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Cognitive effects of adjunctive N-acetyl cysteine in psychosis

Published online by Cambridge University Press:  29 November 2016

M. Rapado-Castro ,
S. Dodd ,
A. I. Bush ,
G. S. Malhi ,
D. R. Skvarc ,
Z. X. On ,
M. Berk  and
O. M. Dean
M. Rapado-Castro
Affiliation:
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain Department of Psychiatry, Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, 161 Barry Street, Carlton South, Victoria, Australia Orygen, The National Centre of Excellence in Youth Mental Health, Victoria, Australia
S. Dodd
Affiliation:
Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, PO Box 291, Geelong, Victoria,Australia Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville, Victoria,Australia
A. I. Bush
Affiliation:
Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville, Victoria,Australia
G. S. Malhi
Affiliation:
Academic Department of Psychiatry, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, Australia Sydney Medical School Northern, University of Sydney, NSW, Australia CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia
D. R. Skvarc
Affiliation:
Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, PO Box 291, Geelong, Victoria,Australia
Z. X. On
Affiliation:
Melbourne School of Psychological Sciences, University of Melbourne, Level 12, Redmond Barry Building 115, Parkville, Victoria, Australia
M. Berk*
Affiliation:
Orygen, The National Centre of Excellence in Youth Mental Health, Victoria, Australia Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, PO Box 291, Geelong, Victoria,Australia Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville, Victoria,Australia Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria, Australia
O. M. Dean
Affiliation:
Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, PO Box 291, Geelong, Victoria,Australia Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville, Victoria,Australia Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria, Australia
*
*Address for correspondence: M. Berk, Deakin University, PO Box 281, Geelong, VIC 3220, Australia. (Email: mikebe@barwonhealth.org.au)
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Abstract

Background

Cognitive deficits are predictors of functional outcome in patients with psychosis. While conventional antipsychotics are relatively effective on positive symptoms, their impact on negative and cognitive symptoms is limited. Recent studies have established a link between oxidative stress and neurocognitive deficits in psychosis. N-acetylcysteine (NAC), a glutathione precursor with glutamatergic properties, has shown efficacy on negative symptoms and functioning in patients with schizophrenia and bipolar disorder, respectively. However, there are few evidence-based approaches for managing cognitive impairment in psychosis. The present study aims to examine the cognitive effects of adjunctive NAC treatment in a pooled subgroup of participants with psychosis who completed neuropsychological assessment in two trials of both schizophrenia and bipolar disorder.

Method

A sample of 58 participants were randomized in a double fashion to receive 2 g/day of NAC (n = 27) or placebo (n = 31) for 24 weeks. Attention, working memory and executive function domains were assessed. Differences between cognitive performance at baseline and end point were examined using Wilcoxon's test. The Mann–Whitney test was used to examine the differences between the NAC and placebo groups at the end point.

Results

Participants treated with NAC had significantly higher working memory performance at week 24 compared with placebo (U = 98.5, p = 0.027).

Conclusions

NAC may have an impact on cognitive performance in psychosis, as a significant improvement in working memory was observed in the NAC-treated group compared with placebo; however, these preliminary data require replication. Glutamatergic compounds such as NAC may constitute a step towards the development of useful therapies for cognitive impairment in psychosis.

Keywords

CognitionglutathioneN-acetyl cysteinepsychosisworking memory
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 5 , April 2017 , pp. 866 - 876
Copyright
Copyright © Cambridge University Press 2016 

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Footnotes

† Equally contributing authors.

References

Adair, JC, Knoefel, JE, Morgan, N (2001). Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease. Neurology 57, 1515–1517.CrossRefGoogle ScholarPubMed
Amen, DG, Taylor, DV, Ojala, K, Kaur, J, Willeumier, K (2013). Effects of brain-directed nutrients on cerebral blood flow and neuropsychological testing: a randomized, double-blind, placebo-controlled, crossover trial. Advances in Mind–Body Medicine 27, 24–33.Google ScholarPubMed
Amen, DG, Wu, JC, Taylor, D, Willeumier, K (2011). Reversing brain damage in former NFL players: implications for traumatic brain injury and substance abuse rehabilitation. Journal of Psychoactive Drugs 43, 1–5.CrossRefGoogle ScholarPubMed
Arango, C, Fraguas, D, Parellada, M (2014). Differential neurodevelopmental trajectories in patients with early-onset bipolar and schizophrenia disorders. Schizophrenia Bulletin 40 (Suppl. 2), S138–S146.CrossRefGoogle ScholarPubMed
Bang, M, Kim, KR, Song, YY, Baek, S, Lee, E, An, SK (2015). Neurocognitive impairments in individuals at ultra-high risk for psychosis: who will really convert? Australian and New Zealand Journal of Psychiatry 49, 462–470.CrossRefGoogle ScholarPubMed
Banks, PJ, Warburton, EC, Brown, MW, Bashir, ZI (2014). Mechanisms of synaptic plasticity and recognition memory in the perirhinal cortex. Progress in Molecular Biology and Translational Science 122, 193–209.CrossRefGoogle ScholarPubMed
Bauer, IE, Pascoe, MC, Wollenhaupt-Aguiar, B, Kapczinski, F, Soares, JC (2014). Inflammatory mediators of cognitive impairment in bipolar disorder. Journal of Psychiatric Research 56, 18–27.CrossRefGoogle ScholarPubMed
Berk, M, Copolov, D, Dean, O, Lu, K, Jeavons, S, Schapkaitz, I, Anderson-Hunt, M, Judd, F, Katz, F, Katz, P, Ording-Jespersen, S, Little, J, Conus, P, Cuenod, M, Do, KQ, Bush, AI (2008 a). N-acetyl cysteine as a glutathione precursor for schizophrenia – a double-blind, randomized, placebo-controlled trial. Biological Psychiatry 64, 361–368.CrossRefGoogle ScholarPubMed
Berk, M, Copolov, DL, Dean, O, Lu, K, Jeavons, S, Schapkaitz, I, Anderson-Hunt, M, Bush, AI (2008 b). N-acetyl cysteine for depressive symptoms in bipolar disorder – a double-blind randomized placebo-controlled trial. Biological Psychiatry 64, 468–475.CrossRefGoogle ScholarPubMed
Berk, M, Malhi, GS, Gray, LJ, Dean, OM (2013). The promise of N-acetylcysteine in neuropsychiatry. Trends in Pharmacological Sciences 34, 167–177.CrossRefGoogle ScholarPubMed
Berk, M, Munib, A, Dean, O, Malhi, GS, Kohlmann, K, Schapkaitz, I, Jeavons, S, Katz, F, Anderson-Hunt, M, Conus, P, Hanna, B, Otmar, R, Ng, F, Copolov, DL, Bush, AI (2011). Qualitative methods in early-phase drug trials: broadening the scope of data and methods from an RCT of N-acetylcysteine in schizophrenia. Journal of Clinical Psychiatry 72, 909–913.CrossRefGoogle ScholarPubMed
Berk, M, Ng, F, Dean, O, Dodd, S, Bush, AI (2008 c). Glutathione: a novel treatment target in psychiatry. Trends in Pharmacological Sciences 29, 346–351.CrossRefGoogle ScholarPubMed
Bombin, I, Mayoral, M, Castro-Fornieles, J, Gonzalez-Pinto, A, de la Serna, E, Rapado-Castro, M, Barbeito, S, Parellada, M, Baeza, I, Graell, M, Paya, B, Arango, C (2013). Neuropsychological evidence for abnormal neurodevelopment associated with early-onset psychoses. Psychological Medicine 43, 757–768.CrossRefGoogle ScholarPubMed
Bora, E, Pantelis, C (2015). Meta-analysis of cognitive impairment in first-episode bipolar disorder: comparison with first-episode schizophrenia and healthy controls. Schizophrenia Bulletin 41, 1095–1104.CrossRefGoogle ScholarPubMed
Bora, E, Yucel, M, Pantelis, C (2009). Cognitive functioning in schizophrenia, schizoaffective disorder and affective psychoses: meta-analytic study. British Journal of Psychiatry 195, 475–482.CrossRefGoogle ScholarPubMed
Bulut, M, Savas, HA, Altindag, A, Virit, O, Dalkilic, A (2009). Beneficial effects of N-acetylcysteine in treatment resistant schizophrenia. World Journal of Biological Psychiatry 10, 626–628.CrossRefGoogle ScholarPubMed
Carmeli, C, Knyazeva, MG, Cuenod, M, Do, KQ (2012). Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial. PLOS ONE 7, e29341.CrossRefGoogle ScholarPubMed
Chan, A, Paskavitz, J, Remington, R, Rasmussen, S, Shea, TB (2008). Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer's disease: a 1-year, open-label pilot study with an 16-month caregiver extension. American Journal of Alzheimer's Disease and Other Dementias 23, 571–585.CrossRefGoogle ScholarPubMed
Chan, A, Remington, R, Kotyla, E, Lepore, A, Zemianek, J, Shea, TB (2010). A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia. Journal of Nutrition, Health and Aging 14, 224–230.CrossRefGoogle ScholarPubMed
Choy, KH, Dean, O, Berk, M, Bush, AI, van den Buuse, M (2010). Effects of N-acetyl-cysteine treatment on glutathione depletion and a short-term spatial memory deficit in 2-cyclohexene-1-one-treated rats. European Journal of Pharmacology 649, 224–228.CrossRefGoogle Scholar
Daban, C, Martinez-Aran, A, Torrent, C, Tabares-Seisdedos, R, Balanza-Martinez, V, Salazar-Fraile, J, Selva-Vera, G, Vieta, E (2006). Specificity of cognitive deficits in bipolar disorder versus schizophrenia. A systematic review. Psychotherapy and Psychosomatics 75, 72–84.CrossRefGoogle ScholarPubMed
Daglas, R, Yucel, M, Cotton, S, Allott, K, Hetrick, S, Berk, M (2015). Cognitive impairment in first-episode mania: a systematic review of the evidence in the acute and remission phases of the illness. International Journal of Bipolar Disorders 3, 9.CrossRefGoogle Scholar
Davis, J, Moylan, S, Harvey, BH, Maes, M, Berk, M (2014). Neuroprogression in schizophrenia: pathways underpinning clinical staging and therapeutic corollaries. Australian and New Zealand Journal of Psychiatry 48, 512–529.CrossRefGoogle ScholarPubMed
Dean, O, Giorlando, F, Berk, M (2011). N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. Journal of Psychiatry and Neuroscience 36, 78–86.CrossRefGoogle ScholarPubMed
Dean, OM, Bush, AI, Copolov, DL, Kohlmann, K, Jeavons, S, Schapkaitz, I, Anderson-Hunt, M, Berk, M (2012). Effects of N-acetyl cysteine on cognitive function in bipolar disorder. Psychiatry and Clinical Neurosciences 66, 514–517.CrossRefGoogle ScholarPubMed
Debnath, M, Venkatasubramanian, G, Berk, M (2015). Fetal programming of schizophrenia: select mechanisms. Neuroscience and Biobehavioral Reviews 49, 90–104.CrossRefGoogle ScholarPubMed
Deepmala, , Slattery, J, Kumar, N, Delhey, L, Berk, M, Dean, O, Spielholz, C, Frye, R (2015). Clinical trials of N-acetylcysteine in psychiatry and neurology: a systematic review. Neuroscience and Biobehavioral Reviews 55, 294–321.CrossRefGoogle ScholarPubMed
Dodd, S, Maes, M, Anderson, G, Dean, OM, Moylan, S, Berk, M (2013). Putative neuroprotective agents in neuropsychiatric disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry 42, 135–145.CrossRefGoogle ScholarPubMed
Driesen, NR, McCarthy, G, Bhagwagar, Z, Bloch, MH, Calhoun, VD, D'Souza, DC, Gueorguieva, R, He, G, Leung, HC, Ramani, R, Anticevic, A, Suckow, RF, Morgan, PT, Krystal, JH (2013). The impact of NMDA receptor blockade on human working memory-related prefrontal function and connectivity. Neuropsychopharmacology 38, 2613–2622.CrossRefGoogle ScholarPubMed
Fett, AK, Viechtbauer, W, Dominguez, MD, Penn, DL, van Os, J, Krabbendam, L (2011). The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neuroscience and Biobehavioral Reviews 35, 573–588.CrossRefGoogle ScholarPubMed
Frydecka, D, Eissa, AM, Hewedi, DH, Ali, M, Drapala, J, Misiak, B, Klosinska, E, Phillips, JR, Moustafa, AA (2014). Impairments of working memory in schizophrenia and bipolar disorder: the effect of history of psychotic symptoms and different aspects of cognitive task demands. Frontiers in Behavioral Neuroscience 8, 416.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Deste, G, Smieskova, R, Barlati, S, Yung, AR, Howes, O, Stieglitz, RD, Vita, A, McGuire, P, Borgwardt, S (2012). Cognitive functioning in prodromal psychosis: a meta-analysis. Archives of General Psychiatry 69, 562–571.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Stone, JM, Broome, MR, Valli, I, Mechelli, A, McLean, MA, Lythgoe, DJ, O'Gorman, RL, Barker, GJ, McGuire, PK (2011). Thalamic glutamate levels as a predictor of cortical response during executive functioning in subjects at high risk for psychosis. Archives of General Psychiatry 68, 881–890.CrossRefGoogle ScholarPubMed
Gelman, A, Hill, J, Yajima, M (2009). Why we (usually) don't have to worry about multiple comparisons (https://arxiv.org/abs/0907.2478).Google Scholar
Goldman, HH, Skodol, AE, Lave, TR (1992). Revising Axis V for DSM-IV: a review of measures of social functioning. American Journal of Psychiatry 149, 1148–1156.Google ScholarPubMed
Gonzalez-Ortega, I, de Los Mozos, V, Echeburua, E, Mezo, M, Besga, A, Ruiz de Azua, S, Gonzalez-Pinto, A, Gutierrez, M, Zorrilla, I, Gonzalez-Pinto, A (2013). Working memory as a predictor of negative symptoms and functional outcome in first episode psychosis. Psychiatry Research 206, 8–16.CrossRefGoogle ScholarPubMed
Gray, JA, Roth, BL (2007). Molecular targets for treating cognitive dysfunction in schizophrenia. Schizophrenia Bulletin 33, 1100–1119.CrossRefGoogle ScholarPubMed
Gunduz-Bruce, H (2009). The acute effects of NMDA antagonism: from the rodent to the human brain. Brain Research Reviews 60, 279–286.CrossRefGoogle ScholarPubMed
Gunduz-Bruce, H, Reinhart, RM, Roach, BJ, Gueorguieva, R, Oliver, S, D'Souza, DC, Ford, JM, Krystal, JH, Mathalon, DH (2012). Glutamatergic modulation of auditory information processing in the human brain. Biological Psychiatry 71, 969–977.CrossRefGoogle ScholarPubMed
Hall, RC (1995). Global assessment of functioning. A modified scale. Psychosomatics 36, 267–275.CrossRefGoogle ScholarPubMed
Hanson, DR, Gottesman, II (2005). Theories of schizophrenia: a genetic–inflammatory–vascular synthesis. BMC Medical Genetics 6, 7.CrossRefGoogle ScholarPubMed
Heinrichs, RW, Zakzanis, KK (1998). Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 12, 426–445.CrossRefGoogle ScholarPubMed
Hill, SK, Reilly, JL, Keefe, RS, Gold, JM, Bishop, JR, Gershon, ES, Tamminga, CA, Pearlson, GD, Keshavan, MS, Sweeney, JA (2013). Neuropsychological impairments in schizophrenia and psychotic bipolar disorder: findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. American Journal of Psychiatry 170, 1275–1284.CrossRefGoogle ScholarPubMed
Hoffer, ME, Balaban, C, Slade, MD, Tsao, JW, Hoffer, B (2013). Amelioration of acute sequelae of blast induced mild traumatic brain injury by N-acetyl cysteine: a double-blind, placebo controlled study. PLOS ONE 8, e54163.CrossRefGoogle ScholarPubMed
Hoffman, RE, Woods, SW, Hawkins, KA, Pittman, B, Tohen, M, Preda, A, Breier, A, Glist, J, Addington, J, Perkins, DO, McGlashan, TH (2007). Extracting spurious messages from noise and risk of schizophrenia-spectrum disorders in a prodromal population. British Journal of Psychiatry 191, 355–356.CrossRefGoogle Scholar
Holmay, MJ, Terpstra, M, Coles, LD, Mishra, U, Ahlskog, M, Oz, G, Cloyd, JC, Tuite, PJ (2013). N-acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases. Clinical Neuropharmacology 36, 103–106.CrossRefGoogle ScholarPubMed
Howes, O, McCutcheon, R, Stone, J (2015). Glutamate and dopamine in schizophrenia: an update for the 21st century. Journal of Psychopharmacology 29, 97–115.CrossRefGoogle Scholar
Javitt, DC, Zukin, SR, Heresco-Levy, U, Umbricht, D (2012). Has an angel shown the way? Etiological and therapeutic implications of the PCP/NMDA model of schizophrenia. Schizophrenia Bulletin 38, 958–966.CrossRefGoogle Scholar
Jayalakshmi, K, Singh, SB, Kalpana, B, Sairam, M, Muthuraju, S, Ilavazhagan, G (2007). N-acetyl cysteine supplementation prevents impairment of spatial working memory functions in rats following exposure to hypobaric hypoxia. Physiology and Behavior 92, 643–650.CrossRefGoogle ScholarPubMed
Kahn, RS, Sommer, IE (2015). The neurobiology and treatment of first-episode schizophrenia. Molecular Psychiatry 20, 84–97.CrossRefGoogle ScholarPubMed
Kantrowitz, JT, Javitt, DC (2010). N-methyl-d-aspartate (NMDA) receptor dysfunction or dysregulation: the final common pathway on the road to schizophrenia? Brain Research Bulletin 83, 108–121.CrossRefGoogle ScholarPubMed
Kapur, S (2003). Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry 160, 13–23.CrossRefGoogle ScholarPubMed
Kay, SR, Fiszbein, A, Opler, LA (1987). The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.CrossRefGoogle ScholarPubMed
Kim, D, Kim, JW, Koo, TH, Yun, HR, Won, SH (2015). Shared and distinct neurocognitive endophenotypes of schizophrenia and psychotic bipolar disorder. Clinical Psychopharmacology and Neuroscience 13, 94–102.CrossRefGoogle ScholarPubMed
Kozicky, JM, Torres, IJ, Silveira, LE, Bond, DJ, Lam, RW, Yatham, LN (2014). Cognitive change in the year after a first manic episode: association between clinical outcome and cognitive performance early in the course of bipolar I disorder. Journal of Clinical Psychiatry 75, e587–e593.CrossRefGoogle ScholarPubMed
Krabbendam, L, Arts, B, van Os, J, Aleman, A (2005). Cognitive functioning in patients with schizophrenia and bipolar disorder: a quantitative review. Schizophrenia Research 80, 137–149.CrossRefGoogle ScholarPubMed
Lavoie, S, Murray, MM, Deppen, P, Knyazeva, MG, Berk, M, Boulat, O, Bovet, P, Bush, AI, Conus, P, Copolov, D, Fornari, E, Meuli, R, Solida, A, Vianin, P, Cuenod, M, Buclin, T, Do, KQ (2008). Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients. Neuropsychopharmacology 33, 2187–2199.CrossRefGoogle ScholarPubMed
Lopez-Jaramillo, C, Lopera-Vasquez, J, Gallo, A, Ospina-Duque, J, Bell, V, Torrent, C, Martinez-Aran, A, Vieta, E (2010). Effects of recurrence on the cognitive performance of patients with bipolar I disorder: implications for relapse prevention and treatment adherence. Bipolar Disorders 12, 557–567.CrossRefGoogle ScholarPubMed
Malhi, GS, Ivanovski, B, Hadzi-Pavlovic, D, Mitchell, PB, Vieta, E, Sachdev, P (2007). Neuropsychological deficits and functional impairment in bipolar depression, hypomania and euthymia. Bipolar Disorders 9, 114–125.CrossRefGoogle ScholarPubMed
Martinez-Aran, A, Penades, R, Vieta, E, Colom, F, Reinares, M, Benabarre, A, Salamero, M, Gasto, C (2002). Executive function in patients with remitted bipolar disorder and schizophrenia and its relationship with functional outcome. Psychotherapy and Psychosomatics 71, 39–46.CrossRefGoogle ScholarPubMed
Martinez-Aran, A, Vieta, E (2015). Cognition as a target in schizophrenia, bipolar disorder and depression. European Neuropsychopharmacology 25, 151–157.CrossRefGoogle ScholarPubMed
Martinez-Cengotitabengoa, M, Mac-Dowell, KS, Leza, JC, Mico, JA, Fernandez, M, Echevarria, E, Sanjuan, J, Elorza, J, Gonzalez-Pinto, A (2012). Cognitive impairment is related to oxidative stress and chemokine levels in first psychotic episodes. Schizophrenia Research 137, 66–72.CrossRefGoogle ScholarPubMed
Martinez-Cengotitabengoa, M, Mico, JA, Arango, C, Castro-Fornieles, J, Graell, M, Paya, B, Leza, JC, Zorrilla, I, Parellada, M, Lopez, MP, Baeza, I, Moreno, C, Rapado-Castro, M, Gonzalez-Pinto, A (2014). Basal low antioxidant capacity correlates with cognitive deficits in early onset psychosis. A 2-year follow-up study. Schizophrenia Research 156, 23–29.CrossRefGoogle ScholarPubMed
Mesholam-Gately, RI, Giuliano, AJ, Goff, KP, Faraone, SV, Seidman, LJ (2009). Neurocognition in first-episode schizophrenia: a meta-analytic review. Neuropsychology 23, 315–336.CrossRefGoogle ScholarPubMed
Millan, MJ, Agid, Y, Brune, M, Bullmore, ET, Carter, CS, Clayton, NS, Connor, R, Davis, S, Deakin, B, DeRubeis, RJ, Dubois, B, Geyer, MA, Goodwin, GM, Gorwood, P, Jay, TM, Joëls, M, Mansuy, IM, Meyer-Lindenberg, A, Murphy, D, Rolls, E, Saletu, B, Spedding, M, Sweeney, J, Whittington, M, Young, LJ (2012). Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nature Reviews. Drug Discovery 11, 141–168.CrossRefGoogle ScholarPubMed
Miskowiak, KW, Ehrenreich, H, Christensen, EM, Kessing, LV, Vinberg, M (2014). Recombinant human erythropoietin to target cognitive dysfunction in bipolar disorder: a double-blind, randomized, placebo-controlled phase 2 trial. Journal of Clinical Psychiatry 75, 1347–1355.CrossRefGoogle ScholarPubMed
Morgan, CJ, Mofeez, A, Brandner, B, Bromley, L, Curran, HV (2004). Acute effects of ketamine on memory systems and psychotic symptoms in healthy volunteers. Neuropsychopharmacology 29, 208–218.CrossRefGoogle ScholarPubMed
Morris, G, Berk, M (2015). The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Medicine 13, 68.CrossRefGoogle ScholarPubMed
Ng, F, Berk, M, Dean, O, Bush, AI (2008). Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. International Journal of Neuropsychopharmacology 11, 851–876.CrossRefGoogle ScholarPubMed
Otte, DM, Sommersberg, B, Kudin, A, Guerrero, C, Albayram, O, Filiou, MD, Frisch, P, Yilmaz, O, Drews, E, Turck, CW, Bilkei-Gorzo, A, Kunz, WS, Beck, H, Zimmer, A (2011). N-acetyl cysteine treatment rescues cognitive deficits induced by mitochondrial dysfunction in G72/G30 transgenic mice. Neuropsychopharmacology 36, 2233–2243.CrossRefGoogle ScholarPubMed
Pantelis, C, Wannan, C, Bartholomeusz, CF, Allott, K, McGorry, PD (2015). Cognitive intervention in early psychosis – preserving abilities versus remediating deficits. Current Opinion in Behavioral Sciences 4, 63–72.CrossRefGoogle Scholar
Potvin, S, Pampoulova, T, Lipp, O, Ait Bentaleb, L, Lalonde, P, Stip, E (2008). Working memory and depressive symptoms in patients with schizophrenia and substance use disorders. Cognitive Neuropsychiatry 13, 357–366.CrossRefGoogle ScholarPubMed
Rajasekaran, A, Venkatasubramanian, G, Berk, M, Debnath, M (2015). Mitochondrial dysfunction in schizophrenia: pathways, mechanisms and implications. Neuroscience and Biobehavioral Reviews 48, 10–21.CrossRefGoogle ScholarPubMed
Rapado-Castro, M, Berk, M, Venugopal, K, Bush, AI, Dodd, S, Dean, OM (2015). Towards stage specific treatments: effects of duration of illness on therapeutic response to adjunctive treatment with N-acetyl cysteine in schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry 57, 69–75.CrossRefGoogle ScholarPubMed
Reichenberg, A, Caspi, A, Harrington, H, Houts, R, Keefe, RS, Murray, RM, Poulton, R, Moffitt, TE (2010). Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: a 30-year study. American Journal of Psychiatry 167, 160–169.CrossRefGoogle ScholarPubMed
Reilly, JL, Sweeney, JA (2014). Generalized and specific neurocognitive deficits in psychotic disorders: utility for evaluating pharmacological treatment effects and as intermediate phenotypes for gene discovery. Schizophrenia Bulletin 40, 516–522.CrossRefGoogle ScholarPubMed
Reus, GZ, Fries, GR, Stertz, L, Badawy, M, Passos, IC, Barichello, T, Kapczinski, F, Quevedo, J (2015). The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders. Neuroscience 300, 141–154.CrossRefGoogle Scholar
Riedel, G, Platt, B, Micheau, J (2003). Glutamate receptor function in learning and memory. Behavioural Brain Research 140, 1–47.CrossRefGoogle ScholarPubMed
Rosa, AR, Magalhães, PV, Czepielewski, L, Sulzbach, MV, Goi, PD, Vieta, E, Gama, CS, Kapczinski, F (2014). Clinical staging in bipolar disorder: focus on cognition and functioning. Journal of Clinical Psychiatry 75, e450–e456.CrossRefGoogle ScholarPubMed
Saetre, P, Emilsson, L, Axelsson, E, Kreuger, J, Lindholm, E, Jazin, E (2007). Inflammation-related genes up-regulated in schizophrenia brains. BMC Psychiatry 7, 46.CrossRefGoogle ScholarPubMed
Samuni, Y, Goldstein, S, Dean, OM, Berk, M (2013). The chemistry and biological activities of N-acetylcysteine. Biochimica et Biophysica Acta 1830, 4117–4129.CrossRefGoogle ScholarPubMed
Shaikh, M, Valmaggia, L, Broome, MR, Dutt, A, Lappin, J, Day, F, Woolley, J, Tabraham, P, Walshe, M, Johns, L, Fusar-Poli, P, Howes, O, Murray, RM, McGuire, P, Bramon, E (2012). Reduced mismatch negativity predates the onset of psychosis. Schizophrenia Research 134, 42–48.CrossRefGoogle ScholarPubMed
Shungu, DC (2012). N-acetylcysteine for the treatment of glutathione deficiency and oxidative stress in schizophrenia. Biological Psychiatry 71, 937–938.CrossRefGoogle ScholarPubMed
Stone, JM, Bramon, E, Pauls, A, Sumich, A, McGuire, PK (2010). Thalamic neurochemical abnormalities in individuals with prodromal symptoms of schizophrenia – relationship to auditory event-related potentials. Psychiatry Research 183, 174–176.CrossRefGoogle ScholarPubMed
van Os, J, Kapur, S (2009). Schizophrenia. Lancet 374, 635–645.CrossRefGoogle ScholarPubMed
Vreeker, A, van Bergen, AH, Kahn, RS (2015). Cognitive enhancing agents in schizophrenia and bipolar disorder. European Neuropsychopharmacology 25, 969–1002.CrossRefGoogle ScholarPubMed
Williams, JB, Kobak, KA (2008). Development and reliability of a Structured Interview Guide for the Montgomery–Åsberg Depression Rating Scale (SIGMA). British Journal of Psychiatry 192, 52–58.CrossRefGoogle ScholarPubMed
Wilson, CJ, Finch, CE, Cohen, HJ (2002). Cytokines and cognition – the case for a head-to-toe inflammatory paradigm. Journal of the American Geriatrics Society 50, 2041–2056.CrossRefGoogle ScholarPubMed
Young, RC, Biggs, JT, Ziegler, VE, Meyer, DA (1978). A rating scale for mania: reliability, validity and sensitivity. British Journal of Psychiatry 133, 429–435.CrossRefGoogle ScholarPubMed
Zabala, A, Rapado, M, Arango, C, Robles, O, de la Serna, E, Gonzalez, C, Rodriguez-Sanchez, JM, Andres, P, Mayoral, M, Bombin, I (2010). Neuropsychological functioning in early-onset first-episode psychosis: comparison of diagnostic subgroups. European Archives of Psychiatry and Clinical Neuroscience 260, 225–233.CrossRefGoogle ScholarPubMed
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