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)

This brief overview proposes a testable oligogenic model of the inheritance of susceptibility to idiopathic schizophrenia: "abnormal" genes at each of a few complementary loci. The model is based on my assumptions as to the likely genetic abnormalities at possibly four or five interacting loci that would permit exorphins, the opioid peptides from some food proteins, especially glutens and possibly caseins, to go from gut to brain and cause symptoms of schizophrenia. Exorphins may reach the brain cerebrospinal fluid (CSF) in harmful amounts because of their genetically increased, receptor-mediated transcellular passage across the gut epithelial barrier plus decreased catabolism by genetically defective enzymes. A schizophrenia-specific, genetically enhanced affinity for exorphins by opioid receptors influencing dopaminergic and other neurons would permit sustained dysfunction at low CSF exorphin concentrations. Tests of each postulated genetic abnormality are suggested. This model is supported by a variety of evidence, including a significant effect of gluten or its absence on relapsed schizophrenic patients, the high correlation of changes in first admission rates for schizophrenia with changes in grain consumption rates, and the rarity of cases of schizophrenia where grains and milk are rare.
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PMID:Genetic hypothesis of idiopathic schizophrenia: its exorphin connection. 285 Nov 66

Cholecystokinin (CCK) is a peptide originally isolated from the gut. It has been investigated as a candidate treatment for schizophrenia on the assumption that the illness is associated with an imbalance between CCK and dopamine in the mesolimbic dopamine system. Many of the studies to assess the efficacy of CCK used open designs and are prone to observer bias and over-optimistic reporting. Most of the studies used CCK as an adjunct to standard neuroleptic treatment and are too small to be able to demonstrate extra efficacy above that of the active compound. Only three out of ten studies using CCK or placebo as an adjunct to neuroleptics reported limited efficacy. Of the 14 placebo-controlled reports only three were in drug-free patients. These were unfortunately too small, or too brief, to draw valid conclusions of efficacy. A summary of these data suggests that although 500 patients have received CCK, its efficacy in the treatment of schizophrenia has not been properly tested.
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PMID:The use of cholecystokinin in schizophrenia: a review. 305 90

It has been suggested that cholecystokinin (CCK), a gut-brain peptide found in high concentrations in the mammalian brain, might be implicated in the neurobiology of anxiety and panic disorder. The administration of CCK tetrapeptide induced panic attacks analogous to spontaneous ones in patients suffering from panic disorder and to a lesser degree in healthy volunteers. In animal models of anxiety, the pretreatment with CCK agonists and antagonists produced, respectively, anxiogenic- and anxiolytic-like action on the exploratory paradigms. On the other hand, CCK could also play a role in the pathophysiology of schizophrenia. The administration of CCK agonists (caerulein, CCK-8s) to rodents results in behavioural effects analogous to those of antipsychotic drugs. However, CCK agonists lack any activity in rodent behavioural models to reveal antipsychotic drugs. A significant reduction of CCK concentration and CCK receptors has been shown in cortical and limbic structures of patients suffering from schizophrenia. Nevertheless, administration of CCK agonists to these patients does not effect their symptoms. Two major conclusions should be drawn: first, CCK is involved in the neurobiology of anxiety; second, changes in the CCK system in schizophrenia could be linked to a cortical neurodegeneration related to this disease.
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PMID:Two faces of cholecystokinin: anxiety and schizophrenia. 873 54

The evidence for a significant genetic contribution to the functional psychoses (schizophrenia and bipolar disorder) is now well established. However, in both cases, the non-mendelian mode of inheritance has made the identification of susceptibility loci particularly challenging. The neuropeptide cholecystokinin (CCK) is present both in the gut and the CNS. Studies of CCK-like immunoreactivity and CCK mRNA levels in human brains have revealed high concentrations in numerous loci and shown colocalisation of CCK with, for example, dopamine and tyrosine hydroxylase. Furthermore, antagonists of CCK-B receptors, which are found most frequently in the brain, inhibit the activity of brain dopamine neurons. Such findings suggest that, with respect to neuropsychiatric disorders, CCK is a suitable candidate for analysis using methods to detect gene variations which have the potential to affect protein structure or expression. In the present study, mutation analyses were carried out on the human CCK gene. Linked polymorphisms were found in the promoter region and in intron 1 close to the 3' mRNA splice acceptor site. However, the allele frequencies of these polymorphisms in samples of individuals affected with either schizophrenia (n=117) or bipolar disorder (n=124) did not differ from those of control subjects (n=234), suggesting that these variations do not confer a predisposition to either of the functional psychoses.
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PMID:Linked polymorphisms upstream of exons 1 and 2 of the human cholecystokinin gene are not associated with schizophrenia or bipolar disorder. 949 15

Olanzapine, a new atypical antipsychotic drug, has been prescribed in the treatment of schizophrenia and psychotic mood disorders for approximately 2.3 million patients worldwide. Considering the increase in olanzapine prescriptions and the increased risk of suicide in this patient population, the number of reported cases of olanzapine overdose may be expected to increase. This report describes the clinical course and serum concentrations in a patient who consumed an olanzapine overdose (800 mg). Profound central nervous system depression and tachycardia without arrhythmia occurred within 2 hours after the ingestion. Additional clinical findings (ie, fever, mutism, agitation, dystonia, akathisia, elevated creatine kinase, and increased leukocyte count) were similar to those of neuroleptic malignant syndrome. After intubation, gut decontamination, and supportive care, the patient recovered and was discharged.
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PMID:Olanzapine overdose with serum concentrations. 1042 35

This paper reports evidence for a possible "chromosome 13 syndrome," which includes panic disorder, kidney or bladder problems, serious headaches, thyroid problems (usually hypothyroid), and/or mitral valve prolapse (MVP). In the course of a genetic linkage study of panic disorder, we noted these medical conditions in individual family members. (We were blind to family relationships and marker data.) We hypothesized that there may exist a subgroup of panic families with these medical conditions, which for simplicity we called it the "syndrome." Subsequently we reclassified the families as with or without the "syndrome" and extended the phenotype for analysis to include the above medical conditions. All these classifications were also done before the analysis and blind to marker data. We then examined our linkage results, looking for significant differences between families with and without the "syndrome" (using several definitions of the "syndrome")-i.e., testing for genetic heterogeneity. When the families with and without bladder/kidney problems were separated from each other, one marker-D13S779 (ATA26D07)-yielded a lod score of over 3 in the families with bladder/kidney problems. This lod score went up to 4.2 in these families when we diagnosed any individual with any one of the "syndrome" conditions as affected. These results were statistically significant even after applying an extremely overconservative Bonferroni correction for multiple tests. We present these results in order to alert other investigators working on panic disorder, for replication. If replicated, one may hypothesize that a candidate gene for the syndrome should be expressed in CNS, kidney, gut, thyroid, etc. We also noted that two independent studies report recent linkage findings between schizophrenia and the same region on chromosome 13. No connection between schizophrenia and panic disorder has ever been reported. Finally, we suggest that genetic studies of psychiatric disorders might prove more fruitful if phenotypes were expanded to include possible manifestations of the disorder in medical (non-mental) symptoms. Am. J. Med. Genet.(Neuropsychiatr. Genet.) 96:24-35, 2000.
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PMID:Potential panic disorder syndrome: clinical and genetic linkage evidence. 1068 48

Psilocybin poisoning produces biphasic reactions composed of a schizophrenic phase and a panic attack-like phase. There is a time lag of several hours between phases, which may be considered an accumulation time in certain sites between the gut and the brain. So far as 5-hydroxytryptamine (5-HT) congeners are concerned, no sites are to be found except the amine precursor uptake and decarboxylation (APUD) system. It is postulated that argyrophil cells (AC) in the foregut, neuroepithelial bodies (NEB) in the lung, and raphe nuclei (RN) in the brainstem axis are relevant to mental disorders. Schizophrenia might be due to the massive destruction of APUD cells, and the paroxysmal release of 5-HT with peptides and panneuroendocrine markers from NEB might be the cause of panic attack.
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PMID:Possible mechanisms of panic attack and schizophrenia via APUD system. 1181 87

The family planning program is not restricted to population control; it also aims at the wider aspect of family welfare and human health. A large number of human diseases are due to genetic abnormalities. Examples are mongolism (Down's syndrome), ovarian dysgenesis (Turner's syndrome), nonfunctional testes (Klinefelter's syndrome), chronic myeloid leukemia, anemia, thalassemia, congenital malformations, and schizophrenia. Mental defects include imbeciles and the feebleminded. Constitutional diseases include diabetes, idiopathic epilepsy, pernicious anemia, and some thyroid abnormalities. Some chronic diseases also have a significant genetic component in their etiology, such as asthma and other allergies. About half of the stillbirths and embryonic wastage are suspected of being due to genetic malformations. Consanguinity has an important bearing on malformations and developmental anomalies. In India, where consanguinity is more frequent, malformations per 1000 births were 8.6 and 3.1 in 2 centers studied. Neural tube defects, harelip, cleft palate, and malformations of the gut and of limbs were prevalent. The population that needs genetic counseling is not large. Persons suffering from hereditary dise ases having a high risk of transmission should be advised to refrain fro m having children. A correct diagnosis, complete family history, and kn owledge of the literature on inherited disease is needed by the counselo rs. Family planning programs should include genetic counseling.
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PMID:Genetic counselling in family planning. 1225 20

Neurotensin (NT) is a brain-gut tridecapeptide that fulfils a dual function, as a neurotransmitter/neuromodulator in the nervous system, and as a paracrine and circulating hormone in the periphery. Three NT receptors, NTS1, NTS2 and NTS3, have been cloned to date. NTS1 and NTS2 belong to the family of G protein-coupled receptors with seven transmembrane domains, whereas NTS3 is a single transmembrane domain protein that belongs to a recently identified family of sorting receptors. Most of the known peripheral and central effects of NT are mediated through NTS1. NTS2 might take part in the analgesic response elicited by central administration of NT; the biological roles of NTS3 are yet to be discovered. Most NT agonists and non-peptide antagonists developed to date have been studied for their NTS1-targeting abilities. Here, we will discuss the potential diagnostic and therapeutic uses of these compounds in cancer, schizophrenia, obesity and pain suppression.
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PMID:Targeting neurotensin receptors with agonists and antagonists for therapeutic purposes. 1263 Feb 97

CART peptides are relatively novel neuropeptides involved in feeding, drug reward and stress. They are formed from a proCART polypeptide that is 89 amino acids in length in the human version. Fragments 42-89 and 49-89 are behaviorally active in feeding and locomotion as well and other functions. These peptides are highly abundant and widely but discretely distributed in the brain, gut, pituitary, adrenals and pancreas. The presence of CART immunoreactivity in specific nuclei of the hypothalamus has led to an examination of icv-injected CART peptides effects on feeding, which have proven to be significantly anorectic. Studies of transgenic animals and humans have also demonstrated a linkage to both obesity and anorexia. Similarly, the localization of CART to sub-regions of the mesolimbic dopamine system has led to demonstration of the effects of CART peptides on locomotor activity and conditioned place preference when injected into the ventral tegmental area (VTA), which are psychostimulant-like in quality. These findings also suggest that CART has the capacity to modulate mesolimbic dopamine, which could have implications for the treatment not only of psychostimulant abuse but also for the treatment of other disorders with mesolimbic dopamine involvement, such as schizophrenia. Other lines of evidence also show that CART peptides are involved in fear and startle behaviors which may have implications for understanding anxiety and stress. An important part of the development of CART mimetics and related drugs would be the identification of CART receptors. At the present time such receptors have not been identified, and much effort should be directed at this problem. Nonetheless, CART peptides offer interesting targets for new drug development for obesity and, potentially, a number of other disorders.
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PMID:CART peptides as targets for CNS drug development. 1276


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