Autism Treatment Research

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Since the launch of Autism Research, there have been exciting advances in the genetics and neuroscience of autism spectrum disorder (ASD). Concomitantly, there has been a significant increase in the number of well-designed and controlled treatment studies, reflecting both the development of new, more effective developmental and behavioural interventions, as well as pressure for research that addresses the immediate needs of affected individuals. Although the complex neurobiology of ASD is an obstacle to the rapid development of novel biological treatments, the genetic findings implicating synaptic processes have finally stimulated the interest of the pharmaceutical industry in ASD. Indeed, the development of mouse models of Fragile X, tuberous sclerosis, and Rett Syndrome has facilitated drug trials for these conditions, whose findings may be more broadly relevant. In parallel with these advances, the increased attention paid to ASD over the last 5–10 years has highlighted the burden of comorbid psychiatric disorders and the need for effective treatments to improve quality of life.

Because of these developments, Autism Research is expanding its scope to include adequately powered treatment studies, with a particular emphasis on research that reveals underlying mechanisms, either by testing causal hypotheses or by revealing variations in responses, which prompts refinement of explanatory models.

What are some of the overarching challenges that treatment research will face over the coming decades? From a scientific perspective, variations in severity and persistence into adulthood indicate the need for a range of treatment approaches. Almost since autism was first described, clinicians and researchers have appreciated that there is no one intervention that is effective for all individuals. Additionally, almost regardless of the approach taken, behavioural and educational interventions seem to be most beneficial for individuals with greater intellectual abilities. The early intervention studies raise the questions of the extent to which treatment gains persist into adolescence or early adult life and whether individuals who show the best response to treatment would also have a better long-term outcome without intervention. Of course, long-term outcome is not the only measure against which interventions should be judged, as improved quality of life during childhood for the individual and his or her family is a worthwhile gain in its own right. But undertaking long-term follow-up studies and understanding why less able individuals often show reduced treatment response are key objectives. Possibly, the most handicapped individuals may benefit from novel pharmacological interventions, as they are more likely to be affected by chromosomal abnormalities and single-gene causes of ASD. Indeed, the recent trials of drug treatments for single-gene aetiologies of ASD illustrate the potential of this approach, but neurophysiological and neuroimaging studies to understand mode of therapeutic action are particularly difficult in these populations.

The vast majority of treatment research for ASD focuses on childhood. Much of this emphasis is justified by the severe behaviours shown by some young children with autism and also the pressure upon parents and siblings. Nevertheless, as new environmental challenges arise in adolescence and adult life, skills learnt much earlier in development may not suffice and different interventions may be required. The education literature on typically developing adults is replete with examples of the differences between child and adult learners, and the need for modified educational approaches in adult life: there is no reason to suppose that ASD will be the exception to these general observations. The focus on male participants in research is almost as striking as the current emphasis on childhood. The exclusion of female research participants is often because of concerns about statistical power or a wish to reduce heterogeneity, but an unintended consequence of this focus is limited research into whether the brain basis of ASD is identical in both sexes as well as whether interventions should differ in emphasis according to sex. These are important omissions, as we have become increasingly aware that the behavioural and cognitive phenotypes in the most able females can differ from that in males, which may partly explain the apparent underdiagnoses of affected women. Some of these women will go on to raise families and almost nothing is known about how to help these mothers succeed in that role. Additionally, we know much less about the skills of able affected women, whereas the identified mathematical, computing, or physical science strengths of some affected men have been instrumental in developing specific vocational opportunities.

Since the description of Theory of Mind deficits in the mid-1980s, studies of speech and language abnormalities in ASD have taken second place to research into the cognitive and brain bases of social deficits. Additionally, the breadth of language abilities across the autistic spectrum illustrates the difficulty of devising interventions appropriate for all. Complete absence of speech is a particular challenge, and to date, there is little evidence that alternative communication systems effectively catalyse the development of speech. On a more positive note, the increasing power of portable computing devices and the efforts to develop specific software for individuals with ASD offers hope that more individuals will be able to use technology to communicate more effectively in the future. In turn, these developments will enable individuals to be included in research studies, who previously might have been unable to communicate responses effectively. Indeed, technological advances will likely offer many opportunities for individuals with ASD to participate more fully and safely in society, and the study of these approaches is becoming a research field in its own right.

Increasingly, researchers are using imaging techniques to search for brain changes that accompany successful interventions. Presently, our ability to devise interventions far outstrips our capacity to interpret meaningfully the accompanying changes in brain activity. In large part the problem reflects the macroscopic resolution of imaging approaches, whereas changes in functional connectivity occur at a cellular level. This impasse seems unlikely to be resolved in the near future and we are likely to need convergent evidence for brain changes as well as judicious use of animal models. Pharmacogenomics has increased in importance for those disorders which show clear drug effects. In ASD, the focus seems more likely to be upon the relationship between allelic variation and behavioural or cognitive treatment responses. Additionally, for home-based interventions, researchers may also need to take into account the environmental consequences of the presence of risk alleles in one or both parents.

Clinicians who treat adolescents and adults with ASD recognise the considerable morbidity caused by severe anxiety and also depression. Although less common, obsessive–compulsive disorder and psychosis impact negatively on quality of life, and the overlap between eating disorders and ASD is increasingly recognised. Well-established treatments for these comorbid disorders are frequently effective in ASD, and the challenge for interventions, such as cognitive behaviour therapy, is how to deliver them efficiently as well as ensuring that individuals continue to use these approaches once therapy has ceased. There are some individuals, however, who suffer from high anxiety despite combined pharmacotherapy and behavioural treatments, and there is a need to understand whether the neurobiological substrate differs from that in the typically developing population. Much earlier in life, it is not uncommon for ASD to be misdiagnosed as ADHD, and the overlap between these two disorders is receiving increasing attention. Some individuals with ASD and problems with inattentiveness and overactivity do not respond adequately to stimulant medication, suggesting that the mechanisms underlying attentional problems may not be identical in ASD and ADHD. Identifying these mechanisms is likely to be particularly important for maximising the academic progress of individuals in education.

Researchers are in the luxurious position of having a scientific education, comprehensive access to empirical papers, and some degree of detachment from the findings of their treatment research. Parents of individuals with ASD are often in a much less fortunate position and have always been particularly vulnerable to claims of cure, for which there is often little or no scientific evidence. The ubiquity of the Internet has increased parents' exposure to claims and advertisements, often from remote locations. The impact on families of ineffective therapies can be substantial in terms of time, disruption of family life, money, and sometimes morbidity. Occasionally, the researcher's role is to investigate the efficacy of questionable treatments because of their public health implications. But the much broader role of the research community is to educate families and the public about what is known about autism and how to effectively assess treatment claims. The efficacy of treatments and their long-term consequences are also of considerable interest to governments, as the monetary costs of ASD are very high, but only a handful of health economists are interested in how and when resources should be allocated to autism intervention. Instead discussion about allocation of government resources often centres on the few individuals who may require intensive and expensive 24-hr care, but there has been little systematic research into how these poor outcomes could be minimised.

Clinicians who deal with ASD, particularly in adult life, tend to have strong focus on quality of life. We need more systematic research into what this means for individuals in the autistic spectrum, although common aspirations seem to be employment, having a home and also a partner, whereas parents may have a strong focus on safety and self-esteem. Much treatment research tend to focus on remediating deficits, but improving quality of life often requires developing individuals' strengths, and there is still much to learn about how to do this effectively for individuals with ASD.

At present, relatively little is known about how social disadvantage impacts outcome in ASD, and often research participants are not representative of the entire population of affected individuals. How does being raised in poverty, or by a single parent, or in the care system affect access and response to treatment? Is additional support needed by these and other populations, and how should they be delivered? Of course, social disadvantage shows a strong correlation with geographical location, and most individuals with ASD do not live in the developed world. With regard to diarrhoea, infectious disease, and malnutrition, there was a concerted effort by the West to help develop educational approaches and manualised treatments suitable for less affluent countries, and a similar global initiative is required for the treatment and education of individuals with ASD outside of the West. But when compared to other developmental disabilities, autism is often seen as occupying a privileged position with regard to visibility and resources, which occasionally results in misguided efforts to pull populations down to the lowest common level of resources. The best response to these initiatives is to ensure that research into treatment for ASD is contextualised in terms of its broader implications as well as arguing cogently for the highest possible quality of life for all individuals with neurodevelopmental disorders.

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