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Currently available treatments for neurodegenerative diseases are exclusively palliative. In Alzheimer's disease (AD) they are focused on the cholinergic deficit and alterations in glutamate function related to neurotoxicity. Finding drugs that can attenuate or reverse neurodegenerative disease progression is challenging in the absence of a complete understanding of the underlying causes. Biomarkers represent any measure that can be used to indicate the presence of a disease state. Biomarkers are critical both for making an accurate diagnosis of each of the neurodegenerative diseases and for assessing their status and response to treatment. They are crucial for clinical trials from their initial design, to patient recruitment, to establishing objective end points. Neurodegenerative disease-associated genes continue to be identified at an ever-increasing rate using genome-wide association studies (GWAS) in cohorts of affected individuals. A large number of candidate genes and loci identified for neurodegenerative diseases, for example, in excess of 120 for AD.
Research into the pharmacotherapy of individuals with pervasive developmental disorders (PDDs) has increased steadily over the last 20 years, and more rapidly over the last several years, as treatment successes have triggered more rigorous study. The use of drugs targeted to possible neurochemical systems involved in the pathophysiology of autistic disorder (autism) have been shown to often reduce aggression, self-injury, and interfering repetitive behavior in these patients (Cook, 1990). No pharmacotherapeutics have yet shown a consistent primary effect on the core social disability of autism. Combined with comprehensive individualized treatment programs, appropriate pharmacotherapy can enhance an autistic person's ability to benefit from educational and behavior modification techniques (McDougle et al., 1994). This chapter will comprehensively highlight significant research in the psychopharmacology of PDDs from the perspective of specific neurochemical systems.
Drug treatment studies focusing on subtypes of PDD, other than autism, have not yet been conducted (McDougle, 2002). Many trials thus far have used heterogeneous samples, including individuals with autism, Asperger's disorder, and PDD not otherwise specified (PDD-NOS). As appropriate, differences in drug response among patients with different PDD subtypes will be highlighted. Because of their rarity, little systematic pharmacologic research has occurred in subjects with Rett's disorder or childhood disintegrative disorder.
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