Harvard Review of Psychiatry - Special Issue on Autism (Mars-Avril 2014)

lundi 17 mars 2014

l’Harvard Review of Psychiatry consacre son numéro de mars-avril 2014 au thème de l’autisme.

1. Frazier JA, McDougle CJ. Introduction. Harvard Review of Psychiatry ;2014 ;22(2):61-64.

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2. Talkowski ME, Minikel EV, Gusella JF. Autism Spectrum Disorder Genetics : Diverse Genes with Diverse Clinical Outcomes. Harvard Review of Psychiatry ;2014 ;22(2):65-75.

Abstract : The last several years have seen unprecedented advances in deciphering the genetic etiology of autism spectrum disorders (ASDs). Heritability studies have repeatedly affirmed a contribution of genetic factors to the overall disease risk. Technical breakthroughs have enabled the search for these genetic factors via genome-wide surveys of a spectrum of potential sequence variations, from common single-nucleotide polymorphisms to essentially private chromosomal abnormalities. Studies of copy-number variation have identified significant roles for both recurrent and nonrecurrent large dosage imbalances, although they have rarely revealed the individual genes responsible. More recently, discoveries of rare point mutations and characterization of balanced chromosomal abnormalities have pinpointed individual ASD genes of relatively strong effect, including both loci with strong a priori biological relevance and those that would have otherwise been unsuspected as high-priority biological targets. Evidence has also emerged for association with many common variants, each adding a small individual contribution to ASD risk. These findings collectively provide compelling empirical data that the genetic basis of ASD is highly heterogeneous, with hundreds of genes capable of conferring varying degrees of risk, depending on their nature and the predisposing genetic alteration. Moreover, many genes that have been implicated in ASD also appear to be risk factors for related neurodevelopmental disorders, as well as for a spectrum of psychiatric phenotypes. While some ASD genes have evident functional significance, like synaptic proteins such as the SHANKs, neuroligins, and neurexins, as well as fragile x mental retardation–associated proteins, ASD genes have also been discovered that do not present a clear mechanism of specific neurodevelopmental dysfunction, such as regulators of chromatin modification and global gene expression. In its sum, the progress from genetic studies to date has been remarkable and increasingly rapid, but the interactive impact of strong-effect genetic lesions coupled with weak-effect common polymorphisms has not yet led to a unified understanding of ASD pathogenesis or explained its highly variable clinical expression. With an increasingly firm genetic foundation, the coming years will hopefully see equally rapid advances in elucidating the functional consequences of ASD genes and their interactions with environmental/experiential factors, supporting the development of rational interventions.

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3. Politte LC, Henry CA, McDougle CJ. Psychopharmacological Interventions in Autism Spectrum Disorder. Harvard Review of Psychiatry ;2014 ;22(2):76-92.

Learning Objectives : After participating in this educational activity, the physician should be better able to 1. Prescribe the appropriate psychotropic medication to treat symptoms of ASD. 2. Identify the side effects of the psychotropic medications used to treat ASD. Autism spectrum disorders (ASDs) are characterized by core deficits in social communication and language, and restrictive and repetitive behaviors that cause significant functional impairment and distress for affected individuals and their caregivers. The increasing prevalence of ASD, most recently estimated as 1 in 88 children, presents an ever-increasing burden on families, schools, medical systems, and society at large. Individuals with ASD commonly present for treatment of associated emotional and behavioral disturbances that include anxiety, symptoms of ADHD, compulsions and other repetitive behaviors, mood lability, irritability, aggression, and sleep disturbance. Psychotropic medications are widely utilized in alleviating these symptoms, though rigorous clinical trials in ASD are lacking for most areas of impairment. Strong evidence from randomized, placebo-controlled trials supports the use of atypical antipsychotics, particularly risperidone and aripiprazole, for managing severe irritability and aggression in ASD. Serotonin reuptake inhibitors are commonly used to treat anxiety and compulsions, though reports of efficacy in the literature are mixed, and behavioral side effects in children are common. Minimal evidence supports the utility of anticonvulsants and traditional mood stabilizers in managing mood lability and aggression. Stimulant and nonstimulant ADHD medications can be effective for reducing hyperactivity, inattention, and impulsivity, though to a lesser degree than in ADHD populations without ASD and with greater risk of adverse effects. Psychopharmacological interventions in development for core symptoms of autism include those that target the glutamatergic and GABAergic neurotransmitter systems and the neuropeptide oxytocin. Further research is needed to establish evidence-based interventions in ASD populations.

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4. Curtin C, Jojic M, Bandini LG. Obesity in Children with Autism Spectrum Disorder. Harvard Review of Psychiatry ;2014 ;22(2):93-103.

Research suggests that the prevalence of obesity in children with autism spectrum disorder (ASD) is at least as high as that seen in typically developing children. Many of the risk factors for children with ASD are likely the same as for typically developing children, especially within the context of today’s obesogenic environment. The particular needs and challenges that this population faces, however, may render them more susceptible to the adverse effects of typical risk factors, and they may also be vulnerable to additional risk factors not shared by children in the general population, including psychopharmacological treatment, genetics, disordered sleep, atypical eating patterns, and challenges for engaging in sufficient physical activity. For individuals with ASD, obesity and its sequelae potentially represent a significant threat to independent living, self-care, quality of life, and overall health.

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5. Hsiao EY. Gastrointestinal Issues in Autism Spectrum Disorder. Harvard Review of Psychiatry ;2014 ;22(2):104-111.

While autism spectrum disorder (ASD) is characterized by communication impairments, social abnormalities, and stereotypic behaviors, several medical comorbidities are observed in autistic individuals. Of these, gastrointestinal (GI) abnormalities are of particular interest given their reported prevalence and correlation with the severity of core autism-related behavioral abnormalities. This review discusses the GI pathologies seen in ASD individuals and the association of particular GI conditions with known genetic and environmental risk factors for autism. It further addresses how GI abnormalities can affect the neuropathological and behavioral features of ASD, as well as the development of autism-related endophenotypes such as immune dysregulation, hyperserotonemia, and metabolic dysfunction. Finally, it presents emerging evidence for a gut-brain connection in autism, wherein GI dysfunction may contribute to the pathogenesis or severity of ASD symptoms.

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6. Hazen EP, Stornelli JL, O’Rourke JA, Koesterer K, McDougle CJ. Sensory Symptoms in Autism Spectrum Disorders. Harvard Review of Psychiatry ;2014 ;22(2):112-124.

The aim of this review is to summarize the recent literature regarding abnormalities in sensory functioning in individuals with autism spectrum disorder (ASD), including evidence regarding the neurobiological basis of these symptoms, their clinical correlates, and their treatment. Abnormalities in responses to sensory stimuli are highly prevalent in individuals with ASD. The underlying neurobiology of these symptoms is unclear, but several theories have been proposed linking possible etiologies of sensory dysfunction with known abnormalities in brain structure and function that are associated with ASD. In addition to the distress that sensory symptoms can cause patients and caregivers, these phenomena have been correlated with several other problematic symptoms and behaviors associated with ASD, including restrictive and repetitive behavior, self-injurious behavior, anxiety, inattention, and gastrointestinal complaints. It is unclear whether these correlations are causative in nature or whether they are due to shared underlying pathophysiology. The best-known treatments for sensory symptoms in ASD involve a program of occupational therapy that is specifically tailored to the needs of the individual and that may include sensory integration therapy, a sensory diet, and environmental modifications. While some empirical evidence supports these treatments, more research is needed to evaluate their efficacy, and other means of alleviating these symptoms, including possible psychopharmacological interventions, need to be explored. Additional research into the sensory symptoms associated with ASD has the potential to shed more light on the nature and pathophysiology of these disorders and to open new avenues of effective treatments.

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7. Pinder-Amaker S. Identifying the Unmet Needs of College Students on the Autism Spectrum. Harvard Review of Psychiatry ;2014 ;22(2):125-137.

Abstract : The number of students entering college with high-functioning autism spectrum disorders (ASDs) is expected to surge in coming years. The diagnostic features and psychiatric risks of ASD, coupled with the transitions and stresses that define college life, present extraordinary challenges for these students, their parents, and institutions of higher education. This article applies a bioecological framework for conceptualizing the systemic strengths and barriers at the secondary and postsecondary levels of education in supporting students with ASD. This theoretical orientation is used to illustrate the importance of offering services and programs in a more coordinated and fluid manner within and between systems to support students more effectively. Evidence-based programs, practices, and interventions associated with successful academic and mental health outcomes for youth and young adults with ASD, as well as for college students with mental health and other challenges, are reviewed for their applicability to the target population. It is proposed that more fluid transitions and improved mental health and academic outcomes for college students with ASD can be achieved by integrating elements from secondary and postsecondary educational systems and also from existing, effective approaches with youth and young adults. Building upon the disjointed, but promising, evidence from youth, young adult, and college mental health literatures, recommendations for developing more effective transition plans for students with ASD are proposed.

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