381
Views
69
CrossRef citations to date
0
Altmetric
Original

Prevention of oxidative stress-mediated neuropathology and improved clinical outcome by adjunctive use of a combination of antioxidants and omega-3 fatty acids in schizophrenia

, , &
Pages 119-131 | Published online: 11 Jul 2009

References

  • Adler LA, Peselow E, Rotrosen J, Duncan E, Lee M, Rosenthal M, et al. Vitamin E treatment of tardive dyskinesia. American Journal of Psychiatr 1993; 150: 1405–1407
  • Adler LA, Rotrosen J, Edson R, Lavori P, Lohr J, Hitzemann R, et al. Vitamin E treatment for tardive dyskinesia. Archives of General Psychiatry 1999; 56: 836–841
  • Allen RG, Balin AK. Oxidative influence on development and differentiation: An overview of a free radical theory of development. Free Radical Biology & Medicine 1989; 6: 631–661
  • Anderson GJ, Connor WE, Corliss JD. Docosahexaenoic acid is the preferred dietary n-3 fatty acid for the development of the brain and retina. Pediatric Research 1990; 27: 89–97
  • Arnold SE, Trojanowski JQ, Gur RE, Blackwell P, Han L-Y, Choi C. Absence of neurodegenerative and neural injury in the cerebral cortex in a sample of elderly patients with schizophrenia. Archives of General Psychiatry 1998; 55: 225–232
  • Arvindakshan M, Ghate M, Ranjekar PK, Evans DR, Mahadik SP. Supplementation with a combination of omega-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophrenia. Schizophrenia Research 2003a; 62: 195–204
  • Arvindakshan M, Sitasawad S, Debsikdar V, Ghate M, Evans D, Horrobin DF, et al. Essential polyunsaturated fatty acid and lipid peroxide levels in never-medicated and medicated schizophrenia patients. Biological Psychiatry 2003b; 53: 56–64
  • Behl C, Rupprecht R, Skutella T, Holsboer F. Haloperidol-induced cell death—mechanism and protection with vitamin E in vitro. NeuroReport 1995; 7: 360–364
  • Bender L. Childhood schizophrenia: Clinical study of 100 schizophrenic children. American Journal of Psychiatry 1947; 17: 40–56
  • Bernstein HG, Krell D, Braunewell KH, Baumann B, Gundelfinger ED, Diekmann S, et al. Increased number of nitric oxide synthase immunoreactive Purkinje cells and dentate nucleus neurons in schizophrenia. Journal of Neurocytology 2001; 30: 661–670
  • Brown S, Birtwistle J, Roe L, Thompson C. The unhealthy lifestyle of people with schizophrenia. Psychological Medicine 1999; 29: 697–701
  • Burgess JR, Kuo C-F. Increased calcium-dependent phospholipase A2 activity in vitamin E, and selenium-deficient rat lung, liver and spleen cytosol is time-dependent and reversible. The Journal of Nutritional Biochemistry 1996; 7: 366–374
  • Cadet JL, Lohr JB. Free radicals and the developmental pathophysiology of schizophrenic burnout. Integrative Psychiatry 1987; 5: 40–48
  • Cadet JL, Perumal AS. Chronic treatment with prolixine causes oxidative stress in rat brain. Biological Psychiatry 1990; 28: 738–740
  • Cannon M, Jones P, Gilvarry C, Rifkin L, Mckenzie K, Foerster A, et al. Premorbid social functioning in schizophrenia and bipolar disorder: Similarities and differences. American Journal of Psychiatry 1997; 154: 1544–1550
  • Cannon M, Jones PB, Murray RM. Obstetric complications and schizophrenia: Historical and meta-analytic review. American Journal of Psychiatry 2002; 159: 1080–1092
  • Catts VS, Catts SV. Apoptosis and schizophrenia: Is the tumor suppressor gene, p53, a candidate susceptibility gene?. Schizophrenia Research 2000; 41: 405–415
  • Christinsen O, Christinsen E. Fat consumption and schizophrenia. Acta Psychiatrica Scandinavica 1988; 78: 587–591
  • Colavitti R, Pani G, Bedogni B, Anzevino R, Borrello S, Waltenberger J, et al. Reactive oxygen species as downstream mediators of angiogenic signaling by vascular endothelial growth factor receptor-2/KDR. The Journal of Biological Chemistry 2002; 277: 3101–3108
  • Collins AR, Dusinska M, Gedik CM, Stetina R. Oxidative damage to DNA: Do we have a reliable biomarker?. Environmental Health Perspectives 1996; 104: 465–469
  • Connor WE, Lin DS, Neuringer M. The Docosahexaenoic Acid (Dha. 22:6n-3) contents of erythrocytes a marker for the DHA content of brain phospholipids?. The FASEB Journal 1993; 7: A152
  • Craig TJ, Siegel C, Hopper K, Lin S, Sartorius N. Outcome in schizophrenia and related disorders compared between developing and developed countries. A recursive partitioning re-analysis of the WHO DOSMD data. The British Journal of Psychiatry 1997; 170: 229–233
  • Cui K, Luo X, Xu K, Ven Murthy MR. Role of oxidative stress in neurodegeneration: Recent developments in assay methods for oxidative stress and nutraceutical antioxidants. Progress in Neuropsychopharmacology & Biological Psychiatry 2004; 28: 771–799
  • Das UN. Can perinatal supplementation of long-chain polyunsaturated fatty acids prevent schizophrenia in adult life?. Medical Science Monitor 2004; 10: HY33–HY37
  • Dawson TM, Dawson VL, Snyder SH. A novel neuronal messenger molecule in brain: The free radical, nitric oxide. Annals of Neurology 1992; 32: 297–311
  • Degreef G, Ashtari M, Bogerts B, Bilder R, Jody DN, Alvir JMJ, et al. Volumes of ventricular system subdivisions measured from magnetic resonance images in first-episode schizophrenic patients. Archives of General Psychiatry 1992; 49: 531–537
  • DeLisi LE, Sakuma M, Tew W, Kushner M, Hoff AL, Grimson R. Schizophrenia as a chronic active brain process: A study of progressive brain structural change subsequent to the onset of schizophrenia. Psychiatry Research 1997; 74: 129–140
  • DeLisi LE, Hoff A, Kushner M, Calev A, Stritzke P. Ventricular enlargement at the onset of psychosis is associated with diagnostic outcome. Biological Psychiatry 1992; 32: 199–201
  • Evans DR, Parikh VV, Khan MM, Coussons C, Buckley PF, Mahadik SP. Red blood cell membrane essential fatty acid metabolism in early psychotic patients following antipsychotic drug treatment. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2003; 69: 393–399
  • Fammy C, Streissguth AP, Unis AS. Mental illness in adults with fetal alcohol syndrome or fetal alcohol effects. American Journal of Psychiatry 1998; 155: 552–554
  • Faraci FM, Brian JE, Jr. Nitric oxide and the cerebral circulation. Stroke 1994; 25: 692–703
  • Fenton WS, Hibbelin J, Knable M. Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia. Biological Psychiatry 2000; 47: 8–21
  • Fish B, Marcus J, Hans S, Auerbach JG, Perdue S. Infants at risk for schizophrenia: Sequelae of a genetic neuro-integrative defect. Archives of General Psychiatry 1992; 49: 221–235
  • Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proceedings of the National Academy of Sciences of the United States of America 1989; 86: 6377–6381
  • Garey LJ, Ong WY, Patel TS, Kanani M, Davis A, Mortimer AM, et al. Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. Journal of Neurology, Neurosurgery and Psychiatry 1998; 65: 446–453
  • Gattaz WF, Hubner CK, Nevalainen TJ, Thuren T, Kinnunen PKJ. Increased serum phospholipase A2 activity in schizophrenia: A replication study. Biological Psychiatry 1990; 28: 495–501
  • Gattaz WF, Schmitt A, Athanasios M. Increased platelet phospholipase A2 activity in schizophrenia. Schizophrenia Research 1995; 16: 1–6
  • Gerding LB, Labbate LA, Meason MO, Santos AB, Arano GW. Alcohol dependence and hospitalization in schizophrenia. Schizophrenia Research 1999; 38: 71–75
  • Glen AIM, Glen EMT, Horrobin DF, Vaddadi KS, Spellman M, Morse-Fisher N, et al. A red cell membrane abnormality in a sub-group of schizophrenic patients: Evidence for two diseases. Schizophrenia Research 1994; 12: 53–61
  • Gupta S, Andreasen NC, Arndt S, Flaum M, Schultz SK, Hubbard WC, et al. Neurological soft signs in neuroleptic-naive and neuroleptic treated schizophrenic patients and normal comparison subjects. American Journal of Psychiatry 1995; 152: 191–196
  • Gur RE, Cowell P, Turetsky BI, Gallacher F, Cannon T, Bilker W, et al. A follow-up magnetic resonance imaging study of schizophrenia. Relationship of neuroanatomical changes to clinical and neurobehavioral measures. Archives of General Psychiatry 1998; 55: 145–152
  • Halliwell B, Gutteridge JMC. Antioxidants of human extracellular fluids. Archives of Biochemistry and Biophysics 1990; 280: 1–8
  • Halliwell B. Role of free radicals in the neurodegenerative diseases: Therapeutic implications for antioxidant treatment. Drugs & Aging 2001; 18: 685–716
  • Hanson DR, Gottesman II. Theories of schizophrenia: A genetic-inflammatory-vascular synthesis. BMC Medical Genetics 2005; 11: 6–7
  • Harrison PJ, Weinberger DR. Schizophrenia genes, gene expression, and neuropathology: On the matter of their convergence. Molecular Psychiatry 2005; 10: 40–68
  • Heckers S. Neuropathology of schizophrenia: Cortex, thalamus, basal ganglia, and neurotransmitter-specific projection system. Schizophrenia Bulletin 1997; 23: 403–421
  • Herken H, Uz E, Ozyurt H, Akyol O. Red blood cell nitric oxide levels in patients with schizophrenia. Schizophrenia Research 2001a; 52: 289–290
  • Herken H, Uz E, Ozyurt H, Sogut S, Virit O, Akyol O. Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia. Molecular Psychiatry 2001b; 6: 66–73
  • Ho L, Pasinetti GM, Horrocks LA, Farooqui AA, Horrobin DF, Peet M, et al. Eicosanoid pathways and psychiatric disorders. Biological Psychiatry 2000; 47: 114S
  • Hoffer A, Osmond H, Smythies J. Schizophrenia; a new approach. II. Result of a year's research. The Journal of Mental Science 1954; 100: 29–45
  • Horrobin DF. Is the main problem in free radical damage caused by radiation, oxygen, and other toxins the loss of membrane essential fatty acids rather than the accumulation of toxic materials?. Medical Hypotheses 1991; 35: 23–36
  • Horrobin DF. Schizophrenia as a membrane lipid disorder which is expressed throughout the body. Prostaglandins, Leukotrienes, and Essential Fatty Acids 1996; 55: 3–8
  • Horrobin DF, Manku MS, Hillman S, Glen IAM. Fatty acid levels in brains of schizophrenics and normal controls. Biological Psychiatry 1991; 30: 795–805
  • Horrocks LA, Farooqui AA. Docosahexaenoic acid in the diet: Its importance in maintenance and restoration of neural membrane function. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2004; 70: 361–372
  • Hungund BL, Mahadik SP. Role of gangliosides in behavioral and biochemical actions of alcohol: Cell membrane structure and function. Alcoholism, Clinical and Experimental Research 1993; 17: 329–339
  • Ikemoto A, Nitta A, Furukawa S, Ohishi M, Nakamura A, Fujii Y, et al. Dietary n-3 fatty acid deficiency decreases nerve growth factor content in rat hippocampus. Neuroscience Letters 2000; 285: 99–102
  • Jablensky A, Sartorius N, Ernberg G, Anker M, Korten A, Cooper JE, et al. Schizophrenia: Manifestations, incidence and course in different cultures. A World Health Organization 10-country study. Psychological Medicine. Monograph Supplement 1992; 20: 1–97
  • Jarskog LF, Glantz LA, Gilmore JH, Lieberman JA. Apoptotic mechanisms in the pathophysiology of schizophrenia. Progress in Neuropsychopharmacology & Biological Psychiatry 2005; 29: 846–858
  • Jeding I, Evans PJ, Akanmu D, Dexter D, Spencer JD, Aruoma OI, et al. Characterization of the potential antioxidant and pro-oxidant actions of some neuroleptic drugs. Biochemical Pharmacology 1995; 49: 359–365
  • Karson CN, Griffin WS, Mrak RE, Husain M, Dawson TM, Snyder SH, et al. Nitric oxide synthase (NOS) in schizophrenia: Increases in cerebellar vermis. Molecular and Chemical Neuropathology 1996; 27: 275–284
  • Katila H, Appleberg B, Rimon R. No differences in phospholipase-A2 activity between acute psychiatric patients and controls. Schizophrenia Research 1997; 26: 103–105
  • Keller A, Castellanos FX, Vaituzis AC, Jeffries NO, Giedd JN, Rapoport JL. Progressive loss of cerebellar volume in childhood-onset schizophrenia. American Journal of Psychiatry 2003; 160: 128–133
  • Keshavan MS, Anderson S, Pettegrew JW. Is schizophrenia due to excessive synaptic pruning in the prefrontal cortex? The Feinberg Hypothesis revisited. Journal of Psychiatric Research 1994; 28: 239–265
  • Keshavan MS, Mallinger AG, Pettegrew JW, Dippold C. Erythrocyte membrane phospholipids in psychotic patients. Psychiatry Research 1993; 49: 89–95
  • Khan MM, Evans DR, Gunna V, Scheffer RE, Parikh VV, Mahadik SP. Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with anti-psychotics. Schizophrenia Research 2002; 58: 1–10
  • Kropp S, Kern V, Lange K, Degner D, Hajak G, Kornhuber J, et al. Oxidative stress during treatment with first- and second- generation anti-psychotics. The Journal of Neuropsychiatry and Clinical Neuroscience 2005; 17: 227–231
  • Lane A, Kinsella A, Murphy P, Byrne M, Keenan J, Colgan K, et al. The anthropometric assessment of dysmorphic features in schizophrenia as an index of its developmental origins. Psychological Medicine 1997; 27: 1155–1172
  • Lawrie SM, Abukmeil SS. Brain abnormality in schizophrenia: A systematic and quantitative review of volumetric magnetic resonance imaging studies. The British Journal of Psychiatry 1998; 172: 119–120
  • Lawrie SM, Whalley H, Kestelman JN, Abukmeil SS, Byrne M, Hodges A, et al. Magnetic resonance imaging of brain in people at high risk of developing schizophrenia. Lancet 1999; 353: 30–33
  • Leon JD. Smoking and vulnerability for schizophrenia. Schizophrenia Bulletin 1996; 22: 405–409
  • Li XM, Chan-Forney J, Julio AV, Bennett VL, Shrikhande S, Keegan DL, et al. Differential effects of olanzapine on the gene expression of superoxide dismutase and the low affinity nerve growth factor receptor. Journal of Neuroscience Research 1999; 56: 72–75
  • Lieberman JA. Is schizophrenia a neurodegenerative disorder? A clinical and neurobiological perspective. Biological Psychiatry 1999; 46: 729–739
  • Lieberman J, Bogerts B, Degreef G, Ashtari AJ. Qualitative assessment of brain morphology in acute and chronic schizophrenia. American Journal of Psychiatry 1992; 149: 784–794
  • Lohr JB, Underhill S, Moir S, Jeste DV. Increased indices of free radical activity in the cerebrospinal fluid of patients with tardive dyskinesia. Biological Psychiatry 1990; 28: 535–539
  • Loven DP, James JF, Biggs L, Little KY. Increased manganese-superoxide dismutase superoxide dismutase activity in postmortem brain from neuroleptic-treated psychotic patients. Biological Psychiatry 1996; 40: 230–232
  • Mahadik SP, Evans D. Essential fatty acids in the treatment of schizophrenia. Drugs of Today 1997; 33: 5–17
  • Mahadik SP, Evans D, Lal H. Oxidative stress and role of antioxidant and omega-3 essential fatty acid supplementation in schizophrenia. Progress in Neuropsychopharmacology & Biological Psychiatry 2001; 25: 463–493
  • Mahadik SP, Gowda S. Antioxidants in the treatment of schizophrenia. Drugs of Today 1996; 32: 1–13
  • Mahadik SP, Mukherjee S. Free radical pathology and the antioxidant defense in schizophrenia. Schizophrenia Research 1996; 19: 1–18
  • Mahadik SP, Scheffer RE. Oxidative injury and potential use of antioxidants in schizophrenia. Prostaglandins, Leukotrienes, and Essential Fatty Acids 1996; 55: 45–54
  • Mahadik SP, Mukherjee S, Correnti EE, Scheffer R, Mahadik J. Elevated plasma lipid peroxides at the onset of non-affective psychosis. Biological Psychiatry 1998; 43: 674–679
  • Mahadik SP, Mulchandani M, Hegde MV, Ranjekar PK. Cultural and socioeconomic differences in dietary intake of essential fatty acids and antioxidants: Effects on the outcome. Phospholipid Spectrum Psychiatric Disorders, D Horrobin, AL Glen, M. Peet. Marius Press, Carnforth, UK 1999a; 167
  • Mahadik SP, Sitasawad V, Mulchandani M. Membrane peroxidation and the neuropathology of schizophrenia. Phospholipid Spectrum Psychiatric Disorders, D Horrobin, AL Glen, M. Peet. Marius Press, Carnforth, UK 1999b; 99
  • Margolis RL, Chung D-M, Post RM. Programmed cell death: Implications for neuropsychiatric disorders. Biological Psychiatry 1994; 35: 946–956
  • Mathalon DH, Sullivan EV, Lim KO, Pfefferbaum A. Progressive brain volume changes and the clinical course of schizophrenia in men: A longitudinal magnetic resonance imaging study. Archives of General Psychiatry 2001; 58: 148–157
  • McCreadie RG, MacDonald E, Wiles D, Campbell G, Paterson JR. The Nithsdale Schizophrenia Surveys. XIV: Plasma lipid peroxide and serum vitamin E levels in patients with and without tardive dyskinesia, and in normal subjects. The British Journal of Psychiatry 1995; 167: 610–617
  • McDonald C, Murray RM. Early and late environmental risk factors for schizophrenia. Brain Research. Brain Research Reviews 2000; 31: 130–137
  • Mellor JE, Laugharne JDE, Peet M. Schizophrenic symptoms and dietary intake of n-3 fatty acids. Schizophrenia Research 1995; 18: 85–86
  • Michel TM, Thome J, Martin D, Nara K, Zwerina S, Tatschner T, et al. Cu, Zn- and Mn-superoxide dismutase levels in brains of patients with schizophrenic psychosis. Journal of Neural Transmission 2004; 111: 1191–1201
  • Montague PR, Gancayco CD, Winn MJ, Marchase RB, Friedlander MJ. Role of NO production in NMDA receptor-mediated neurotransmitter release in cerebral cortex. Science 1994; 263: 973–977
  • Morrow JD, Frei B, Longmire AW, Gaziano JM, Lynch SN, Shyr Y, et al. Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers: Smoking as a cause of oxidative damage. The New England Journal of Medicine 1995; 332: 1198–1203
  • Mukherjee S, Mahadik SP, Scheffer R, Correnti EE, Kelkar H. Impaired antioxidant defense at the onset of psychosis. Schizophrenia Research 1996; 19: 19–26
  • Mukherjee S, Mahadik SP, Horrobin DF, Jenkins K, Correnti E, Scheffer R. Membrane fatty acid composition of fibroblasts from schizophrenic patients. Biological Psychiatry 1994; 35: 700
  • Muller DPR. Neurological disease. Antioxidants in Disease Mechanisms and Therapy , H Sies. Academic Press, New York 1997; 557
  • Niznikiewicz M, Kubicki M, Shenton M. Recent structural and functional imaging findings in schizophrenia. Current Opinion in Psychiatry 2003; 16: 123–147
  • Noh JS, Kang HJ, Kim EY, Sohn S, Chung YK, Kim SU, et al. Haloperidol-induced neuronal apoptosis: Role of p38 and c-Jun-NH(2)-terminal protein kinase. Journal of Neurochemistry 2000; 75: 2327–2334
  • Noponen M, Sanfilipo M, Samanich K, Ryer H, Angrist B, Wolkin A, et al. Elevated PLA2 activity in schizophrenics and other psychiatric patients. Biological Psychiatry 1993; 34: 641–649
  • Olanow CW. A radical hypothesis for neurodegeneration. Trends in Neurosciences 1993; 16: 439–444
  • Pall HS, Williams AC, Blake DR, Lunec J. Evidence of enhanced lipid peroxidation in the cerebrospinal fluid of patients taking phenothiazines. Lancet 1987; 2: 596–599
  • Parikh V, Evans DR, Khan MM, Mahadik SP. Nerve growth factor in never-medicated first-episode psychotic and medicated chronic schizophrenic patients: Possible implications for treatment outcome. Schizophrenia Research 2003b; 60: 117–123
  • Parikh V, Khan MM, Mahadik SP. Differential effects of anti-psychotics on expression of antioxidant enzymes and membrane lipid peroxidation in rat brain. Journal of Psychiatric Research 2003a; 37: 43–51
  • Peet M, Horrobin DF, the E-E Multicentre Study Group. A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. Journal of Psychiatric Research 2002; 36: 7–18
  • Peet M, Laugharne J, Rangarajan N, Reynolds GP. Tardive dyskinesia, lipid peroxidation, and sustained amelioration with vitamin E treatment. International Clinical Psychopharmacology 1993; 8: 151–153
  • Peet M, Laugharne JD, Mellor J, Ramchand CN. Essential fatty acid deficiency in erythrocyte membranes from chronic schizophrenic patients, and the clinical effects of dietary supplementation. Prostaglandins, Leukotrienes, and Essential Fatty Acids 1996; 55: 71–75
  • Peet M, Stokes C. Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs 2005; 65: 1051–1059
  • Peet M, Mellor J. Double blind placebo controlled trial of n-3 polyunsaturated fatty acids as an adjunct to neuroleptics. Ninth Schizophrenia Winter Workshop 1998; 54
  • Perkins D, Lieberman J, Gu H, Tohen M, McEvoy J, Green A, et al. Predictors of anti-psychotic treatment response in patients with first-episode schizophrenia, schizoaffective and schizophreniform disorders. The British Journal of Psychiatry 2004; 185: 18–24
  • Pillai A, Parikh V, Terry Jr AV, Mahadik SP. Long-term antipsychotic treatments and crossover studies in rats: Differential effects of typical and atypical agents on the expression of antioxidant enzymes and lipid peroxidation in adult rat brain. Journal of Psychiatric Research, In press
  • Pitsikas N, Algeri S. Deterioration of spatial and nonsocial reference working memory in aged rats: Protective effect of life-long caloric restriction. Neurobiology of Aging 1992; 13: 369–373
  • Pryor WA, Stone K. Oxidants in cigarette smoke: Radicals hydrogen peroxide, peroxinitrate, and peroxinitrate. Annals of the New York Academy of Sciences 1993; 1012: 12–28
  • Psimadas D, Messini-Nikolaki N, Zafiropoulou M, Fortos A, Tsilimigaki S, Piperakis SM. DNA damage and repair efficiency in lymphocytes from schizophrenic patients. Cancer Letters 2004; 204: 33–40
  • Rafalowska U, Liu G-J, Floyd RA. Peroxidation induced changes in synaptosomal transport of dopamine and γ-aminobutyric acid. Free Radical Biology & Medicine 1989; 6: 485–492
  • Ramirez J, Garnica R, Boll MC, Montes S, Rios C. Low concentration of nitrite and nitrate in the cerebrospinal fluid from schizophrenic patients: A pilot study. Schizophrenia Research 2004; 68: 357–361
  • Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, et al. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Research 2003; 121: 109–122
  • Reddy R, Keshavan M, Yao JK. Reduced plasma antioxidants in first-episode patients with schizophrenia. Schizophrenia Research 2003; 62: 205–212
  • Reddy R, Yao J. Free radical pathology in schizophrenia: A review. Prostaglandins, Leukotrienes, and Essential Fatty Acids 1996; 55: 33–43
  • Reddy R, Mahadik SP, Mukherjee S, Murthy JN. Enzymes of the antioxidant defense system in chronic schizophrenic patients. Biological Psychiatry 1991; 30: 309–312
  • Reiter RJ. Oxidative processes and anti-oxidative defense mechanisms in the aging brain. The FASEB Journal 1995; 9: 526–533
  • Rice-Evans CA, Diplock AT. Current status of antioxidant therapy. Free Radical Biology & Medicine 1993; 15: 77–96
  • Ross BM, Hudson C, Erlich J, Warsh JJ, Kish SJ. Increased phospholipid breakdown in schizophrenia: Evidence for the involvement of a calcium-dependent phospholipase A2. Archives of General Psychiatry 1997; 54: 487–494
  • Rotrosen J, Wolkin A. Phospholipid and prostaglandin hypotheses of schizophrenia. Psychopharmacology: The Third Generation of Progress, HY Meltzer. Raven Press, New York 1987; 759
  • Roy D, Pathak DN, Singh R. Effects of chlorpromazine on the activities of antioxidant enzymes and lipid peroxidation in the various regions of aging rat brain. Journal of Neurochemistry 1984; 42: 628–633
  • Scheffer RD, Bradley J, Mahadik SP. Elevated lipid peroxidation and phospholipase A2: Possible mechanism of the lower cell membrane essential polyunsaturated fatty acids in schizophrenia. Biological Psychiatry 1999; 43: 101
  • Schwartz RD, Skolnick P, Paul SM. Regulation of gamma-aminobutyric acid/barbiturate receptor gated chloride ion flux in brain vesicles by phospholipase A2: Possible role of oxygen radicals. Journal of Neurochemistry 1988; 50: 565–571
  • Selemon LD, Rajkowska G, Goldman-Rakic PS. Abnormally high neuronal density in the schizophrenic cortex. Archives of General Psychiatry 1995; 52: 805–818
  • Senitz D, Winkelmann E. Neuronal structure abnormality in the orbito-frontal cortex of schizophrenics. Journal fur Hirnforschung 1991; 32: 149–158
  • Shah S, Vankar GK, Telang SD, Ramchand CN, Peet M. Eicosapentaenoic acid (EPA) as an adjunct in the treatment of schizophrenia. Schizophrenia Research 1998; 29: 158
  • Shriqui CL, Bradjewejn J, Annable L, Jones BD. Vitamin E in the treatment of tardive dyskinesia: A double-blind placebo-controlled study. American Journal of Psychiatry 1992; 149: 391–393
  • Simopoulos AP. Omega-3 fatty acids in health and disease, and in growth and development. The American Journal of Clinical Nutrition 1991; 54: 438–463
  • Smalheiser NR, Swanson DR. Calcium-dependent phospholipase A2 and schizophrenia. Letter to the Editor. Archives of General Psychiatry 1998; 55: 752–753
  • Sohal RS, Ku H-H, Agarwal S, Forster MJ, Lal H. Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging, and in response to food restriction in the mouse. Mechanisms of Ageing and Development 1994; 74: 121–133
  • Strassnig M, Brar JS, Ganguli R. Nutritional assessment of patients with schizophrenia: A preliminary study. Schizophrenia Bulletin 2003; 29: 393–397
  • Suboticanec K, Folnegovic V, Korbar M, Mestrovic B, Buzina R. Vitamin C status in chronic schizophrenia. Biological Psychiatry 1990; 28: 959–966
  • Suddath RL, Christison GW, Torrey EF, Casanova MF, Weinberger DR. Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. The New England Journal of Medicine 1990; 322: 789–794
  • Taneli F, Pirildar S, Akdeniz F, Uyanik BS, Ari Z. Serum nitric oxide metabolite levels and the effect of antipsychotic therapy in schizophrenia. Archives of Medical Research 2004; 35: 401–405
  • Tsai G, Goff DC, Chang RW, Flood J, Baer L, Coyle JT. Markers of glutaminergic neurotransmission and oxidative stress associated with tardive dyskinesia. American Journal of Psychiatry 1998; 155: 1207–1213
  • Urakubo A, Jarskog LF, Lieberman JA, Gilmore JH. Prenatal exposure to maternal infection alters cytokine expression in the placenta, amniotic fluid, and fetal brain. Schizophrenia Research 2001; 47: 27–36
  • Vaddadi KS, Courtney P, Gilleard CJ, Manku MS, Horrobin DF. A double-blind trial of essential fatty acids supplementation in patients with tardive dyskinesia. Psychiatry Research 1989; 27: 313–323
  • Van Den Berg JJM, Op Den Kamp JAF, Lubin BH, Kuypers FA. Conformational changes in oxidized phospholipids and their preferential hydrolysis by phospholipase A2: A monolayer study. Biochemistry 1993; 32: 4962–4967
  • Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Archives of General Psychiatry 1987; 44: 660–669
  • Weinberger DR, Berman KF, Zec RF. Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. Archives of General Psychiatry 1986; 43: 114–124
  • Wood KA, Youle RJ. Apoptosis and free radicals. Annals of the New York Academy of Sciences 1994; 738: 400–407
  • Wu A, Ying Z, Gomez-Pinilla F. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. Journal of Neurotrauma 2004; 21: 1457–1467
  • Wyatt RJ. Early intervention of schizophrenia: Can the course of the illness be altered?. Biological Psychiatry 1995; 38: 1–3
  • Yao JK, Leonard S, Reddy RD. Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients. Schizophrenia Research 2000a; 42: 7–17
  • Yao JK, Leonard S, Reddy RD. Increased nitric oxide radicals in postmortem brain from patients with schizophrenia. Schizophrenia Bulletin 2004; 30: 923–934
  • Yao JK, Reddy R, McElhinny LG, van Kammen DP. Effects of haloperidol on antioxidant defense system enzymes in schizophrenia. Journal of Psychiatric Research 1998a; 32: 385–391
  • Yao JK, Reddy R, van Kammen DP. Abnormal age-related changes of plasma antioxidant proteins in schizophrenia. Psychiatry Research 2000b; 97: 137–151
  • Yao JK, Reddy R, van Kammen DP. Reduced level of plasma antioxidant uric acid in schizophrenia. Psychiatry Research 1998b; 80: 29–39
  • Yao JK, Reddy RD, van Kammen DP. Oxidative damage and schizophrenia: An overview of the evidence and its therapeutic implications. CNS Drugs 2001; 15: 287–310
  • Yao JK, van Kammen DP, Welker JA. Red cell membrane dynamics in schizophrenia. II. Fatty acid composition. Schizophrenia Research 1994; 13: 217–226
  • Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY. Elevated blood superoxide dismutase in neuroleptic-free schizophrenia: Association with positive symptoms. Psychiatry Research 2003; 117: 85–88

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.