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Tourette syndrome is a neurodevelopmental disorder characterized by motor and vocal tics--rapid, repetitive, stereotyped movements or vocalizations. Tourette syndrome typically has a prepubertal onset, and boys are more commonly affected than girls. Symptoms usually begin with transient bouts of simple motor tics. By age 10 years, most children are aware of nearly irresistible somatosensory urges that precede the tics. These urges likely reflect a defect in sensorimotor gating because they intrude into the child's conscious awareness and become a source of distraction and distress. A momentary sense of relief typically follows the completion of a tic. Over the course of hours, tics occur in bouts, with a regular intertic interval. Tics increase during periods of emotional excitement and fatigue. Tics can become "complex" in nature and appear to be purposeful. Tics can be willfully suppressed for brief intervals and can be evoked by the mere mention of them. Tics typically diminish during periods of goal-directed behavior, especially those that involve both heightened attention and fine motor or vocal control, as occur in musical and athletic performances. Over the course of months, tics wax and wane. New tics appear, often in response to new sources of somatosensory irritation, such as the appearance of a persistent vocal tic (a cough) following a cold. Over the course of years, tic severity typically peaks between 8 and 12 years of age. By the end of the second decade of life, many individuals are virtually tic free. Less than 20% of cases continue to experience clinically impairing tics as adults. Tics rarely occur in isolation, and other coexisting conditions--such as behavioral disinhibition, hypersensitivity to a broad range of sensory stimuli, problems with visual motor integration, procedural learning difficulties, attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, depression, anxiety, and emotional instability--are often a greater source of impairment than the tics themselves. Emerging behavioral treatments of Tourette syndrome are based in part on an understanding of the moment-to-moment experience of somatosensory urges and motor response. With identification of specific genes of major effect and advances in our understanding of the neural circuitry of sensorimotor gating, habit formation, and procedural memory--together with insights from postmortem brain studies, in vivo brain imaging, and electrophysiologic recordings--we might be on the threshold of a deeper understanding of the phenomenology and natural history of Tourette syndrome.
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PMID:Tourette syndrome: the self under siege. 1697 Aug 64

Several lines of evidence suggest a meaningful association between obsessive-compulsive disorder and Tourette syndrome, including comorbidity, phenomenologic overlap, evidence from family and genetic studies, and the possible role of basal ganglia circuitry in both conditions. Obsessive-compulsive behaviors occur frequently in patients who have Tourette syndrome and tend to have a later onset than tics. Despite commonalities, the approaches to treating tics and obsessive-compulsive symptoms are actually quite distinct. A specialized form of cognitive behavior therapy and pharmacotherapy with a potent serotonin reuptake inhibitor are the two established first-line therapies for obsessive-compulsive disorder. An adequate trial of a serotonin reuptake inhibitor is 10 to 12 weeks in duration at doses near the upper end of the recommended range for age and weight. Cases of obsessive-compulsive disorder that do not sufficiently improve with serotonin reuptake inhibitors might benefit from adjunctive low-dose antipsychotic (eg, risperidone) medication whether or not tics are present. Warnings about an increased risk of suicidality among children and adolescents taking antidepressants for pediatric depression extend to those taking the medications for obsessive-compulsive disorder, but the risk-to-benefit ratio is more favorable in this latter population because several serotonin reuptake inhibitors have been shown to be efficacious in obsessive-compulsive disorder.
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PMID:Obsessive-compulsive disorder in Tourette syndrome. 1697 Aug 72

The dopamine transporter (DAT) is a target for the development of pharmacotherapies for a number of central disorders including Parkinson's disease, Alzheimer's disease, schizophrenia, Tourette's syndrome, Lesch-Nyhan disease, attention deficit hyperactivity disorder (ADHD), obesity, depression, and stimulant abuse as well as normal aging. Considerable effort continues to be devoted to the development of new ligands for the DAT. In this review, we present some of the more interesting ligands developed during the last few years from the 3-phenytropane, 1,4-dialkylpiperazine, phenylpiperidine, and benztropine classes of DAT uptake inhibitors as well as a few less studied miscellaneous DAT uptake inhibitors. Studies related to the therapeutic potential of some of the more studied compounds are presented. A few of the compounds have been studied as pharmacotherapies for Parkinson's disease, ADHD, and obesity. However, most of the drug discovery studies have been directed toward pharmacotherapies for stimulant abuse (mainly cocaine). A number of the compounds showed decreased cocaine maintained responding in rhesus monkeys trained to self-administer cocaine. One compound, GBR 12,909, was evaluated in a Phase 1 clinical trial.
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PMID:Dopamine transporter ligands: recent developments and therapeutic potential. 1701 60

Neuronal nicotinic acetylcholine receptors (nAChRs), ubiquitously distributed in the human brain, are implicated in various neurophysiological processes and in the pathophysiology and/or treatment strategies of Alzheimer's and Parkinson's diseases, Tourette's syndrome, epilepsy, schizophrenia, depression, and anxiety, as well as being particularly affected in tobacco dependence/withdrawal. In the past two decades, researchers have developed an extensive series of radioligands for the assessment of nAChRs in vivo through emission tomography, PET and SPECT. Several radioligands, derivatives of A-85380: 2-[(18)F]FA, 6-[(18)F]FA and 5-[(123)I]IA, are now being employed for the evaluation of nAChR in humans with PET and SPECT. Displaying better imaging properties than (11)C-nicotine and a better toxicity profile than epibatidine analogs, they have allowed quantification of thalamic nAChR in the human brain. Nevertheless, A-85380 derivatives still exhibit slow brain kinetics and a moderate signal-to-noise ratio. Current research efforts on the part of PET/SPECT radiochemists, therefore, have focused on development of new, highly specific and highly selective nAChR radioligands with improved brain kinetics that are able to localize high-affinity nAChRs in vivo. Key examples of new PET/SPECT ligands that are derived from several different structural classes are discussed along with a review of their chemical as well as their in vitro and/or in vivo properties. In particular, new PET nAChR radioligands will be examined that either present faster brain kinetics allowing simple and reliable quantification approaches or higher binding potentials suitable for the evaluation of extrathalamic nAChR.
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PMID:The quest for Eldorado: development of radioligands for in vivo imaging of nicotinic acetylcholine receptors in human brain. 1707 85

Deep brain stimulation (DBS) now plays an important role in the treatment of Parkinson's disease, tremor, and dystonia. DBS may also have a role in the treatment of other disorders such as obsessive-compulsive disorder, Tourette's syndrome, and depression. The neuropsychologist plays a crucial role in patient selection, follow-up, and management of intra-operative and post-operative effects (Pillon, 2002; Saint-Cyr & Trepanier, 2000). There is now emerging evidence that DBS can induce mood, cognitive, and behavioral changes. These changes can have dramatic effects on patient outcome. There have been methodological problems with many of the studies of DBS on mood, cognition, and behavior. The neuropsychologist needs to be aware of these issues when following up patients, and constructing future studies. Additionally, this article will review all aspects of the DBS procedure that can result in mood, cognitive, and behavioral effects and what role(s) the neuropsychologist should play in screening and follow-up.
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PMID:Deep brain stimulation and the role of the neuropsychologist. 1736 83

The boundaries between obsessive-compulsive disorder (OCD) and other neuropsychiatric disorders remain unresolved and may well differ from one disorder to another. Endophenotypes are heritable, quantitative traits hypothesized to more closely represent genetic risk for complex polygenic mental disorders than overt symptoms and behaviors. They may have a role in identifying how closely these disorders are associated with another and with other mental disorders with which they share major comorbidity. This review maps the nosological relationships of OCD to other neuropsychiatric disorders, using OCD as the prototype disorder and endophenotype markers, such as cognitive, imaging, and molecular data as well as results from demographic, comorbidity, family, and treatment studies. Despite high comorbidity rates, emerging evidence suggests substantial endophenotypic differences between OCD and anxiety disorders, depression, schizophrenia, and addictions, though comparative data is lacking and the picture is far from clear. On the other hand, strong relationships between OCD, Tourette syndrome, body dysmorphic disorder, hypochondriasis, grooming disorders, obsessive-compulsive personality disorder, and pediatric autoimmune neuropsychiatric disorders associated with streptococcus are likely. Studies designed to delineate the cause, consequences, and common factors are a challenging but essential goal for future research in this area.
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PMID:Obsessive-compulsive disorder: boundary issues. 1751 81

The use of deep brain stimulation (DBS) has recently been expanding for the treatment of many neurologic disorders such as Parkinson disease, dystonia, essential tremor, Tourette's syndrome, cluster headache, epilepsy, depression, and obsessive compulsive disorder. The target structures for DBS include specific segregated territories within limbic, associative, or motor regions of very small subnuclei. In this review, we summarize current clinical techniques for DBS, the cognitive/mood/motor outcomes, and the relevant neuroanatomy with respect to functional territories within specific brain targets. Future development of new techniques and technology that may include a more direct visualization of "motor" territories within target structures may prove useful for avoiding side effects that may result from stimulation of associative and limbic regions. Alternatively, newer procedures may choose and specifically target non-motor territories for chronic electrical stimulation.
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PMID:Limbic, associative, and motor territories within the targets for deep brain stimulation: potential clinical implications. 1761 33

Deep brain stimulation is a minimally invasive targeted neurosurgical intervention that enables structures deep in the brain to be stimulated electrically by an implanted pacemaker. It has become the treatment of choice for Parkinson's disease, refractory to, or complicated by, drug therapy. Its efficacy has been demonstrated robustly by randomized, controlled clinical trials, with multiple novel brain targets having been discovered in the last 20 years. Multifarious clinical indications for deep brain stimulation now exist, including dystonia and tremor in movement disorders; depression, obsessive-compulsive disorder and Tourette's syndrome in psychiatry; epilepsy, cluster headache and chronic pain, including pain from stroke, amputation, trigeminal neuralgia and multiple sclerosis. Current research argues for novel indications, including hypertension and orthostatic hypotension. The development, principles, indications and effectiveness of the technique are reviewed here. While deep brain stimulation is a standard and widely accepted treatment for Parkinson's disease after 20 years of experience, in chronic pain it remains restricted to a handful of experienced, specialist centers willing to publish outcomes despite its use for over 50 years. Reasons are reviewed and novel approaches to appraising clinical evidence in functional neurosurgery are suggested.
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PMID:Deep brain stimulation: indications and evidence. 1785 Jan 94

For 20 years, deep brain stimulation (DBS) at high frequency has been developed as a substitute for the classical lesioning methods previously used in stereotactic and functional neurosurgery. This method has proven its efficacy, based on its reversibility and adaptability: two factors that are responsible for low morbidity. The method has been initially developed for and applied to movement disorders in several target areas; such as the thalamus, the pallidum and the subthalamic nucleus. It has now also been extended to other indications, such as epilepsy, dystonias and cluster headache and, more recently, to psychiatric disorders, such as obsessive-compulsive disorder, Gilles de la Tourette tics and depression. Several other disorders are currently under investigation and these may become new indications in the future. The mechanism of action is likely to be complex; associating cell-firing inhibition, neurotransmitter depletion, jamming and excitation of inhibitory pathways that lead to functional inhibition, mimicking the effects of lesioning of the stimulated structures. High-frequency stimulation of the subthalamic nucleus induces neuroprotection in animal models but has not yet been demonstrated in human patients suffering from Parkinson's disease. Technological development will enhance and refine the effects of high-frequency stimulation, and allow further extension of this method to new targets and new indications.
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PMID:What the future holds for deep brain stimulation. 1803 54

In this review paper, studies focusing on the neuropsychological characteristics of childhood-onset obsessive-compulsive disorder (OCD) were evaluated. The literature search covered the MedLine and PsycInfo databases through June 2006. The presented results are of those that focus on the processes of attention, memory, and executive functions related to the aspects of the measured instruments used. The aim of this review was to provide a general neuropsychological profile of childhood-onset OCD based on the reviewed studies. In general, results showed that there is no clear evidence that the neuropsychological aspects of childhood-onset OCD differ from those of adult-onset OCD. In parallel with this, the processes of attention and memory in OCD are observed to be selective and biased, and this bias is directed towards threat-relevant stimuli related to obsessions and compulsions. In addition, dysfunction in memory and visuospatial processes in OCD patients do not result from memory impairment per se, but rather from an impaired ability to apply efficiently elaborated strategies. In childhood-onset OCD, the various lines of evidence consistently include impairment of response suppression and motor inhibition abilities; there is less consistent evidence for reduced set shifting, fluency, conceptual thinking, and planning ability. Whereas clinical observation suggests that a central problem in OCD is at the meta-memory level and that people with OCD have less meta-cognitive ability, processing of meta-cognition in childhood-onset OCD has not been investigated adequately. Finally, the results of the reviewed studies were evaluated in terms of the effects of basic co-morbidity, such as depression, Tourette's disorder, tic disorder, and other confounding variables.
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PMID:[Neuropsychological profile of childhood-onset obsessive-compulsive disorder]. 1806 20


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