotics}}. {Pediatr Res};2009 (May);65(5):520-523.
Rett Syndrome (RTT) is caused in more than 60% of cases by nonsense mutations in the MECP2 gene. So far, no curative therapy for RTT has become available. In other genetic disorders, it has been shown that aminoglycosides can cause a read-through of nonsense mutations with an efficiency of up to 20%. The aim of this study was to evaluate if this therapeutic concept is applicable to RTT. HeLa cells were transfected with eukaryotic expression vectors carrying mutant alleles of frequently occurring MECP2 nonsense mutations that were N-terminally fused to a FLAG tag. Transfected cells were incubated 24 h in the presence of gentamicin. The expression of full-length protein was analyzed by Western blotting and immunofluorescent cell staining. In the presence of gentamicin a read-through varying between 10 and 21.8% was found, depending on the nucleotide sequence context of the nonsense mutations. The full-length protein was located correctly in the nucleus. We have shown that aminoglycoside-mediated read-through of nonsense mutations in the MECP2 gene can be achieved in vitro with efficiency comparable with that seen in other disorders.
2. Dhossche DM, Reti IM, Wachtel LE. {{Catatonia and autism: a historical review, with implications for electroconvulsive therapy}}. {J Ect};2009 (Mar);25(1):19-22.
Current autism research is historically separated from catatonia and other childhood psychotic disorders, although catatonia and autism share several common symptoms (mutism, echolalia, stereotypic speech and repetitive behaviors, posturing, grimacing, rigidity, mannerisms, and purposeless agitation). Electroconvulsive therapy (ECT) effectively treats catatonia and catatonia-related conditions of intractable compulsions, tics, and self-injury in people with autism. We assess the incidence of catatonic symptoms in autism, examine emerging ECT indications in people with autism and related developmental disorders, and encourage ethical debate and legal-administrative action to assure equal access to ECT for people with autism.
3. Kanne SM, Abbacchi AM, Constantino JN. {{Multi-informant ratings of psychiatric symptom severity in children with autism spectrum disorders: the importance of environmental context}}. {J Autism Dev Disord};2009 (Jun);39(6):856-864.
4. Riby D, Hancock PJ. {{Looking at movies and cartoons: eye-tracking evidence from Williams syndrome and autism}}. {J Intellect Disabil Res};2009 (Feb);53(2):169-181.
BACKGROUND: Autism and Williams syndrome (WS) are neuro-developmental disorders associated with distinct social phenotypes. While individuals with autism show a lack of interest in socially important cues, individuals with WS often show increased interest in socially relevant information. METHODS: The current eye-tracking study explores how individuals with WS and autism preferentially attend to social scenes and movie extracts containing human actors and cartoon characters. The proportion of gaze time spent fixating on faces, bodies and the scene background was investigated. RESULTS: While individuals with autism preferentially attended to characters’ faces for less time than was typical, individuals with WS attended to the same regions for longer than typical. For individuals with autism atypical gaze behaviours extended across human actor and cartoon images or movies but for WS atypicalities were restricted to human actors. CONCLUSIONS: The reported gaze behaviours provide experimental evidence of the divergent social interests associated with autism and WS.
5. Seida JK, Ospina MB, Karkhaneh M, Hartling L, Smith V, Clark B. {{Systematic reviews of psychosocial interventions for autism: an umbrella review}}. {Dev Med Child Neurol};2009 (Feb);51(2):95-104.
AIM: A wide range of psychosocial interventions for the treatment of individuals with autism-spectrum disorders (ASDs) have been evaluated in systematic reviews. We conducted an umbrella review of systematic reviews of the effectiveness of psychosocial interventions for ASD. METHOD: Comprehensive searches were conducted in 25 bibliographic databases, relevant journals and reference lists up to May 2007. Studies included were systematic reviews on any psychosocial intervention for individuals with ASDs. Two reviewers independently assessed study relevance and quality. RESULTS: Thirty systematic reviews were included. The majority of reviews evaluated interventions based on behavioural theory (n=9) or communication-focused (n=7) therapies. Positive intervention outcomes were reported in the majority of the reviews. Methodological quality of the reviews was generally poor. INTERPRETATION: The reviews reported positive outcomes for many of the interventions, suggesting that some form of treatment is favourable over no treatment. However, there is little evidence for the relative effectiveness of these treatment options. Many of the systematic reviews had methodological weaknesses that make them vulnerable to bias. There is a need for further systematic reviews that adhere to strict scientific methods and for primary studies that make direct comparisons between different treatment options.
6. Stichter JP, Randolph JK, Kay D, Gage N. {{The use of structural analysis to develop antecedent-based interventions for students with autism}}. {J Autism Dev Disord};2009 (Jun);39(6):883-896.
7. Wachtel LE, Contrucci-Kuhn SA, Griffin M, Thompson A, Dhossche DM, Reti IM. {{ECT for self-injury in an autistic boy}}. {Eur Child Adolesc Psychiatry};2009 (Jul);18(7):458-463.
OBJECTIVE: Self-injurious behavior presents a significant challenge in autism, and first-line psychopharmacological and behavioral interventions have limited efficacy in some patients. These intractable cases may be responsive to electroconvulsive therapy. CLINICAL PICTURE: This article presents an eight-year-old boy with autism, mental retardation, prominent mood lability and a five-year history of extreme self-injurious behavior towards his head, averaging 109 self-injurious attempts hourly. The patient was at high risk for serious head trauma, and required usage of bilateral arm restraints and protective equipment (i.e., padding on shoulders, arms, and legs). All areas of daily functioning were profoundly impacted by dangerous self-injury. TREATMENT: Fifteen bilateral ECT treatments resulted in excellent mood stabilization and reduction of self-injury to 19 attempts hourly, and maintenance ECT was pursued. The patient was able to return to developmentally-appropriate educational and social activities. CONCLUSION: ECT should be considered in the treatment algorithm of refractory cases of severe self-injury in autism.
