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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty-three controlled trials of the effects of niacin, vitamin B6, and multivitamins on mental functions are reviewed. The results are interpreted with emphasis on the methodological quality of the trials. It turns out that virtually all trials show serious short-comings: in the number of participants, the presentation of baseline characteristics and outcomes, and the description of changes in concomitant treatments. Only in autistic children are some positive results are found with very high dosages of vitamin B6 combined with magnesium, but further evidence is needed before more definitive conclusions can be drawn. For many other indications (hyperactive children, children with Down's syndrome, IQ changes in healthy schoolchildren, schizophrenia, psychological functions in healthy adults and geriatric patients) there is no adequate support from controlled trials in favor of vitamin supplementation.
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PMID:Niacin and vitamin B6 in mental functioning: a review of controlled trials in humans. 182 3

The niacin test (oral administration of 200 mg of nicotine acid) was done in 33 schizophrenics and 18 endogenous depressed drug-free patients in the presence of intense symptomatology. The erythema reaction was found in 25 schizophrenics (76%) and in all depressed patients. No significant differences in basal clinical features between schizophrenics with and without erythema reaction were found. The measurements of maximal increase of the left ear lap temperature after nicotine acid administration as well as time needed to note such increase did not show significant differences between schizophrenic patients with and without erythema reaction, and patients with endogenous depression. The results show a limited usefulness of the niacin test in schizophrenia. Nevertheless, the results suggest the possibility that among the small number of schizophrenics there is metabolic defect probably connected with the low activity of PGE1 prostaglandins.
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PMID:[The niacin test in schizophrenia]. 208 15

Vitamins are a group of organic compounds occurring naturally in food and are necessary for good health. Lack of a vitamin may lead to a specific deficiency syndrome, which may be primary (due to inadequate diet) or secondary (due to malabsorption or to increased metabolic need), and it is rational to use high-dose vitamin supplementation in situations where these clinical conditions exist. However, pharmacological doses of vitamins are claimed to be of value in a wide variety of conditions which have no, or only a superficial, resemblance to the classic vitamin deficiency syndromes. The enormous literature on which these claims are based consists mainly of uncontrolled clinical trials or anecdotal reports. Only a few studies have made use of the techniques of randomisation and double-blinding. Evidence from such studies reveals a beneficial therapeutic effect of vitamin E in intermittent claudication and fibrocystic breast disease and of vitamin C in pressure sores, but the use of vitamin A in acne vulgaris, vitamin E in angina pectoris, hyperlipidaemia and enhancement of athletic capacity, of vitamin C in advanced cancer, and niacin in schizophrenia has been rejected. Evidence is conflicting or inconclusive as to the use of vitamin C in the common cold, asthma and enhancement of athletic capacity, of pantothenic acid in osteoarthritis, and folic acid (folacin) in neural tube defects. Most of the vitamins have been reported to cause adverse effects when ingested in excessive doses. It is therefore worthwhile to consider the risk-benefit ratio before embarking upon the use of high-dose vitamin supplementation for disorders were proof of efficacy is lacking.
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PMID:Vitamin therapy in the absence of obvious deficiency. What is the evidence? 623 Feb 19

There is evidence that schizophrenia may be related to excess biological activity of dopamine, deficient synthesis of a prostaglandin and to the presence of a normal opioid in excess or of an abnormal opioid. These three groups of observations seem to be interrelated since opioids are able to inhibit the formation of prostaglandin E1 and prostaglandin E1 and dopamine inhibit each other's effects. A low prostaglandin E1 level will therefore produce and apparent dopamine excess. Niacin causes flushing, apparently by stimulating production of prostaglandin E1. Much larger doses of oral niacin are required to produce flushing in schizophrenics than in normal individuals. Most schizophrenics do not flush when given 250 mg orally and this may be a simple biochemically-based test for a major group of schizophrenics.
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PMID:Schizophrenia: a biochemical disorder? 738 16

Clinical, biochemical and genetic evidence now indicates that schizophrenia is a disorder of membrane phospholipid metabolism associated with increased loss of highly polyunsaturated fatty acids from membranes owing to enhanced activity of a phospholipase A2. This changes the properties of membranes throughout the body and is responsible for such physical abnormalities as reduced vasodilator responses to niacin and histamine and altered immunological functions. A modest membrane abnormality is likely to produce its most serious consequences in the brain, which requires the co-ordinated sequential and parallel activities of millions of neurons. The concept leads to testable proposals for relatively simple and safe treatment modalities.
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PMID:Schizophrenia as a membrane lipid disorder which is expressed throughout the body. 888 16

Clinical definitions of schizophrenia are unreliable and difficult to use. The niacin flush test, which involves prostaglandin-induced vasodilatation, offers a method of exploring essential fatty acid metabolism in schizophrenic patients and may serve to define a subgroup of patients. In a multicentre study of schizophrenic patients with negative symptoms, we have examined the clinical accompaniments of the niacin response. Patients failing to flush with niacin showed significantly reduced levels of arachidonic and docosahexaenoic acids. Conversion from non-flushing to flushing during the 6 month supplementation period was predicted by an increase in arachidonic acid levels in red blood cell membranes irrespective of nature of supplementation. In this study, patients were selected for their negative symptoms and, therefore, it was not surprising that further measures of negative or positive symptoms did not predict flushing. However, an increased score for affective symptoms was significantly associated with a positive flush response. The stability of the niacin test needs to be examined in relation to the periodicity of symptoms in schizophrenia and manic depressive illness. New information on the anandamide system suggests that it may be associated with periodic phenomena and should be investigated in relation to the niacin test.
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PMID:Membrane fatty acids, niacin flushing and clinical parameters. 888 17

Several lines of evidence implicate altered phospholipid-dependent signal transduction (PDST) in the pathophysiology of schizophrenia. Niacin induces vasodilation through mechanisms requiring intact PDST. Thus, an altered response to a challenge dose of niacin may reflect disturbances in these signalling processes in this disorder. In the present study, niacin-induced vasodilation was estimated quantitatively in schizophrenic and comparison bipolar affective disorder and healthy subjects using thermocouple sensors to measure the change in skin temperature relative to core body and ambient room temperature. Twelve (42.9%) of 28 schizophrenic subjects did not vasodilate in response to a 200-mg niacin challenge dose, whereas only 1 of 18 (6%) bipolar disorder subjects and none of 28 controls showed impaired response (Fisher's Exact Test, p < .0001). These findings support the notion that the schizophrenic syndromes are biochemically heterogeneous and suggest the existence of a subgroup of schizophrenic subjects in whom phospholipid-dependent signalling responses may be impaired.
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PMID:The niacin challenge test: clinical manifestation of altered transmembrane signal transduction in schizophrenia? 904 82

Three problems in identifying genes causing schizophrenia and other developmental disorders may be locus heterogeneity, high disease allele frequency, and unknown mode of inheritance. The DNA polymorphism-diet-cofactor-development (DDCD) hypothesis addresses the first two. The gene-teratogen model addresses the third. The DDCD hypothesis is that schizophrenia results in part from brain abnormality in utero from the aggregate effect of multiple mutations of small effect of genes related to important cofactors (e.g., folate, cobalamin, or pyridoxine) potentiated by maternal dietary deficiency of these cofactors and by pregnancy. The effect results from insufficiency of the cofactors and from resulting effects such as impaired DNA synthesis, immune deficiency, effects on niacin and serotonin metabolism, and teratogens, e.g., hyperhomocysteinemia. The hypothesis addresses all of the unusual features of schizophrenia: e.g., decreased brain gray matter, birth-month effect, geographical differences, socioeconomic predilection, association with obstetrical abnormalities, decreased incidence of rheumatoid arthritis, and association with famine and viral epidemics. In the gene-teratogen model, a teratogenic effect in utero produces a developmental disorder through a teratogenic locus and a modifying or specificity locus, as well as through environmental factors. An example is the major intrauterine effect seen in offspring of phenylketonuric mothers. Thus, the mode of inheritance of genes acting prenatally may in some cases be fundamentally different from that of genes acting postnatally. The model is interesting because it is simple and because teratogenic loci will be difficult to locate by conventional linkage mapping techniques due to misspecification of the affection status of both mother and affected children. A new study design is suggested for identifying teratogenic loci.
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PMID:DNA polymorphism-diet-cofactor-development hypothesis and the gene-teratogen model for schizophrenia and other developmental disorders. 1040 96

Complex illnesses may result from the interaction or addition of multiple factors. We examined the familial co-distribution of two abnormalities common in schizophrenia: impaired auditory sensory gating and impaired flush response to niacin. In ten families, the obligate carrier parent had sensory-gating deficits, while eight of the ten parents without a family history of schizophrenia had impaired flush response. No parents had both deficits. The data are consistent with a theory suggesting the interaction of these two factors in some cases of schizophrenia.
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PMID:Co-distribution of sensory gating and impaired niacin flush response in the parents of schizophrenics. 1054 Oct 7

Recent research suggests that deficient uptake or excessive breakdown of membrane phospholipids may be associated with schizophrenia. We review available clinical research on abnormalities in membrane fatty acid composition and metabolism in schizophrenia, and therapeutic trials of fatty acid in this disorder. All potentially relevant English-language articles were identified from the medical and psychiatric literature with the aid of computer searches using key words such as lipids, phospholipids, prostaglandins and schizophrenia. All studies which include human subjects are reviewed. Empirical studies related to membrane hypotheses of schizophrenia focus on: 1) assessment of prostaglandins (PG) and their essential fatty acid (EFA) precursors in the tissues of patients with schizophrenia; 2) evaluation of the niacin flush test as a possible diagnostic marker; 3) evaluation of phospholipase enzyme activity; 4) NMR spectroscopy studies of brain phospholipid metabolism; and 5) therapeutic trials of PG precursors for the treatment of schizophrenia. The most consistent clinical findings include red blood cell fatty acid membrane abnormalities, NMR spectroscopy evidence of increased phospholipid turnover and a therapeutic effect of omega-3 fatty acid supplementation of neuroleptic treatment in some schizophrenia patients. Studies of EFA metabolism have proved fruitful for generating and testing novel etiologic hypotheses and new therapeutic agents for schizophrenia. Greater attention to factors that influence tissue EFA levels such as diet, tobacco and alcohol are required to reconcile inconsistent findings. Treatment studies, although promising, require independent replication.
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PMID:Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia. 1065 Apr 44


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