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Nutritional Neuroscience
An International Journal on Nutrition, Diet and Nervous System
Volume 23, 2020 - Issue 2
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Improvement of cognitive function in schizophrenia with N-acetylcysteine: A theoretical review

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References

  • Saha S, Chant D, Welham J, McGrath J. A systematic review of the prevalence of schizophrenia. PLoS Med 2005;2(5):e141.
  • Brekke J, Kay DD, Lee KS, Green MF. Biosocial pathways to functional outcome in schizophrenia. Schizophr Res 2005;80(2–3):213–25.
  • Haro JM, Edgell ET, Frewer P, Alonso J, Jones PB. The European schizophrenia outpatient health outcomes study: baseline findings across country and treatment. Acta Psychiatr Scand 2003;107:7–15.
  • Schennach-Wolff R, Jager M, Seemuller F, Obermeier M, Messer T, Laux G, et al. Defining and predicting functional outcome in schizophrenia and schizophrenia spectrum disorders. Schizophr Res 2009;113(2–3):210–7.
  • Fett AK, Viechtbauer W, Dominguez MD, Penn DL, van Os J, Krabbendam L. The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neurosci Biobehav Rev 2011;35(3):573–88.
  • Gopalakrishnan R, Behere RV, Sharma PS. Factors affecting well-being and socio-occupational functioning in schizophrenia patients following an acute exacerbation: a hospital based observational study. Indian J Psychol Med 2015;37(4):423–8.
  • Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 1996;153(3):321–9.
  • Lipkovich IA, Deberdt W, Csernansky JG, Sabbe B, Keefe RS, Kollack-Walker S. Relationships among neurocognition, symptoms and functioning in patients with schizophrenia: a path-analytic approach for associations at baseline and following 24 weeks of antipsychotic drug therapy. BMC Psychiatry 2009;9(44):1–12.
  • Han M, Zhang XY, Chen DC, Tan YL, Song CS, Yu YH, et al. Cognitive differences in schizophrenia on long-term treatments with clozapine, risperidone and typical antipsychotics. Int Clin Psychopharmacol 2015;30(2):89–95.
  • Swartz MS, Stroup TS, McEvoy JP, Davis SM, Rosenheck RA, Keefe RS, et al. What CATIE found: results from the schizophrenia trial. Psychiatr Serv 2008;59(5):500–6.
  • Goldberg TE, Goldman RS, Burdick KE, Malhotra AK, Lencz T, Patel RC, et al. Cognitive improvement after treatment with second-generation antipsychotic medications in first-episode schizophrenia: is it a practice effect? Arch Gen Psychiatry 2007;64(10):1115–22.
  • Kahn RS, Keefe RS. Schizophrenia is a cognitive illness: time for a change in focus. JAMA Psychiatry 2013;70(10):1107–12.
  • Newton DF, Naiberg MR, Goldstein BI. Oxidative stress and cognition amongst adults without dementia or stroke: implications for mechanistic and therapeutic research in psychiatric disorders. Psychiatry Res 2015;227(2–3):127–34.
  • 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 Res 2003;121(2):109–22.
  • Higuchi Y. Chromosomal DNA fragmentation in apoptosis and necrosis induced by oxidative stress. Biochem Pharmacol 2003;66(8):1527–35.
  • Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol 1997;82(2):191–295.
  • Dringen R, Hirrlinger J. Glutathione pathways in the brain. Biological Chem 2003;384(4):505–16.
  • Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr 2004;134(4):489–92.
  • Bains JS, Shaw CA. Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Reviews 1997;25:335–58.
  • Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, et al. N-acetyl cysteine as a glutathione precursor for schizophrenia – a double-blind, randomized, placebo-controlled trial. Biol Psychiatry 2008;64(5):361–8.
  • Lavoie S, Murray MM, Deppen P, Knyazeva MG, Berk M, Boulat O, et al. Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients. Neuropsychopharmacology 2008;33(9):2187–99.
  • Singh SP, Singh V. Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia. CNS Drugs 2011;25(10):859–85.
  • Addington J, Addington D. Cognitive functioning in first-episode schizophrenia. J Psychiatry Neurosci 2002;27(3):188–92.
  • Nuechterlein KH, Subotnik KL, Green MF, Ventura J, Asarnow RF, Gitlin MJ, et al. Neurocognitive predictors of work outcome in recent-onset schizophrenia. Schizophr Bull 2011;37(Suppl 2):S33–S40.
  • Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 1998;12(3):426–45.
  • Tolman AW, Kurtz MM. Neurocognitive predictors of objective and subjective quality of life in individuals with schizophrenia: a meta-analytic investigation. Schizophr Bull 2012;38(2):304–15.
  • Mesholam-Gately RI, Goff KP, Faraone SV, Seidman LJ, Guiliano AJ. Supplemental material for neurocognition in first-episode schizophrenia: A meta-analytic review. Neuropsychology 2009;23(3):315–36.
  • Matsui M, Sumiyoshi T, Arai H, Higuchi Y, Kurachi M. Cognitive functioning related to quality of life in schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 2008;32(1):280–7.
  • Narvaez JM, Twamley EW, McKibbin CL, Heaton RK, Patterson TL. Subjective and objective quality of life in schizophrenia. Schizophr Res 2008;98(1–3):201–8.
  • Green MF, Nuechterlein KH, Gold JM, Barch DM, Cohen J, Essock S, et al. Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria. Biol Psychiatry 2004;56(5):301–7.
  • Keefe RS, Fenton WS. How should DSM-V criteria for schizophrenia include cognitive impairment? Schizophr Bull 2007;33(4):912–20.
  • Mde G D, Viechtbauer W, Simons CJ, van Os J, Krabbendam L. Are psychotic psychopathology and neurocognition orthogonal? A systematic review of their associations. Psychol Bull 2009;135(1):157–71.
  • Van Oel CJ, Sitskoorn MM, Cremer MPM, Kahn RS. School performance as a premorbid marker for schizophrenia: a twin study. Schizophr Bull 2002;28(3):401–14.
  • Harvey PD. Cognitive and functional impairments in elderly patients with schizophrenia: a review of the recent literature. Harv Rev Psychiatry 2001;9:59–68.
  • Jeste DV, Twamley EW, Eyler Zorrilla LT, Golshan S, Patterson TL, Palmer BW. Aging and outcome in schizophrenia. Acta Psychiatr Scand 2003;107:336–43.
  • Elvevåg B, Goldberg TE. Cognitive impairment in schizophrenia is the core of the disorder. Crit Rev Neurobiol 2000;14(1):1–21.
  • Unschuld PG, Buchholz AS, Varvaris M, van Zijl PC, Ross CA, Pekar JJ, et al. Prefrontal brain network connectivity indicates degree of both schizophrenia risk and cognitive dysfunction. Schizophr Bull 2014;40(3):653–64.
  • Sakurai H, Bies RR, Stroup ST, Keefe RS, Rajji TK, Suzuki T, et al. Dopamine D2 receptor occupancy and cognition in schizophrenia: analysis of the CATIE data. Schizophr Bull 2013;39(3):564–74.
  • Carruthers SP, Gurvich CT, Rossell SL. The muscarinic system, cognition and schizophrenia. Neurosci Biobehav Rev 2015;55:393–402.
  • Mulero J, Zafrilla P, Martinez-Cacha A. Oxidative stress, frailty and cognitive decline. J Nutr Health Aging 2011;15(9):756–60.
  • Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science 1996;273:59–63.
  • Praticὸ D, Clark CM, Liun F, Lee VYM, Rokach J, Trojanowski JQ. Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch Neurol 2002;59:972–6.
  • Benzi G, Moretti A. Age and peroxidative stress-related modifications of the cerebral enzymatic activities linked to mitochondria and the glutathione system. Free Radic Biol Med 1995;19(1):77–101.
  • Jenner P, Dexter DT, Sian J, Schapira AHV, Marsden CD. Oxidative stress as a cause of nigral cell death in Parkinson’s disease and incidental Lewy body disease. Ann Neurol 1992;32:S82–S7.
  • Kim HA, Miller AA, Drummond GR, Thrift AG, Arumugam TV, Phan TG, et al. Vascular cognitive impairment and Alzheimer’s disease: role of cerebral hypoperfusion and oxidative stress. Naunyn Schmiedebergs Arch Pharmacol 2012;385(10):953–9.
  • Talarowska M, Galecki P, Maes M, Gardner A, Chamielec M, Orzechowska A, et al. Malondialdehyde plasma concentration correlates with declarative and working memory in patients with recurrent depressive disorder. Mol Biol Rep 2012;39(5):5359–66.
  • Martinez-Cengotitabengoa M, Mac-Dowell KS, Leza JC, Mico JA, Fernandez M, Echevarria E, et al. Cognitive impairment is related to oxidative stress and chemokine levels in first psychotic episodes. Schizophr Res 2012;137(1–3):66–72.
  • Zhang XY, Chen DC, Tan YL, Tan SP, Wang ZR, Yang FD, et al. The interplay between BDNF and oxidative stress in chronic schizophrenia. Psychoneuroendocrinology 2015;51:201–8.
  • Choi YB, Lipton SA. Redox modulation of the NMDA receptor. Cell Mol Life Sci 2000;57:1535–41.
  • Coyle JT. Glutamate and schizophrenia: beyond the dopamine hypothesis. Cell Mol Neurobiol 2006;26(4–6):363–84.
  • Zavodnick AD, Ali R. N-acetylcysteine and metabotropic glutamate receptors: implications for the treatment of schizophrenia: a literature review. Psychiatr Q 2014;85(2):177–85.
  • Slack SE, Pezet S, McMahon SB, Thompson SWN, Malcangio M. Brain-derived neurotrophic factor induces NMDA receptor subunit one phosphorylation via ERK and PKC in the rat spinal cord. Eur J Neurosci 2004;20(7):1769–78.
  • Emiliani FE, Sedlak TW, Sawa A. Oxidative stress and schizophrenia: recent breakthroughs from an old story. Curr Opin Psychiatry 2014;27(3):185–190.
  • Othmen BL, Mechri A, Fendri C, Bost M, Chazot G, Gaha L, et al. Altered antioxidant defense system in clinically stable patients with schizophrenia and their unaffected siblings. Prog Neuropsychopharmacol Biol Psychiatry 2008;32(1):155–9.
  • Yao JK, Leonard S, Reddy R. Altered glutathione redox state in schizophrenia. Dis Markers 2006;22:83–93.
  • Zhang XY, Zhou DF, Shen YC, Zhang PY, Zhang WF, Liang J, et al. Effects of risperidone and haloperidol on superoxide dismutase and nitric oxide in schizophrenia. Neuropharmacology 2012;62(5–6):1928–34.
  • Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol 2008;11(6):851–76.
  • Yao JK, Reddy R. Oxidative stress in schizophrenia: pathogenetic and therapeutic implications. Antioxid Redox Signal 2011;15(7):1999–2002.
  • Zhang XY, Tan YL, Cao LY, Wu GY, Xu Q, Shen Y, et al. Antioxidant enzymes and lipid peroxidation in different forms of schizophrenia treated with typical and atypical antipsychotics. Schizophr Res 2006;81(2–3):291–300.
  • Flatow J, Buckley P, Miller BJ. Meta-analysis of oxidative stress in schizophrenia. Biol Psychiatry 2013;74(6):400–9.
  • Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13(2):261–76.
  • Do KQ, Trabesinger AH, Kirsten-Krüger M, Lauer CJ, Dydak U, Hell D, et al. Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J of Neuroscience 2000;12:3721–8.
  • Matsuzawa D, Obata T, Shirayama Y, Nonaka H, Kanazawa Y, Yoshitome E, et al. Negative correlation between brain glutathione level and negative symptoms in schizophrenia: a 3T 1H-MRS study. PLoS One 2008;3(4):e1944.
  • Wood SJ, Berger GE, Wellard RM, Proffitt TM, McConchie M, Berk M, et al. Medial temporal lobe glutathione concentration in first episode psychosis: a 1H-MRS investigation. Neurobiol Dis 2009;33(3):354–7.
  • Mukherjee S, Mahadik SP, Scheffer R, Correnti EE, Kelkar H. Impaired antioxidant defense at the onset of psychosis. Schizophr Res 1996;19:19–26.
  • Gonzalez-Liencres C, Tas C, Brown EC, Erdin S, Onur E, Cubukcoglu Z, et al. Oxidative stress in schizophrenia: a case-control study on the effects on social cognition and neurocognition. BioMed Central 2014;14:268–88.
  • Dean O, van den Buuse M, Berk M, Copolov DL, Mavros C, Bush A. N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and d-amphetamine-treated rats: relevance to schizophrenia and bipolar disorder. Neurosci Lett 2011;499(3):149–53.
  • Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine – a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol 2007;7(4):355–9.
  • Berk M, Malhi GS, Gray LJ, Dean OM. The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci 2013;34(3):167–77.
  • Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther 2014;141(2):150–9.
  • Deepmala SJ, Kumar N, Delhey L, Berk M, Dean O, et al. Clinical trials of N-acetylcysteine in psychiatry and neurology: a systematic review. Neurosci Biobehav Rev 2015;55:294–321.
  • Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med 1989;6(6):593–7.
  • Bošković M, Vovk T, Grabnar I, Plesničar BK. Oxidative stress in schizophrenia. Curr Neuropharmacol 2011;9(2):301–12.
  • Zhang XY, Chen da C, Xiu MH, Tang W, Zhang F, Liu L, et al. Plasma total antioxidant status and cognitive impairments in schizophrenia. Schizophr Res 2012;139(1–3):66–72.
  • Farokhnia M, Azarkolah A, Adinehfar F, Khodaie-Ardakani MR, Hosseini SM, Yekehtaz H, et al. N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol 2013;36(6):185–92.
  • Conus P, Seidman LJ, Fournier M, Xin L, Cleusix M, Baumann PS, et al. N-acetylcysteine in a double-blind randomized placebo-controlled trial: toward biomarker-guided treatment in early psychosis. Schizophr Bull 2017;44(2):317–27.
  • Rapado-Castro M, Berk M, Venugopal K, Bush AI, Dodd S, Dean OM. Towards stage specific treatments: effects of duration of illness on therapeutic response to adjunctive treatment with N-acetyl cysteine in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2015;57:69–75.
  • Michie PT. What has MMN revealed about the auditory system in schizophrenia? Int J of Psychophysiol 2001;42(2):177–94.
  • Turetsky BI, Calkins ME, Light GA, Olincy A, Radant AD, Swerdlow NR. Neurophysiological endophenotypes of schizophrenia: the viability of selected candidate measures. Schizophr Bull 2006;33(1):69–94.
  • Butler PD, Javitt DC. Early-stage visual processing deficits in schizophrenia. Curr Opin Psychiatry 2005;18(2):151–7.
  • Javitt DC, Liederman E, Cienfuegos A, Shelley AM. Panmodal processing imprecision as a basis for dysfunction of transient memory storage systems in schizophrenia. Schizophr Bull 1999;25:763–75.
  • Neill E, Rossell SL. Executive functioning in schizophrenia: the result of impairments in lower order cognitive skills? Schizophr Res 2013;150(1):76–80.
  • Chatterjee A. Reduced glutathione: a radioprotector or a modulator of DNA-repair activity? Nutrients 2013;5(2):525–42.
  • Bulut M, Savas HA, Altindag A, Virit O, Dalkilic A. Beneficial effects of N-acetylcysteine in treatment resistant schizophrenia. World J Biol Psychiatry 2009;10(4 Pt 2):626–8.
  • Dean O, Giorlando F, Berk M. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci 2011;36(2):78–86.
  • Keller WR, Kum LM, Wehring HJ, Koola MM, Buchanan RW, Kelly DL. A review of anti-inflammatory agents for symptoms of schizophrenia. J Psychopharmacol 2013;27(4):337–42.
  • Arakawa M, Ito Y. N-acetylcysteine and neurodegenerative diseases: basic and clinical pharmacology. Cerebellum 2007;6(4):308–14.
  • Chen G, Shi J, Hu Z, Hang C. Inhibitory effect on cerebral inflammatory response following traumatic brain injury in rats: a potential neuroprotective mechanism of N-acetylcysteine. Mediators Inflamm 2008: Article ID 716458. p. 8.
  • Hope S, Melle I, Aukrust P, Agartz I, Lorentzen S, Steen NE, et al. Osteoprotegerin levels in patients with severe mental disorders. J Psychiatry Neurosci 2010;35(5):304–10.
  • Mufaddel AA, Osman OT, Al-Hassani G, Al-Bedwawi S, Hashim MJ. Basal ganglia calcification in psychiatric inpatients: a case-control study. Cogn and Behav Neurol 2016;29(3):139–43.
  • Marinescu I, Udriştoiu I, Marinescu D. Choroid plexus calcification: clinical, neuroimaging and histopathological correlations in schizophrenia. Rom J Morphol Embryol 2013;54(2):365–9.
  • Bersani G, Garavini A, Taddei I, Tanfani G, Nordio M, Pancheri P. Computed tomography study of pineal calcification in schizophrenia. Eur Psychiatry 1999;14(3):163–6.
  • Sandyk R. The relationship of thought disorder to third ventricle width and calcification of the pineal gland in chronic schizophrenia. Int J of Neurosci 1993;68:53–9.
  • Pasch A, Schaffner T, Huynh-Do U, Frey BM, Frey FJ, Farese S. Sodium thiosulfate prevents vascular calcifications in uremic rats. Kidney Int 2008;74(11):1444–53.
  • Subhash N, Sriram R, Kurian GA. Sodium thiosulfate protects brain in rat model of adenine induced vascular calcification. Neurochem Int 2015;90:193–203.

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