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Book Reviews

Treatment of Neurodevelopmental Disorders

Targeting Neurobiological Mechanisms

Hamilton, Donald R. MD

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Journal of Developmental & Behavioral Pediatrics: July/August 2015 - Volume 36 - Issue 6 - p 425
doi: 10.1097/DBP.0000000000000183
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Advances in genomics, neuroimaging, and brain development over the last several decades have led to an increased understanding of neurodevelopmental disorders. This book updates current knowledge and highlights ongoing research into specific neurodevelopmental disorders by describing mechanisms that may help guide future research and targeted interventions. The genetics, molecular dysregulation, and neurobiology of single gene disorders including Fragile X syndrome, tuberous sclerosis, Rett syndrome, Cardio-facio-cutaneous syndrome (and related disorders), Angelman syndrome, Phenylketonuria, and Muscular Dystrophies are covered with recent research studies and potential new treatment options highlighted. Complex disorders represented by Down syndrome, schizophrenia, attention-deficit hyperactivity disorder, depression, and autism are also reviewed, with complete overviews of current research efforts, as well as future treatment projections. Chapters provide a short overview of each disorder including symptoms, clinical description, incidence, diagnosis, and a review of current evidence-based treatments, before focusing on current research into the pathology, genetics, and molecular dysfunctions related to each disorder.

The opening chapter begins by presenting an overview of the dynamic process of neurodevelopment including the trajectory of brain development along with genetic and environmental factors that influence changes. Mechanisms of gene-environment interaction for disorders are introduced with an emphasis on current research and models used to investigate the neurobiological aspects of these disorders. Research efforts to identify biomarkers that may be used to guide diagnosis and monitor targeted interventions are discussed. The discovery of the mTOR pathway and its association with tuberous sclerosis is one of the areas covered for targeted interventions. The use of rapamycin to reverse overactivation of mTOR proteins in tuberous sclerosis has been reported to limit and reverse some of the manifestations of this disorder and shows great promise for the future. This dysregulation of the mTOR system has also been identified in other disorders including Fragile X syndrome and some autism spectrum disorders leading to the possibility of commonalities in pathologic mechanisms across different disorders. Chapters on tuberous sclerosis, Fragile X syndrome, and Down syndrome provide very detailed descriptions on current research into the commonalities of mechanisms identified between these disorders and other neurologic conditions as illustrated in similarities seen between Alzheimer's disease and Down syndrome. The development and use of targeted treatments to improve cognition and decrease neuropsychiatric problems is proposed as strong possibilities as we develop a better understanding of the neurobiology of these diseases. Current research using specific animal models, in addition to clinical trials is discussed to help the reader better understand ongoing efforts and progress in these important areas of neuroscience.

Although biologic and pharmaceutical treatments for specific disorders are extensively covered in this text, the authors also emphasize the need for “multifaceted therapies” for neurodevelopmental conditions. Ongoing therapies for developmental deficits in speech/language, motor, and cognitive domains are strongly recommended in addition to the importance of sleep, nutrition, and exercise to minimize stress plus enhance mood and cognition functions. The use of clinician-directed technology is recommended as a therapeutic resource and a tool to improve communication, social, and academic skills. Computerized cognitive training for neural system impairments in schizophrenia and programs focusing on working memory, cognitive flexibility, and inhibition in attention-deficit hyperactivity disorders are also showing promise in some clinical and neuroimaging research studies as interventional options.

The final chapter, “Translating Treatments from the Laboratory to the Clinic” discusses ways clinicians can use this information in daily clinical practice. The authors state their intent through this book is to stimulate new ways of thinking about the treatments of neurodevelopmental disorders. Although the information contained in some chapters is dense, detailed, and research focused, it is an easily readable text, which I would recommend to clinicians seeking an update on neurodevelopmental disorders and current research. Personally, I intend to keep this as a reference and review it in the future when faced with these clinical practice challenges.

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