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)

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.
 ...
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.
 ...
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.
 ...
PMID:Is schizophrenia a metabolic brain disorder? Membrane phospholipid dysregulation and its therapeutic implications. 1268 61

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.
 ...
PMID:A "new-old" way of thinking about brain disorder, cerebral excitability--the fundamental property of nervous tissue. 1553 32

Insufficient availability of n-3 polyunsaturated fatty acids (PUFAs) during pre- and neonatal development decreases accretion of docosahexaenoic acid (DHA, 22:6n-3) in the developing brain and is associated with sub-optimal sensory and cognitive function in humans, altered behavior in animals, and may contribute to neurodevelopmental disorders such as attention deficit hyperactivity disorder and schizophrenia. This study examined the effects of variation in dietary availability of n-3 PUFAs on brain fatty acid composition and the consequent effects on locomotor activity in male and female Long-Evans rats. Rats were raised from conception using purified diets and breeding protocols designed to produce four groups with distinct brain phospholipid compositions varying in DHA content and/or the proportion of n-3 and n-6 PUFAs. Locomotor behavior was measured for a 2-h period on postnatal days 28, 42, 56, and 70. In males, decreased brain DHA produced alterations in activity that were most pronounced post-adolescence and with the greatest decrease in DHA. However, the behavioral effects in males were not linearly related to brain DHA level. In contrast, no significant effects of variation in brain fatty acid composition were observed in females. This suggests that variation in brain DHA content produces sex-specific alterations in locomotor activity and that the neurochemical alterations underlying the observed behavioral changes vary depending on the degree of DHA depletion.
 ...
PMID:Sex-specific effects of brain LC-PUFA composition on locomotor activity in rats. 1687 5

The brain is a lipid-rich organ containing mostly complex polar phospholipids, sphingolipids, gangliosides and cholesterol. These lipids are involved in the structure and function of cell membranes in the brain. The glycerophospholipids in the brain contain a high proportion of polyunsaturated fatty acids (PUFA) derived from the essential fatty acids, linoleic acid and alpha-linolenic acid. The main PUFA in the brain are docosahexaenoic acid (DHA, all cis 4,7,10,13,16,19-22:6) derived from the omega 3 fatty acid, alpha-linolenic acid, and arachidonic acid (AA, all cis 5,8,11,14-20:4) and docosatetraenoic acid (all cis 7,10,13,16-22:4), both derived from the omega 6 fatty acid, linoleic acid. Experimental studies in animals have shown that diets lacking omega 3 PUFA lead to substantial disturbances in neural function, which in most circumstances can be restored by the inclusion of omega 3 PUFA in the diet. In the past 10 years there has been an emerging interest in treating neuropsychological disorders (depression and schizophrenia) with omega 3 PUFA. This paper discusses the clinical studies conducted in the area of depression and omega 3 PUFA and the possible mechanisms of action of these PUFA. It is clear from the literature that DHA is involved in a variety of processes in neural cells and that its role is far more complex than simply influencing cell membrane properties.
 ...
PMID:Omega 3 fatty acids and the brain: review of studies in depression. 1739 37

Classical antipsychotics like haloperidol are suggested to increase oxidative stress and oxidative cell injury in the brain. Pro-oxidant effect of haloperidol may influence the course and treatment outcomes of schizophrenia. Dietary supplementation of either antioxidants or omega-3 fatty acids was found to improve symptoms of schizophrenia. Thus we decided to assess the impact of combining omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol. Ongoing haloperidol treatment of 17 schizophrenia patients was supplemented with 1000 mg capsule of omega-3 fatty acids (180 mg EPA+120 mg DHA) bid, vitamin E 400 IU bid and vitamin C 1000 mg/day. Patients were assessed with Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), Simpson Angus Scale (SAS) and Barnes Akathisia Rating Scale (BARS) over a 4 month period. Gluthatione peroxidase, superoxide dismutase, malondialdehyde, vitamin E and C levels were also evaluated at baseline and at the end of study. BPRS, SANS, SAS and BARS scores obtained at follow-up visits were significantly lower compared to baseline. Superoxide dismutase level was significantly lower at the end of study. No significant differences were detected in other laboratory parameters. Our results support the beneficial effect of the supplementation on positive and negative symptoms of schizophrenia as well as the severity of side effects induced by haloperidol. The effect of supplementation on akathisia is especially noteworthy and it has not been investigated in previous studies.
 ...
PMID:The impact of omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: an open-label pilot study. 1768 87

Prior clinical studies suggest that chronic treatment with atypical antipsychotic medications increase erythrocyte and postmortem prefrontal cortex (PFC) omega-3 fatty acid composition in patients with schizophrenia (SZ). However, because human tissue phospholipid omega-3 fatty acid composition is potentially influenced by multiple extraneous variables, definitive evaluation of this putative mechanism of action requires an animal model. In the present study, we determined the effects of chronic treatment with the atypical antipsychotic risperidone (RISP, 3.0 mg/kg/d) on erythrocyte and PFC omega-3 fatty acid composition in rats maintained on a diet with or without the dietary omega-3 fatty acid precursor, alpha-linolenic acid (ALA, 18:3n-3). Chronic RISP treatment resulted in therapeutically-relevant plasma RISP and 9-OH-RISP concentrations (18+/-2.6 ng/ml), and significantly increased erythrocyte docosahexaenoic acid (DHA, 22:6n-3, +22%, p=0.0003) and docosapentaenoic acid (22:5n-3, +18%, p=0.01) composition, and increased PFC DHA composition (+7%, p=0.03) in rats maintained on the ALA+ diet. In contrast, chronic RISP did not alter erythrocyte or PFC omega-3 fatty acid composition in rats maintained on the ALA- diet. Chronic RISP treatment did not alter erythrocyte or PFC arachidonic acid (AA, 20:4n-6) composition. These data suggest that chronic RISP treatment significantly augments ALA-DHA biosynthesis, and preferentially increases peripheral and central membrane omega-3 fatty acid composition. Augmented omega-3 fatty acid biosynthesis and membrane composition represents a novel mechanism of action that may contribute in part to the efficacy of RISP in the treatment of SZ.
 ...
PMID:Chronic risperidone treatment preferentially increases rat erythrocyte and prefrontal cortex omega-3 fatty acid composition: evidence for augmented biosynthesis. 1899 32

Previous studies with postmortem brain tissues showed abnormalities not only in n-3 long-chain polyunsaturated fatty acids (PUFA) but also in phospholipid metabolism in the cortex of individuals with schizophrenia and mood disorder. In this study we investigated whether there is similar abnormality in n-3 long-chain PUFAs and/or in phospholipid profile in the hippocampus of schizophrenia and bipolar disorder patients compared to unaffected controls. Using high-performance liquid chromatography/electrospray ionization-mass spectrometry (LC/MS), the phospholipid contents in the postmortem hippocampus from 35 individuals with schizophrenia, 34 individuals with bipolar disorder and 35 controls were evaluated. Unlike the previous findings form orbitofrontal cortex, we found no significant differences in either n-3 long-chain PUFA or total phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC). However, docosapentaenoic acid (n-6, 22:5n-6)-PS and 22:5n-6-PC were significantly lower in individuals with schizophrenia or bipolar disorder than the controls. When fatty acid contents were estimated from PS, PE and PC, 22:5n-6 was significantly lower in both patient groups compared to the controls. From these results we concluded that DHA loss associated with these psychiatric disorders may be specific to certain regions of the brain. The selective decrease in 22:5n-6 without affecting DHA contents suggests altered lipid metabolism, particularly n-6 PUFA rather than n-3 PUFA, in the hippocampus of individuals with schizophrenia or bipolar disorder.
 ...
PMID:Phospholipid profile in the postmortem hippocampus of patients with schizophrenia and bipolar disorder: no changes in docosahexaenoic acid species. 2005 43

Sex differences in the symptomatology and course of illness have been reported among schizophrenic patients. Hence, the principal objective of the present study was to investigate sex differences in the concentrations of the lipid peroxidation metabolites MDA and 4-HNE, and in the membrane phospholipid levels of ARA, EPA and DHA in patients with schizophrenia. A total of 46 paranoid schizophrenics (25 women) with short-term evolution who were in an acute psychotic stage and 40 healthy controls (23 women) participated in the study. Psychopathology was evaluated by BPRS and PANSS. Lipid peroxidation sub-products (MDA, 4-HNE) and fatty acid levels (ARA, EPA, DHA) were determined in erythrocyte membranes. The men in both groups showed higher lipid peroxidation levels and those values were higher in schizophrenic patients than controls, with only EPA fatty acid concentrations found to be lower in the former than the latter. These results suggest that men may suffer greater oxidative neuronal damage than women, and that this could worsen the course of illness and result in greater disease severity.
 ...
PMID:Sex differences in lipid peroxidation and fatty acid levels in recent onset schizophrenia. 2342 76


1 2 Next >>