Introduction: novel therapies in developmental disabilities--hope, reason, and evidence

Complementary and alternative medicine (CAM) is used both alongside (complementary) and as a substitute for (alternative) conventional therapies. Although CAM use is reported to be high among children with typical development, reported rates for CAM use to address symptoms of children with developmental disabilities may be higher. Increased use in this population may relate to hope for amelioration of symptoms, concerns regarding side effects of conventional treatments, and a need on the part of families to participate in decision making regarding their child's care. Primary health care providers may find that the child's needs are best served when they maintain a dialogue with families to evaluate the evidence supporting novel therapies. Interventions need to be assessed in an evidence based fashion whether or not they are initially preceived as CAM. This issue of Mental Retardation and Developmental Disabilities Research Reviews contains reviews of CAM used to treat several developmental disabilities as well as some broader discussions related to the determinants of CAM use, current efforts to evaluate novel therapies, and how to consider the possibility of placebo effects.     

Selective Mutism and Its Relations to Social Anxiety Disorder and Autism Spectrum Disorder

In current classification systems, selective mutism (SM) is included in the broad anxiety disorders category. Indeed, there is abundant evidence showing that anxiety, and social anxiety in particular, is a prominent feature of SM. In this article, we point out that autism spectrum problems in addition to anxiety problems are sometimes also implicated in SM. To build our case, we summarize evidence showing that SM, social anxiety disorder (SAD), and autism spectrum disorder (ASD) are allied clinical conditions and share communalities in the realm of social difficulties. Following this, we address the role of a prototypical class of ASD symptoms, restricted and repetitive behaviors and interests (RRBIs), which are hypothesized to play a special role in the preservation and exacerbation of social difficulties. We then substantiate our point that SM is sometimes more than an anxiety disorder by addressing its special link with ASD in more detail. Finally, we close by noting that the possible involvement of ASD in SM has a number of consequences for clinical practice with regard to its classification, assessment, and treatment of children with SM and highlight a number of directions for future research.

     

Response monitoring, the error-related negativity, and differences in social behavior in autism

Children with autism not only display social impairments but also significant individual differences in social development. Understanding the source of these differences, as well as the nature of social impairments, is important for improved diagnosis and treatments for these children. Current theory and research suggests that individual differences in response monitoring, a specific function of the anterior cingulate cortex (ACC), may contribute to social-emotional and social-cognitive impairments and individual differences in autism. To examine this hypothesis, we used a modified flanker task to assess an ERP index of response monitoring, the error-related negativity (ERN), in a sample of higher function children with autism (HFA) and an IQ-matched control sample. The results revealed a significant Diagnostic group by Verbal IQ interaction on ERN amplitude indicating that the most verbally capable HFA children displayed significantly larger ERN amplitudes than did the control children. Within the HFA sample, greater ERN amplitude was also related to parent reports of fewer symptoms of social interaction impairments, fewer internalizing problems, but more externalizing problems, although these associations were reduced to nonsignificance when medication status was controlled. The latter results complement previous observations from imaging studies of a significant association between ACC activity and social symptoms and impairments in autism. The implications of these results for future research on brain-behavior relations, as well as treatment related research with children with autism are discussed.     

Old and new controversies in the alternative treatment of attention-deficit hyperactivity disorder

Use of complementary and alternative medicine (CAM) for treatment of attention-deficit hyperactivity disorder (ADHD) has become widespread in both referral and primary care populations. We review the purported mechanism of action and available evidence for selected CAM therapies for ADHD. Enduring controversies, such as elimination of artificial food additives, colors, and/or preservatives; the effect of sugar on behavior in children; and the use of EEG biofeedback, have been well studied but lack support as effective sole treatments for ADHD. The initial evidence for some emerging CAM therapies, such as essential fatty acid supplementation, yoga, massage, homeopathy, and green outdoor spaces, suggests potential benefits as part of an overall ADHD treatment plan. More rigorously designed studies are needed to evaluate their effectiveness as single therapy for ADHD.     

Sensory Integration as a Treatment for Automatically Maintained Stereotypy

According to sensory integration (SI) theory, many symptoms of autism are caused by an inability to integrate and adaptively respond to sensory input. Despite little evidence supporting SI, this form of therapy is a popular treatment for children with autism. Should these treatments work, they should be most effective for behavior maintained by sensory consequences (automatically maintained). SI activities may make these sensory consequences less reinforcing. The purpose of this study was to determine whether SI treatments could reduce automatically‐maintained stereotypy. Five individuals with autism participated. An occupational therapist prescribed sensory activities that competed with stereotypy for SI treatments. Two types of SI treatments were tested: sensory diets and brushing with deep‐pressure therapy. The effect of these treatments on stereotypy was evaluated in an ABAB design. Neither the sensory diet alone, brushing and deep pressure alone, nor both treatments combined were effective interventions for stereotypy. These results do not support the use of SI as a treatment for stereotypy. Copyright © 2015 John Wiley & Sons, Ltd.     

AEDs and psychotropic drugs in children with autism and epilepsy

The efficacy of antiepileptic drugs (AEDs) and psychotropic medications in children with autism is limited to the treatment of seizures or to specific behaviors such as irritability, impulsivity, hyperactivity, repetitive behaviors, or aggression. The reliability and value of the available data--to determine the efficacy of these medications in autism--are limited by lack of controlled clinical trials, the small number of subjects, the heterogeneity of the population studied, and the brief duration of most drug trials. Indeed, few controlled clinical trials using AEDs in autism, with or without seizures, have been conducted. Because some AEDs also have a positive effect on mood, the benefits that children with autism sometimes obtain from these medications may not be due to the treatment of the abnormal electrical activity or the seizures per se but to an effect on common neuronal systems responsible for both behavior and epilepsy. The relationship between epilepsy and autism, and specifically the effects that abnormal electrical activity may have on the developing brain, may provide some valuable insights into the type of studies that are needed to help us understand the pathophysiology of autism.     

Epileptic encephalopathies and their relationship to developmental disorders: do spikes cause autism?

Epileptic encephalopathies are progressive clinical and electroencephalographic syndromes where deterioration is thought to be caused by frequent seizures and abundant EEG epileptiform activity. Seizures occur in approximately 10-15% of children with pervasive developmental disorders (PDD) and 8-10% have epileptiform EEG abnormalities without seizures. Thirty percent of children with PDD have regression of social behavior and language at 2-3 years of age. Some authors speculate that the regression is caused by epileptiform activity even in the absence of overt clinical seizures ("autism with epileptic regression") and suggest that elimination of the epileptiform activity, either medically or surgically, should lead to improvement in behavior. This review examines the data showing that interictal epileptiform discharges are associated with transient clinical dysfunction and discusses the implications of these observations for autistic behavioral abnormalities. The results of resective surgery, vagal nerve stimulation, and multiple subpial transaction on children with autism and epileptiform EEG abnormalities are also discussed. I conclude that there is no evidence that interictal discharges per se cause (or contribute to) the complex behavioral phenotype of autism. There is no justification to support the use of anticonvulsant medication or surgery in children with PDD without seizures; that is, there is no evidence that treatment to eliminate EEG spikes will have a therapeutic effect on the behavioral abnormalities of PDD and autism.     

Designing mouse behavioral tasks relevant to autistic-like behaviors

The importance of genetic factors in autism has prompted the development of mutant mouse models to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (1) face validity, i.e., resemblance to the human symptoms; (2) construct validity, i.e., similarity to the underlying causes of the disease; and (3) predictive validity, i.e., expected responses to treatments that are effective in the human disease. There is a growing need for mouse behavioral tasks with all three types of validity for modeling the symptoms of autism. We are in the process of designing a set of tasks with face validity for the defining features of autism: deficits in appropriate reciprocal social interactions, deficits in verbal social communication, and high levels of ritualistic repetitive behaviors. Social approach is tested in an automated three-chambered apparatus that offers the subject a choice between a familiar environment, a novel environment, and a novel environment containing a stranger mouse. Preference for social novelty is tested in the same apparatus, with a choice between the start chamber, the chamber containing a familiar mouse, and the chamber containing a stranger mouse. Social communication is evaluated by measuring the ultrasonic distress vocalizations emitted by infant mouse pups and the parental response of retrieving the pup to the nest. Resistance to change in ritualistic repetitive behaviors is modeled by forcing a change in habit, including reversal of the spatial location of a reinforcer in a T-maze task and in the Morris water maze. Mouse behavioral tasks that may model additional features of autism are discussed, including tasks relevant to anxiety, seizures, sleep disturbances, and sensory hypersensitivity. Applications of these tests include (1) behavioral phenotyping of transgenic and knockout mice with mutations in genes relevant to autism, (2) characterization of mutant mice derived from random chemical mutagenesis, (3) DNA microarray analyses of genes in inbred strains of mice that differ in social interaction, social communication and resistance to change in habit, and (4) evaluation of proposed therapeutics for the treatment of autism.     

The Findings of a Cochrane Meta-Analysis of Couple Therapy in Adult Depression: Implications for Research and Clinical Practice

The association between depressive symptoms and distressed intimate relationships supported the assumption that couple therapy, by focusing on the interpersonal context of depression, might be more effective as a treatment for depression than individual psychotherapy or drug therapy. This issue was addressed by a Cochrane meta-analysis assessing the evidence from clinical trials of couple therapy for depression in comparison with individual psychotherapy, drug therapy, and no/minimal intervention, including fourteen studies with 651 participants. No study was found free of bias and the quality of the evidence was low, with major problems of small sample sizes, missing outcome data, selective reporting, lack of information on random sequence generation and allocation concealment, recruitment of people not representative of clinical practice, and allegiance bias. The meta-analysis showed that both couple therapy and individual psychotherapy improved depressive symptoms at end of treatment and after 6 months or longer, with moderate effect sizes, without any difference between the two treatments. Couple therapy was more effective in reducing couple distress. This effect was larger in studies with distressed couples only and should be considered as relevant in its own right. Couple therapy is a viable option for the treatment of a depressed partner, especially in discordant couples. Future research should address several issues left open to provide a sound empirical foundation for clinical practice.     

Current knowledge on motor disorders in children with autism spectrum disorder (ASD)

Motor symptomatology in autism is currently poorly understood, and still not included in the autism spectrum disorder (ASD) diagnostic criteria, although some studies suggest the presence of motor disturbances in this syndrome. We provide here a literature review on early motor symptoms in autism, focusing on studies on psychomotor issues (tone, postural control, manual dexterity, handedness, praxis). The approach adopted in research to study altered motor behaviors is generally global and there is no detailed semiology of the motor or neuromotor disorders observed in people with ASD. This global approach does not enable understanding of the neuro-developmental mechanisms involved in ASD. Identification of clinical neuro-psychomotor profiles in reference to a standard would help to better understand the origin and the nature of the disorders encountered in ASD, and would thus give new directions for treatment.     

Treating the core features of autism: are we there yet?

A wide variety of nonestablished treatments have been proposed as "cures" for the core features of autism and are used frequently despite having largely escaped scientific scrutiny. In contrast, a growing body of empirical evidence supports the use of a few forms of theory-based and empirically validated treatment for some aspects of the core features of autism. These include behavioral/psychoeducational interventions and specific forms of medication treatment, which can produce significant improvements in communication, social interaction, and problem behaviors that both maintain over time and generalize across settings. While there is no doubt that treatment and educational services for persons with autism have improved over the past 6 decades, it also appears that significant issues remain with respect to (1) the routine application of validated treatments for the majority of cases with autism, (2) the resistance to even validated forms of treatment for a substantial minority of cases with autism, and (3) the extent to which validated treatments effectively treat the specific core features of autism that are most disabling for persons with autism and their families.     

Altered face scanning and impaired recognition of biological motion in a 15-month-old infant with autism

Mounting clinical evidence suggests that abnormalities of social engagement in children with autism are present even during infancy. However, direct experimental documentation of these abnormalities is still limited. In this case report of a 15-month-old infant with autism, we measured visual fixation patterns to both naturalistic and ambiguous social stimuli: video scenes of a caregiver and point-light animations of human action. Results suggested that viewing patterns of the child with autism were driven by the physical contingencies of the stimuli rather than by their social context. If corroborated in larger studies, this observation would advance the hypothesis that mechanisms of social development which rely on preferential engagement with socially contingent conspecifics - and which emerge in the very first weeks of life in typical infants - are developmentally derailed in children with autism.     

Family therapy as a treatment for children: a critical review of outcome research.

The value of family therapy as a treatment for child psychopathology is considered by reviewing pertinent outcome research. Fourteen studies that met three criteria are included in the review: (a) a child or adolescent was the identified patient or referral; (b) therapy included at least one parent and the child; and (c) outcome was evaluated in terms of the child's symptoms. There are major shortcomings in most of the available data, with only two well-controlled studies. Some empirical evidence does exist that family therapy is an effective treatment for children; the data from studies of adolescents are especially encouraging. However, insufficient data are available for comparing the relative merits of conjoint family treatment and individual child therapy. If the value of family therapy as a treatment alternative or, ideally, as the "treatment of choice" for a referred individual child is to be established, more and better controlled comparative outcome studies will be necessary. Suggestions for future research are presented emphasizing the need for a developmental perspective by recommending, for example, the use of factorial designs in which the intervenaction of treatment and age can be analyzed.     

Decreasing Psychiatric Symptoms by Increasing Choice in Services for Adults with Histories of Homelessness

Despite the increase in consumer-driven interventions for homeless and mentally ill individuals, there is little evidence that these programs enhance psychological outcomes. This study followed 197 homeless and mentally ill adults who were randomized into one of two conditions: a consumer-driven “Housing First” program or “treatment as usual” requiring psychiatric treatment and sobriety before housing. Proportion of time homeless, perceived choice, mastery, and psychiatric symptoms were measured at six time points. Results indicate a direct relationship between Housing First and decreased homelessness and increased perceived choice; the effect of choice on psychiatric symptoms was partially mediated by mastery. The strong and inverse relationship between perceived choice and psychiatric symptoms supports expansion of programs that increase consumer choice, thereby enhancing mastery and decreasing psychiatric symptoms.     

Exercise Training for Persons with Alzheimer's Disease and Caregivers: A Review of Dyadic Exercise Interventions

Alzheimer's disease (AD) is the most common form of dementia and the prevalence will increase dramatically in the next decades. Although exercise has shown benefits for people with dementia due to AD as well as their caregivers, the impact of a dyadic exercise intervention including both groups as study participants remains to be determined. The authors review the current clinical evidence for dyadic exercise interventions, which are exercise regimens applied to both the person with dementia and the caregiver. A total of 4 controlled trials were reviewed. This review shows that dyadic exercise interventions are feasible and may produce a positive effect on functional independence and caregiver burden. However, there was insufficient evidence to support a benefit of dyadic exercise intervention on cognitive performance and on behavioral and neuropsychiatric symptoms in participants with dementia due to AD. A dyadic exercise intervention improves functional independence and caregiver burden. However, there is a need for well-designed randomized controlled clinical trials to confirm these benefits and to investigate several important points such as the effects of a dyadic exercise intervention on cognitive and noncognitive outcomes of AD, the optimal intensity of exercise training, and the cost effectiveness of such a program.     

Motor proficiency and emotional/behavioural disturbance in autism and Asperger's disorder: another piece of the neurological puzzle?

The relationship of motor proficiency with emotional/behavioural disturbance, autistic symptoms and communication disturbance was investigated in children diagnosed with autism and Asperger's disorder (AD). The Movement Assessment Battery for Children was used as a measure of motor impairment, and the Developmental Behavioural Checklist was used as a measure of emotional/behavioural disturbance in the following groups: AD (n?=?22), high functioning autism (HFA) (n?=?23), LFA (n?=?8) and typically developing children (n?=?20). The HFA group had more difficulty with motor items, such as ball skills and balance, than did the AD group. There were significant positive correlations between impairments in motor proficiency (in particular ball skills and balance) and emotional/behavioural disturbance, autistic symptoms and communication disturbance. These findings are consistent with the hypothesis that there are qualitative and quantitative differences in the motor profile between autism and AD. In addition, the association between motor proficiency impairment and emotional/behavioural disturbance in autism and AD emphasizes the importance for screening of co-occurring emotional/behavioural symptoms in individuals with motor difficulties. These findings have implications for the potential use of adjunct motor measures in the diagnosis and definition of autism spectrum disorders.     

Variability in Adaptive Behavior in Autism: Evidence for the Importance of Family History

Adaptive behavior in autism is highly variable and strongly related to prognosis. This study explored family history as a potential source of variability in adaptive behavior in autism. Participants included 77 individuals (mean age = 18) with average or better intellectual ability and autism. Parents completed the Family History Interview about the presence of broader autism phenotype symptoms and major psychiatric disorders in first degree relatives. Adaptive behavior was assessed via the Vineland Adaptive Behavior Scales (VABS). Based on family history variables, age, and intelligence quotient (IQ), 87% of participants were correctly classified as having impaired or average VABS scores. Family history of depression and shyness accounted for the most variance in VABS scores, and they had the greatest influence on VABS Socialization scores in particular. Possible underlying mechanisms include genetics, psychosocial factors, and social resources. This study provides initial evidence of the importance of family history to adaptive behavior in autism and has implications for genetics and treatment.     

Genetic Studies of Autism: From the 1970s into the Millennium

Reviewers in the 1960s and early 1970s were skeptical about any substantial role for genetic factors in the etiology of autism. A realization that the 2% rate of autism in siblings (as estimated at that time) was far above the general population base rate, and that this suggested a possible high genetic liability, led to the first small-scale twin study of autism. The replicated evidence from both twin and family studies undertaken in the 1970s and 1980s indicated both strong genetic influences and the likelihood that they applied to a phenotype that was much broader than the traditional diagnostic category of autism. Medical and chromosomal findings also indicated genetic heterogeneity. Advances in molecular genetics led to genome-wide scans of affected relative pair samples with a positive log of the odds to base 10 score for a location on chromosome 7. The major remaining research challenges and the likely clinical benefits that should derive from genetic research are considered in relation to both current knowledge and that anticipated to emerge from research over the next decade.