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

Although schizophrenia may result from dysfunction of the cerebral cortex the possible indirect involvement of the basal ganglia may be important as this neural system provides a major neural system through which the cortex affects behavior. Processing of cortical input occurs within the striatum, which is the main component of the basal ganglia, where excitatory cortical input is transformed to oppositely modulate the output nuclei of the basal ganglia. The details of this transformation, as well as the role of dopamine in this process, are beginning to unfold. Striatal projections to the globus pallidus, through connections with the subthalamic nucleus, modulate excitatory input to the output neurons of the basal ganglia, GABAergic neurons in the internal segment of the globus pallidus and in the substantia nigra, whereas striatal projections directly to these neurons, provide inhibitory inputs. Thus, cortically driven activity in these two striatal output pathways oppositely modulate the output neurons of the basal ganglia. Dopamine appears to play a crucial role in this transformation. D1 and D2 dopamine receptors are specifically expressed by striatonigral and striatopallidal neurons, respectively. The direct action of dopamine through these receptors appears to oppositely modulate the responsiveness of striatal output pathways to cortical input. Insights into the role of dopaminergic function within the basal ganglia may have direct relevance to the development of treatments for schizophrenia.
 ...
PMID:The neostriatal mosaic: multiple levels of compartmental organization. 152 20

Clinical improvement in psychotic symptoms is not immediate when neuroleptic treatment is commenced. Previous studies have demonstrated the development of biochemical tolerance to the effects of neuroleptics on the dopamine system. This study demonstrates a relationship between this biochemical change and the clinical changes occurring in the patients. The results can be explained in terms of dopamine receptor changes in a way that is compatible with the Dopamine Hypothesis for schizophrenia.
 ...
PMID:The relationship between clinical and biochemical changes following neuroleptic treatment in schizophrenia. 170 80

[3H]Dopamine (DA) uptake by platelet storage granules was determined in 26 schizophrenic male patients, paranoid type (14 acute stage; 12 in remission) and 20 age-matched, normal controls. Maximum velocity (Vmax) of DA uptake was significantly higher in acute patients, than patients in remission or controls (p less than 0.05). The apparent Michaelis constant (Km) of DA uptake in acute patients was also significantly different from chronic patients (p less than 0.05). Preincubation with reserpine (10(-4), 10(-5) M) produced a substantial diminution of DA uptake, while haloperidol (10(-4), 10(-5) M) did not affect the assay. Considering that a DA dysequilibrium in schizophrenia may be expressed not only in the brain, but also in the periphery and that an increased amount of DA accumulated in the vesicles, implies that an increased quantity of catecholamine is available for release, our findings suggest additional evidence for the role of DA overactivity in the pathophysiology of this disorder.
 ...
PMID:[3H]dopamine uptake by platelet storage granules in schizophrenia. 172 25

Dopamine receptors belong to a superfamily of receptors that exert their biological effects through guanine nucleotide-binding (G) proteins. Two main dopamine receptor subtypes have been identified, D1 and D2, which differ in their pharmacological and biochemical characteristics. D1 stimulates adenylyl cyclase activity, whereas D2 inhibits it. Both receptors are primary targets for drugs used to treat many psychomotor diseases, including Parkinson's disease and schizophrenia. Whereas the dopamine D1 receptor has been cloned, biochemical and behavioural data indicate that dopamine D1-like receptors exist which either are not linked to adenylyl cyclase or display different pharmacological activities. We report here the cloning of a gene encoding a 477-amino-acid protein with strong homology to the cloned D1 receptor. The receptor, called D5, binds drugs with a pharmacological profile similar to that of the cloned D1 receptor, but displays a 10-fold higher affinity for the endogenous agonist, dopamine. As with D1, the dopamine D5 receptor stimulates adenylyl cyclase activity. Northern blot and in situ hybridization analyses reveal that the receptor is neuron-specific, localized primarily within limbic regions of the brain; no messenger RNA was detected in kidney, liver, heart or parathyroid gland. The existence of a dopamine D1-like receptor with these characteristics had not been predicted and may represent an alternative pathway for dopamine-mediated events and regulation of D2 receptor activity.
 ...
PMID:Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. 182 62

Dopamine receptors belong to the family of G protein-coupled receptors. On the basis of the homology between these receptors, three different dopamine receptors (D1, D2, D3) have been cloned. Dopamine receptors are primary targets for drugs used in the treatment of psychomotor disorders such as Parkinson's disease and schizophrenia. In the management of socially withdrawn and treatment-resistant schizophrenics, clozapine is one of the most favoured antipsychotics because it does not cause tardive dyskinesia. Clozapine, however, has dissociation constants for binding to D2 and D3 that are 4 to 30 times the therapeutic free concentration of clozapine in plasma water. This observation suggests the existence of other types of dopamine receptors which are more sensitive to clozapine. Here we report the cloning of a gene that encodes such a receptor (D4). The D4 receptor gene has high homology to the human dopamine D2 and D3 receptor genes. The pharmacological characteristics of this receptor resembles that of the D2 and D3 receptors, but its affinity for clozapine is one order of magnitude higher. Recognition and characterization of this clozapine neuroleptic site may prove useful in the design of new types of drugs.
 ...
PMID:Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. 184 Jun 45

Receptors for dopamine have been classified into two functional types, D1 and D2. They belong to the family of receptors acting through G (or guanine nucleotide-binding) proteins. D2 receptors inhibit adenylyl cyclase, but D1 receptors stimulate adenylyl cyclase and activate cyclic AMP-dependent protein kinases. Dopamine D1 and D2 receptors are targets of drug therapy in many psychomotor disorders, including Parkinson's disease and schizophrenia, and may also have a role in drug addiction and alcoholism. D1 receptors regulate neuron growth and differentiation, influence behaviour and modify dopamine D2 receptor-mediated events. We report here the cloning of the D1 receptor gene, which resides on an intronless region on the long arm of chromosome 5, near two other members of the G-linked receptor family. The expressed protein, encoded by 446 amino acids, binds drugs with affinities identical to the native human D1 receptor. The presence of a D1 receptor gene restriction fragment length polymorphism will be helpful for future disease linkage studies.
 ...
PMID:Human dopamine D1 receptor encoded by an intronless gene on chromosome 5. 197 40

Dopamine (DA) has been shown to be involved in reward-related (incentive) learning but not stimulus-stimulus (s-s) associative learning. Schizophrenic individuals receive neuroleptics (DA receptor blockers) for therapy and therefore may have impaired incentive learning. To test this hypothesis, in experiment 1, schizophrenic outpatients receiving haloperidol or flupenthixol and matched controls were tested on tasks involving incentive or s-s learning. Patients were also given the Brief Psychiatric Rating Scale (BPRS). Results showed the patients to be significantly impaired in every task. However, only impairments of s-s learning were correlated with psychiatric state. Thus, deficits on the tasks involving incentive learning were interpreted as resulting from neuroleptic drugs rather than psychiatric state. Experiment 2 tested 26 schizophrenic inpatients receiving a variety of neuroleptics (converted to chloropromazine equivalency (CPZEQ)) on the same tasks. A blood sample was collected from the patients and from age-matched controls and prolactin levels were found to be significantly higher in the patients. Multiple regression analysis was used on patient data to determine whether prolactin level or CPZEQ were related to performance. It was found that incentive learning but not s-s associative learning was significantly predicted by one of these two indexes of neuroleptic drug dose. The results of these experiments provide some support for the hypothesis that neuroleptics might impair incentive but not s-s associative learning in schizophrenics. The observation that neuroleptics affect human incentive learning might lead to more efficient use of behavior modification programs in the treatment of schizophrenia.
 ...
PMID:Do neuroleptics impair learning in schizophrenic patients? 198 Jun 12

Basal serum amino acids (including central monoamine precursors), central monoamines, and hormones were studied in schizophrenic patients (drug-naive; n = 20; drug-withdrawn for 3 or more days, n = 67; neuroleptic-treated, n = 23) and healthy subjects (n = 90) to answer the following questions: (1) Do neuroleptic-withdrawn and neuroleptic-naive patients differ on these serum measures? (2) What are the effects of neuroleptic treatment on these measures? (3) On which variables do drug-free and neuroleptic-treated patients differ? Because serum amino acid, central monoamine, and hormone levels were similar in drug-naive and drug-withdrawn patients, data from these groups ("drug-free") were combined and compared to those of healthy subjects and neuroleptic-treated patients. Asparagine, citrulline, phenylalanine, and cysteine were higher, while tyrosine, tryptophan, and the ratio of tryptophan to competing amino acids were significantly lower in drug-free schizophrenic patients than in healthy subjects. Dopamine was increased, and melatonin and thyroid hormones were decreased in drug-free schizophrenic patients compared to healthy subjects. Norepinephrine, epinephrine, and prolactin were higher in neuroleptic-treated men compared to drug-free male patients or healthy men. These results are consistent with the hypothesis of dopaminergic overactivity in schizophrenia, which might be caused by altered amino acid precursor availability and could be related to the decrease in melatonin and reduction in thyroid hormone levels.
 ...
PMID:Serum amino acids, central monoamines, and hormones in drug-naive, drug-free, and neuroleptic-treated schizophrenic patients and healthy subjects. 198 23

Dopamine uptake sites, labelled by 3 nM [3H]GBR 12935, were reduced by 28-34% in post-mortem Parkinson's diseased striata (n = 22) compared to control striata (n = 28). There was no significant difference between post-mortem striata from schizophrenics (n = 16) and controls. Both dopamine D1 and D2 receptors are consistently elevated in Parkinson's diseased striata from patients who have not been medicated with L-dopa pre-mortem. Both these receptors are down-regulated by L-dopa pre-mortem. In schizophrenia, however, while the density of D1 receptors is similar to control, the D2 receptors are consistently elevated.
 ...
PMID:Dopamine uptake sites and dopamine receptors in Parkinson's disease and schizophrenia. 213 80

Hypersensitivity to sensory stimulation is a prominent characteristic of both schizophrenia and mania. Neurophysiological recordings suggest a common deficit in a central neuronal sensory gating mechanism which regulates sensitivity to repeated auditory stimuli. Dopamine and norepinephrine are hypothesized to have major roles in these illnesses, but their role in aberrant sensory processing has not yet been proved. Presumptive evidence for effects of catecholamines on sensory processing comes from psychophysiological studies of normal subjects challenged with stimulants who show decreased sensory gating, and studies of psychotic patients treated with neuroleptics who show improved function. Studies of similar phenomena in animals show comparable effects of catecholamines on sensory processing, both behaviorally and at the single neuron level. In this study, gating of auditory evoked potentials (EPs) during treatment of both illnesses was compared with plasma dopamine and norepinephrine metabolites. Comparisons of medicated and unmedicated states showed that schizophrenic patients have a fixed deficit in sensory gating, which is a familial trait, unchanged by medication. During acute illness, they have an additional transient hypersensitivity to stimuli, manifested as smaller EPs, which seems to be mediated by dopamine. Manic patients have only the deficit in sensory gating, which is transient and seems to be mediated by norepinephrine. Thus, similar neurophysiological deficits in the two psychoses are associated with different biochemical abnormalities, which may explain similarities in acute symptoms and differences in other aspects of the illnesses, such as their response to treatment.
 ...
PMID:Sensory physiology and catecholamines in schizophrenia and mania. 233 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>