Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Compelling evidence indicates that the long (D2L) and the short (D2S) isoform of dopamine (DA) D2 receptors serve distinct physiological functions in vivo. To address the involvement of these isoforms in the control of synaptic transmission in the striatum, we measured the sensitivity to D2 receptor stimulation of glutamate- and GABA-mediated currents recorded from striatal neurons of three mutant mice, in which the expression of D2L and D2S receptors was either ablated or variably altered. Our data indicate that both isoforms participate in the presynaptic inhibition of GABA transmission in the striatum, while the D2-receptor-dependent modulation of glutamate release preferentially involves the D2S receptor. Accordingly, the inhibitory effects of the DA D2 receptor agonist quinpirole (10 microM) on GABA(A)-mediated spontaneous inhibitory postsynaptic currents (IPSCs)correlate with the total number of D2 receptor sites in the striatum, irrespective of the specific receptor isoform expressed. In contrast, glutamate-mediated spontaneous excitatory postsynaptic currents (EPSCs) were significantly inhibited by quinpirole only when the total number of D2 receptor sites, normally composed by both D2L and D2S receptors in a ratio favoring the D2L isoform, was modified to express only the D2S isoform at higher than normal levels. Understanding the physiological roles of DA D2 receptors in the striatum is essential for the treatment of several neuropsychiatric conditions, such as Parkinson's disease, Tourette's syndrome, schizophrenia, and drug addiction.
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PMID:Differential contribution of dopamine D2S and D2L receptors in the modulation of glutamate and GABA transmission in the striatum. 1548 38

The five subtypes of dopaminergic receptors exhibit different transduction, cerebral localization, regulation, pharmacological, and physiological roles, explaining their multiple pathophysiological implications in different neuropsychiatric conditions which result, at least in part from anomalous dopaminergic neurotransmission: Parkinson's disease, schizophrenia, addiction, migraine, mode disorders, Gilles de la Tourette disease, hyperactivity syndrome with attention deficit. The wide range of pharmacological implications explains the diversity of the therapeutic approaches perspectives for development of new drugs for these neuropsychiatric conditions.
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PMID:[Central dopaminergic receptors (Part II): pathophysiological and therapeutic considerations]. 1549 28

This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood- and adult-onset schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages.
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PMID:Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia. 1550 Oct 91

The objective of this study was to assess tic persistence and tic-associated impairment in referred youth with Tourette's Disorder (TD). Subjects were 50 youth (ages 6-17 years) who met DSM-IV diagnostic criteria for TD, were referred to a specialized TD program, and were evaluated by clinical and structured diagnostic interview. Tic severity and impairment was measured using the Yale Global Tic Severity Scale. The total tic score at or above minimal range defined tic persistence, and a TD impairment score at or above moderate range defined tic-associated impairment. Results were assessed during administration of the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiological Version. Mean age of onset of TD was 5.1 +/- 2.3 years, and mean illness duration was 5.6 +/- 3.2 years. At baseline, 88% of subjects met threshold criteria for at least mild tics, but only 30% met criteria for tic-associated impairment. At 2-year follow-up, 82% of these subjects met criteria for tic persistence (NS change from baseline), but only 14% met criteria for TD-associated impairment (p < .04 change from baseline). Although tics followed a persistent course in the majority of youth with TD, they were infrequently associated with impairment. There was a significant reduction in the proportion of youth with TD impairment from baseline to follow-up. These results support the view that TD is a persistent disorder, but suggest a dissociation between tic persistence and tic-associated dysfunction.
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PMID:Reexamining Tic persistence and Tic-associated impairment in Tourette's Disorder: findings from a naturalistic follow-up study. 1550 22

Pimozide is an antipsychotic drug of the diphenylbutylpiperidine class. In the US, it is FDA-approved only as a backup treatment for Gilles de la Tourette syndrome, although it has been used in other countries for many years as a treatment for schizophrenia. In the past 20 years, pimozide has been found to be especially efficacious in the treatment of monosymptomatic hypochondriacal psychoses and is used by psychiatrists and dermatologists for this off-label purpose. In particular, pimozide is considered the treatment of choice for delusions of parasitosis. In addition, pimozide has been found to be efficacious in the treatment of body dysmorphic disorder, metastatic melanoma, trichotillomania, and trigeminal and postherpetic neuralgia. This review aims to familiarize physicians, especially dermatologists, on the uses of pimozide in dermatologic practice. A review of the literature was performed and the relevant information synthesized to give a complete overview of the drug and its therapeutic uses in dermatology.
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PMID:Pimozide in dermatologic practice: a comprehensive review. 1555 35

Cigarette smoking rates in the American population are approximately 23%, whereas rates of smoking in clinical and population studies of individuals with neuropsychiatric disorders are typically two- to four-fold higher. Studies conducted in a variety of neuropsychiatric populations [e.g. attention-deficit hyperactivity disorder (ADHD), Alzheimer's disease, schizophrenia] have collectively suggested that nicotine may be efficacious in remediating selected cognitive deficits associated with these disorders, thus providing a framework for understanding the specific vulnerability of these patients to smoking initiation and maintenance. However, the specific gain in cognitive performance produced by nicotine administration in healthy subjects with normal cognitive function is less clear. This article reviews our current understanding of central nicotinic acetylcholine receptor (nAChRs) systems in normal and neuropsychiatric disease states and, specifically, their role with respect to cognitive dysfunction and clinical symptoms in several specific neuropsychiatric populations, including ADHD, Alzheimer's disease, Parkinson's disease, Tourette's Disorder, schizophrenia and affective disorders. The potential benefits of nicotinic agents for therapeutic use in neuropsychiatric disorders is discussed, as well as directions for further research in this area.
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PMID:Nicotinic receptor mechanisms and cognition in normal states and neuropsychiatric disorders. 1558 13

One of the most serious and difficult-to-treat conditions in child and adolescent psychiatry is self-injurious behavior (SIB). SIB can be associated with a number of psychiatric disorders, including mental retardation, schizophrenia, borderline personality disorder, pervasive developmental disorders, stereotypic movement disorder, and Tourette's Disorder. A variety of neurosurgical procedures have been used to treat both intractable SIB and severe Tourette's Disorder. Understandably, there are few reports concerning psychosurgery in children and adolescents for any condition or disorder. This report describes the use of cingulotomy and subsequent limbic leucotomy in an adolescent boy with Tourette's Disorder for SIB. His repetitive and medically serious SIB and failure of all other treatments prompted this intervention after careful, comprehensive review and discussion. Following the second surgery, the severity and frequency of his SIB were reduced.
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PMID:Psychosurgery for self-injurious behavior in Tourette's disorder. 1566 44

The neuronal nicotinic acetylcholine receptor alpha7 (nAChR alpha7) may be involved in cognitive deficits in Schizophrenia and Alzheimer's disease. A fast pharmacological characterization of homomeric alpha7 receptors is mostly hampered by their low functional expression levels in heterologous expression systems. In the present study expression of homomeric nAChR alpha7 was achieved in GH3 rat pituitary cells. Alpha7 subunits were heterologously expressed as components of [125I]-labeled alpha-bungarotoxin binding nAChRs (Bmax: 1.2 pmol/mg protein). Function of the expressed alpha7 ion channels was assessed by patch-clamp recording and calcium imaging. While acetylcholine-induced currents desensitized within much less than 1 s, calcium-sensitive fluorescence transients peaked after 5-10 s and returned to background levels within 30 s only. The fluorescence signal was blocked by isradipine and removal of extracellular sodium indicated that in these cells opening of rapidly desensitizing alpha7 nAChR triggers calcium influx via voltage-gated, DHP-sensitive calcium channels. In this cellular system, agonists revealed the following rank order of potency: epibatidine>anatoxin A>AAR17779>ABT-594>DMPP>nicotine>GTS-21>cytisine>ABT-418>acetylcholine>choline>ABT-089. All of the signals were inhibited by the alpha7 antagonists alpha-bungarotoxin (pIC50: 7.4) and methyllycaconitine (pIC50: 7.8). Further, marketed antidepressants showed antagonistic activity with the following rank order of potency: fluoxetine>imipramine>paroxetine>sertraline. These data illustrate that coupling to voltage-gated calcium channels allows a rapid and reliable functional examination of nAChR alpha7.
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PMID:Coupling of human nicotinic acetylcholine receptors alpha 7 to calcium channels in GH3 cells. 1569 60

Obsessive compulsive disorder (OCD) is a highly debilitating neuropsychiatric condition with estimated lifetime prevalence of 2-3%, more than twice that of schizophrenia. However, in contrast to other neuropsychiatric conditions of a comparable or lesser prevalence, relatively little is understood about the aetiology, neural substrates and cognitive profile of OCD. Despite strong evidence for OCD being familial, with risk to first-degree relatives much greater than for the background population, its genetic underpinnings have not yet been adequately delineated. Although cognitive dysfunction is evident in the everyday behaviour of OCD sufferers and is central to contemporary psychological models, theory-based studies of neurocognitive function have yet to reveal a reliable cognitive signature, and interpretation has often been confounded by failures to control for co-morbidities. The neuroimaging findings in OCD are amongst the most robust reported in the psychiatric literature, with structural and functional abnormalities frequently reported in orbitofrontal cortex, anterior cingulate cortex, and caudate nucleus. In spite of this, our relative lack of understanding of OCD neurochemical processes continues to impede progress in the development of novel pharmacological treatment approaches. Integrating the neurobiological, cognitive, and clinical findings, we propose that OCD might usefully be conceptualised in terms of lateral orbitofrontal loop dysfunction, and that failures in cognitive and behavioural inhibitory processes appear to underlie many of the symptoms and neurocognitive findings. We highlight existing limitations in the literature, and the potential utility of endophenotypes in overcoming these limitations. We propose that neurocognitive indices of inhibitory functions may represent a useful heuristic in the search for endophenotypes in OCD. This has direct implications not only for OCD but also for putative obsessive-compulsive spectrum conditions including attention deficit hyperactivity disorder, Tourette's syndrome, and trichotillomania (compulsive hair pulling).
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PMID:The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers. 1582 May 46

BACKGROUND: Topiramate is a new antiepileptic drug, originally designed as an oral hypoglycaemic subsequently approved as anticonvulsant. It has increasingly been used in the treatment of numerous psychiatric conditions and it has also been associated with weight loss potentially relevant in reversing weight gain induced by psychotropic medications. This article reviews pharmacokinetic and pharmacodynamic profile of topiramate, its biological putative role in treating psychiatric disorders and its relevance in clinical practice. METHODS: A comprehensive search from a range of databases was conducted and papers addressing the topic were selected. RESULTS: Thirty-two published reports met criteria for inclusion, 4 controlled and 28 uncontrolled studies. Five unpublished controlled studies were also identified in the treatment of acute mania. CONCLUSIONS: Topiramate lacks efficacy in the treatment of acute mania. Increasing evidence, based on controlled studies, supports the use of topiramate in binge eating disorders, bulimia nervosa, alcohol dependence and possibly in bipolar disorders in depressive phase. In the treatment of rapid cycling bipolar disorders, as adjunctive treatment in refractory bipolar disorder in adults and children, schizophrenia, posttraumatic stress disorder, unipolar depression, emotionally unstable personality disorder and Gilles de la Tourette's syndrome the evidence is entirely based on open label studies, case reports and case series. Regarding weight loss, findings are encouraging and have potential implications in reversing increased body weight, normalisation of glycemic control and blood pressure. Topiramate was generally well tolerated and serious adverse events were rare.
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PMID:Review of the use of Topiramate for treatment of psychiatric disorders. 1584 41


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