Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients

Ranjekar, P. K.; Hinge, Ashwini; Hegde, Mahabaleshwar V.; Ghate, M.R.; Kale, Anvita; Sitasawad, Sandhya L.; Wagh, U. V.; Debsikdar, Vijay B; Mahadik, Sahebarao P.

doi:10.1016/s0165-1781(03)00220-8

Cited by 340 publications

(234 citation statements)

References 58 publications

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“…7,8 Epidemiological observations point to a decreased dietary n-3 polyunsaturated fatty acid (PUFA) intake being associated with an increased prevalence of bipolar disorder. 9 Blood DHA levels 10,11 and postmortem prefrontal cortex DHA levels are 16.5% lower in bipolar patients compared to normal controls. 12 Two randomized clinical trials have shown n-3 PUFA supplementation to be beneficial in treating bipolar symptoms.…”

Section: Introductionmentioning

confidence: 96%

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

et al. 2006

Mol Psychiatry

258

151

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Decreased docosahexaenoic acid (DHA) and brain-derived neurotrophic factor (BDNF) have been implicated in bipolar disorder. It also has been reported that dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) for 15 weeks in rats, increased their depression and aggression scores. Here, we show that n-3 PUFA deprivation for 15 weeks decreased the frontal cortex DHA level and reduced frontal cortex BDNF expression, cAMP response element binding protein (CREB) transcription factor activity and p38 mitogen-activated protein kinase (MAPK) activity. Activities of other CREB activating protein kinases were not significantly changed. The addition of DHA to rat primary cortical astrocytes in vitro, induced BDNF protein expression and this was blocked by a p38 MAPK inhibitor. DHA's ability to regulate BDNF via a p38 MAPK-dependent mechanism may contribute to its therapeutic efficacy in brain diseases having disordered cell survival and neuroplasticity.

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Section: Introductionmentioning

confidence: 96%

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

et al. 2006

Mol Psychiatry

258

151

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“…Decreased omega-3 fatty acid levels have been found in blood and postmortem brain cell membranes in several neuropsychiatric conditions (Schachter et al, 2005), in particular schizophrenia (Berger et al, 2006;Fenton et al, 2000;McNamara et al, 2007), bipolar affective disorders (Chiu et al, 2003;Hitzemann et al, 1984;Mahadik et al, 1996;Ranjekar et al, 2003), major depression (FrasureSmith et al, 2004;McNamara et al, 2006;Mischoulon and Fava, 2000;Peet et al, 1998), and attention deficit (hyperactivity) disorder (Burgess et al, 2000;Stevens et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Ethyl-Eicosapentaenoic Acid in First-Episode Psychosis. A 1H-MRS Study

Berger

Wood

Wellard

et al. 2008

Neuropsychopharmacol

107

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Ethyl-eicosapentaenoic acid (E-EPA) is an omega-3 fatty acid that has been used in a range of neuropsychiatric conditions with some benefits. However, its mechanism of action is unknown. Here, we investigate its effects on in vivo brain metabolism in first-episode psychosis (FEP). Proton magnetic resonance spectroscopy at 3 T was performed in the temporal lobes of 24 FEP patients before and after 12 weeks of treatment in the context of a larger double-blind, placebo-controlled E-EPA augmentation study. Treatment group effects for glutathione (F1,12 ¼ 6.1, p ¼ 0.03), and a hemisphere-by-group interaction for glutamine/glutamate (F1,20 ¼ 4.4, p ¼ 0.049) were found. Glutathione increased bilaterally and glutamate/glutamine increased in the left hemisphere following E-EPA administration. Improvement in negative symptoms correlated with metabolic brain changes, particularly glutathione (r ¼ À0.57). These results suggest that E-EPA augmentation alters glutathione availability and modulates the glutamine/glutamate cycle in early psychosis, with some of the metabolic brain changes being correlated with negative symptom improvement. Larger confirmatory studies of these postulated metabolic brain effects of E-EPA are warranted.

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“…Significant GSH deficiency has subsequently been reported (Altuntas et al, 2000). Reduced levels of the major antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), have also been found in patients with schizophrenia compared with controls (Ben Othmen et al, 2007;Li et al, 2006;Ranjekar et al, 2003). Others have reported unchanged levels for these three enzymes (Srivastava et al, 2001), or altered concentrations of individual enzymes (Abdalla et al, 1986;Akyol et al, 2002;Altuntas et al, 2000;DietrichMuszalska et al, 2005;Herken et al, 2001;Kuloglu et al, 2002c ;Zhang et al, 2006a).…”

Section: Assays Of Oxidants and Antioxidantsmentioning

confidence: 99%

“…A concomitant reduction in GSH : GSSG ratio, inverse correlations between age and GSSG and between age and GR, as well as the loss of normal correlations that exist in ; 82 (Zoroglu et al, 2002) ; 46 ; 20 (Taneli et al, 2004) (Herken et al, 2001) ; 25 (Kuloglu et al, 2002c) Unchanged 50 (Abdalla et al, 1986) Decreased 48 (Altuntas et al, 2000) ; 31 (Ranjekar et al, 2003) ; 46 (Yao et al, 1998a) Assays of oxidative products TBARS/MDA Plasma Increased 26 (Mahadik et al, 1998) ; 100 ; 25 (Kuloglu et al, 2002c) ; 92 (Zhang et al, 2006a) ; 47 (Dietrich-Muszalska and Olas, 2007) ; 60 (Ben Othmen et al, 2007) Unchanged 31 (Ranjekar et al, 2003 (Zhang et al, 2003) ; 16 (Evans et al, 2003) ; 48 (Dakhale et al, 2004) No reversal of oxidants, antioxidants¡MDA with treatment 20 (Taneli et al, 2004) ; 40 (Sarandol et al, 2007a) Preclinical studies Rats Reversal of haloperidolinduced oxidative stress Clozapine, olanzapine, risperidone (Pillai et al, 2007) In-vitro cell studies Reversal of induced oxidative stress…”

Section: Assays Of Oxidants and Antioxidantsmentioning

confidence: 99%

Oxidative stress in psychiatric disorders: evidence base and therapeutic implications

Berk

Dean

et al. 2008

Int. J. Neuropsychopharm.

865

569

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Oxidative stress has been implicated in the pathogenesis of diverse disease states, and may be a common pathogenic mechanism underlying many major psychiatric disorders, as the brain has comparatively greater vulnerability to oxidative damage. This review aims to examine the current evidence for the role of oxidative stress in psychiatric disorders, and its academic and clinical implications. A literature search was conducted using the Medline, Pubmed, PsycINFO, CINAHL PLUS, BIOSIS Previews, and Cochrane databases, with a time-frame extending to September 2007. The broadest data for oxidative stress mechanisms have been derived from studies conducted in schizophrenia, where evidence is available from different areas of oxidative research, including oxidative marker assays, psychopharmacology studies, and clinical trials of antioxidants. For bipolar disorder and depression, a solid foundation for oxidative stress hypotheses has been provided by biochemical, genetic, pharmacological, preclinical therapeutic studies and one clinical trial. Oxidative pathophysiology in anxiety disorders is strongly supported by animal models, and also by human biochemical data. Pilot studies have suggested efficacy of N-acetylcysteine in cocaine dependence, while early evidence is accumulating for oxidative mechanisms in autism and attention deficit hyperactivity disorder. In conclusion, multi-dimensional data support the role of oxidative stress in diverse psychiatric disorders. These data not only suggest that oxidative mechanisms may form unifying common pathogenic pathways in psychiatric disorders, but also introduce new targets for the development of therapeutic interventions.

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Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients

Cited by 340 publications

References 58 publications

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

Ethyl-Eicosapentaenoic Acid in First-Episode Psychosis. A 1H-MRS Study

Oxidative stress in psychiatric disorders: evidence base and therapeutic implications

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