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Biomedical subjects

M Peet

Publications and source records attributed to M Peet.

At least 19 recordsLinked to original sources

Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia.

Evidence that the metabolism of phospholipids and polyunsaturated fatty acids (PUFA) is abnormal in schizophrenia provided the rationale for intervention studies using PUFA supplementation. An initial open label study indicating efficacy for n-3 PUFA in schizophrenia led to two small double-blind pilot studies. The first study was designed to distinguish between the possible effects of two different n-3 PUFA: eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA). Forty-five schizophrenic patients on stable antipsychotic medication who were still symptomatic were treated with either EPA, DHA or placebo for 3 months. Improvement on EPA measured by the Positive and Negative Syndrome Scale (PANSS) was statistically superior to both DHA and placebo using changes in percentage scores on the total PANSS. EPA was significantly superior to DHA for positive symptoms using ANOVA for repeated measures. In the second placebo-controlled study, EPA was used as a sole treatment, though the use of antipsychotic drugs was still permitted if this was clinically imperative. By the end of the study, all 12 patients on placebo, but only eight out of 14 patients on EPA, were taking antipsychotic drugs. Despite this, patients taking EPA had significantly lower scores on the PANSS rating scale by the end of the study. It is concluded that EPA may represent a new treatment approach to schizophrenia, and this requires investigation by large-scale placebo-controlled trials.

Adult↗

Health care providers' information seeking: recent research.

Recent research studies describe typical information-seeking behavior of doctors, nurses, and other health care providers. This review identifies and analyzes thirty-nine studies and nine reviews published since 1990. The researchers are from many disciplines and often work in multi-disciplinary teams. They have used both quantitative and qualitative methods to gather self-report and observational data. In spite of the increased availability of online bibliographic and full-text sources in this decade, health care providers are using the same sources they used twenty years ago. Self-report studies usually show a higher use of published literature than of advice from colleagues; observational studies usually show the opposite.

Databases, Bibliographic↗

Retinal function as a marker for cell membrane omega-3 fatty acid depletion in schizophrenia: a pilot study.

BACKGROUND: There is a growing body of evidence that abnormalities of the cell membrane, particularly depletion of n-3 essential fatty acids (EFA), are found in patients suffering from schizophrenia. These fatty acids particularly Docosohexaenoic acid (DHA) are found in particularly high concentrations in the photoreceptor cells of the retina and abnormalities of light sensitivity have been reported in patients with schizophrenia. Animal studies have demonstrated that reduced EFA levels are associated with changes in the electrophysiological response of the retina to light as measured by the electroretinogram (ERG). METHODS: We measured the ERG of 9 patients with schizophrenia and 9 age and sex matched control subjects. All but one of the patients was medicated. RESULTS: Schizophrenic subjects had significantly reduced a-wave amplitudes on the ERG when compared with control subjects and the a-wave amplitude was independent of the dose of antipsychotic agents being taken. The a-wave of the ERG is thought to reflect activity of the photoreceptor cells. CONCLUSIONS: These findings support the hypothesis that patients with schizophrenia have abnormalities of photoreceptor function, which may be a result of reduced levels of n-3 EFA in the cell membrane.

Adaptation, Ocular↗

The role of essential fatty acids in chronic fatigue syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA.

OBJECTIVE: To replicate the treatment study by Behan et al. (1990) using current research criteria for Chronic Fatigue Syndrome (CFS). METHOD: Fifty patients who fulfilled the Oxford Criteria for CFS were randomly allocated to treatment with either Efamol Marine or placebo for 3 months. They were seen monthly and completed a physical symptoms checklist and the Beck Inventory for Depression and reported if they were the same, better or worse at the end of the study. RESULTS: Symptoms generally improved with time but not significantly and there were no significant differences between the treatment and placebo groups. Pretreatment red-cell membrane (RBC) lipids of patients compared with age-and sex-matched normal controls showed no significant differences. DISCUSSION: The results of this study contrast sharply with the previous study where 85% of patients had a clinically significant improvement of symptoms with Efamol Marine over a 3-month treatment period.

Adolescent↗

Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients.

BACKGROUND: It has been hypothesized that depletion of cell membrane n3 polyunsaturated fatty acids (PUFA), particularly docosahexanoic acid (DHA), may be of etiological importance in depression. METHODS: We measured the fatty acid composition of phospholipid in cell membranes from red blood cells (RBC) of 15 depressive patients and 15 healthy control subjects. RESULTS: Depressive patients showed significant depletions of total n3 PUFA and particularly DHA. Incubation of RBC from control subjects with hydrogen peroxide abolished all significant differences between patients and controls. CONCLUSIONS: These findings suggest that RBC membranes in depressive patients show evidence of oxidative damage. Possible interpretations, and implications for the etiology and treatment of depression, are discussed.

Adolescent↗

Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients.

BACKGROUND: There is a hypothesis that lack of n-3 polyunsaturated fatty acids (PUFAs) is of aetiological importance in depression. Docosahexaenoic acid, a member of the n-3 PUFA family, is a crucial component of synaptic cell membranes. The aim of this study was to measure RBC membrane fatty acids in a group of depressed patients relative to a well matched healthy control group. METHOD: Red blood cell (RBC) membrane levels, and dietary PUFA intake were measured in 10 depressed patients and 14 matched healthy control subjects. RESULTS: There was a significant depletion of RBC membrane n-3 PUFAs in the depressed subjects which was not due to reduced calorie intake. Severity of depression correlated negatively with RBC membrane levels and with dietary intake of n-3 PUFAs. CONCLUSION: Lower RBC membrane n-3 PUFAs are associated with the severity of depression. LIMITATIONS: Although patient numbers were small, confounding factors were well controlled for and the results were highly significant. Results of the dietary data would tend to be weakened due to the limitations associated with dietary assessment. CLINICAL RELEVANCE: The findings raise the possibility that depressive symptoms may be alleviated by n-3 PUFA supplementation.

Adult↗

Association of the Ban I dimorphic site at the human cytosolic phospholipase A2 gene with schizophrenia.

There is evidence of increased phospholipid breakdown in cell membranes of patients suffering from schizophrenia. This may be related to increased levels of the enzyme cytosolic phospholipase A2 (cPLA2) which have been reported in schizophrenic subjects. We have identified a Ban I dimorphic site on the first intron of the cPLA2 gene. Schizophrenic subjects were found to have a significant excess of the A2/A2 homozygote relative to healthy control subjects. Genetically determined alterations in phospholipase activity may thus underlie the reported abnormalities of phospholipid metabolism in schizophrenia.

Cytosol↗

Fatty acids and schizophrenia.

In a controlled study of red cell membrane fatty acids in patients with schizophrenia, substantial depletions of fatty acids from both the n-6 and n-3 series were demonstrated. Arachidonic acid and docosahexaenoic acid were particularly depleted. In a separate study, dietary analysis revealed no deficiency of fatty acid intake in this patient group, but greater intake of n-3 fatty acids was associated with less severe symptomatology. Dietary supplementation for six weeks with 10 g per day of concentrated fish oil (MaxEPA) led to significant improvement in schizophrenic symptoms. This clinical improvement was related to the increased level of n-3 fatty acids in red cell membranes. These findings form part of a growing body of research data suggestive of an abnormality in cell membrane fatty acid composition in schizophrenia. The preliminary evidence for clinically effective dietary manipulation to correct such an abnormality opens up novel and exciting therapeutic possibilities.

Case-Control Studies↗

Reduced susceptibility to oxidative damage of erythrocyte membranes from medicated schizophrenic patients.

Susceptibility to non-enzymatic peroxidation of erythrocyte membranes from medicated schizophrenic patients relative to healthy control subjects was investigated by measuring internalization into erythrocytes of ethylene glycol, cellobiotol or mannitol, with or without preincubation with cumene hydroperoxide or with chlorpromazine. The main finding was that erythrocytes from schizophrenic patients were less susceptible than those from control subjects to non-enzymatic oxidative damage from cumene hydroperoxide, as measured by internalization of cellobiotol and mannitol. At baseline before incubation, there was reduced internalization of cellobiotol and mannitol and this was reduced even further by preincubation with chlorpromazine. It is suggested that previous findings of fatty acid deficits in erythrocyte membranes from neuroleptic-treated schizophrenic patients are unlikely to have resulted from non-enzymatic oxidative damage of the membrane. Furthermore, it is suggested that depleted erythrocyte membrane essential fatty acids are more likely to be the result of the schizophrenic process rather than antipsychotic drug treatment, and that antipsychotic drugs may even offer protection against membrane lipid peroxidation.

Adolescent↗

Decreased tyrosine transport in fibroblasts from schizophrenics: implications for membrane pathology.

Two independent studies reported recently have shown a significant decrease in Vmax of tyrosine transport in fibroblasts grown from schizophrenics' skin compared with controls. It has also been shown that tyrosine transport into the brain is decreased in schizophrenics compared with controls. In view of the importance of these findings in elucidating the biochemical mechanism(s) associated with schizophrenia, we have studied the kinetics of tyrosine transport and the levels of monoamine oxidase (MAO) activity in fibroblasts grown from the skins of schizophrenics and unrelated control subjects. Using the Lineweaver-Burk plot, the Eadie Hostee plot and the Hanes plot we have calculated the Km and Vmax for tyrosine transport. We have found a significant decrease in the Km and Vmax values for tyrosine transport in schizophrenics compared with control fibroblast samples. No changes were observed in the levels of MAO. Using Lineweaver-Burk plot (1/S Versus 1/V) it has been shown that the tyrosine transport inhibition is uncompetitive. This finding proposes that the inhibition is in the substrate transport protein complex, which may be taking place during the transit of the substrate through the cell membrane. From the observed findings and from the literature evidence we suggest that the altered metabolism of phospholipids in schizophrenics, such as deficiency of arachidonic acid and docosahexaenoic acid, may be contributing to this observed phenomena.

Adolescent↗

Essential fatty acid deficiency in erythrocyte membranes from chronic schizophrenic patients, and the clinical effects of dietary supplementation.

There is now convincing evidence that membrane phospholipid metabolism is abnormal in schizophrenic patients. Our own studies, consistent with those of other research groups, have shown marked depletion of essential fatty acids, particularly arachidonic acid and docosahexanoic acid, in red blood cell membranes from schizophrenic patients relative to healthy control subjects. We also present preliminary evidence that similar abnormalities are present in first degree relatives of schizophrenic patients. Furthermore, it appears that changes in diet, which modify membrane levels of fatty acids, can have significant effects upon symptoms of schizophrenia and tardive dyskinesia (TD). Thus, we have found that schizophrenic patients who eat more (n-3) fatty acids in their normal diet have less severe symptoms. In a pilot study of (n-3) fatty acid supplementation we observed significant improvement in both schizophrenic symptoms and tardive dyskinesia over a 6 week period.

Arachidonic Acids↗

Does the Nursing Care Plan help in the management of psychiatric risk?

The Nursing Care Plan (NCP) is routinely used to direct the nursing care of psychiatric in-patients, but the impact of NCPs on patient care and clinical outcome is not firmly established. NCPs from 246 patients, chosen at random from admissions to acute psychiatric wards, were analysed. The NCPs were scored for quality and also specifically for the presence of recorded risk assessment and appropriate level of nursing supervision. NCPs were evaluated in relation to psychiatric risk factors present prior to admission, and in relation to risk behaviour during hospitalization. Quality of NCP records was generally poor, with scores in all areas assessed being approximately half of the possible maximum. Patients with a perceived high risk of suicide prior to admission had significantly better NCP quality than other patients, but about a third of these high risk patients had no recorded risk assessment or supervision level in the nursing notes. Patients who had actually self-harmed within 4 weeks prior to admission were more likely to have a recorded risk assessment but did not score more highly than the rest of the patient population on any other measures of NCP quality. Patients who had made suicidal threats prior to admission but who were not deemed to be of high suicide risk before admission had significantly lower quality NCPs and were less likely to have a record of supervision level than the rest of the patients. The highest rate of supervision records occurred in patients who had shown dangerous behaviour prior to admission. Outcome in terms of two risk behaviours during admission (self-harm and violence) was not related to whether or not risk assessment and supervision levels had been recorded. Patients admitted compulsorily to hospital were more likely to have a supervision level recorded but were also more likely to abscond. It is concluded that issues of psychiatric risk were not adequately addressed in this sample of NCPs. Furthermore, the data raise serious questions about the usefulness of the NCP in helping to predict and prevent risky behaviour amongst psychiatric in-patients.

Acute Disease↗

Drug-induced mania.

Mania can occur by chance association during drug treatment, particularly in patients predisposed to mood disorder. Single case reports are unreliable, and evidence must be sought from large series of treated patients, particularly those with a matched control group. Drugs with a definite propensity to cause manic symptoms include levodopa, corticosteroids and anabolic-androgenic steroids. Antidepressants of the tricyclic and monoamine oxidase inhibitor classes can induce mania in patients with pre-existing bipolar affective disorder. Drugs which are probably capable of inducing mania, but for which the evidence is less scientifically secure, include other dopaminergic anti-Parkinsonian drugs, thyroxine, iproniazid and isoniazid, sympathomimetic drugs, chloroquine, baclofen, alprazolam, captopril, amphetamine and phencyclidine. Other drugs may induce mania rarely and idiosyncratically. Management involves discontinuation or dosage reduction of the suspected drug, if this is medically possible, and treatment of manic symptoms with antipsychotic drugs or lithium.

Adrenal Cortex Hormones↗

Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants.

The rate of treatment-emergent switch into mania has been calculated from all available clinical trial data on the selective serotonin re-uptake inhibitors (SSRIs) fluoxetine, fluvoxamine, paroxetine, and sertraline, relative to comparative groups treated with tricyclic antidepressants (TCAs) or placebo. In predominantly unipolar depressives, the rate of manic switch is less than 1% and differences between drugs and placebo are statistically but not clinically significant. In bipolar depressives, manic switch occurs substantially more often with TCAs (11.2%) than with SSRIs (3.7%) or placebo (4.2%).

Antidepressive Agents, Tricyclic↗