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)

Acute akathisia is a common and disturbing side effect of classic antipsychotic medication. Some evidence suggests a role for iron deficiency in chronic and tardive akathisia. In acute akathisia, however, the data are contradictory. Serum iron and ferritin levels of 33 inpatients with acute akathisia during classic neuroleptic medication were compared with those of 23 patients on classic neuroleptics without this side effect. Akathisia was rated by means of the Hillside Akathisia Scale. The groups were balanced for age (mean 38.5+/-14.5), medication (butyrophenone- and phenothiazine-derived neuroleptics) and diagnosis (schizophrenia, schizoaffective disorder, psychotic affective disorder). Patients with acute akathisia had significantly lower serum ferritin levels than the patients in the control group. However, the ferritin (56. 94+/-39.54 ng/ml) and iron (88.52+/-40.0 mg/dl) levels in these patients were within the normal range (ferritin 30-300 ng/dl, iron 80-180 mg/dl). No correlations between serum iron or ferritin and akathisia ratings could be found. Although some reduction in serum ferritin was found in patients with acute akathisia compared to patients without akathisia, the difference was small and the ferritin levels were within the range of the normal population. These findings suggest a minor role for iron deficiency in acute akathisia.
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PMID:Serum iron and ferritin in acute neuroleptic akathisia. 1076 Mar 78

Previous studies have suggested that akathisia is associated with poor acute clinical response to antipsychotics and that low serum iron levels are associated with emergence of akathisia. To examine these relationships during routine clinical treatment, we studied patients with DSM-IV schizophrenia or schizoaffective disorder undergoing hospital treatment for acute psychotic exacerbations with doctor's choice medications. There were 34 subjects observed for at least 2 weeks. They were assessed at baseline and weekly by one rater with the Anchored Brief Psychiatric Rating Scale and by another rater with the Barnes Rating Scale for akathisia, with the two raters blind to each other's ratings. Serum ferritin and transferrin levels were obtained at baseline. Seventeen subjects developed akathisia. Subjects with and without akathisia did not differ in change in thinking disturbance or anxiety-depression scores over 2 weeks, or in serum ferritin or transferrin levels. We conclude that mild akathisia by itself is not strongly associated with initial response to low to moderate doses of antipsychotics in the acute clinical setting. Limitations of the study are discussed.
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PMID:Is akathisia associated with poor clinical response to antipsychotics during acute hospital treatment? 1093 35

This review covers certain novel aspects of catecholamine signaling in neurons that involve redox systems and synaptic plasticity. The redox hypothesis suggests that one important factor in neurocomputation is the formation of new synapses and the removal of old ones (synaptic plasticity), which is modulated in part by the redox balance at the synapse between reactive oxygen species (ROS) (such as hydrogen peroxide and the nitric oxide radical) and neuroprotective antioxidants (such as ascorbate, glutathione, and catecholamines). Catecholamines, in particular dopamine, which signals positive reinforcement, may play a key role in this activity. Dopamine has powerful antioxidant properties by several separate mechanisms-direct ROS scavenging, activation of the synthesis of antioxidant proteins, and possibly via dismuting complexes with iron inside endosomes or in catecholaminergic synaptic vesicles. This may contribute to synaptic growth and reinforcement-directed learning. On the other hand, catecholamines are easily oxidized to toxic quinones on the neuromelanin pathway. This might contribute under certain circumstances to synaptic deletion. Evidence is presented that abnormalities in this system may contribute to the pathogenesis of Parkinson's disease and schizophrenia.
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PMID:Redox aspects of signaling by catecholamines and their metabolites. 1122 69

The use of functional magnetic resonance imaging (fMRI) techniques for evaluation of pharmacologic stimuli has great potential for understanding neurotransmitter dynamics for a number of brain disorders, such as drug abuse, schizophrenia, epilepsy, or neurodegeneration. Unfortunately, blood oxygenation level-dependent (BOLD) imaging at common fields strengths, such as 1.5 or 3 T, has very low sensitivity and contrast-to-noise ratios (CNRs). We demonstrate here the utility of using an intravascular superparamagnetic iron oxide contrast agent with a long plasma half-life for evaluation of hemodynamic changes related to dopaminergic stimuli using amphetamine or the cocaine analog 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT). We refer to this technique as increased relaxation with iron oxide nanoparticles (IRON). Results obtained here show that even at field strengths as high as 4.7 T, one can obtain increases in CNR by factors of 2-3 over BOLD imaging that lead to greater than an order of magnitude increase in statistical power with greatly increased sensitivity to hemodynamic changes in brain regions difficult to observe using BOLD imaging. Furthermore, use of the intravascular contrast agent allows for a meaningful physiologic parameter to be measured (relative cerebral blood volume (rCBV)), compared to conventional BOLD imaging.
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PMID:Improved mapping of pharmacologically induced neuronal activation using the IRON technique with superparamagnetic blood pool agents. 1174 3

A 33-year-old male patient began to develop schizophrenia-like symptoms and slowly progressive cerebellar ataxia. He was 170 cm tall and he had mild frontal baldness. Psychiatrically he was aconative, only willing to do nothing all day long after admission. He had neither hallucinations nor delusions, and his mental acuity was normal. Neurological examination revealed positive cerebellar signs including clumsiness in F-N-T and K-H-T and dysdiadochokinesis. He could neither stand up nor walk because of ataxia. The brain MRI showed severe cerebellar atrophy with normal basal ganglia. His EEG and the value of NCV were within normal range, whereas electroretinography showed a notable abnormality, pointing to the extremely small b-wave, resulting in a negative shape of the ERG. Although he was eating sufficiently, the level of serum iron and ferritin remained constantly low. The serum copper level was within normal range, whereas the serum ceruloplasmin level was mildly decreased. A hepatic biopsy indicated no accumulation of copper or iron. This case suggests the importance of the investigation of the serum iron and ceruloplasmin levels in patients who have cerebellar degeneration with psychosis.
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PMID:[A case of cerebellar degeneration with schizophrenia-like psychosis, severe iron deficiency, hypoceruloplasminemia and abnormal electroretinography: a new syndrome?]. 1188 36

Schizophrenia, the most severe psychiatric disorder, is characterized by heterogeneity of clinical signs, often categorized into positive and negative symptoms. Among a wide array of competing biological mechanisms, altered cerebral energy metabolism and mitochondrial dysfunction have been suggested to play an important role in the pathophysiology of schizophrenia. In this study we investigated mitochondrial complex I in platelets of 113 schizophrenic patients divided into three groups (acute psychotic episode, chronic active state and residual schizophrenia) and 37 control subjects. Complex I was analysed at the level of enzymatic activity, mRNA and protein levels by enzyme kinetics, RT-PCR and Western blot analyses, respectively. Complex I activity in platelets of schizophrenic patients altered with disease state presenting high specificity and sensitivity. Thus, increased activity was associated with psychotic symptomology, while its decrease was observed in patients with residual schizophrenia. The relationship between the clinical state and complex I activity in schizophrenia was further supported by its positive correlation with the severity of patients' positive symptoms assessed by clinical ratings. In addition, similar alterations were observed at the levels of mRNA and protein of the 24- and 51-kDa iron-sulfur flavoprotein subunits of the complex. Taken together these results point to the potential of platelet complex I to turn into a reliable novel marker for schizophrenia. At present, definitive diagnosis depends only on descriptive behavioral and symptomatic information, therefore a peripheral measurable specific marker will contribute to diagnosis and monitoring of the disease.
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PMID:State-dependent alterations in mitochondrial complex I activity in platelets: a potential peripheral marker for schizophrenia. 1239 53

The pathophysiology of akathisia still remains controversial. Iron deficiency was proposed to be an important factor in the development of akathisia. In the present study, it was aimed to compare levels of serum iron and linked variables in chronic akathisic (n=30), and non-akathisic patients (n=30) with schizophrenia and healthy controls (n=30) because of the controversy in the association of iron and akathisia. The Barnes Akathisia Scale for akathisia and Simpson-Angus Rating Scale for extrapyramidal side effects were used. Serum iron and linked variables and hematological profile of the patients and control subjects were determined. Serum iron levels were significantly lower both in akathisic and non-akathisic groups compared to the control group (P<0.001). Moreover, akathisic patients had significantly lower iron levels than non-akathisic patients (P<0.05). Total iron binding capacity was significantly higher in patients with akathisia compared to the control group (P<0.01). Although non-akathisic patients had a mild increase in total iron binding capacity, it was not statistically significant compared to the control group (P>0.05). Ferritin levels were determined to be significantly lower in both groups compared to the control group (P<0.01). In addition, there was a significant difference in ferritin levels between the patients with and without akathisia (P<0.05). In conclusion, our results support the hypothesis that an association between akathisia and iron metabolism exists.
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PMID:Serum iron levels in schizophrenic patients with or without akathisia. 1265 Sep 48

The fact that glutamate, dopamine, iron and reactive oxygen species are potentially individually highly neurotoxic molecules is well known. The purpose of this review is to examine the less well known complex ways in which their normal biological, as well as their neurotoxic activity, are interconnected in relation to fundamental neuronal functions. These functions include synaptic plasticity (formation and removal of synapses), endocytosis-based recycling of receptors for neurotransmitters and neuromodulators, the role of the redox balance between reactive oxygen species and antioxidants in synaptic function, and the possible role of iron-catecholamine complexes in antioxidant protection and intraneuronal iron transport. These systems are closely involved in several diseases of the nervous system including Parkinson's disease, schizophrenia and Alzheimer's disease. In all these oxidative stress and a failure of antioxidant defenses are involved. In the former two the neurotoxicity of catecholaminergic o-quinones is important. In the later excessive oxidation of neuronal membranes and excessive endocytosis and receptor recycling may be an important factor.
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PMID:The neurotoxicity of glutamate, dopamine, iron and reactive oxygen species: functional interrelationships in health and disease: a review-discussion. 1283 12

According to the DSM IV, pica is a trouble of alimentary behavior, which is characterized by the ingestion of non-nutriment substances during at least on the month. The main objective of this study conducted at the Clermont-de-l'Oise Interdepartmental Medical Center is to evaluate pica's prevalence for hospitalized patients. Secondary objectives are to describe clinical characteristics, complications and outcome upon the different therapeutic approaches. The patients hospitalized in the Adult and/or Pediatric Department of Psychiatry, which fulfilled the 4 criteria of the DSM IV, were considered eligible for the study. In order to better evaluate the severity of behavioral troubles evoked by item D of DSM IV definition, we elaborated specific severity and preoccupation scales. The severity scale reflects the complications due to the ingestion of the non-nutriment substances, the encountered risks in the case of persistence of these troubles as well as the patient's management. The preoccupation scale reflects the medical team's involvement towards the patient in order to prevent life-threatening complications. The two scales are graded from 0 to 5 according to the severity or to the degree of preoccupation, respectively. Only patients with scores 3 were considered as fulfilling the severity criteria. Among the 943 hospitalized patients at a selected time period, 23 adult patients have been considered eligible. According to these data, prevalence of pica was estimated at 2.44%. This value may seem an underestimation when compared to the values reported in the medical literature, which range from 9 to 25%. Additionally, among the 108 hospitalized infant patients, none fulfilled DSM IV criteria, which is surprising, as pica is relatively common in childhood. These results may be explained by the use of the more restrictive criteria of the DSM IV and also by the difficulties encountered in considering pica as an independent medical condition. Indeed, pica is often a secondary diagnosis associated with other psychiatric conditions characterized by profound mental deterioration. Two pathogenic factors were constantly searched in the medical records: iron-deficiency anemia and psychopathology. Cultural factors can be a priori eliminated, as most of these patients are in rupture with their family environment since low ages. Only two patients presented with iron-deficiency anemia and its correction did not result in pica's improvement. These findings do not support the -studies presenting pica as an iron-deficiency anemia induced trouble, which regress after a well-conducted iron replacement. Most patients were found to have precocious lack of affect in their medical history. All patients presented other associated psychiatric troubles including severe mental impairment (48%) and dysharmonic development (26%), as well as autistic troubles and schizophrenia. These data concur with other studies, which associate pica to other psychiatric disorders. Gluttony is a widely represented symptom in our study population (87%) and predisposes to food aspiration. It is the mark of frenetic orality and concerns comestible as well as non-comestible compounds. The ingestion of non-nutriment compounds could therefore be considered as an incapacity of discerning among different mouth-introduced substances. Auto- and hetero-aggressive disorders have been reported in 77% of the patients. These behaviors arise mostly in the phase of seeking of substances, especially if these are particularly attractive. The enhancement of the -anxiety, which often arises in the eventuality of hindering of the act, as well as the soothing effect of the ingestion, suggests a compulsive activity. This compulsive activity could be related to an addictive conduct. Pica could therefore be related to obsessive-compulsive disorders and benefit from its specific therapy, either behavioral or chemotherapy with serotonin-recapture inhibitors. The most common clinical forms of pica were phytophagia and geophagia, probably due to the facility of access to these substances. However, 31 distinct substances have been identified in our study. Pica's evolution often implies severe complications, which are sometimes life threatening in spite of a well-conducted treatment. Severity factors include the iteration of medical and surgical complications, as well as the type of ingested products. Our results show a high incidence of surgical complications, essentially gastro-intestinal. Due to the elevated incidence of complications and to the high rate of mortality, some authors proposed systematical search of pica for any gastro-intestinal troubles arising in patients suffering from mental disorders. For these patients for whom anamnesis is often difficult, a standard X-ray of the abdomen is an essential imaging study. Respiratory complications come in second position and infectious complications are seen mostly for the geo- and coprophagia-suffering patients, which contract intestinal parasitosis. Because of its multifactor causality, treatment of pica is complex, and results are often deceiving. Symptomatic neuroleptic therapy results in transient improvement and is indicated especially in delirious patients. Psychotherapy with behavioral approaches and different institutional approaches can be proposed. Indeed, pica could be considered as an acquired behavior, which could benefit from cognitive and behavioral therapies. Institutional management including supportive and compassionate care, restoration of self-confidence is interesting for these patients. Some authors even suggest that pica might be considered as a good indicator of the institution's care quality.
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PMID:[Pica: a descriptive study of patients in a speciality medical center]. 1461 90

A number of essential trace elements play a major role in various metabolic pathways. Selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) are essential trace elements that have been studied in many diseases, including autoimmune, neurological, and psychiatric disorders. However, the findings of previous research on the status of trace elements in patients with schizophrenia have been controversial. We studied these elements in patients with a DSM-IV diagnosis of schizophrenia and compared them with sex- and age-matched healthy controls. Plasma Cu concentrations were significantly higher (p < 0.01) and Mn and Fe concentrations were lower (p < 0.05 and p < 0.05, respectively) in schizophrenic patients than in controls. Se and Zn concentrations and protein levels did not differ between patients and healthy controls. These observations suggest that alterations in essential trace elements Mn, Cu, and Fe may play a role in the pathogenesis of schizophrenia. However, findings from trace element levels in schizophrenia show a variety of results that are difficult to interpret.
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PMID:Plasma manganese, selenium, zinc, copper, and iron concentrations in patients with schizophrenia. 1507 9


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