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)

Nearly 1% of the world population suffers from schizophrenia, and neuroleptics are the major class of drugs used to treat this disorder. Neuroleptics are associated with wide variety of extrapyramidal side effects, such as akathesia, dystonia, neuroleptic malignant syndrome, Parkinson-ism and tardive dyskinesia. Despite the awareness that neuroleptics could cause extrapyramidal side effects, these drugs remain the most effective means of treating schizophrenia and Tourette's syndrome, as well as for the management of behavioral disorders in developmentally disabled individuals. Tardive dyskinesia is a complex hyperkinetic syndrome consisting of choriform, athetoid or rhythmically abnormal involuntary movements. Estimates of the prevalence rate of tardive dyskinesia in patients receiving neuroleptics range from 0.5-70%, with an average prevalence rate of 24%. Despite much research, the pathogenesis of tardive dyskinesia remains elusive. So far, various neurochemical hypotheses have been proposed for the development of tardive dyskinesia. These include dopaminergic hypersensitivity, disturbed balance between dopamine and cholinergic systems, dysfunctions of striatonigral GABAergic neurons and excitotoxicity. Similarly, different suppressive agents have been tried with limited success. Recently, the role of oxidative stress and structural abnormality in the pathophysiology of tardive dyskinesia has gained much impetus. Induction of free radicals by neuroleptic drugs leading to the oxidative stress and resultant structural abnormality could be the key factor in the pathogenesis of tardive dyskinesia. This hypothesis has been supported by numerous reports that chronic neuroleptic treatment increases free radical production and causes structural damage. More recently, the genetic vulnerability for the predisposition for the development of tardive dyskinesia, i.e., pharmacogenetic aspect of tardive dyskinesia, is also gaining impetus as a research area, and is discussed in detail in this article.
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PMID:Pathophysiology and drug therapy of tardive dyskinesia: current concepts and future perspectives. 1266 7

Acetylcholine (ACh) is an important neurotransmitter of the CNS that binds both nicotinic and muscarinic receptors to exert its action. However, the mechanisms underlying the effects of cholinergic receptors have still not been completely elucidated. Central cholinergic neurons, mainly located in basal forebrain, send their projections to different structures including the cortex. The cortical innervation is diffuse and roughly topographic, which has prompted some authors to suspect a modulating role of ACh on the activity of the cortical network rather than a direct synaptic role. The cholinergic system is implicated in functional, behavioural and pathological states including cognitive function, nicotine addiction, Alzheimer's disease, Tourette's syndrome, epilepsies and schizophrenia. As these processes depend on the activation of glutamatergic and GABAergic systems, the cholinergic terminals must exert their effects via the modulation of excitatory and/or inhibitory neurotransmission. However, the understanding of cholinergic modulation is complex because it is the result of a mixture of positive and negative modulation, implying that there are various types, or even subtypes, of cholinergic receptors. In this review, we summarize the current knowledge on central cholinergic systems (projections and receptors) and then aim to focus on the implications for ACh in the modulation of cortical neuronal activity.
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PMID:Cholinergic modulation of the cortical neuronal network. 1269 Apr 58

As the prevalence of tobacco use has decreased, it has become clear that individuals with mental illness comprise a substantial portion of the remaining smokers. Seventy to eighty percent of patients with schizophrenia smoke and their smoking is established before their first psychotic episodes or the initiation of treatment. Many patients with schizophrenia, and approximately 50% of their first degree relatives have abnormalities in auditory sensory gating and/or smooth pursuit eye movements. These abnormalities are corrected by nicotine, and they appear to be transmitted as autosomal dominant traits. Evidence is accumulating that these abnormalities reflect genetic variations in nicotine receptor number and function, that may increase susceptibility for schizophrenia. Recent studies suggest that bupropion, added to treatment with an atypical antipsychotic, can enhance the likelihood of smoking cessation or reduction in patients with schizophrenia. The prevalence of smoking is also substantially increased among patients with bipolar disorder, perhaps especially so among those with psychotic features. Nicotine delivered by gum or transdermal patch can provide short term relief for exacerbations of Tourette's Syndrome, but its use is limited by frequent toxicity, primarily nausea.
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PMID:The importance of nicotinic acetylcholine receptors in schizophrenia, bipolar disorder and Tourette's syndrome. 1276 15

Acute rheumatic fever (ARF) is an autoimmune disorder that is triggered by group A beta-hemolytic streptococcal infections. ARF consists of several combinations of carditis, polyarthritis and Sydenham's chorea, and rarely seen erythema marginatum and subcutaneous nodules. Sydenham's chorea is seen in about 20% of patients with ARF. As a late symptom of ARF, Sydenham's chorea usually occurs 3 months or longer after the streptococcal infection. Sydenham's chorea is a neuropsychiatric disorder that may present with emotional lability, anxiety, obsessive compulsive symptoms, attention deficit and hyperactivity symptoms or tics. Obsessive-compulsive symptoms occur in 70% of patients with Sydenham's chorea. The role of the autoimmune mechanisms and the dysfunction of the basal ganglia have been demonstrated in Sydenham's chorea. Antibodies against group A beta-hemolytic streptococcus cross-react with basal ganglia. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) shares the same mechanism with Sydenham's chorea, but PANDAS has not been shown to require penicillin prophylaxis. Thus it is important to distinguish between them. Sydenham's chorea is associated with adulthood OCD, Tourette syndrome and schizophrenia. These features make Sydenham's chorea an explanatory model for obsessive-compulsive disorder (OCD) and related disorders. This poststreptococcal disorder provides a treatment opportunity with new therapies like antibiotic therapy, plasma exchange and intravenous immunoglobulin therapy for psychiatric disorders. In this paper we summarize the phenomenological and treatment studies of OCD, attention deficit and hyperactivity disorder (ADHD), and tic disorders in subjects with ARF, with or without Sydenham's chorea.
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PMID:[Acute rheumatic fever, Sydenham's chorea and psychopathology]. 1279 66

Striatal cholinergic interneurons located in the dorsal striatum and nucleus accumbens are amenable to influences of the dopaminergic mesolimbic pathway, which is a pathway involved in reward and reinforcement and targeted by several drugs of abuse. Dopamine and acetylcholine neurotransmission and their interactions are essential to striatal function, and disruptions to these systems lead to a variety of clinical disorders. Dopamine regulates acetylcholine release through dopamine receptors that are localized directly on striatal cholinergic interneurons. The dopamine D2 receptor, which attenuates acetylcholine release, has been implicated in drug relapse and is targeted by therapeutic drugs that are used to treat a variety of neurological disorders including Tourette Syndrome, Parkinson's disease and schizophrenia. The present study provides the first direct evidence for the localization of dopamine D2 receptors on striatal cholinergic interneurons of the rat brain using dual labeling immunocytochemistry procedures. Using light microscopy, dopamine D2 receptors were localized on the cell somata and dendritic and axonal processes of striatal cholinergic interneurons in the dorsal striatum and nucleus accumbens of the rat brain. These findings provide a foundation for understanding the specific roles that cholinergic neuronal network systems and interacting dopaminergic signaling pathways play in striatal function and in a variety of clinical disorders including drug abuse and addiction.
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PMID:Localization of dopamine D2 receptors on cholinergic interneurons of the dorsal striatum and nucleus accumbens of the rat. 1296 26

INTRODUCTION: With the introduction of newer atypical antipsychotic agents, a question emerged, concerning their use as complementary pharmacotherapy or even as monotherapy in mental disorders other than psychosis. MATERIAL AND METHOD: MEDLINE was searched with the combination of each one of the key words: risperidone, olanzapine and quetiapine with key words that refered to every DSM-IV diagnosis other than schizophrenia and other psychotic disorders, bipolar disorder and dementia and memory disorders. All papers were scored on the basis of the JADAD index. RESULTS: The search returned 483 papers. The selection process restricted the sample to 59 papers concerning Risperidone, 37 concerning Olanzapine and 4 concerning Quetiapine (100 in total). Ten papers (7 concerning Risperidone and 3 concerning Olanzapine) had JADAD index above 2. Data suggest that further research would be of value concerning the use of risperidone in the treatment of refractory OCD, Pervasive Developmental disorder, stuttering and Tourette's syndrome, and the use of olanzapine for the treatment of refractory depression and borderline personality disorder. DISCUSSION: Data on the off-label usefulness of newer atypical antipsychotics are limited, but positive cues suggest that further research may provide with sufficient hard data to warrant the use of these agents in a broad spectrum of psychiatric disorders, either as monotherapy, or as an augmentation strategy.
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PMID:Off-label indications for atypical antipsychotics: A systematic review. 1497 68

Nicotine addiction is the single largest preventable cause of morbidity and mortality in the Western World. Smoking is not any more just a bad habit, but a substance addiction problem. The pharmacological aspects of nicotine show that this substance has a broad distribution in the different body compartnents, due mainly to its lipophilic characteristic. There are nicotinic receptors as members of cholinergic receptors' family. They are located in neuromuscular junction and in the central nervous system (CNS). Although they are similar, pentameric structure with an ionic channel to sodium, there are some differences in the protein chains characteristics. Repeated administration of nicotine in rats, results in the sensitization phenomenon, which produces increase in the behavioral locomotor activity response. It has been found that most psychostimulants-induced behavioral sensitization through a nicotine receptor activation. Nicotine receptors in CNS are located mainly in presynaptic membrane and in that way they regulated the release of several neurotransmitters, among them acetylcholine, dopamine, serotonin, and norepinephrine. In some activities like sleep-wake cycle, nicotine receptors have a functional significance. Nicotine receptor stimulation promotes wake time, reduces both, total sleep time and rapid eye movement sleep (REMS). About nicotine dependence, this substance full fills all the criteria for dependence and withdrawal syndrome. There are some people that have more vulnerability for to become nicotine dependent, those are psychiatric patients. Among them schizophrenia, major depression, anxiety disorders and attention deficit disorder, represent the best example in this area. Nicotine may have some beneficial effects, among them are some neuroprotective effects in disorders like Parkinson's disease, and Gilles de la Tourette' syndrome. Also there are several evidences that support the role of nicotine in cognitive improvement functions like attention, concentration, and memory. Finally there are several strategies to deal with nicotine dependence, Nicotine Replacement Therapy (NRT), which are nicotine chewing-gum, transdermal nicotine patches, and nicotine inhalators device. Also some antidepressants like bupropion has shown to be effective in smoking cessation treatment. To know more about nicotine phenomenon would be important, because that will allow a more mature perspective about the damage and beneficial effects of that substance.
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PMID:Nicotine dependence and psychiatric disorders. 1501 38

Considerable progress has been achieved by functional brain imaging over the past 20 years in uncovering the biological basis of major psychiatric disorders and to more effectively target therapeutics. Radioligand techniques, especially the PET (positron emission tomography) method, are specific and sensitive tools for quantitative in vivo imaging of molecular pathways and molecular interactions within brain tissues. Since 1980s, advances in neuroimaging and neurophysiological techniques have provided tremendous merits for investigations into different psychiatric disorders. PET and SPECT (single photon emission computer tomography) neuroreceptor imaging, especially in schizophrenia has been an extremely fruitful area of research. Evidences from these studies suggest that schizophrenia affects various cortical and subcortical regions involved in cognitive, emotional, and motivational aspects of human behavior. PET and SPECT provide useful data in studying the fundamental neurobiology of mood disorders. Both techniques are playing a central role in studying patients with new methods and ligands for specific receptor subtypes, and are likely to increase the application of PET/SPECT in the development of new pharmacotherapies. Nuclear medicine plays an important role in studying patients with other psychiatric disorders such as obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), anxiety, etc. Some forms of OCD seem to share a common genetic etiology with Tourette-syndrome (TS) and to be a facultative part of the TS phenotypic spectrum. In conclusion, PET and SPECT methods seem to be helpful in the diagnosis and management of patients with different psychiatric disorders and may provide a better understanding of clinical symptomatology or the relationship of these physiological parameters to the patient's prognosis. Additionally, radionuclide techniques may improve medical therapy by demonstrating individual biochemical abnormalities of altered brain functions.
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PMID:[Functional imaging in mental disorders]. 1503 21

The importance of genetics in understanding the etiology of mental illness has become increasingly clear in recent years, as more evidence has mounted that almost all neuropsychiatric disorders have a genetic component. It has also become clear, however, that these disorders are etiologically complex, and multiple genetic and environmental factors contribute to their makeup. So far, traditional linkage mapping studies have not definitively identified specific disease genes for neuropsychiatric disorders, although some potential candidates have been identified via these methods (e.g. the dysbindin gene in schizophrenia; Straub et al., 2002; Schwab et al., 2003). For this reason, alternative approaches are being attempted, including studies in genetically isolated populations. Because isolated populations have a high degree of genetic homogeneity, their use may simplify the process of identifying disease genes in disorders where multiple genes may play a role. Several areas of Latin America contain genetically isolated populations that are well suited for the study of neuropsychiatric disorders. Genetic studies of several major psychiatric illnesses, including bipolar disorder, major depression, schizophrenia, Tourette Syndrome, alcohol dependence, attention deficit hyperactivity disorder, and obsessive-compulsive disorder, are currently underway in these regions. In this paper we highlight the studies currently being conducted by our groups in the Central Valley of Costa Rica to illustrate the potential advantages of this population for genetic studies.
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PMID:Genetic studies of neuropsychiatric disorders in Costa Rica: a model for the use of isolated populations. 1509 11

Psychosurgical procedures have been used for the treatment of intractable mental illness for more than 50 years. With improvements in surgical techniques, including new implantable stimulators, advances in functional neuroimaging, and progress in our fundamental understanding of the pathophysiology of mental illness there is a renewed interest in neurosurgical treatment of refractory psychiatric illness. This article will review the history of psychosurgery and recent developments in surgical techniques and implantable devices used in this context. The results of psychosurgery for the treatment of several psychiatric conditions and neuropsychiatric symptoms will be presented, including obsessive-compulsive disorder, Tourette's syndrome, depression, anxiety, aggression, self-injurious behavior, and schizophrenia. Lastly, a perspective on the current and future role of psychosurgery for the treatment of mental illnesses will be discussed.
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PMID:Neurosurgical interventions for neuropsychiatric syndromes. 1535 58


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