Saturday, September 24, 2011

Effective therapies for autism

A report prepared by Vanderbilt Evidence-based Practice Center in the US presents the results of a meta-analysis of the scientific literature regarding effective therapies for ASD. This study takes the published results of 159 studies and identifies which medical and behavioural therapies appear to be effective at treating the symptoms and core challenges. Of the 159 studies, the report finds only 13 well designed studies, with 90 being poorly designed. In terms of medical treatments, respiridone and aripiprazole are somewhat effective in reducing challenging behaviours, despite noteable side-effects. Intensive behavioural intervention also shows promise, and further research in this area for the age group of <2 year-olds is required. This is the most comprehensive assessment of the current state of ASD therapies, based on evidence-based practice. The report consists of a preliminary summary of the study followed by a 100+ pages of study details.
This report, free online, is essential reading for those in the ASD community. Given the large amount of research currently undertaken, new and revised therapies are sure to be additionally relevant in the very near future. 
Download the report yourself, here.

Monday, September 19, 2011

Twin spin

Autism spectrum disorder (ASD), while once considered to be induced by ‘bad’ parenting, is now considered a prototype complex genetic disorder on the basis of twin, family, and other genetic studies. Consistently, the heritable liability in ASD is estimated as between 80-90% (reviewed by Ronald & Hoekstra, 2011). However, not all ASD cases are inherited, and de novo (non-inherited or ‘sporadic’) mutations contribute to 5-20% of ASD cases (Marshall et al., 2008; Sebat J et al., 2007; Zhao X et al., 2007; Pinto et al., 2010; Levy D et al., 2011).  Factors such as parental age, multiple births, and foetal infection may increase the risk of de novo mutations (see Blog entry: Vaccination preventing autism).
            A recent twin study, which received a large amount of coverage in the popular press, has calculated a lower heritability estimate for ASD and a greater non-inherited contribution (Hallmayer J et al., 2011).  Hallmayer and colleagues (2011) therefore suggested that the non-inherited risk factors (environmental ‘triggers’) such as parental age, multiple births, and/or foetal infections, contribute to ASD aetiology.  Other perinatal risk factors for ASD have been suggested by recent data (see ARA Blog entry from Saturday, July 16, 2011), while previous studies highlighted a role for parental age and multiple births as factors increasing the risk of sporadic (rather than familial) ASD (Croen LA et al., 2002; Gardener H et al., 2009).
            However, the concordance data in the Hallmayer and coworkers study (2011) does not differ markedly from that of other ASD studies and, as a result, the methodology employed has been criticized by experts in the field (see SFARI comments at:  There is also concern that exclusion from their dataset of patients with some types of ASD may likewise affect their findings.
            This paper has been reviewed in detail on other blog sites:
            Therefore, while ASD is a prototypic complex genetic disorder, and the exact percentage contribution of non-heritable prenatal factors to selected ASD populations (compared to the contribution of heritable factors) varies, it also appears that these values can also vary depending on the statistical methods employed to analyze the data.

by Naomi Bishop

Key Reference:
Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A, Collins J, Smith K, Lotspeich L, Croen LA, Ozonoff S, Lajonchere C, Grether JK, Risch N.
Arch Gen Psychiatry 2011, Jul 4 [Epub ahead of print]

Vaccination preventing autism

The Wakefield paper (Wakefield A et al., 1998), suggesting a link between the measles, mumps, rubella (MMR) vaccine and autism, was subsequently shown to be fraudulent and to have “killed children" (McBrien J et al., 2000; European Centre for Disease Prevention and Control (ECDC) - Surveillance and Communication Unit report, 2008; Godlee F et al., 2011; Poland & Jacobson, 2011).  Furthermore, many high-quality independent studies have confirmed there is no link between autism spectrum disorder (ASD) the MMR vaccine (Taylor B et al., 1999, 2002; Dales L et al., 2001; Farrington CP et al., 2001; Fombonne & Chakrabarti S, 2001; Kaye JA et al., 2001; Demicheli V et al., 2005; Fombonne E et al., 2006; Cox & Kirkham, 2007; Hornig M et al., 2008; Gerber & Offit, 2009) or, indeed, any other vaccine (Price CS et al., 2010). The media has been criticized for its role in the MMR debacle (Roger D, 2003; Speers & Lewis, 2004; Hilton S et al., 2007; Katelaris A, 2007), but lay readers need to be aware that one ‘scientific’ journal is continuing to publish misleading studies on this topic (for example, see the discussion at
            Multiple twin, family, and genetic-association studies have demonstrated that ASD is a classic complex genetic disorder. Most studies calculate heritability estimates of between 0.8-0.9 (80-90%) for ASD (reviewed by Ronald & Hoekstra, 2011). By contrast, non-inherited (referred to as de novo) mutations are calculated as contributing to between 5-20% of ASD cases, and contribute more to severe ASD than to milder ASD (Marshall et al., 2008; Sebat J et al., 2007; Zhao X et al., 2007; Pinto et al., 2010; Levy D et al., 2011).  ASD risk factors may include increased parental age (see ARA Blog entry from Saturday, July 9, 2011), which is known to lead to increases in chromosomal abnormalities.  Likewise, in utero infection has been suggested to increase the risk of ASD.  The evidence for increased risk of ASD associated with foetal rubella syndrome (FRS) is the strongest (Chess S, 1971, 1977; Chess S et al., 1978). This evidence is limited to the output of a single research lab, but has been supported by animal studies and case studies.  The link between other viral infections, such as CMV, and ASD remains weak.
            On the basis of the increased link between FRS and ASD, a recent study has calculated how many ASD cases have been prevented by the use of rubella vaccination in the USA (Berger BE et al., 2011). Rubella virus infection is known to cause chromosomal anomalies (Plotkin SA et al., 1965; Nusbacher J et al., 1967; Konishi S et al., 1970; Ansari & Mason, 1977) and, while the vast majority children with FRS will not have ASD, there may be an increased risk of disruption of ASD-implicated genes in early infection in utero.  Other mechanisms for increasing the risk of ASD are also possible. This recent study, therefore, indicates that rubella vaccination has prevented thousands of cases of ASD in the USA alone (Berger BE et al., 2011).

by Naomi Bishop

Key reference: Berger BE, Navar-Boggan AM, Omer SB. BMC Public Health 11: 340 (2011)

Saturday, September 3, 2011

ASD in Down syndrome

Criteria of ASD are often applied to individuals with Down syndrome even though the validity of the criteria in this population is unclear. About 5% of individuals with Down syndrome exhibit repetitive stereotypic movements, but do they also have social communication deficits? There is also a greater incidence of intellectual disability in Down syndrome, that may cloud or confuse diagnosis of social communication skills. A recent report from the Kennedy Kreiger details the co-mobities. The importance of making these distinctions means that more appropriate interventions can be trialled. The other interesting observation comes from a consideration of the genetics. In Down syndrome, over 350 genes are present in excess on chromosome 21, compared to one gene in deficit in ASD, for example. This results in a reduced brain size in Down syndrome, but potentially increased brain size in ASD. What is particularly interesting is that 40% of individuals with Down syndrome have ASD (either PDD or autism). Therefore, despite (nearly all) individuals with Down syndrome having a defined and consistent genetic imbalance, not all of them develop ASD, motor stereotypies or display disruptive behaviour. The question now for researchers is Why? The challenge raised by the authors of the above study for educators is to develop a range of targetted interventions.