Internet‐delivered psychological treatments: from innovation to implementation

Internet interventions, and in particular Internet‐delivered cognitive behaviour therapy (ICBT), have existed for at least 20 years. Here we review the treatment approach and the evidence base, arguing that ICBT can be viewed as a vehicle for innovation. ICBT has been developed and tested for several psychiatric and somatic conditions, and direct comparative studies suggest that therapist‐guided ICBT is more effective than a waiting list for anxiety disorders and depression, and tends to be as effective as face‐to‐face CBT. Studies on the possible harmful effects of ICBT are also reviewed: a significant minority of people do experience negative effects, although rates of deterioration appear similar to those reported for face‐to‐face treatments and lower than for control conditions. We further review studies on change mechanisms and conclude that few, if any, consistent moderators and mediators of change have been identified. A recent trend to focus on knowledge acquisition is considered, and a discussion on the possibilities and hurdles of implementing ICBT is presented. The latter includes findings suggesting that attitudes toward ICBT may not be as positive as when using modern information technology as an adjunct to face‐to‐face therapy (i.e., blended treatment). Finally, we discuss future directions, including the role played by technology and machine learning, blended treatment, adaptation of treatment for minorities and non‐Western settings, other therapeutic approaches than ICBT (including Internet‐delivered psychodynamic and interpersonal psychotherapy as well as acceptance and commitment therapy), emerging regulations, and the importance of reporting failed trials.     

Perinatal mental health: a review of progress and challenges

Perinatal mental health has become a significant focus of interest in recent years, with investment in new specialist mental health services in some high‐income countries, and inpatient psychiatric mother and baby units in diverse settings. In this paper, we summarize and critically examine the epidemiology and impact of perinatal mental disorders, including emerging evidence of an increase of their prevalence in young pregnant women. Perinatal mental disorders are among the commonest morbidities of pregnancy, and make an important contribution to maternal mortality, as well as to adverse neonatal, infant and child outcomes. We then review the current evidence base on interventions, including individual level and public health ones, as well as service delivery models. Randomized controlled trials provide evidence on the effectiveness of psychological and psychosocial interventions at the individual level, though it is not yet clear which women with perinatal mental disorders also need additional support for parenting. The evidence base on psychotropic use in pregnancy is almost exclusively observational. There is little research on the full range of perinatal mental disorders, on how to improve access to treatment for women with psychosocial difficulties, and on the effectiveness of different service delivery models. We conclude with research and clinical implications, which, we argue, highlight the need for an extension of generic psychiatric services to include preconception care, and further investment into public health interventions, in addition to perinatal mental health services, potentially for women and men, to reduce maternal and child morbidity and mortality.     

Treatment engagement of individuals experiencing mental illness: review and update

Individuals living with serious mental illness are often difficult to engage in ongoing treatment, with high dropout rates. Poor engagement may lead to worse clinical outcomes, with symptom relapse and rehospitalization. Numerous variables may affect level of treatment engagement, including therapeutic alliance, accessibility of care, and a client's trust that the treatment will address his/her own unique goals. As such, we have found that the concept of recovery‐oriented care, which prioritizes autonomy, empowerment and respect for the person receiving services, is a helpful framework in which to view tools and techniques to enhance treatment engagement. Specifically, person‐centered care, including shared decision making, is a treatment approach that focuses on an individual's unique goals and life circumstances. Use of person‐centered care in mental health treatment models has promising outcomes for engagement. Particular populations of people have historically been difficult to engage, such as young adults experiencing a first episode of psychosis, individuals with coexisting psychotic and substance use disorders, and those who are homeless. We review these populations and outline how various evidence‐based, recovery‐oriented treatment techniques have been shown to enhance engagement. Our review then turns to emerging treatment strategies that may improve engagement. We focus on use of electronics and Internet, involvement of peer providers in mental health treatment, and incorporation of the Cultural Formulation Interview to provide culturally competent, person‐centered care. Treatment engagement is complex and multifaceted, but optimizing recovery‐oriented skills and attitudes is essential in delivery of services to those with serious mental illness.     

The efficacy of app‐supported smartphone interventions for mental health problems: a meta‐analysis of randomized controlled trials

Although impressive progress has been made toward developing empirically‐supported psychological treatments, the reality remains that a significant proportion of people with mental health problems do not receive these treatments. Finding ways to reduce this treatment gap is crucial. Since app‐supported smartphone interventions are touted as a possible solution, access to up‐to‐date guidance around the evidence base and clinical utility of these interventions is needed. We conducted a meta‐analysis of 66 randomized controlled trials of app‐supported smartphone interventions for mental health problems. Smartphone interventions significantly outperformed control conditions in improving depressive (g=0.28, n=54) and generalized anxiety (g=0.30, n=39) symptoms, stress levels (g=0.35, n=27), quality of life (g=0.35, n=43), general psychiatric distress (g=0.40, n=12), social anxiety symptoms (g=0.58, n=6), and positive affect (g=0.44, n=6), with most effects being robust even after adjusting for various possible biasing factors (type of control condition, risk of bias rating). Smartphone interventions conferred no significant benefit over control conditions on panic symptoms (g=–0.05, n=3), post‐traumatic stress symptoms (g=0.18, n=4), and negative affect (g=–0.08, n=5). Studies that delivered a cognitive behavior therapy (CBT)‐based app and offered professional guidance and reminders to engage produced larger effects on multiple outcomes. Smartphone interventions did not differ significantly from active interventions (face‐to‐face, computerized treatment), although the number of studies was low (n≤13). The efficacy of app‐supported smartphone interventions for common mental health problems was thus confirmed. Although mental health apps are not intended to replace professional clinical services, the present findings highlight the potential of apps to serve as a cost‐effective, easily accessible, and low intensity intervention for those who cannot receive standard psychological treatment.     

The effectiveness of psychodynamic psychotherapies: An update

This paper provides a comprehensive review of outcome studies and meta‐analyses of effectiveness studies of psychodynamic therapy (PDT) for the major categories of mental disorders. Comparisons with inactive controls (waitlist, treatment as usual and placebo) generally but by no means invariably show PDT to be effective for depression, some anxiety disorders, eating disorders and somatic disorders. There is little evidence to support its implementation for post‐traumatic stress disorder, obsessive‐compulsive disorder, bulimia nervosa, cocaine dependence or psychosis. The strongest current evidence base supports relatively long‐term psychodynamic treatment of some personality disorders, particularly borderline personality disorder. Comparisons with active treatments rarely identify PDT as superior to control interventions and studies are generally not appropriately designed to provide tests of statistical equivalence. Studies that demonstrate inferiority of PDT to alternatives exist, but are small in number and often questionable in design. Reviews of the field appear to be subject to allegiance effects. The present review recommends abandoning the inherently conservative strategy of comparing heterogeneous “families” of therapies for heterogeneous diagnostic groups. Instead, it advocates using the opportunities provided by bioscience and computational psychiatry to creatively explore and assess the value of protocol‐directed combinations of specific treatment components to address the key problems of individual patients.     

The “online brain”: how the Internet may be changing our cognition

The impact of the Internet across multiple aspects of modern society is clear. However, the influence that it may have on our brain structure and functioning remains a central topic of investigation. Here we draw on recent psychological, psychiatric and neuroimaging findings to examine several key hypotheses on how the Internet may be changing our cognition. Specifically, we explore how unique features of the online world may be influencing: a) attentional capacities, as the constantly evolving stream of online information encourages our divided attention across multiple media sources, at the expense of sustained concentration; b) memory processes, as this vast and ubiquitous source of online information begins to shift the way we retrieve, store, and even value knowledge; and c) social cognition, as the ability for online social settings to resemble and evoke real‐world social processes creates a new interplay between the Internet and our social lives, including our self‐concepts and self‐esteem. Overall, the available evidence indicates that the Internet can produce both acute and sustained alterations in each of these areas of cognition, which may be reflected in changes in the brain. However, an emerging priority for future research is to determine the effects of extensive online media usage on cognitive development in youth, and examine how this may differ from cognitive outcomes and brain impact of uses of Internet in the elderly. We conclude by proposing how Internet research could be integrated into broader research settings to study how this unprecedented new facet of society can affect our cognition and the brain across the life course.     

Effectiveness of programs for reducing the stigma associated with mental disorders. A meta‐analysis of randomized controlled trials

The stigma associated with mental disorders is a global public health problem. Programs to combat it must be informed by the best available evidence. To this end, a meta‐analysis was undertaken to investigate the effectiveness of existing programs. A systematic search of PubMed, PsycINFO and Cochrane databases yielded 34 relevant papers, comprising 33 randomized controlled trials. Twenty‐seven papers (26 trials) contained data that could be incorporated into a quantitative analysis. Of these trials, 19 targeted personal stigma or social distance (6,318 participants), six addressed perceived stigma (3,042 participants) and three self‐stigma (238 participants). Interventions targeting personal stigma or social distance yielded small but significant reductions in stigma across all mental disorders combined (d=0.28, 95% CI: 0.17‐0.39, p<0.001) as well as for depression (d=0.36, 95% CI: 0.10‐0.60, p<0.01), psychosis (d=0.20, 95% CI: 0.06‐0.34, p<0.01) and generic mental illness (d=0.30, 95% CI: 0.10‐0.50, p<0.01). Educational interventions were effective in reducing personal stigma (d=0.33, 95% CI: 0.19‐0.42, p<0.001) as were interventions incorporating consumer contact (d=0.47, 95% CI: 0.17‐0.78, p<0.001), although there were insufficient studies to demonstrate an effect for consumer contact alone. Internet programs were at least as effective in reducing personal stigma as face‐to‐face delivery. There was no evidence that stigma interventions were effective in reducing perceived or self‐stigma. In conclusion, there is an evidence base to inform the roll out of programs for improving personal stigma among members of the community. However, there is a need to investigate methods for improving the effectiveness of these programs and to develop interventions that are effective in reducing perceived and internalized stigma.     

Review and Meta‐analysis of Pharmacotherapy for Binge‐eating Disorder

This study evaluated available controlled treatment studies to determine utility of pharmacotherapy for binge‐eating disorder (BED). The authors identified randomized placebo‐controlled trials testing pharmacotherapy‐only treatments and controlled trials testing pharmacotherapy with psychotherapy treatments. Meta‐analysis was performed on placebo‐controlled trials with data for attrition, remission, and weight loss. Qualitative review was performed on remaining controlled treatment literature. A total of 33 studies were considered of which 14 studies with a total of 1,279 patients were included in the meta‐analysis of pharmacotherapy‐only treatment and 8 studies with a total of 683 patients were included in the qualitative review of pharmacotherapy combined with psychotherapy interventions. No evidence suggested significant differences between medication and placebo for attrition. Evidence suggested that pharmacological treatments have a clinically significant advantage over placebo for achieving short‐term remission from binge eating (48.7% vs. 28.5%) and for weight loss, although weight losses are not substantial. No data exist to allow evaluation of longer‐term effects of pharmacotherapy‐only treatment for BED. Combining medications with psychotherapy interventions failed to significantly enhance binge outcomes, although specific medications (orlistat, topiramate) enhanced weight losses achieved with cognitive behavioral therapy and behavioral weight loss. In summary, BED patients can be advised that certain pharmacotherapies may enhance likelihood of stopping binge eating short term, but that longer‐term effects are unknown. Although some weight loss may occur, it is unlikely to be substantial with available medications. Combining medications with cognitive or behavioral treatments is unlikely to enhance binge outcomes, but specific medications (orlistat, topiramate) may enhance weight losses, albeit modestly.     

A meta‐review of “lifestyle psychiatry”: the role of exercise,smoking, diet and sleep in the prevention and treatment of mental disorders

There is increasing academic and clinical interest in how “lifestyle factors” traditionally associated with physical health may also relate to mental health and psychological well‐being. In response, international and national health bodies are producing guidelines to address health behaviors in the prevention and treatment of mental illness. However, the current evidence for the causal role of lifestyle factors in the onset and prognosis of mental disorders is unclear. We performed a systematic meta‐review of the top‐tier evidence examining how physical activity, sleep, dietary patterns and tobacco smoking impact on the risk and treatment outcomes across a range of mental disorders. Results from 29 meta‐analyses of prospective/cohort studies, 12 Mendelian randomization studies, two meta‐reviews, and two meta‐analyses of randomized controlled trials were synthesized to generate overviews of the evidence for targeting each of the specific lifestyle factors in the prevention and treatment of depression, anxiety and stress‐related disorders, schizophrenia, bipolar disorder, and attention‐deficit/hyperactivity disorder. Standout findings include: a) convergent evidence indicating the use of physical activity in primary prevention and clinical treatment across a spectrum of mental disorders; b) emerging evidence implicating tobacco smoking as a causal factor in onset of both common and severe mental illness; c) the need to clearly establish causal relations between dietary patterns and risk of mental illness, and how diet should be best addressed within mental health care; and d) poor sleep as a risk factor for mental illness, although with further research required to understand the complex, bidirectional relations and the benefits of non‐pharmacological sleep‐focused interventions. The potentially shared neurobiological pathways between multiple lifestyle factors and mental health are discussed, along with directions for future research, and recommendations for the implementation of these findings at public health and clinical service levels.     

Post‐GWAS in Psychiatric Genetics: A Developmental Perspective on the “Other” Next Steps

As psychiatric genetics enters an era where gene identification is finally yielding robust, replicable genetic associations and polygenic risk scores, it is important to consider next steps and delineate how that knowledge will be applied to ultimately ameliorate suffering associated with substance use and psychiatric disorders. Much of the post‐genome‐wide association study discussion has focused on the potential of genetic information to elucidate the underlying biology and use this information for the development of more effective pharmaceutical treatments. In this review we focus on additional areas of research that should follow gene identification. By taking genetic findings into longitudinal, developmental studies, we can map the pathways by which genetic risk manifests across development, elucidating the early behavioral manifestations of risk, and studying how various environments and interventions moderate that risk across developmental stages. The delineation of risk across development will advance our understanding of mechanism, sex differences and risk and resilience processes in different racial/ethnic groups. Here, we review how the extant twin study literature can be used to guide these efforts. Together, these new lines of research will enable us to develop more informed, tailored prevention and intervention efforts.     

Secondary psychoses: an update

Psychotic disorders due to a known medical illness or substance use are collectively termed secondary psychoses. In this paper, we first review the historic evolution of the concept of secondary versus primary psychosis and how this distinction supplanted the earlier misleading classification of psychoses into organic and functional. We then outline the clinical features and approach to the diagnosis of secondary psychotic disorders. Features such as atypical presentation, temporal relation to detectable medical cause, evidence of direct physiological causal relationship to the etiological agent, and the absence of evidence of a primary psychotic illness that may better explain the presentation suggest consideration of a secondary psychosis. Finally, we discuss how careful studies of secondary psychotic disorders can help elucidate the pathophysiology of primary, or idiopathic, psychotic disorders such as schizophrenia. We illustrate this issue through a discussion of three secondary psychotic disorders — psychoses associated with temporal lobe epilepsy, velocardiofacial syndrome, and N‐methyl D‐aspartate (NMDA) receptor encephalitis — that can, respectively, provide neuroanatomical, genetic, and neurochemical models of schizophrenia pathogenesis.     

Using structured decision‐making to set restoration objectives when multiple values and preferences exist

Achieving global targets for restoring native vegetation cover requires restoration projects to identify and work toward common management objectives. This is made challenging by the different values held by concerned stakeholders, which are not often accounted for. Additionally, restoration is time‐dependent and yet there is often little explicit acknowledgment of the time frames required to achieve outcomes. Here, we argue that explicitly incorporating value and time considerations into stated objectives would help to achieve restoration goals. We reviewed the peer‐reviewed literature on restoration of terrestrial vegetation and found that while there is guidance on how to identify and account for stakeholder values and time considerations, there is little evidence these are being incorporated into decision‐making processes. In this article, we explore how a combination of stakeholder surveys and workshops can be used within a structured decision‐making framework to facilitate the integration of diverse stakeholder values and time frame considerations to set restoration objectives. We demonstrate this approach with a case of restoration decision‐making at a regional scale (southeast Queensland, Australia) with a view to this experience supporting similar restoration projects elsewhere.     

Epigenetics and memory: causes,consequences and treatments for post‐traumatic stress disorder and addiction

Understanding the interaction between fear and reward at the circuit and molecular levels has implications for basic scientific approaches to memory and for understanding the etiology of psychiatric disorders. Both stress and exposure to drugs of abuse induce epigenetic changes that result in persistent behavioral changes, some of which may contribute to the formation of a drug addiction or a stress‐related psychiatric disorder. Converging evidence suggests that similar behavioral, neurobiological and molecular mechanisms control the extinction of learned fear and drug‐seeking responses. This may, in part, account for the fact that individuals with post‐traumatic stress disorder have a significantly elevated risk of developing a substance use disorder and have high rates of relapse to drugs of abuse, even after long periods of abstinence. At the behavioral level, a major challenge in treatments is that extinguished behavior is often not persistent, returning with changes in context, the passage of time or exposure to mild stressors. A common goal of treatments is therefore to weaken the ability of stressors to induce relapse. With the discovery of epigenetic mechanisms that create persistent molecular signals, recent work on extinction has focused on how modulating these epigenetic targets can create lasting extinction of fear or drug‐seeking behavior. Here, we review recent evidence pointing to common behavioral, systems and epigenetic mechanisms in the regulation of fear and drug seeking. We suggest that targeting these mechanisms in combination with behavioral therapy may promote treatment and weaken stress‐induced relapse.     

Assessing the Evidence Base for Restoration in South Africa

If restoration is to become effective, able to compete for limited funds and truly adaptive, it must become evidence‐based. Three of the conditions essential for the establishment and advancement of evidence‐based restoration are (1) collection of baseline information; (2) setting clearly defined goals; and (3) relevant and adequate monitoring. Using a literature review, complemented with an online survey, we reviewed 10 restoration programs in South Africa to assess whether current restoration practice meets these conditions. The review showed good collection of baseline information and the setting of restoration goals that span ecological and socioeconomic considerations. However, to a large extent goals were poorly defined, there was more monitoring of inputs than outcomes, and monitoring of ecological indicators was inconsistent. These shortcomings can undermine restoration impacts, as well as the future sustainability of these expensive programs. We conclude with recommendations on how to mainstream the requirements of evidence‐based restoration into current and proposed restoration programs.     

Associative and sensorimotor cortico‐basal ganglia circuit roles in effects of abused drugs

The mammalian forebrain is characterized by the presence of several parallel cortico‐basal ganglia circuits that shape the learning and control of actions. Among these are the associative, limbic and sensorimotor circuits. The function of all of these circuits has now been implicated in responses to drugs of abuse, as well as drug seeking and drug taking. While the limbic circuit has been most widely examined, key roles for the other two circuits in control of goal‐directed and habitual instrumental actions related to drugs of abuse have been shown. In this review we describe the three circuits and effects of acute and chronic drug exposure on circuit physiology. Our main emphasis is on drug actions in dorsal striatal components of the associative and sensorimotor circuits. We then review key findings that have implicated these circuits in drug seeking and taking behaviors, as well as drug use disorders. Finally, we consider different models describing how the three cortico‐basal ganglia circuits become involved in drug‐related behaviors. This topic has implications for drug use disorders and addiction, as treatments that target the balance between the different circuits may be useful for reducing excessive substance use.     

Sex in the wild: How and why field‐based studies contribute to solving the problem of sex*

Why and how sexual reproduction is maintained in natural populations, the so‐called “queen of problems,” is a key unanswered question in evolutionary biology. Recent efforts to solve the problem of sex have often emphasized results generated from laboratory settings. Here, we use a survey of representative “sex in the wild” literature to review and synthesize the outcomes of empirical studies focused on natural populations. Especially notable results included relatively strong support for mechanisms involving niche differentiation and a near absence of attention to adaptive evolution. Support for a major role of parasites is largely confined to a single study system, and only three systems contribute most of the support for mutation accumulation hypotheses. This evidence for taxon specificity suggests that outcomes of particular studies should not be more broadly extrapolated without extreme caution. We conclude by suggesting steps forward, highlighting tests of niche differentiation mechanisms in both laboratory and nature, and empirical evaluation of adaptive evolution‐focused hypotheses in the wild. We also emphasize the value of leveraging the growing body of genomic resources for nonmodel taxa to address whether the clearance of harmful mutations and spread of beneficial variants in natural populations proceeds as expected under various hypotheses for sex.     

Progress in understanding mood disorders: optogenetic dissection of neural circuits

Major depression is characterized by a cluster of symptoms that includes hopelessness, low mood, feelings of worthlessness and inability to experience pleasure. The lifetime prevalence of major depression approaches 20%, yet current treatments are often inadequate both because of associated side effects and because they are ineffective for many people. In basic research, animal models are often used to study depression. Typically, experimental animals are exposed to acute or chronic stress to generate a variety of depression‐like symptoms. Despite its clinical importance, very little is known about the cellular and neural circuits that mediate these symptoms. Recent advances in circuit‐targeted approaches have provided new opportunities to study the neuropathology of mood disorders such as depression and anxiety. We review recent progress and highlight some studies that have begun tracing a functional neuronal circuit diagram that may prove essential in establishing novel treatment strategies in mood disorders. First, we shed light on the complexity of mesocorticolimbic dopamine (DA) responses to stress by discussing two recent studies reporting that optogenetic activation of midbrain DA neurons can induce or reverse depression‐related behaviors. Second, we describe the role of the lateral habenula circuitry in the pathophysiology of depression. Finally, we discuss how the prefrontal cortex controls limbic and neuromodulatory circuits in mood disorders .     

The role of protein complexes in human genetic disease

Many human genetic disorders are caused by mutations in protein‐coding regions of DNA. Taking protein structure into account has therefore provided key insight into the molecular mechanisms underlying human genetic disease. Although most studies have focused on the intramolecular effects of mutations, the critical role of the assembly of proteins into complexes is being increasingly recognized. Here, we review multiple ways in which consideration of protein complexes can help us to understand and explain the effects of pathogenic mutations. First, we discuss disorders caused by mutations that perturb intersubunit interactions in homomeric and heteromeric complexes. Second, we address how protein complex assembly can facilitate a dominant‐negative mechanism, whereby mutated subunits can disrupt the activity of wild‐type protein. Third, we show how mutations that change protein expression levels can lead to damaging stoichiometric imbalances. Finally, we review how mutations affecting different subunits of the same heteromeric complex often cause similar diseases, whereas mutations in different interfaces of the same subunit can cause distinct phenotypes.     

Competing regression models for longitudinal data

The choice of an appropriate family of linear models for the analysis of longitudinal data is often a matter of concern for practitioners. To attenuate such difficulties, we discuss some issues that emerge when analyzing this type of data via a practical example involving pretest–posttest longitudinal data. In particular, we consider log‐normal linear mixed models (LNLMM), generalized linear mixed models (GLMM), and models based on generalized estimating equations (GEE). We show how some special features of the data, like a nonconstant coefficient of variation, may be handled in the three approaches and evaluate their performance with respect to the magnitude of standard errors of interpretable and comparable parameters. We also show how different diagnostic tools may be employed to identify outliers and comment on available software. We conclude by noting that the results are similar, but that GEE‐based models may be preferable when the goal is to compare the marginal expected responses.     

Non-Specialist Psychosocial Interventions for Children and Adolescents with Intellectual Disability or Lower-Functioning Autism Spectrum Disorders: A Systematic Review

Background

The development of effective treatments for use by non-specialists is listed among the top research priorities for improving the lives of people with mental illness worldwide. The purpose of this review is to appraise which interventions for children with intellectual disabilities or lower-functioning autism spectrum disorders delivered by non-specialist care providers in community settings produce benefits when compared to either a no-treatment control group or treatment-as-usual comparator.

Methods and Findings

We systematically searched electronic databases through 24 June 2013 to locate prospective controlled studies of psychosocial interventions delivered by non-specialist providers to children with intellectual disabilities or lower-functioning autism spectrum disorders. We screened 234 full papers, of which 34 articles describing 29 studies involving 1,305 participants were included. A majority of the studies included children exclusively with a diagnosis of lower-functioning autism spectrum disorders (15 of 29, 52%). Fifteen of twenty-nine studies (52%) were randomized controlled trials and just under half of all effect sizes (29 of 59, 49%) were greater than 0.50, of which 18 (62%) were statistically significant. For behavior analytic interventions, the best outcomes were shown for development and daily skills; cognitive rehabilitation, training, and support interventions were found to be most effective for improving developmental outcomes, and parent training interventions to be most effective for improving developmental, behavioral, and family outcomes. We also conducted additional subgroup analyses using harvest plots. Limitations include the studies'' potential for performance bias and that few were conducted in lower- and middle-income countries.

Conclusions

The findings of this review support the delivery of psychosocial interventions by non-specialist providers to children who have intellectual disabilities or lower-functioning autism spectrum disorders. Given the scarcity of specialists in many low-resource settings, including many lower- and middle-income countries, these findings may provide guidance for scale-up efforts for improving outcomes for children with developmental disorders or lower-functioning autism spectrum disorders.

Protocol Registration

PROSPERO CRD42012002641 Please see later in the article for the Editors'' Summary