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)

Based on the lower levels of long-chain polyunsaturated analogs of essential fatty acids (EPUFAs) in plasma membrane phospholipids of red blood cells, brain and cultured skin fibroblasts from schizophrenic patients, a defective utilization (uptake, conversion to EPUFAs and incorporation into membrane phospholipids) of precursor EFAs has been suggested. Utilization of radiolabeled linoleic (LA, 18:2(n-6)) and alpha-linolenic (ALA, 18:3(n-3)) acids was studied in cultured skin fibroblasts from patients with established schizophrenia and at the first episode of psychosis, and normal controls. Uptake and incorporation of both the EFAs were similar in fibroblasts from both groups of patients studied compared with normal controls. However, although the utilization of LA into arachidonic acid (AA, 20:4n-6) was similar in patients and controls, the utilization of eicosapentaenoic acid (EPA, 20:5(n-3)) into docosahexaenoic acid (DHA, 22:6(n-3)) was significantly lower in first-episode psychotic patients (patients, 96.33 +/- 27.16 versus normals, 161.66 +/- 26.33 nmoles per mg total protein; P = < 0.001). This data indicates that the level of delta 6- as well as delta 5-desaturase may be normal. However, the levels of delta 4-desaturase may be lower in fibroblasts from schizophrenic patients even at the first episode of psychosis.
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PMID:Utilization of precursor essential fatty acids in culture by skin fibroblasts from schizophrenic patients and normal controls. 888 25

Omega-3 fatty acids (ALA, EPA, DHA) are essential polyunsaturated fatty acids. Due to their pivotal involvement in signal transduction processes in the CNS, a role for these fatty acids in psychiatric disorders has been postulated. This review summarizes the latest findings on the physiological function of these compounds in the CNS and gives a comprehensive overview on the emerging therapeutic role of these psychoactive drugs in psychiatric disorders, with special emphasis being put on affective disorders and schizophrenia.
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PMID:[Omega-3 fatty acids in psychiatry]. 1069 34

The dysregulation of membrane phospholipid metabolism exists throughout the body from the onset of psychosis in schizophrenic patients. This dysregulation is primarily due to altered contents of phospholipid bound EPUFAs, AA and DHA. These EPUFAs are highly enriched in the brain and are crucial for brain and behavioral development. A phospholipid metabolic defect may preexist the onset of psychosis, even through early embryonic stages. Because these membrane phospholipids play a crucial role in the membrane receptor-mediated signal transduction of several neuro-transmitters and growth factors, their altered metabolism may contribute to the reported abnormal information processing in schizophrenia. Severity of symptoms seems to correlate with the membrane AA and DHA status, which is influenced by patients' dietary intake and lifestyle. Such a metabolic defect can be prevented, however, and some membrane pathology can be corrected by dietary supplementation with a combination of AA and DHA and antioxidants such as vitamins E and C. In schizophrenia, it may be advisable to provide supplementation at the early stages of illness, when brain has a high degree of plasticity. Finally, at this time, supplementation has to be considered as an augmentation of conventional antipsychotic treatment.
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PMID:Is schizophrenia a metabolic brain disorder? Membrane phospholipid dysregulation and its therapeutic implications. 1268 61

Dehydroepiandrosterone is the most abundant adrenal androgen and also functions as a neurosteroid. Serum concentrations decline with age and can serve as a prognostic factor in both critical illnesses and breast cancer progression. Evidence is accruing in support of dehydroepiandrosterone supplementation in adrenal insufficiency, hypopituitarism, osteoporosis, systemic lupus erythematosus, depression and schizophrenia. Research is ongoing at both the basic and the clinical level to elucidate mechanisms of action and establish efficacy and safety, as well as to expand new areas of potential application for this multi-faceted hormone.
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PMID:Clinical uses and misuses of dehydroepiandrosterone. 1464 16

Dehydroepiandrosterone (DHEA) and its sulfate derivative DHEA-S are neurosteroids, produced in the brain, and neuroactive steroids, produced in the adrenals and affecting the brain. We compared the ratios of serum cortisol/DHEA or DHEA-S in schizophrenia patients with normal subjects, and determined the correlation of these ratios with psychopathology and distress. Early morning plasma concentrations of DHEA, DHEA-S, and cortisol were determined by radioimmunassay in 40 medicated schizophrenia inpatients, and 15 healthy subjects with similar age and sex distribution. Subjects were assessed for psychopathology using the Positive and Negative Syndrome Scale (PANSS) and the Montgomery and Asberg Depression Rating Scale (MADRS), anxiety, anger, emotional and somatic distress levels. Schizophrenia inpatients demonstrated significantly higher levels of state and trait anxiety, anger expression index, emotional and somatic self-reported distress scores. Cortisol/DHEA and cortisol/DHEA-S ratios were significantly higher in schizophrenia patients than in healthy comparison subjects. Both ratios correlated positively with age and duration of illness; cortisol/DHEA-S ratio also showed positive association with age of illness onset. When age, illness duration and age of onset were controlled, cortisol/DHEA-S ratio significantly correlated with severity of depression (MADRS, r=0.33, p=0.048), state and trait anxiety (r=0.43, p=0.008 and r=0.40, p=0.014, respectively), trait anger (r=0.41, p=0.012), angry temperament (r=0.46, p=0.004), anger expression index (r=0.36, p=0.033), and hostility (r=0.42, p=0.010). No significant association was found between these ratios and severity of psychopathology, and type or dosage of antipsychotic agents. Thus, elevated cortisol/DHEA and/or cortisol/DHEA-S ratios in schizophrenia patients are positively associated with higher scores for anxiety and anger, depression and hostility, age and age of onset/duration of illness, but are independent of severity of psychopathology (PANSS) and antipsychotic treatment.
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PMID:Elevation of the cortisol/dehydroepiandrosterone ratio in schizophrenia patients. 1516 35

Dehydroepiandrosterone (DHEA) is a major circulating neurosteroid in humans and its administration has demonstrated efficacy in the improvement of mood, with increased energy, interest, confidence and activity levels. Since recent findings have suggested the role of neurosteroids in general, and DHEA in particular, in the symptomatology and pharmacotherapy of schizophrenia patients with chronic illness, we investigated DHEA and DHEA-S blood levels in individuals in their first-episode of psychosis in order to exclude effects of age, chronic illness, long-term treatment and institutionalization. Blood levels for DHEA, DHEA-S and cortisol were obtained for 37 first-episode schizophrenia subjects and 27 normal age- and sex-matched controls and correlated with a range of clinical and side-effect rating scales. Baseline DHEA and DHEA-S levels were significantly higher in schizophrenia patients (p<0.05 and p<0.001, respectively). No gender differences were noted in DHEA levels; however, DHEA-S levels were significantly higher in male patients. DHEA-S levels inversely correlated with severity of illness (p<0.05) and aggressive behavior (p<0.05). Patients with higher DHEA-S levels tended to have shorter hospitalizations. Results suggest that individuals in their first-episode of schizophrenia psychosis may develop a neurosteroid response to the first onset of psychosis, which may be associated with a reduction in various adverse clinical features including aggression. Such a putative mechanism may become desensitized with the onset of chronic illness. While preliminary, these results further imply the role of these neurosteroids in the pathophysiology and management of schizophrenia.
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PMID:Increased circulatory dehydroepiandrosterone and dehydroepiandrosterone-sulphate in first-episode schizophrenia: relationship to gender, aggression and symptomatology. 1547 14

Cerebral excitability is normally distributed, and pubertal age is a distinguishing factor. The final developmental event in CNS comprising selective pruning of excitatory synapses coincides with puberty. With early puberty, excess excitation and synaptic density, we have photic susceptibility, paroxysmal EEGs, disturbed circadian rhythms, paroxysmal disorders treated with drugs lowering excitation. Manic-depressive psychosis accords with this. Migraine with paroxysmal EEG, photophobia, hemianopsia, scintillating scotomas, excess excitation in the visual system, benefits from lowering excitation. With late puberty, attenuated CNS, we have disorders in need of raising excitation to avoid breakdown of circuitry, insufficient fill-in mechanism, silent spots, subjectively experienced only--objectively verifiable psychosis: i.e., schizophrenia treated with convulsant neuroleptics. By affecting pubertal age, we affect the distribution of excitation and of post-pubertal brain disorders in accordance with their level of excitation. Excitation is equally important in chronic disorders: l'dopa adversity in Parkinsonism could be due to further lowering of excitation in patients with a deficiency, a schizophrenia-like psychosis develops. Given unavoidable adversity of anti-psychotics, and a marked rise in suicide in schizophrenic and manic-depressive since their introduction, we want to prevent the occurrence of disorders at the extremes, whether very early or late puberty. DHA normalises excitability at all levels of excitation. An adequate daily intake of DHA, before puberty as well as after, might probably reduce or eliminate a development of psychopathology. Lithium is a robust neurotropic agent, and lithiation of the drinking water could be a way of reducing suicide, homicide, violent behaviour, and drug abuse.
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PMID:A "new-old" way of thinking about brain disorder, cerebral excitability--the fundamental property of nervous tissue. 1553 32

Dehydroepiandrosterone has been recently recognized as neuroactive steroid with several vital neurophysiological activities on membrane receptors, such as N-methyl-d-aspartate, and gamma-aminobutyric acid receptors and on genomic androgen receptors. DHEA does also have an antiglucocorticoid effect. So far, the relevance of this neuroactive steroid to psychiatric disorders is not well known. In this study, plasma levels of DHEA were determined with a highly sensitive and specific gas-chromatography/mass-spectrometry method in 23 outpatients suffering from Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia compared with 23 healthy control subjects matched for age and sex. Plasma levels of DHEA were found to be strongly elevated in the group of schizophrenic patients (mean+/-SD=90.9+/-61.4 nmol/l) compared to that of control subjects (mean+/-SD=24.0+/-17.9 nmol/l) and the difference was highly significant (t=5.018, df=44, p<0.0001). This statistically significant difference was also found when we divided the groups of schizophrenics and controls in subgroups of males (t=4.536, df=24, p=0.0001) and females (t=2.777, df=18, p=0.0124). These results suggest that DHEA may have some role in the pathophysiology of schizophrenia due to its complex mechanism of action in the brain involving genomic and non-genomic components. Therefore, its study may provide further understanding of the pathophysiology of psychoses and open new avenues for their treatment.
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PMID:Plasma dehydroepiandrosterone levels are strongly increased in schizophrenia. 1641 63

Dehydroepiandrosterone (DHEA) or their sulfate conjugate (DHEAS) (together abbreviated DHEA(S)) exert multiple effects in the central nervous system, and may be involved in the pathophysiological processes in schizophrenia. This prospective study aimed to investigate whether serum cortisol/DHEA(S) molar ratios are associated with response to antipsychotic treatment during the exacerbation of schizophrenia. Serum DHEA(S) and cortisol were determined at baseline, and 2 and 4 weeks later for 43 medicated schizophrenia inpatients with acute exacerbation. The patients were treated with stable doses of antipsychotic agents up to 2 weeks prior to entering the study and for the 4-week duration of the study after which they were classified as either responders or nonresponders to treatment. Findings suggest that responders had significantly higher serum cortisol levels and cortisol/DHEA(S) ratios compared with nonresponders. These differences remained significant at three time points controlling for gender, age, severity of symptoms and emotional distress, benzodiazepines, type or dosage of antipsychotic agents, and background variables. The logistic regression model shows advantages of both cortisol/DHEA(S) molar ratios vs serum cortisol and DHEA(S) concentrations for prediction of responsivity to antipsychotic treatment. No significant canonical correlations were observed between changes from baseline through end-of-study in hormonal values and severity of symptoms and emotional distress among responders and nonresponders. Thus, these data provide evidence that elevated serum cortisol and cortisol/DHEA(S) ratios may serve as markers of biological mechanisms that are involved in responsivity of schizophrenia patients to antipsychotic treatment.
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PMID:Cortisol/dehydroepiandrosterone ratio and responses to antipsychotic treatment in schizophrenia. 1587 Aug 35

There is evidence that neurosteroids such as DHEA and its sulfated form DHEAS can modulate cognitive function. We hypothesize that DHEA/S concentrations may be linked to cognitive impairment in schizophrenia. The aim of this pilot study was to test this hypothesis by examining the relationship between blood levels of DHEAS and cognitive function. The performance of 26 stable medicated chronic schizophrenia patients in a range of neuropsychological domains including verbal memory (Wechsler Memory Scale), executive function (AIM), memory of faces (PFMT), memory for objects (VOLT) and identification of facial emotional expressions (PEAT) was assessed. Single morning blood samples were assayed for levels of DHEAS and cortisol. Significant associations were found between DHEAS levels and DHEAS/Cortisol ratio and verbal memory, executive function and memory for faces. The relationship was independent of the age related reduction in DHEAS levels. These preliminary results suggest that DHEAS may be associated with cognitive impairment in schizophrenia.
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PMID:Blood DHEAS concentrations correlate with cognitive function in chronic schizophrenia patients: a pilot study. 1615 59


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