Abstract
In this chapter we review the evidence of the effectiveness of N-acetylcysteine (NAC) in psychiatric disorders excluding disorders of addiction. Each of these disorders is reviewed individually with the most up-to-date evidence for the usage of NAC in their treatment along with recommendations when possible. There was not enough evidence to make recommendations for anxiety and attention deficit hyperactivity disorder, but the available studies were promising. More evidence was available for other psychiatric disorders reviewed with mixed recommendations for autism spectrum disorder, bipolar disorder, depression, impulse-control disorders (i.e., onychophagia, trichotillomania, excoriation disorder), obsessive-compulsive disorder, and schizophrenia. Given that NAC positively modulates many underlying pathophysiological mechanisms associated with psychiatric disorders, it is a very promising therapy that requires further study.
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References
Afshar H, Roohafza H, Mohammad-Beigi H, Haghighi M, Jahangard L, Shokouh P, Sadeghi M, Hafezian H (2012) N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychopharmacol 32(6):797–803. https://doi.org/10.1097/JCP.0b013e318272677d
Anderson G, Jacob A, Bellivier F, Geoffroy PA (2016) Bipolar disorder: the role of the kynurenine and melatonergic pathways. Curr Pharm Des 22(8):987–1012
APA (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Association, Washington, DC
Assies J, Mocking RJ, Lok A, Ruhe HG, Pouwer F, Schene AH (2014) Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity. Acta Psychiatr Scand 130(3):163–180. https://doi.org/10.1111/acps.12265
Avcil S, Uysal P, Avcil M, Alisik M, Bicer C (2017) Dynamic thiol/disulfide homeostasis in children with attention deficit hyperactivity disorder and its relation with disease subtypes. Compr Psychiatry 73:53–60. https://doi.org/10.1016/j.comppsych.2016.11.003
Bartlett AA, Singh R, Hunter RG (2017) Anxiety and epigenetics. Adv Exp Med Biol 978:145–166. https://doi.org/10.1007/978-3-319-53889-1_8
Bergman O, Ben-Shachar D (2016) Mitochondrial oxidative phosphorylation system (OXPHOS) deficits in schizophrenia: possible interactions with cellular processes. Can J Psychiatr 61(8):457–469. https://doi.org/10.1177/0706743716648290
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 (2008a) N-acetyl cysteine as a glutathione precursor for schizophrenia–a double-blind, randomized, placebo-controlled trial. Biol Psychiatry 64(5):361–368. https://doi.org/10.1016/j.biopsych.2008.03.004
Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI (2008b) N-acetyl cysteine for depressive symptoms in bipolar disorder–a double-blind randomized placebo-controlled trial. Biol Psychiatry 64(6):468–475. https://doi.org/10.1016/j.biopsych.2008.04.022
Berk M, Jeavons S, Dean OM, Dodd S, Moss K, Gama CS, Malhi GS (2009) Nail-biting stuff? The effect of N-acetyl cysteine on nail-biting. CNS Spectr 14(7):357–360
Berk M, Dean O, Cotton SM, Gama CS, Kapczinski F, Fernandes BS, Kohlmann K, Jeavons S, Hewitt K, Allwang C, Cobb H, Bush AI, Schapkaitz I, Dodd S, Malhi GS (2011a) The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. J Affect Disord 135(1–3):389–394. https://doi.org/10.1016/j.jad.2011.06.005
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 (2011b) Qualitative methods in early-phase drug trials: broadening the scope of data and methods from an RCT of N-acetylcysteine in schizophrenia. J Clin Psychiatry 72(7):909–913. https://doi.org/10.4088/JCP.09m05741yel
Berk M, Dean OM, Cotton SM, Gama CS, Kapczinski F, Fernandes B, Kohlmann K, Jeavons S, Hewitt K, Moss K, Allwang C, Schapkaitz I, Cobb H, Bush AI, Dodd S, Malhi GS (2012) Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial. BMC Med 10:91. https://doi.org/10.1186/1741-7015-10-91
Berk M, Dean OM, Cotton SM, Jeavons S, Tanious M, Kohlmann K, Hewitt K, Moss K, Allwang C, Schapkaitz I, Robbins J, Cobb H, Ng F, Dodd S, Bush AI, Malhi GS (2014) The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry 75(6):628–636. https://doi.org/10.4088/JCP.13m08454
Bloch MH, Panza KE, Grant JE, Pittenger C, Leckman JF (2013) N-Acetylcysteine in the treatment of pediatric trichotillomania: a randomized, double-blind, placebo-controlled add-on trial. J Am Acad Child Adolesc Psychiatry 52(3):231–240. https://doi.org/10.1016/j.jaac.2012.12.020
Boldrini P, Fusco A, Nicoletti F, Badiani A, Saso L (2017) Potential use of modulators of oxidative stress as add-on therapy in patients with anxiety disorders. Curr Drug Targets 18. https://doi.org/10.2174/1389450118666170425153356
Bonvicini C, Faraone SV, Scassellati C (2017) Common and specific genes and peripheral biomarkers in children and adults with attention-deficit/hyperactivity disorder. World J Biol Psychiatry:1–52. https://doi.org/10.1080/15622975.2017.1282175
Brewer JA, Potenza MN (2008) The neurobiology and genetics of impulse control disorders: relationships to drug addictions. Biochem Pharmacol 75(1):63–75. https://doi.org/10.1016/j.bcp.2007.06.043
Buie T, Campbell DB, Fuchs GJ 3rd, Furuta GT, Levy J, Vandewater J, Whitaker AH, Atkins D, Bauman ML, Beaudet AL, Carr EG, Gershon MD, Hyman SL, Jirapinyo P, Jyonouchi H, Kooros K, Kushak R, Levitt P, Levy SE, Lewis JD, Murray KF, Natowicz MR, Sabra A, Wershil BK, Weston SC, Zeltzer L, Winter H (2010a) Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 125(Suppl 1):S1–S18. https://doi.org/10.1542/peds.2009-1878C
Buie T, Fuchs GJ 3rd, Furuta GT, Kooros K, Levy J, Lewis JD, Wershil BK, Winter H (2010b) Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs. Pediatrics 125(Suppl 1):S19–S29. https://doi.org/10.1542/peds.2009-1878D
Bulut M, Savas HA, Altindag A, Virit O, Dalkilic A (2009) Beneficial effects of N-acetylcysteine in treatment resistant schizophrenia. World J Biol Psychiatry 10(4 Pt 2):626–628. https://doi.org/10.1080/15622970903144004
Callaly E, Walder K, Morris G, Maes M, Debnath M, Berk M (2015) Mitochondrial dysfunction in the pathophysiology of bipolar disorder: effects of pharmacotherapy. Mini Rev Med Chem 15(5):355–365
Canitano R, Pallagrosi M (2017) Autism spectrum disorders and schizophrenia spectrum disorders: excitation/inhibition imbalance and developmental trajectories. Front Psych 8:69. https://doi.org/10.3389/fpsyt.2017.00069
Carlsson ML (2001) On the role of prefrontal cortex glutamate for the antithetical phenomenology of obsessive compulsive disorder and attention deficit hyperactivity disorder. Prog Neuro-Psychopharmacol Biol Psychiatry 25(1):5–26
Carvalho AF, Macedo DS, Goulia P, Hyphantis TN (2013) N-acetylcysteine augmentation to tranylcypromine in treatment-resistant major depression. J Clin Psychopharmacol 33(5):719–720. https://doi.org/10.1097/JCP.0b013e31829839c6
CDC (2012) Prevalence of autism spectrum disorders—autism and developmental disabilities monitoring network, 14 Sites, United States, 2008. Morbidity and Mortality Weekly Report
Celebi F (2017) N-acetylcysteine may reduce repetitive behaviors in children with autism: a case series. Psychiatry Clin Psychopharmacol:1–4. https://doi.org/10.1080/24750573.2017.1309817
Chakrabarty K, Bhattacharyya S, Christopher R, Khanna S (2005) Glutamatergic dysfunction in OCD. Neuropsychopharmacology 30(9):1735–1740. https://doi.org/10.1038/sj.npp.1300733
Cikankova T, Sigitova E, Zverova M, Fisar Z, Raboch J, Hroudova J (2016) Mitochondrial dysfunctions in bipolar disorder: effect of the disease and pharmacotherapy. CNS Neurol Disord Drug Targets 16(2):176–186
de Sousa RT, Machado-Vieira R, Zarate CA Jr, Manji HK (2014) Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder. Expert Opin Ther Targets 18(10):1131–1147. https://doi.org/10.1517/14728222.2014.940893
de Sousa RT, Streck EL, Forlenza OV, Brunoni AR, Zanetti MV, Ferreira GK, Diniz BS, Portela LV, Carvalho AF, Zarate CA Jr, Gattaz WF, Machado-Vieira R (2015) Regulation of leukocyte tricarboxylic acid cycle in drug-naive bipolar disorder. Neurosci Lett 605:65–68. https://doi.org/10.1016/j.neulet.2015.08.022
Dean O, Giorlando F, Berk M (2011) N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci 36(2):78–86. https://doi.org/10.1503/jpn.100057
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 Clin Neurosci 66(6):514–517. https://doi.org/10.1111/j.1440-1819.2012.02392.x
Dean OM, Gray KM, Villagonzalo KA, Dodd S, Mohebbi M, Vick T, Tonge BJ, Berk M (2017) A randomised, double blind, placebo-controlled trial of a fixed dose of N-acetyl cysteine in children with autistic disorder. Aust N Z J Psychiatry 51(3):241–249. https://doi.org/10.1177/0004867416652735
Deepmala SJ, 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. Neurosci Biobehav Rev 55:294–321. https://doi.org/10.1016/j.neubiorev.2015.04.015
Dimatelis JJ, Hsieh JH, Sterley TL, Marais L, Womersley JS, Vlok M, Russell VA (2015) Impaired energy metabolism and disturbed dopamine and glutamate signaling in the striatum and prefrontal cortex of the spontaneously hypertensive rat model of attention-deficit hyperactivity disorder. J Mol Neurosci 56(3):696–707. https://doi.org/10.1007/s12031-015-0491-z
Dinan TG (2009) Inflammatory markers in depression. Curr Opin Psychiatry 22(1):32–36. https://doi.org/10.1097/YCO.0b013e328315a561
Dinan TG, Cryan JF (2017) The microbiome-gut-brain axis in health and disease. Gastroenterol Clin N Am 46(1):77–89. https://doi.org/10.1016/j.gtc.2016.09.007
Erny D, Hrabe de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, Keren-Shaul H, Mahlakoiv T, Jakobshagen K, Buch T, Schwierzeck V, Utermohlen O, Chun E, Garrett WS, McCoy KD, Diefenbach A, Staeheli P, Stecher B, Amit I, Prinz M (2015) Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 18(7):965–977. https://doi.org/10.1038/nn.4030
Faizi M, Salimi A, Rasoulzadeh M, Naserzadeh P, Pourahmad J (2014) Schizophrenia induces oxidative stress and cytochrome C release in isolated rat brain mitochondria: a possible pathway for induction of apoptosis and neurodegeneration. Iran J Pharm Res 13(Suppl):93–100
Farokhnia M, Azarkolah A, Adinehfar F, Khodaie-Ardakani MR, Hosseini SM, Yekehtaz H, Tabrizi M, Rezaei F, Salehi B, Sadeghi SM, Moghadam M, Gharibi F, Mirshafiee O, Akhondzadeh S (2013) 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 36(6):185–192. https://doi.org/10.1097/wnf.0000000000000001
Fontenelle LF, Oostermeijer S, Harrison BJ, Pantelis C, Yucel M (2011) Obsessive-compulsive disorder, impulse control disorders and drug addiction: common features and potential treatments. Drugs 71(7):827–840. https://doi.org/10.2165/11591790-000000000-00000
Frye RE, James SJ (2014) Metabolic pathology of autism in relation to redox metabolism. Biomark Med 8(3):321–330. https://doi.org/10.2217/bmm.13.158
Frye RE, Rossignol DA (2014) Treatments for biomedical abnormalities associated with autism spectrum disorder. Front Pediatry 2:66. https://doi.org/10.3389/fped.2014.00066
Frye RE, Rossignol DA (2016) Identification and treatment of pathophysiological comorbidities of autism spectrum disorder to achieve optimal outcomes. Clin Med Insights Pediatr 10:43–56. https://doi.org/10.4137/CMPed.S38337
Frye RE, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, Hubanks A, Gaylor DW, Walters L, James SJ (2013a) Effectiveness of methylcobalamin and folinic acid treatment on adaptive behavior in children with autistic disorder is related to glutathione redox status. Autism Res Treat 2013:609705. https://doi.org/10.1155/2013/609705
Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA (2013b) Cerebral folate receptor autoantibodies in autism spectrum disorder. Mol Psychiatry 18(3):369–381. https://doi.org/10.1038/mp.2011.175
Frye RE, Casanova MF, Fatemi SH, Folsom TD, Reutiman TJ, Brown GL, Edelson SM, Slattery JC, Adams JB (2016a) Neuropathological mechanisms of seizures in autism spectrum disorder. Front Neurosci 10:192. https://doi.org/10.3389/fnins.2016.00192
Frye RE, Delhey L, Slattery J, Tippett M, Wynne R, Rose S, Kahler SG, Bennuri SC, Melnyk S, Sequeira JM, Quadros E (2016b) Blocking and binding folate receptor alpha autoantibodies identify novel autism spectrum disorder subgroups. Front Neurosci 10:80. https://doi.org/10.3389/fnins.2016.00080
Frye RE, Slattery J, Delhey L, Furgerson B, Strickland T, Tippett M, Sailey A, Wynne R, Rose S, Melnyk S, Jill James S, Sequeira JM, Quadros EV (2016c) Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial. Mol Psychiatry 23(2):247–256. https://doi.org/10.1038/mp.2016.168
Garcia RJ, Francis L, Dawood M, Lai ZW, Faraone SV, Perl A (2013) Attention deficit and hyperactivity disorder scores are elevated and respond to N-acetylcysteine treatment in patients with systemic lupus erythematosus. Arthritis Rheum 65(5):1313–1318. https://doi.org/10.1002/art.37893
Ghanizadeh A, Derakhshan N (2012) N-acetylcysteine for treatment of autism, a case report. J Res Med Sci 17(10):985–987
Ghanizadeh A, Moghimi-Sarani E (2013) A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders. BMC Psychiatry 13:196. https://doi.org/10.1186/1471-244x-13-196
Ghanizadeh A, Derakhshan N, Berk M (2013) N-acetylcysteine versus placebo for treating nail biting, a double blind randomized placebo controlled clinical trial. Antiinflamm Antiallergy Agents Med Chem 12(3):223–228
Grant JE, Odlaug BL, Kim SW (2009) N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry 66(7):756–763. https://doi.org/10.1001/archgenpsychiatry.2009.60
Grant JE, Odlaug BL, Chamberlain SR, Keuthen NJ, Lochner C, Stein DJ (2012) Skin picking disorder. Am J Psychiatry 169(11):1143–1149. https://doi.org/10.1176/appi.ajp.2012.12040508
Grant JE, Chamberlain SR, Redden SA, Leppink EW, Odlaug BL, Kim SW (2016) N-acetylcysteine in the treatment of excoriation disorder: a randomized clinical trial. JAMA Psychiat 73(5):490–496. https://doi.org/10.1001/jamapsychiatry.2016.0060
Hardan AY, Fung LK, Libove RA, Obukhanych TV, Nair S, Herzenberg LA, Frazier TW, Tirouvanziam R (2012) A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry 71(11):956–961. https://doi.org/10.1016/j.biopsych.2012.01.014
James SJ, Melnyk S, Jernigan S, Hubanks A, Rose S, Gaylor DW (2008) Abnormal transmethylation/transsulfuration metabolism and DNA hypomethylation among parents of children with autism. J Autism Dev Disord 38(10):1976. https://doi.org/10.1007/s10803-008-0614-2
Kantrowitz JT, Javitt DC (2010) N-methyl-d-aspartate (NMDA) receptor dysfunction or dysregulation: the final common pathway on the road to schizophrenia? Brain Res Bull 83(3–4):108–121. https://doi.org/10.1016/j.brainresbull.2010.04.006
Kim HK, Andreazza AC (2012) The relationship between oxidative stress and post-translational modification of the dopamine transporter in bipolar disorder. Expert Rev Neurother 12(7):849–859. https://doi.org/10.1586/ern.12.64
Kunz M, Gama CS, Andreazza AC, Salvador M, Cereser KM, Gomes FA, Belmonte-de-Abreu PS, Berk M, Kapczinski F (2008) Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 32(7):1677–1681. https://doi.org/10.1016/j.pnpbp.2008.07.001
Lafleur DL, Pittenger C, Kelmendi B, Gardner T, Wasylink S, Malison RT, Sanacora G, Krystal JH, Coric V (2006) N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder. Psychopharmacology 184(2):254–256. https://doi.org/10.1007/s00213-005-0246-6
Li X, Zhang W, Tang J, Tan L, Luo XJ, Chen X, Yao YG (2015) Do nuclear-encoded core subunits of mitochondrial complex I confer genetic susceptibility to schizophrenia in Han Chinese populations? Sci Rep 5:11076. https://doi.org/10.1038/srep11076
Magalhaes PV, Dean OM, Bush AI, Copolov DL, Malhi GS, Kohlmann K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Berk M (2011a) N-acetyl cysteine add-on treatment for bipolar II disorder: a subgroup analysis of a randomized placebo-controlled trial. J Affect Disord 129(1–3):317–320. https://doi.org/10.1016/j.jad.2010.08.001
Magalhaes PV, Dean OM, Bush AI, Copolov DL, Malhi GS, Kohlmann K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Berk M (2011b) N-acetylcysteine for major depressive episodes in bipolar disorder. Rev Bras Psiquiatr 33(4):374–378
Magalhaes PV, Dean OM, Bush AI, Copolov DL, Weisinger D, Malhi GS, Kohlmann K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Berk M (2012) Systemic illness moderates the impact of N-acetyl cysteine in bipolar disorder. Prog Neuro-Psychopharmacol Biol Psychiatry 37(1):132–135. https://doi.org/10.1016/j.pnpbp.2011.11.011
Magalhaes PV, Dean OM, Bush AI, Copolov DL, Malhi GS, Kohlmann K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Berk M (2013) A preliminary investigation on the efficacy of N-acetyl cysteine for mania or hypomania. Aust N Z J Psychiatry 47(6):564–568. https://doi.org/10.1177/0004867413481631
Markarian Y, Larson MJ, Aldea MA, Baldwin SA, Good D, Berkeljon A, Murphy TK, Storch EA, McKay D (2010) Multiple pathways to functional impairment in obsessive-compulsive disorder. Clin Psychol Rev 30(1):78–88. https://doi.org/10.1016/j.cpr.2009.09.005
Marler S, Sanders KB, Veenstra-VanderWeele J (2014) N-acetylcysteine as treatment for self-injurious behavior in a child with autism. J Child Adolesc Psychopharmacol 24(4):231–234. https://doi.org/10.1089/cap.2013.0137
Merikangas KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RM, Petukhova M, Kessler RC (2007) Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry 64(5):543–552. https://doi.org/10.1001/archpsyc.64.5.543
Messias E, Chen CY, Eaton WW (2007) Epidemiology of schizophrenia: review of findings and myths. Psychiatr Clin North Am 30(3):323–338
Miller JL, Angulo M (2014) An open-label pilot study of N-acetylcysteine for skin-picking in Prader-Willi syndrome. Am J Med Genet A 164a(2):421–424. https://doi.org/10.1002/ajmg.a.36306
Mocelin R, Herrmann AP, Marcon M, Rambo CL, Rohden A, Bevilaqua F, de Abreu MS, Zanatta L, Elisabetsky E, Barcellos LJ, Lara DR, Piato AL (2015) N-acetylcysteine prevents stress-induced anxiety behavior in zebrafish. Pharmacol Biochem Behav 139 Pt B:121–126. https://doi.org/10.1016/j.pbb.2015.08.006
Monpays C, Deslauriers J, Sarret P, Grignon S (2016) Mitochondrial dysfunction in schizophrenia: determination of mitochondrial respiratory activity in a two-hit mouse model. J Mol Neurosci 59(4):440–451. https://doi.org/10.1007/s12031-016-0746-3
Moore CM, Biederman J, Wozniak J, Mick E, Aleardi M, Wardrop M, Dougherty M, Harpold T, Hammerness P, Randall E, Renshaw PF (2006) Differences in brain chemistry in children and adolescents with attention deficit hyperactivity disorder with and without comorbid bipolar disorder: a proton magnetic resonance spectroscopy study. Am J Psychiatry 163(2):316–318. https://doi.org/10.1176/appi.ajp.163.2.316
Morris G, Berk M (2015) The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Med 13:68. https://doi.org/10.1186/s12916-015-0310-y
Morris G, Carvalho AF, Anderson G, Galecki P, Maes M (2016) The many neuroprogressive actions of tryptophan catabolites (TRYCATs) that may be associated with the pathophysiology of neuro-immune disorders. Curr Pharm Des 22(8):963–977
Nagano T, Mizuno M, Morita K, Nawa H (2015) Pathological implications of oxidative stress in patients and animal models with schizophrenia: the role of epidermal growth factor receptor signaling. Curr Top Behav Neurosci 29:429–446. https://doi.org/10.1007/7854_2015_399
Nikoo M, Radnia H, Farokhnia M, Mohammadi MR, Akhondzadeh S (2015) N-acetylcysteine as an adjunctive therapy to risperidone for treatment of irritability in autism: a randomized, double-blind, placebo-controlled clinical trial of efficacy and safety. Clin Neuropharmacol 38(1):11–17. https://doi.org/10.1097/wnf.0000000000000063
NIMH (2016) Schizophrenia
Odlaug BL, Grant JE (2007) N-acetyl cysteine in the treatment of grooming disorders. J Clin Psychopharmacol 27(2):227–229. https://doi.org/10.1097/01.jcp.0000264976.86990.00
Ozcan D, Seckin D (2016) N-Acetylcysteine in the treatment of trichotillomania: remarkable results in two patients. J Eur Acad Dermatol Venereol 30(9):1606–1608. https://doi.org/10.1111/jdv.13690
Paydary K, Akamaloo A, Ahmadipour A, Pishgar F, Emamzadehfard S, Akhondzadeh S (2016) N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder: randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther 41(2):214–219. https://doi.org/10.1111/jcpt.12370
Perlov E, Philipsen A, Hesslinger B, Buechert M, Ahrendts J, Feige B, Bubl E, Hennig J, Ebert D, Tebartz van Elst L (2007) Reduced cingulate glutamate/glutamine-to-creatine ratios in adult patients with attention deficit/hyperactivity disorder–a magnet resonance spectroscopy study. J Psychiatr Res 41(11):934–941. https://doi.org/10.1016/j.jpsychires.2006.12.007
Pinto AC, Andrade TC, Brito FF, Silva GV, Cavalcante ML, Martelli AC (2017) Trichotillomania: a case report with clinical and dermatoscopic differential diagnosis with alopecia areata. An Bras Dermatol 92(1):118–120. https://doi.org/10.1590/abd1806-4841.20175136
Rajasekaran A, Venkatasubramanian G, Berk M, Debnath M (2015) Mitochondrial dysfunction in schizophrenia: pathways, mechanisms and implications. Neurosci Biobehav Rev 48:10–21. https://doi.org/10.1016/j.neubiorev.2014.11.005
Rapado-Castro M, Dodd S, Bush AI, Malhi GS, Skvarc DR, On ZX, Berk M, Dean OM (2017) Cognitive effects of adjunctive N-acetyl cysteine in psychosis. Psychol Med 47(5):866–876. https://doi.org/10.1017/s0033291716002932
Rodrigues-Barata AR, Tosti A, Rodriguez-Pichardo A, Camacho-Martinez F (2012) N-acetylcysteine in the treatment of trichotillomania. Int J Trichol 4(3):176–178. https://doi.org/10.4103/0974-7753.100090
Rose S, Melnyk S, Pavliv O, Bai S, Nick TG, Frye RE, James SJ (2012) Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry 2:e134. https://doi.org/10.1038/tp.2012.61
Rose S, Frye RE, Slattery J, Wynne R, Tippett M, Melnyk S, James SJ (2014) Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines. Transl Psychiatry 4:e377. https://doi.org/10.1038/tp.2014.15
Rose S, Bennuri SC, Wynne R, Melnyk S, James SJ, Frye RE (2017) Mitochondrial and redox abnormalities in autism lymphoblastoid cells: a sibling control study. FASEB J 31(3):904–909. https://doi.org/10.1096/fj.201601004R
Rossignol DA, Frye RE (2012a) Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry 17(3):290–314. https://doi.org/10.1038/mp.2010.136
Rossignol DA, Frye RE (2012b) A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Mol Psychiatry 17(4):389–401. https://doi.org/10.1038/mp.2011.165
Rossignol DA, Frye RE (2014) Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Front Physiol 5:150. https://doi.org/10.3389/fphys.2014.00150
Rossignol DA, Genuis SJ, Frye RE (2014) Environmental toxicants and autism spectrum disorders: a systematic review. Transl Psychiatry 4:e360. https://doi.org/10.1038/tp.2014.4
Sagvolden T, Johansen EB, Aase H, Russell VA (2005) A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes. Behav Brain Sci 28(3):397–419. https://doi.org/10.1017/s0140525x05000075
Samuni Y, Goldstein S, Dean OM, Berk M (2013) The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta 1830(8):4117–4129. https://doi.org/10.1016/j.bbagen.2013.04.016
Sarris J, Oliver G, Camfield DA, Dean OM, Dowling N, Smith DJ, Murphy J, Menon R, Berk M, Blair-West S, Ng CH (2015) N-acetyl cysteine (NAC) in the treatment of obsessive-compulsive disorder: a 16-week, double-blind, randomised, placebo-controlled study. CNS Drugs 29(9):801–809. https://doi.org/10.1007/s40263-015-0272-9
Schmitt A, Malchow B, Hasan A, Falkai P (2014) The impact of environmental factors in severe psychiatric disorders. Front Neurosci 8:19
Sigitova E, Fisar Z, Hroudova J, Cikankova T, Raboch J (2017) Biological hypotheses and biomarkers of bipolar disorder. Psychiatry Clin Neurosci 71(2):77–103. https://doi.org/10.1111/pcn.12476
Silva-Netto R, Jesus G, Nogueira M, Tavares H (2014) N-acetylcysteine in the treatment of skin-picking disorder. Rev Bras Psiquiatr 36(1):101. https://doi.org/10.1590/1516-4446-2013-1154
Strawn JR, Saldana SN (2012) Treatment with adjunctive N-acetylcysteine in an adolescent with selective serotonin reuptake inhibitor-resistant anxiety. J Child Adolesc Psychopharmacol 22(6):472–473. https://doi.org/10.1089/cap.2012.0066
Stutzman D, Dopheide J (2015) Acetylcysteine for treatment of autism spectrum disorder symptoms. Am J Health Syst Pharm 72(22):1956–1959. https://doi.org/10.2146/ajhp150072
Taylor M, Bhagwandas K (2014) N-acetylcysteine in trichotillomania: a panacea for compulsive skin disorders? Br J Dermatol 171(5):1253–1255. https://doi.org/10.1111/bjd.13080
Ting JT, Feng G (2008) Glutamatergic synaptic dysfunction and obsessive-compulsive disorder. Curr Chem Genomics 2:62–75. https://doi.org/10.2174/1875397300802010062
Tuncel OK, Sarisoy G, Bilgici B, Pazvantoglu O, Cetin E, Unverdi E, Avci B, Boke O (2015) Oxidative stress in bipolar and schizophrenia patients. Psychiatry Res 228(3):688–694. https://doi.org/10.1016/j.psychres.2015.04.046
Verma P, Singh A, Nthenge-Ngumbau DN, Rajamma U, Sinha S, Mukhopadhyay K, Mohanakumar KP (2016) Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction. BBA Clin 6:153–158. https://doi.org/10.1016/j.bbacli.2016.10.003
Viggiano D, Vallone D, Ruocco LA, Sadile AG (2003) Behavioural, pharmacological, morpho-functional molecular studies reveal a hyperfunctioning mesocortical dopamine system in an animal model of attention deficit and hyperactivity disorder. Neurosci Biobehav Rev 27(7):683–689
Warton FL, Howells FM, Russell VA (2009) Increased glutamate-stimulated release of dopamine in substantia nigra of a rat model for attention-deficit/hyperactivity disorder--lack of effect of methylphenidate. Metab Brain Dis 24(4):599–613. https://doi.org/10.1007/s11011-009-9166-1
Waterdrinker A, Berk M, Venugopal K, Rapado-Castro M, Turner A, Dean OM (2015) Effects of N-acetyl cysteine on suicidal ideation in bipolar depression. J Clin Psychiatry 76(5):665. https://doi.org/10.4088/JCP.14l09378
Willcutt EG (2012) The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics 9(3):490–499. https://doi.org/10.1007/s13311-012-0135-8
Wink LK, Adams R, Wang Z, Klaunig JE, Plawecki MH, Posey DJ, McDougle CJ, Erickson CA (2016) A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder. Mol Autism 7:26. https://doi.org/10.1186/s13229-016-0088-6
Wu K, Hanna GL, Rosenberg DR, Arnold PD (2012) The role of glutamate signaling in the pathogenesis and treatment of obsessive-compulsive disorder. Pharmacol Biochem BehavPharmacology, Biochemistry, and Behavior 100(4):726–735. https://doi.org/10.1016/j.pbb.2011.10.007
Yazici KU, Percinel I (2015) N-acetylcysteine augmentation in children and adolescents diagnosed with treatment-resistant obsessive-compulsive disorder: case series. J Clinical Psychopharmacology 35(4):486–489. https://doi.org/10.1097/jcp.0000000000000362
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1 Electronic Supplementary Material
Supplementary Table 12.1
Anxiety (DOCX 13 kb)
Supplementary Table 12.2
Attention-deficit hyperactivity disorder (ADHD) (DOCX 14 kb)
Supplementary Table 12.3
Autism (DOCX 17 kb)
Supplementary Table 12.4
Bipolar disorder (BD) (DOCX 17 kb)
Supplementary Table 12.5
Depressive disorder (DOCX 14 kb)
Supplementary Table 12.6
Impulse control disorder (DOCX 17 kb)
Supplementary Table 12.7
Obsessive compulsive disorder (OCD) (DOCX 17 kb)
Supplementary Table 12.8
Schizophrenia (DOCX 15 kb)
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Slattery, J., Frye, R.E. (2019). Application of N-Acetylcysteine in Psychiatric Disorders. In: Frye, R., Berk, M. (eds) The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine. Adis, Singapore. https://doi.org/10.1007/978-981-10-5311-5_12
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