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)

The presence of high concentrations of both dopamine and cholecystokinin (CCK) in the striatum and in various limbic structures suggests that the CCK may not only influence dopaminergic transmission, but it also may be relevant to the psychopathology of schizophrenia and to the therapeutic effects of neuroleptics. By using a synaptosomal fraction isolated from the mouse cerebral cortex and [propionyl-3H]CCK8-sulphate ([3H]CCK8S) as a ligand, a single binding site for [3H]CCK8 with a KD value of 1.04 nM and a Bmax value of 42.9 fmol/mg protein was identified. The competitive inhibition of [3H]CCK8S binding by related peptides produced an order of potency of CCK8-sulphated (IC50 = 5.4 nM) greater than CCK8-unsulfated (IC50 = 40 nM) and greater than CCK4 (IC50 = 125 nM). The regional distribution of [3H]CCK8S binding in the mouse brain was highest in the olfactory bulb (34.3 +/- 5.6 fmol/mg protein) greater than cerebral cortex greater than cerebellum greater than olfactory tubercle greater than striatum greater than pons-medulla greater than mid brain greater than hippocampus greater than hypothalamus (12.4 +/- 2.1 fmol/mg protein). The repeated administration of haloperidol (2.5 mg/kg/tid) increased the binding of [3H]CCK8S in cerebral cortex from 31.8 +/- 1.7 to 38.9 +/- 5.2 fmol/mg protein. The varied distribution of CCK8S receptors may signify nonuniform functions for the octapeptide in the brain.
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PMID:Characterization of [3H]cholecystokinin octapeptide binding to mouse brain synaptosomes: effects of neuroleptics. 362 61

Cholecystokinin (CCK), a neuropeptide which fulfills almost all criteria for neurotransmitter status, has been co-localized with dopamine in midbrain mesolimbic and mesocortical neurons that have been implicated in the pathogenesis of schizophrenia. Preclinical research suggests that CCK may in part act to enhance central dopaminergic activity. In an attempt to evaluate the role of CCK relative to the dopamine hyperactivity hypothesis of schizophrenia, in the present investigation the putative CCK receptor antagonist, proglumide, was administered to four schizophrenic patients in a double-blind, placebo-controlled study. All patients were receiving concurrent neuroleptic medication, but were still significantly symptomatic. Proglumide was without effect on the patients' psychosis ratings. Potential reasons for this negative finding are discussed.
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PMID:Does the cholecystokinin antagonist proglumide possess antipsychotic activity? 373 85

Eight neuroleptic-resistant schizophrenic patients were treated with ceruletide, a cholecystokinin-like peptide, in a placebo-controlled, double-blind, crossover study. Ceruletide or placebo was administered intramuscularly twice a day for 4 consecutive days while patients were maintained on a constant dose of fluphenazine. There were no changes in either the positive or negative symptoms of schizophrenia between the periods of placebo and ceruletide administration. To further characterize ceruletide actions we also administered it to seven normal volunteers and evaluated its effects on cognition and mood. Volunteers were administered ceruletide (0.3 micrograms/kg or 0.6 micrograms/kg) or saline placebo intramuscularly. Ceruletide had no effects on recent or remote memory or attention, but the higher dose did cause a significant increase in fatigue. These results suggest that although CCK-like peptides lack antipsychotic or cognitive effects they do induce mild sedation. This sedation may be part of a "satiety-like" state induced by peripheral administration of CCK.
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PMID:The effects of cholecystokinin-like peptides in schizophrenics and normal human subjects. 389 99

Concentrations of vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and gastrin in the cerebrospinal fluid (CSF) was studied in patients with endogenous depression, non-endogenous depression, mania, schizophrenia and a control group. All patients were classified according to various diagnostic systems. In the group of non-endogenously depressed patients CSF-VIP levels (median 16 pmol/l) were found significantly lowered compared to controls (median = 32 pmol/l) and endogenous depression (26 pmol/l). Going through the non-endogenous group it appeared that the low CSF-VIP was due to a group of patients with a former diagnosis of endogenous depression or a present diagnosis of possible endogenous depression. Moreover, this group was clinically characterized by 'dysphoric/hysterical features', 'reversed diurnal variation' (i.e. worst in the evening), and 'lack of clearly circumscribed episode'. In many aspects this group seems similar to the atypical depressions described as monoamineoxidase responders. Concerning CSF-CCK and CSF-gastrin no significant differences between the examined groups were demonstrated.
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PMID:Neuropeptides in the cerebrospinal fluid (CSF) in psychiatric disorders. 393 76

Immunoreactive somatostatin, bombesin, and cholecystokinin were measured in cerebrospinal fluid of normal subjects and patients with anorexia nervosa, depression, mania, and schizophrenia. Somatostatin-like immunoreactivity was decreased in anorexic and depressed patients. Bombesin-like immunoreactivity tended to be decreased in schizophrenics. Cholecystokinin-like immunoreactivity did not differ between groups. These data suggest a possible function for neuropeptides in regulation of human behavior.
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PMID:Altered neuropeptide concentrations in cerebrospinal fluid of psychiatric patients. 612 76

Cholecystokinin-like immunoreactivity (CCK) and somatostatin-like immunoreactivity (SRIF) were determined in fourteen brains from patients dying with a diagnosis of schizophrenia and in twelve brains from control cases. The schizophrenics had been rated during life and were divided into two groups on the basis of the presence or absence of negative symptoms (affective flattening and poverty of speech). CCK was reduced in temporal cortex of the schizophrenics and in hippocampus and amygdala of those patients with negative symptoms. SRIF was reduced in the hippocampus in samples from the latter group. The selectivity of these changes to limbic lobe may reflect the presence of a degenerative process in that area. The association of changes in hippocampus and amygdala with negative symptoms of schizophrenia suggests a separate mechanism underlying these symptoms.
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PMID:Reduced cholecystokinin-like and somatostatin-like immunoreactivity in limbic lobe is associated with negative symptoms in schizophrenia. 613 69

Antipsychotic properties of cholecystokinin have been suggested both in laboratory studies and in some open clinical trials, mainly in patients suffering from chronic schizophrenia. Eighteen patients (14 males, 4 females) meeting Research Diagnostic Criteria for schizophrenia had been receiving neuroleptics at a dosage that had not changed for 3 months, and to which the patients were at best only partially responsive. The patients were randomized into groups that received weekly intravenous injections of 10 micrograms of CCK-8 or normal saline over 8 weeks. Neuroleptic medication was unchanged for the study. Baseline and weekly assessments were carried out using the Brief Psychiatric Rating Scale (BPRS) and the Schizophrenia Subscale of the Present State Examination (SS-PSE). Analysis of covariance revealed significant differences between CCK-8 and placebo over the study period on the Thought Disturbance Factor and Total Score of the BPRS, and on the Nuclear Syndrome, Total Delusion Factor, and Total Score of the SS-PSE. No important side effects were noted. It is concluded that CCK-8 has definite antipsychotic properties in patients with chronic schizophrenia. Clinical trials in neuroleptic-free patients are warranted.
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PMID:Cholecystokinin-octapeptide in chronic schizophrenia: a double-blind placebo-controlled study. 615 44

In Huntington's disease, there is a decrease of the neuropeptides, substance P, enkephalins, and cholecystokinin in the striatonigral system, whereas in Parkinson's disease an increase of substance P is found in the substantia nigra. Several neuropeptides should be involved in Alzheimer's disease: substance P, endorphins, vasopressin, ACTH, somatostatin, vasoactive intestinal peptide, cholecystokinin, neurotensin, delta sleep-inducing peptide. Alterations of substance P, vasoactive intestinal peptide, cholecystokinin, somatostatin, and endorphins may be related to the pathophysiology of schizophrenia. Delta sleep-inducing peptide may interfere in addiction pathology.
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PMID:Putative peptide neurotransmitters in human neuropathology: a review of topography and clinical implications. 618 57

The human brain contains several peptides with probable synaptic actions, some of which form complex neuronal networks in the limbic lobe (amygdala, hippocampus and temporal cortex). A limbic lobe abnormality has been postulated in schizophrenia on the basis of similarities between schizophrenic symptoms and symptoms in cases of known limbic pathology. Cholecystokinin (CCK), somatostatin (SRIF), neurotensin (NT), vasoactive intestinal polypeptide (VIP) and substance P (SP)-like immunoreactivities were measured by radioimmunoassay in 10 brain areas of 14 schizophrenics and 12 controls. In the schizophrenic group symptoms had been rated in life and the group was divided into Type I (n = 7) and Type II (n = 7) subgroups on the basis of the absence or presence of morbid negative symptoms. In control brains each peptide showed a characteristic distribution with high levels in cortex (CCK), limbic lobe (SOM, NT, VIP) or striatal areas (SP) and low levels of each of the peptides in thalamus. Significant (P less than 0.05) differences between groups were: reductions of CCK and SOM in hippocampus and CCK in amygdala in Type II schizophrenics, and CCK in the temporal cortex of the total schizophrenic group; and elevations of VIP in amygdala in Type I schizophrenics and of SP in the hippocampus in the total schizophrenic group. The findings could not be explained by variables such as age, delay between death and necropsy or to neuroleptic medication. These clinical-state related alterations in the peptide content of the limbic system in schizophrenia may illuminate the pathophysiological basis of the disease, particularly the distinction between Type I and II syndromes.
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PMID:Peptides, the limbic lobe and schizophrenia. 619 24

Vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and gastrin in the cerebrospinal fluid (CSF) were studied in patients with endogenous depression, non-endogenous depression, mania, schizophrenia and a control group. All patients were classified according to ICD-9 and the group of depressions was further classified according to the Newcastle Rating Scales for depression (Carney et al. 1965) (N-I). In the group of non-endogenously depressed patients, CSF-VIP levels (median 16 pmol/l) were found to be significantly lower than those of controls (median = 32 pmol/l) and endogenous depressives (36 pmol/l). In the non-endogenous group, it appeared that the low CSF-VIP was due to a group of patients who, during a past or present depressive episode, had been diagnosed as suffering from endogenous depression. Moreover, this group was clinically characterized by 'dysphoric/hysterical features', 'reversed diurnal variation' (i.e. worse in the evening), and 'lack of clearly circumscribed episodes'. In many aspects this group seems similar to the atypical depressives described as monoamine oxidase inhibitor responders. Concerning CSF-CCK and CSF-gastrin, no significant differences between the examined groups were demonstrated.
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PMID:Vasoactive intestinal polypeptide decreased in cerebrospinal fluid (CSF) in atypical depression. Vasoactive intestinal polypeptide, cholecystokinin and gastrin in CSF in psychiatric disorders. 624 Dec 14


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