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Several lines of evidence suggest that the neuropeptide oxytocin (OT) may be involved in the pathophysiology of obsessive-compulsive behavior in humans and repetitive grooming behavior in animals. Trichotillomania (TTM), which is characterized by chronic hair pulling, may be conceptualized as a disorder of pathologic grooming. To investigate the role of OT in TTM, the cerebrospinal fluid (CSF) levels of OT in nine women with TTM and nine healthy female controls were measured. Early findings from this ongoing study fail to demonstrate a significant difference in CSF OT levels between women with TTM and healthy female controls.
While the etiologies of pervasive developmental disorders (PDDs) appear complicated, multifactorial, and relatively poorly understood research over the last 30 to 40 years has implicated certain neurochemicals in the pathophysiology of these diseases. From these studies, a great deal of evidence has emerged supporting a role for serotonergic dysfunction in individuals with autism and related disorders. Recent clinical trials of drugs influencing serotonergic systems have demonstrated promising effects in children, adolescents, and adults with PDDs.
This chapter presents several experimental approaches performed in the Laboratory of the Biology of Addictive Diseases to characterize the relationship of gene variations with heroin addiction and pharmacogenomics. Although opioid receptors often subserve similar physiological functions, activation of the kappa-opioid receptor (KOPr) by exogenous agonists produces dysphoria in humans and aversive effects in experimental animals, in contrast to activation of mu-opioid receptor (MOPr). Opiate addiction is a chronic relapsing disorder that is treated world-wide with methadone. The genes studied are usually those which have been shown to be involved in some aspects of development of addiction. In some studies, multiple genes, all hypothesized to be potentially involved in opioid addiction, have been studied. In other cases, genome-wide association studies (GWAS) have been performed to identify regions of chromosomes which may influence vulnerability to the development of addiction. These studies usually do not identify specific genes within chromosome regions.
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.
The phenomenological features of 35 obsessive–compulsive disorder (OCD) patients with a lifetime history of tics were compared to 35 age- and sex-matched OCD patients without tics. Seven categories of obsessions and nine categories of compulsions were determined using the symptom checklist of the Yale–Brown Obsessive–Compulsive Scale (YBOCS). Discriminant function analysis revealed that, compared to their counterparts without tics, OCD patients with tics had more touching, tapping, rubbing, blinking and staring rituals, and fewer cleaning rituals, but did not differ on obsessions. These preliminary findings suggest that the types of compulsions present may help to discriminate between two putative subgroups of OCD, i.e. those with and without tics.
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