Generic placeholder image

Current Psychopharmacology

Editor-in-Chief

ISSN (Print): 2211-5560
ISSN (Online): 2211-5579

General Review Article

Role of Neurochemicals in Schizophrenia

Author(s): Sher Singh, Deepa Khanna* and Sanjeev Kalra

Volume 9, Issue 2, 2020

Page: [144 - 161] Pages: 18

DOI: 10.2174/2211556009666200401150756

Abstract

Background: Schizophrenia is a complex, unpredictable and severe psychiatric disorder, which affects several domains of cognition, behavior and characterized by positive, negative, and cognitive symptoms. Etiology of schizophrenia represents the involvement of environmental factors, role of genes, social stressors, like discrimination or economic hardship, relationships, childhood difficulty, use of cannabis in adolescence, maternal stress, nutritional deficiencies, maternal infections, intrauterine growth retardation, and complications of pregnancy, while pathophysiology represents dysfunctional neurotransmission of dopamine, stress-associated signaling cascades (gabanergic, glutamatergic, cholinergic, serotonin, and adrenergic singling cascades) and enzymatic changes (acetylcholinesterase, catechol-o-methyl-transferase, monoamine oxidase, and phosphodiesterase).

Objective: The objective of the current review is to determine the role of pathophysiological hypothesis impairments leading to positive, negative and cognitive symptoms of schizophrenia.

Methods: Various pathophysiological hypotheses of schizophrenia were identified through searching relevant databases including PubMed, Scopus, and Web of Science up to the year 2019, using the keywords schizophrenia, role of dopamine, acetylcholine, oxidative stress, and inflammation in schizophrenia.

Results: Alterations in the neurotransmission of dopamine, stress-associated signaling cascades (Gabanergic, glutamatergic, cholinergic, serotonin, and adrenergic singling cascades) and enzymatic changes (acetylcholinesterase, catechol-o-methyl-transferase, monoamine oxidase, and phosphodiesterase) were compiled in this review for easy learning of Schizophrenia.

Conclusion: Schizophrenia is a major illness defined by delusions, hallucinations, disorganized behavior, and cognitive difficulties such as memory loss. This review aims to provide a brief overview of neurotransmitter role as well as other pathophysiological alterations in schizophrenia. A focus on more predictive animal models and specific biomarkers for positive, negative and cognitive symptoms will help to identify and develop novel therapeutic agents with fewer side effects.

Keywords: Acetylcholine, dopamine, GABA, neuro-inflammation and mitochondrial dysfunctioning, oxidative stress, pathophysiology, schizophrenia.

Graphical Abstract
[1]
Picchioni MM, Murray RM, Schizophrenia BMJ. 2007; 335(7610): 91-5.
[http://dx.doi.org/10.1136/bmj.39227.616447.be] [PMID: 17626963]
[2]
Patel KR, Cherian J, Gohil K, Atkinson D. Schizophrenia: overview and treatment options. P T 2014; 39(9): 638-45.
[PMID: 25210417]
[3]
Kaneko K. Negative symptoms and cognitive impairments in schizophrenia: two key symptoms negatively influencing social functioning. Yonago Acta Med 2018; 61(2): 91-102.
[http://dx.doi.org/10.33160/yam.2018.06.001] [PMID: 29946215]
[4]
Carlborg A, Winnerbäck K, Jönsson EG, Jokinen J, Nordström P. Suicide in schizophrenia. Expert Rev Neurother 2010; 10(7): 1153-64.
[http://dx.doi.org/10.1586/ern.10.82] [PMID: 20586695]
[5]
Altamura C, Fagiolini A, Galderisi S, Rocca P, Rossi A. Schizophrenia today: epidemiology, diagnosis, course and models of care. J Psychopathol 2014; 20: 223-43.
[6]
Mas-Exposito L, Mazo AE, San Emeterio M, Teixido M, Lalucat Jo L. Physical health and schizophrenia in clinical practice guidelines and consensus statements. J Addict Res Ther 2012; S8: 1-5.
[7]
Howes OD, Kapur S. The dopamine hypothesis of schizophrenia: version III--the final common pathway. Schizophr Bull 2009; 35(3): 549-62.
[http://dx.doi.org/10.1093/schbul/sbp006] [PMID: 19325164]
[8]
Patrick RP, Ames BN. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. FASEB J 2015; 29(6): 2207-22.
[http://dx.doi.org/10.1096/fj.14-268342] [PMID: 25713056]
[9]
Hu W, MacDonald ML, Elswick DE, Sweet RA. The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies. Ann N Y Acad Sci 2015; 1338: 38-57.
[http://dx.doi.org/10.1111/nyas.12547] [PMID: 25315318]
[10]
Basu AC, Tsai GE, Ma CL, et al. Targeted disruption of serine racemase affects glutamatergic neurotransmission and behavior. Mol Psychiatry 2009; 14(7): 719-27.
[http://dx.doi.org/10.1038/mp.2008.130] [PMID: 19065142]
[11]
Sarter M, Bruno JP. Cognitive functions of cortical acetylcholine: toward a unifying hypothesis. Brain Res Brain Res Rev 1997; 23(1-2): 28-46.
[http://dx.doi.org/10.1016/S0165-0173(96)00009-4] [PMID: 9063585]
[12]
Hertel P, Fagerquist MV, Svensson TH. Enhanced cortical dopamine output and antipsychotic-like effects of raclopride by alpha2 adrenoceptor blockade. Science 1999; 286(5437): 105-7.
[http://dx.doi.org/10.1126/science.286.5437.105] [PMID: 10506554]
[13]
Kumar A, Yadav M, Parle M, Dhingra S, Dhull DK. Potential drug targets and treatment of schizophrenia. Inflammopharmacology 2017; 25(3): 277-92.
[http://dx.doi.org/10.1007/s10787-017-0340-5] [PMID: 28353125]
[14]
Barch DM, Ceaser A. Cognition in schizophrenia: core psychological and neural mechanisms. Trends Cogn Sci (regul ed) 2012; 16(1): 27-34.
[http://dx.doi.org/10.1016/j.tics.2011.11.015] [PMID: 22169777]
[15]
Smaga I, Niedzielska E, Gawlik M, et al. Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 2. Depression, anxiety, schizophrenia and autism. Pharmacol Rep 2015; 67(3): 569-80.
[http://dx.doi.org/10.1016/j.pharep.2014.12.015] [PMID: 25933971]
[16]
Najjar S, Pearlman DM. Neuroinflammation and white matter pathology in schizophrenia: systematic review. Schizophr Res 2015; 161(1): 102-12.
[http://dx.doi.org/10.1016/j.schres.2014.04.041] [PMID: 24948485]
[17]
Maurer I, Zierz S, Möller H. Evidence for a mitochondrial oxidative phosphorylation defect in brains from patients with schizophrenia. Schizophr Res 2001; 48(1): 125-36.
[http://dx.doi.org/10.1016/S0920-9964(00)00075-X] [PMID: 11278159]
[18]
Timothy J. What is catatonic schizophrenia? christian nordqvist 2017. Available at: https://www.healthline. com/health/catatonic-schizophrenia
[19]
An SK, Lee E, Kim JJ, et al. Greater impairment in negative emotion evaluation ability in patients with paranoid schizophrenia. Yonsei Med J 2006; 47(3): 343-53.
[http://dx.doi.org/10.3349/ymj.2006.47.3.343] [PMID: 16807983]
[20]
Pinkham AE, Harvey PD, Penn DL. Paranoid individuals with schizophrenia show greater social cognitive bias and worse social functioning than nonparanoid individuals with schizophrenia. Schizophr Res Cogn 2016; 3: 33-8.
[http://dx.doi.org/10.1016/j.scog.2015.11.002] [PMID: 27990352]
[21]
Kuperberg GR. Language in schizophrenia Part 1: an Introduction. Lang Linguist Compass 2010; 4(8): 576-89.
[http://dx.doi.org/10.1111/j.1749-818X.2010.00216.x] [PMID: 20936080]
[22]
Arciniegas DB. psychosis. continuum (minneap minn) 2015; 21(3 behavioral neurology and neuropsychiatry): 715-36.
[PMID: 26039850]
[23]
Gur RE, Kohler CG, Ragland JD, et al. Flat affect in schizophrenia: relation to emotion processing and neurocognitive measures. Schizophr Bull 2006; 32(2): 279-87.
[http://dx.doi.org/10.1093/schbul/sbj041] [PMID: 16452608]
[24]
Chalasani P, Krishnamurthy K, David H. Catatonia, schizophrenia, and affective disorders - Diagnostic associations in different cultural settings. Indian J Psychiatry 2011; 53(1): 49-52.
[http://dx.doi.org/10.4103/0019-5545.75564] [PMID: 21431009]
[25]
Morrens M, Hulstijn W, Sabbe B. Psychomotor slowing in schizophrenia. Schizophr Bull 2007; 33(4): 1038-53.
[http://dx.doi.org/10.1093/schbul/sbl051] [PMID: 17093141]
[26]
Keefe RS, Lobel DS, Mohs RC, et al. Diagnostic issues in chronic schizophrenia: kraepelinian schizophrenia, undifferentiated schizophrenia, and stateindependent negative symptoms. Schizophr Res 1991; 4(2): 71-9.
[http://dx.doi.org/10.1016/0920-9964(91)90026-N] [PMID: 2039764]
[27]
Shah R, Grover S, Kulhara P. Coping in residual schizophrenia: Re-analysis of ways of coping checklist. Indian J Med Res 2017; 145(6): 786-95.
[http://dx.doi.org/10.4103/ijmr.IJMR_1927_14] [PMID: 29067981]
[28]
Kim Y. [Residual Schizophrenia] Ryoikibetsu Shokogun Shirizu 2003; (38): 50-2.
[PMID: 12876927]
[29]
Miller JN, Black DW. Schizoaffective disorder: a review. Ann Clin Psychiatry 2019; 31(1): 47-53.
[http://dx.doi.org/10.3109/10401239109147967] [PMID: 30699217]
[30]
Abrams DJ, Rojas DC, Arciniegas DB. Is schizoaffective disorder a distinct categorical diagnosis? A critical review of the literature. Neuropsychiatr Dis Treat 2008; 4(6): 1089-109.
[http://dx.doi.org/10.2147/NDT.S4120] [PMID: 19337453]
[31]
Koola MM, Fawcett JA, Kelly DL. Case report on the management of depression in schizoaffective disorder, bipolar type focusing on lithium levels and measurement-based care. J Nerv Ment Dis 2011; 199(12): 989-90.
[http://dx.doi.org/10.1097/NMD.0b013e3182392d8f] [PMID: 22134460]
[32]
Sahakyan L, Kwapil TR. Hits and false alarms in recognition memory show differential impairment in positive and negative schizotypy. J Abnorm Psychol 2019; 128(6): 633-43.
[http://dx.doi.org/10.1037/abn0000441] [PMID: 31318242]
[33]
Mitra S, Mahintamani T, Kavoor AR, Nizamie SH. Negative symptoms in schizophrenia. Ind Psychiatry J 2016; 25(2): 135-44.
[http://dx.doi.org/10.4103/ipj.ipj_30_15] [PMID: 28659691]
[34]
Kirschner M, Aleman A, Kaiser S. Secondary negative symptoms - A review of mechanisms, assessment and treatment. Schizophr Res 2017; 186: 29-38.
[http://dx.doi.org/10.1016/j.schres.2016.05.003] [PMID: 27230288]
[35]
Tripathi A, Kar SK, Shukla R. Cognitive deficits in schizophrenia: understanding the biological correlates and remediation strategies. Clin Psychopharmacol Neurosci 2018; 16(1): 7-17.
[http://dx.doi.org/10.9758/cpn.2018.16.1.7] [PMID: 29397662]
[36]
Keefe RS, Eesley CE, Poe MP. Defining a cognitive function decrement in schizophrenia. Biol Psychiatry 2005; 57(6): 688-91.
[http://dx.doi.org/10.1016/j.biopsych.2005.01.003] [PMID: 15780858]
[37]
Lavretsky H. History of schizophrenia as a psychiatric disorder Clinical handbook of schizophrenia. New York: Guilford Press 2008; pp. 3-12.
[38]
Baumeister AA, Francis JL. Historical development of the dopamine hypothesis of schizophrenia. J Hist Neurosci 2002; 11(3): 265-77.
[http://dx.doi.org/10.1076/jhin.11.3.265.10391] [PMID: 12481477]
[39]
Brisch R, Saniotis A, Wolf R, et al. The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue. Front Psychiatry 2014; 5: 47.
[PMID: 24904434]
[40]
Lodge DJ, Grace AA. Hippocampal dysregulation of dopamine system function and the pathophysiology of schizophrenia. Trends Pharmacol Sci 2011; 32(9): 507-13.
[http://dx.doi.org/10.1016/j.tips.2011.05.001] [PMID: 21700346]
[41]
Yoon JH, Minzenberg MJ, Raouf S, D’Esposito M, Carter CS. Impaired prefrontal-basal ganglia functional connectivity and substantia nigra hyperactivity in schizophrenia. Biol Psychiatry 2013; 74(2): 122-9.
[http://dx.doi.org/10.1016/j.biopsych.2012.11.018] [PMID: 23290498]
[42]
Shen L-H, Liao M-H, Tseng YC. Recent advances in imaging of dopaminergic neurons for evaluation of neuropsychiatric disorders. J Biomed Biotechnol 2012; 2012: 259349.
[http://dx.doi.org/10.1155/2012/259349] [PMID: 22570524]
[43]
O’Donnell P, Grace AA. Dysfunctions in multiple interrelated systems as the neurobiological bases of schizophrenic symptom clusters. Schizophr Bull 1998; 24(2): 267-83.
[http://dx.doi.org/10.1093/oxfordjournals.schbul.a033325] [PMID: 9613625]
[44]
Sommer IE, Slotema CW, Daskalakis ZJ, Derks EM, Blom JD, van der Gaag M. The treatment of hallucinations in schizophrenia spectrum disorders. Schizophr Bull 2012; 38(4): 704-14.
[http://dx.doi.org/10.1093/schbul/sbs034] [PMID: 22368234]
[45]
Abi-Dargham A, Rodenhiser J, Printz D, et al. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci USA 2000; 97(14): 8104-9.
[http://dx.doi.org/10.1073/pnas.97.14.8104] [PMID: 10884434]
[46]
Cazorla M, de Carvalho FD, Chohan MO, et al. Dopamine D2 receptors regulate the anatomical and functional balance of basal ganglia circuitry. Neuron 2014; 81(1): 153-64.
[http://dx.doi.org/10.1016/j.neuron.2013.10.041] [PMID: 24411738]
[47]
Strange PG. Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacol Rev 2001; 53(1): 119-33.
[PMID: 11171942]
[48]
Newman-Tancredi A. The importance of 5-HT1A receptor agonism in antipsychotic drug action: rationale and perspectives. Curr Opin Investig Drugs 2010; 11(7): 802-12.
[PMID: 20571976]
[49]
Li P, Snyder GL, Vanover KE. Dopamine targeting drugs for the treatment of schizophrenia: past, present and future. Curr Top Med Chem 2016; 16(29): 3385-403.
[http://dx.doi.org/10.2174/1568026616666160608084834] [PMID: 27291902]
[50]
Uno Y, Coyle JT. Glutamate hypothesis in schizophrenia. Psychiatry Clin Neurosci 2019; 73(5): 204-15.
[http://dx.doi.org/10.1111/pcn.12823] [PMID: 30666759]
[51]
Saudou F, Hen R. 5-Hydroxytryptamine receptor subtypes in vertebrates and invertebrates. Neurochem Int 1994; 25(6): 503-32.
[http://dx.doi.org/10.1016/0197-0186(94)90150-3] [PMID: 7894328]
[52]
Selvaraj S, Arnone D, Cappai A, Howes O. Alterations in the serotonin system in schizophrenia: a systematic review and meta-analysis of postmortem and molecular imaging studies. Neurosci Biobehav Rev 2014; 45: 233-45.
[http://dx.doi.org/10.1016/j.neubiorev.2014.06.005] [PMID: 24971825]
[53]
Sorensen SM, Kehne JH, Fadayel GM, et al. Characterization of the 5-HT2 receptor antagonist MDL 100907 as a putative atypical antipsychotic: behavioral, electrophysiological and neurochemical studies. J Pharmacol Exp Ther 1993; 266(2): 684-91.
[PMID: 8102646]
[54]
De Deurwaerdère P, Di Giovanni G. Serotonergic modulation of the activity of mesencephalic dopaminergic systems: therapeutic implications. Prog Neurobiol 2017; 151: 175-236.
[http://dx.doi.org/10.1016/j.pneurobio.2016.03.004] [PMID: 27013075]
[55]
Roth BL, Hanizavareh SM, Blum AE. Serotonin receptors represent highly favorable molecular targets for cognitive enhancement in schizophrenia and other disorders. Psychopharmacology (Berl) 2004; 174(1): 17-24.
[http://dx.doi.org/10.1007/s00213-003-1683-8] [PMID: 15205874]
[56]
Yoshida K, Higuchi H, Hishikawa Y. Marked improvement of tardive dystonia after replacing haloperidol with risperidone in a schizophrenic patient. Clin Neuropharmacol 1998; 21(1): 68-9.
[PMID: 9579290]
[57]
Meltzer D. Perspective and the measurement of costs and benefits for cost-effectiveness analysis in schizophrenia. J Clin Psychiatry 1999; 60(Suppl. 3): 32-5.
[PMID: 10073375]
[58]
King MV, Sleight AJ, Woolley ML, Topham IA, Marsden CA, Fone KC. 5-HT6 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing consolidation--an effect sensitive to NMDA receptor antagonism. Neuropharmacology 2004; 47(2): 195-204.
[http://dx.doi.org/10.1016/j.neuropharm.2004.03.012] [PMID: 15223298]
[59]
Yang AC, Tsai SJ. New targets for schizophrenia treatment beyond the dopamine hypothesis. Int J Mol Sci 2017; 18(8): E1689.
[http://dx.doi.org/10.3390/ijms18081689] [PMID: 28771182]
[60]
Kerner B. Glutamate neurotransmission in psychotic disorders and substance abuse. Open Psychiatry J 2009; 3: 1-8.
[http://dx.doi.org/10.2174/1874354400903010001] [PMID: 19898680]
[61]
Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmüller B. Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci Lett 1980; 20(3): 379-82.
[http://dx.doi.org/10.1016/0304-3940(80)90178-0] [PMID: 6108541]
[62]
Eggers AE. A serotonin hypothesis of schizophrenia. Med Hypotheses 2013; 80(6): 791-4.
[http://dx.doi.org/10.1016/j.mehy.2013.03.013] [PMID: 23557849]
[63]
Ellaithy A, Younkin J, González-Maeso J, Logothetis DE. Positive allosteric modulators of metabotropic glutamate 2 receptors in schizophrenia treatment. Trends Neurosci 2015; 38(8): 506-16.
[http://dx.doi.org/10.1016/j.tins.2015.06.002] [PMID: 26148747]
[64]
Alberati D, Moreau JL, Lengyel J, et al. Glycine reuptake inhibitor RG1678: a pharmacologic characterization of an investigational agent for the treatment of schizophrenia. Neuropharmacology 2012; 62(2): 1152-61.
[http://dx.doi.org/10.1016/j.neuropharm.2011.11.008] [PMID: 22138164]
[65]
Evins AE, Fitzgerald SM, Wine L, Rosselli R, Goff DC. Placebo-controlled trial of glycine added to clozapine in schizophrenia. Am J Psychiatry 2000; 157(5): 826-8.
[http://dx.doi.org/10.1176/appi.ajp.157.5.826] [PMID: 10784481]
[66]
Javitt DC, Silipo G, Cienfuegos A, et al. Adjunctive high-dose glycine in the treatment of schizophrenia. Int J Neuropsychopharmacol 2001; 4(4): 385-91.
[http://dx.doi.org/10.1017/S1461145701002590] [PMID: 11806864]
[67]
Spear N, Gadient RA, Wilkins DE, et al. Preclinical profile of a novel metabotropic glutamate receptor 5 positive allosteric modulator. Eur J Pharmacol 2011; 659(2-3): 146-54.
[http://dx.doi.org/10.1016/j.ejphar.2011.02.003] [PMID: 21335002]
[68]
Cioffi CL. Modulation of NMDA receptor function as a treatment for schizophrenia. Bioorg Med Chem Lett 2013; 23(18): 5034-44.
[http://dx.doi.org/10.1016/j.bmcl.2013.07.019] [PMID: 23916256]
[69]
Anis NA, Berry SC, Burton NR, Lodge D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol 1983; 79(2): 565-75.
[http://dx.doi.org/10.1111/j.1476-5381.1983.tb11031.x] [PMID: 6317114]
[70]
Parle M, Kadian R. Behavioral models of psychosis. Int Res J Pharm 2013; 7: 26-30.
[http://dx.doi.org/10.7897/2230-8407.04706]
[71]
Parle M, Kadian R. Non behavioral models of psychosis. Int Res J Pharm 2013; 4: 89-95.
[http://dx.doi.org/10.7897/2230-8407.04815]
[72]
Battisti JJ, Shreffler CB, Uretsky NJ, Wallace LJ. NMDA antagonists block expression of sensitization of amphetamine- and apomorphine-induced stereotypy. Pharmacol Biochem Behav 2000; 67(2): 241-6.
[http://dx.doi.org/10.1016/S0091-3057(00)00324-5] [PMID: 11124387]
[73]
Jadi MP, Behrens MM, Sejnowski TJ. Abnormal gamma oscillations in N-methyl-D-aspartate receptor hypofunction models of schizophrenia. Biol Psychiatry 2016; 79(9): 716-26.
[http://dx.doi.org/10.1016/j.biopsych.2015.07.005] [PMID: 26281716]
[74]
Gonzalez-Burgos G, Cho RY, Lewis DA. Alterations in cortical network oscillations and parvalbumin neurons in schizophrenia. Biol Psychiatry 2015; 77(12): 1031-40.
[http://dx.doi.org/10.1016/j.biopsych.2015.03.010] [PMID: 25863358]
[75]
Ellenbroek BA, Prinssen EP. Can 5-HT3 antagonists contribute toward the treatment of schizophrenia? Behav Pharmacol 2015; 26(1-2): 33-44.
[http://dx.doi.org/10.1097/FBP.0000000000000102] [PMID: 25356732]
[76]
Samadi R, Soluti S, Daneshmand R, Assari S, Manteghi AA. Efficacy of risperidone augmentation with ondansetron in the treatment of negative and depressive symptoms in schizophrenia: a randomized clinical trial. Iran J Med Sci 2017; 42(1): 14-23.
[PMID: 28293046]
[77]
Levitt P, Eagleson KL, Powell EM. Regulation of neocortical interneuron development and the implications for neurodevelopmental disorders. Trends Neurosci 2004; 27(7): 400-6.
[http://dx.doi.org/10.1016/j.tins.2004.05.008] [PMID: 15219739]
[78]
Maglóczky Z, Freund TF. Impaired and repaired inhibitory circuits in the epileptic human hippocampus. Trends Neurosci 2005; 28(6): 334-40.
[http://dx.doi.org/10.1016/j.tins.2005.04.002] [PMID: 15927690]
[79]
Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 2005; 6(4): 312-24.
[http://dx.doi.org/10.1038/nrn1648] [PMID: 15803162]
[80]
Sanacora G, Saricicek A. GABAergic contributions to the pathophysiology of depression and the mechanism of antidepressant action. CNS Neurol Disord Drug Targets 2007; 6(2): 127-40.
[http://dx.doi.org/10.2174/187152707780363294] [PMID: 17430150]
[81]
Belmonte MK, Cook EH Jr, Anderson GM, et al. Autism as a disorder of neural information processing: directions for research and targets for therapy. Mol Psychiatry 2004; 9(7): 646-63.
[http://dx.doi.org/10.1038/sj.mp.4001499] [PMID: 15037868]
[82]
Perry TL, Kish SJ, Buchanan J, Hansen S. Gammaaminobutyric-acid deficiency in brain of schizophrenic patients. Lancet 1979; 1(8110): 237-9.
[http://dx.doi.org/10.1016/S0140-6736(79)90767-0] [PMID: 84898]
[83]
Bird JM. Computed tomographic brain studies and treatment response in schizophrenia. Can J Psychiatry 1985; 30(4): 251-4.
[http://dx.doi.org/10.1177/070674378503000407] [PMID: 3874681]
[84]
Glantz LA, Lewis DA. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry 2000; 57(1): 65-73.
[http://dx.doi.org/10.1001/archpsyc.57.1.65] [PMID: 10632234]
[85]
Kalus P, Müller TJ, Zuschratter W, Senitz D. The dendritic architecture of prefrontal pyramidal neurons in schizophrenic patients. Neuroreport 2000; 11(16): 3621-5.
[http://dx.doi.org/10.1097/00001756-200011090-00044] [PMID: 11095531]
[86]
Lewis DA, Gonzalez-Burgos G. Pathophysiologically based treatment interventions in schizophrenia. Nat Med 2006; 12(9): 1016-22.
[http://dx.doi.org/10.1038/nm1478] [PMID: 16960576]
[87]
Gill KM, Grace AA. The role of α5 GABAA receptor agonists in the treatment of cognitive deficits in schizophrenia. Curr Pharm Des 2014; 20(31): 5069-76.
[http://dx.doi.org/10.2174/1381612819666131216114612] [PMID: 24345268]
[88]
Gaur N, Gautam S, Gaur M, Sharma P, Dadheech G, Mishra S. The biochemical womb of schizophrenia: a review. Indian J Clin Biochem 2008; 23(4): 307-27.
[http://dx.doi.org/10.1007/s12291-008-0071-x] [PMID: 23105779]
[89]
Thomas JR, Tandon R. Cholinergic mechanisms in schizophrenia: current concept. Curr Psychos Ther Rep 2006; 4: 20-6.
[http://dx.doi.org/10.1007/BF02629410]
[90]
Vizi ES, Kobayashi O, Töröcsik A, et al. Heterogeneity of presynaptic muscarinic receptors involved in modulation of transmitter release. Neuroscience 1989; 31(1): 259-67.
[http://dx.doi.org/10.1016/0306-4522(89)90048-1] [PMID: 2549449]
[91]
Tsai G, Coyle JT. Glutamatergic mechanisms in schizophrenia. Annu Rev Pharmacol Toxicol 2002; 42: 165-79.
[http://dx.doi.org/10.1146/annurev.pharmtox.42.082701.160735] [PMID: 11807169]
[92]
Tzavara ET, Bymaster FP, Felder CC, et al. Dysregulated hippocampal acetylcholine neurotransmission and impaired cognition in M2, M4 and M2/M4 muscarinic receptor knockout mice. Mol Psychiatry 2003; 8(7): 673-9.
[http://dx.doi.org/10.1038/sj.mp.4001270] [PMID: 12874603]
[93]
Martin LF, Kem WR, Freedman R. Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia. Psychopharmacology (Berl) 2004; 174(1): 54-64.
[http://dx.doi.org/10.1007/s00213-003-1750-1] [PMID: 15205879]
[94]
Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol 2013; 11(3): 315-35.
[http://dx.doi.org/10.2174/1570159X11311030006] [PMID: 24179466]
[95]
Arnsten AF. The neurobiology of thought: the groundbreaking discoveries of Patricia Goldman-Rakic 1937-2003. Cereb Cortex 2013; 23(10): 2269-81.
[http://dx.doi.org/10.1093/cercor/bht195] [PMID: 23926115]
[96]
Takahashi H. PET neuroimaging of extrastriatal dopamine receptors and prefrontal cortex functions. J Physiol Paris 2013; 107(6): 503-9.
[http://dx.doi.org/10.1016/j.jphysparis.2013.07.001] [PMID: 23851135]
[97]
Patel SS, Attard A, Jacobsen P, Shergill S. Acetylcholinesterase Inhibitors (AChEI’s) for the treatment of visual hallucinations in schizophrenia: a case report. BMC Psychiatry 2010; 10: 68.
[http://dx.doi.org/10.1186/1471-244X-10-68] [PMID: 20822516]
[98]
Stryjer R, Strous RD, Bar F, et al. Beneficial effect of donepezil augmentation for the management of comorbid schizophrenia and dementia. Clin Neuropharmacol 2003; 26(1): 12-7.
[http://dx.doi.org/10.1097/00002826-200301000-00004] [PMID: 12567159]
[99]
Sharma T, Reed C, Aasen I, Kumari V. Cognitive effects of adjunctive 24-weeks Rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind investigation. Schizophr Res 2006; 85(1-3): 73-83.
[http://dx.doi.org/10.1016/j.schres.2006.03.037] [PMID: 16797163]
[100]
Bora E, Veznedaroğlu B, Kayahan B. The effect of galantamine added to clozapine on cognition of five patients with schizophrenia. Clin Neuropharmacol 2005; 28(3): 139-41.
[http://dx.doi.org/10.1097/01.wnf.0000162555.68729.04] [PMID: 15965314]
[101]
Samochocki M, Höffle A, Fehrenbacher A, et al. Galantamine is an allosterically potentiating ligand of neuronal nicotinic but not of muscarinic acetylcholine receptors. J Pharmacol Exp Ther 2003; 305(3): 1024-36.
[http://dx.doi.org/10.1124/jpet.102.045773] [PMID: 12649296]
[102]
Youdim MB, Edmondson D, Tipton KF. The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci 2006; 7(4): 295-309.
[http://dx.doi.org/10.1038/nrn1883] [PMID: 16552415]
[103]
Finberg JP. Update on the pharmacology of selective inhibitors of MAO-A and MAO-B: focus on modulation of CNS monoamine neurotransmitter release. Pharmacol Ther 2014; 143(2): 133-52.
[http://dx.doi.org/10.1016/j.pharmthera.2014.02.010] [PMID: 24607445]
[104]
Wayment HK, Schenk JO, Sorg BA. Characterization of extracellular dopamine clearance in the medial prefrontal cortex: role of monoamine uptake and monoamine oxidase inhibition. J Neurosci 2001; 21(1): 35-44.
[http://dx.doi.org/10.1523/JNEUROSCI.21-01-00035.2001] [PMID: 11150317]
[105]
Bodkin JA, Cohen BM, Salomon MS, Cannon SE, Zornberg GL, Cole JO. Treatment of negative symptoms in schizophrenia and schizoaffective disorder by selegiline augmentation of antipsychotic medication. A pilot study examining the role of dopamine. J Nerv Ment Dis 1996; 184(5): 295-301.
[http://dx.doi.org/10.1097/00005053-199605000-00005] [PMID: 8627275]
[106]
Gupta S, Droney T, Kyser A, Keller P. Selegiline augmentation of antipsychotics for the treatment of negative symptoms in schizophrenia. Compr Psychiatry 1999; 40(2): 148-50.
[http://dx.doi.org/10.1016/S0010-440X(99)90119-0] [PMID: 10080262]
[107]
Buchanan RW, Weiner E, Kelly DL, et al. Rasagiline in the treatment of the persistent negative symptoms of schizophrenia. Schizophr Bull 2015; 41(4): 900-8.
[http://dx.doi.org/10.1093/schbul/sbu151] [PMID: 25368372]
[108]
Axelrod J, Tomchick R. Enzymatic O-methylation of epinephrine and other catechols. J Biol Chem 1958; 233(3): 702-5.
[PMID: 13575440]
[109]
Williams HJ, Owen MJ, O’Donovan MC. Is COMT a susceptibility gene for schizophrenia? Schizophr Bull 2007; 33(3): 635-41.
[http://dx.doi.org/10.1093/schbul/sbm019] [PMID: 17412710]
[110]
Brisch R, Bernstein HG, Krell D, et al. Dopamineglutamate abnormalities in the frontal cortex associated with the catechol-O-methyltransferase (COMT) in schizophrenia. Brain Res 2009; 1269: 166-75.
[http://dx.doi.org/10.1016/j.brainres.2009.02.039] [PMID: 19268435]
[111]
Kontis D, Theochari E, Fryssira H, et al. COMT and MTHFR polymorphisms interaction on cognition in schizophrenia: an exploratory study. Neurosci Lett 2013; 537: 17-22.
[http://dx.doi.org/10.1016/j.neulet.2013.01.012] [PMID: 23353103]
[112]
Tunbridge EM, Bannerman DM, Sharp T, Harrison PJ. Catechol-o-methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex. J Neurosci 2004; 24(23): 5331-5.
[http://dx.doi.org/10.1523/JNEUROSCI.1124-04.2004] [PMID: 15190105]
[113]
Barrow J, Akuma D. Discovery and evaluation of nonnitrocatechol COMT inhibitors for treatment of psychiatric conditions. Schizophr Bull 2017; 43: S62-3.
[http://dx.doi.org/10.1093/schbul/sbx021.165]
[114]
Bhakta SG, Light GA, Talledo JA, et al. Tolcaponeenhanced neurocognition in healthy adults: neural basis and predictors. Int J Neuropsychopharmacol 2017; 20(12): 979-87.
[http://dx.doi.org/10.1093/ijnp/pyx074] [PMID: 29020372]
[115]
Clelland CL, Drouet V, Rilett KC, et al. Evidence that COMT genotype and proline interact on negative-symptom outcomes in schizophrenia and bipolar disorder. Transl Psychiatry 2016; 6(9): e891.
[http://dx.doi.org/10.1038/tp.2016.157] [PMID: 27622935]
[116]
Chopra K, Baveja A, Kuhad A. MMPs: a novel drug target for schizophrenia. Expert Opin Ther Targets 2015; 19(1): 77-85.
[http://dx.doi.org/10.1517/14728222.2014.957672] [PMID: 25214056]
[117]
Lepeta K, Kaczmarek L. Matrix metalloproteinase-9 as a novel player in synaptic plasticity and schizophrenia. Schizophr Bull 2015; 41(5): 1003-9.
[http://dx.doi.org/10.1093/schbul/sbv036] [PMID: 25837304]
[118]
Creese I, Burt DR, Snyder SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. J Neuropsychiatry Clin Neurosci 1996; 8(2): 223-6.
[http://dx.doi.org/10.1176/jnp.8.2.223] [PMID: 9081563]
[119]
Saldaña M, Bonastre M, Aguilar E, Marin C. Role of nigral NFkappaB p50 and p65 subunit expression in haloperidol-induced neurotoxicity and stereotyped behavior in rats. Eur Neuropsychopharmacol 2006; 16(7): 491-7.
[http://dx.doi.org/10.1016/j.euroneuro.2006.01.001] [PMID: 16500086]
[120]
Kim SH, Seo MS, Jeon WJ, et al. Haloperidol regulates the phosphorylation level of the MEK-ERKp90RSK signal pathway via protein phosphatase 2A in the rat frontal cortex. Int J Neuropsychopharmacol 2008; 11(4): 509-17.
[http://dx.doi.org/10.1017/S1461145707008292] [PMID: 18272021]
[121]
Kowalski J, Blada P, Kucia K, Madej A, Herman ZS. Neuroleptics normalize increased release of interleukin- 1 β and tumor necrosis factor-α from monocytes in schizophrenia. Schizophr Res 2001; 50(3): 169-75.
[http://dx.doi.org/10.1016/S0920-9964(00)00156-0] [PMID: 11439237]
[122]
Bošković M, Vovk T, Kores Plesničar B, Grabnar I. Oxidative stress in schizophrenia. Curr Neuropharmacol 2011; 9(2): 301-12.
[http://dx.doi.org/10.2174/157015911795596595] [PMID: 22131939]
[123]
Monji A, Kato TA, Mizoguchi Y, et al. Neuroinflammation in schizophrenia especially focused on the role of microglia. Prog Neuropsychopharmacol Biol Psychiatry 2013; 42: 115-21.
[http://dx.doi.org/10.1016/j.pnpbp.2011.12.002] [PMID: 22192886]
[124]
Meyer U. Developmental neuroinflammation and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2013; 42: 20-34.
[http://dx.doi.org/10.1016/j.pnpbp.2011.11.003] [PMID: 22122877]
[125]
Müller N, Schwarz MJ. COX-2 inhibition in schizophrenia and major depression. Curr Pharm Des 2008; 14(14): 1452-65.
[http://dx.doi.org/10.2174/138161208784480243] [PMID: 18537668]
[126]
Pandurangi AK, Buckley PF. Inflammation, antipsychotic drugs, and evidence for effectiveness of antiinflammatory agents in schizophrenia. Curr Top Behav Neurosci 2020; 44: 227-44.
[http://dx.doi.org/10.1007/7854_2019_91] [PMID: 30993585]
[127]
MacDonald ML, Naydenov A, Chu M, Matzilevich D, Konradi C. Decrease in creatine kinase messenger RNA expression in the hippocampus and dorsolateral prefrontal cortex in bipolar disorder. Bipolar Disord 2006; 8(3): 255-64.
[http://dx.doi.org/10.1111/j.1399-5618.2006.00302.x] [PMID: 16696827]
[128]
Rajasekaran A, Venkatasubramanian G, Berk M, Debnath M. Mitochondrial dysfunction in schizophrenia: pathways, mechanisms and implications. Neurosci Biobehav Rev 2015; 48: 10-21.
[http://dx.doi.org/10.1016/j.neubiorev.2014.11.005] [PMID: 25446950]
[129]
Yadav M, Parle M, Kadian M, Sharma K. A review on psychosis and anti-psychotic plants. Asian J Pharm Clin Res 2015; 8: 24-8.
[130]
Mahadik SP, Evans DR. Is schizophrenia a metabolic brain disorder? Membrane phospholipid dysregulation and its therapeutic implications. Psychiatr Clin North Am 2003; 26(1): 85-102.
[http://dx.doi.org/10.1016/S0193-953X(02)00033-3] [PMID: 12683261]
[131]
Matsumoto J, Nakanishi H, Kunii Y, et al. Decreased 16:0/20:4-phosphatidylinositol level in the postmortem prefrontal cortex of elderly patients with schizophrenia. Sci Rep 2017; 7: 45050.
[http://dx.doi.org/10.1038/srep45050] [PMID: 28332626]
[132]
Horrobin DF, Glen AI, Vaddadi K. The membrane hypothesis of schizophrenia. Schizophr Res 1994; 13(3): 195-207.
[http://dx.doi.org/10.1016/0920-9964(94)90043-4] [PMID: 7841132]
[133]
Wood PL, Holderman NR. Dysfunctional glycosynapses in schizophrenia: disease and regional specificity. Schizophr Res 2015; 166(1-3): 235-7.
[http://dx.doi.org/10.1016/j.schres.2015.05.017] [PMID: 26004690]
[134]
du Bois TM, Deng C, Huang XF. Membrane phospholipid composition, alterations in neurotransmitter systems and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29(6): 878-88.
[http://dx.doi.org/10.1016/j.pnpbp.2005.04.034] [PMID: 16005134]
[135]
Rodríguez B, Nani JV, Almeida PGC, Brietzke E, Lee RS. hayashi maf.neuropeptides and oligopeptidases in schizophrenia. neurosci biobehav rev 2019.pii: s0149-7634(19)30397-
[136]
Nair NP, Lal S, Bloom DM. Cholecystokinin peptides, dopamine and schizophrenia--a review. Prog Neuropsychopharmacol Biol Psychiatry 1985; 9(5-6): 515-24.
[http://dx.doi.org/10.1016/0278-5846(85)90011-9] [PMID: 2868491]
[137]
Ballaz S. The unappreciated roles of the cholecystokinin receptor CCK(1) in brain functioning. Rev Neurosci 2017; 28(6): 573-85.
[http://dx.doi.org/10.1515/revneuro-2016-0088] [PMID: 28343167]
[138]
Bourin M, Malinge M, Vasar E, Bradwejn J. Two faces of cholecystokinin: anxiety and schizophrenia. Fundam Clin Pharmacol 1996; 10(2): 116-26.
[http://dx.doi.org/10.1111/j.1472-8206.1996.tb00154.x] [PMID: 8737954]
[139]
Montgomery SA, Green MC. The use of cholecystokinin in schizophrenia: a review. Psychol Med 1988; 18(3): 593-603.
[http://dx.doi.org/10.1017/S0033291700008278] [PMID: 3054990]
[140]
Zuardi AW, Crippa JA, Hallak JE, et al. A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation. Curr Pharm Des 2012; 18(32): 5131-40.
[http://dx.doi.org/10.2174/138161212802884681] [PMID: 22716160]
[141]
Kasckow J, Nemeroff CB. The neurobiology of neurotensin: focus on neurotensin-dopamine interactions. Regul Pept 1991; 36(2): 153-64.
[http://dx.doi.org/10.1016/0167-0115(91)90053-J] [PMID: 1666685]
[142]
Kinkead B, Nemeroff CB. Neurotensin, schizophrenia, and antipsychotic drug action. Int Rev Neurobiol 2004; 59: 327-49.
[http://dx.doi.org/10.1016/S0074-7742(04)59013-X] [PMID: 15006494]
[143]
Griebel G. Neuropeptide receptor ligands for the treatment of schizophrenia: focus on neurotensin and tachykinins. Curr Pharm Des 2015; 21(26): 3807-12.
[http://dx.doi.org/10.2174/1381612821666150605105859] [PMID: 26044977]
[144]
Binder EB, Kinkead B, Owens MJ, Nemeroff CB. The role of neurotensin in the pathophysiology of schizophrenia and the mechanism of action of antipsychotic drugs. Biol Psychiatry 2001; 50(11): 856-72.
[http://dx.doi.org/10.1016/S0006-3223(01)01211-2] [PMID: 11743941]
[145]
Horacek J, Bubenikova-Valesova V, Kopecek M, et al. Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. CNS Drugs 2006; 20(5): 389-409.
[http://dx.doi.org/10.2165/00023210-200620050-00004] [PMID: 16696579]
[146]
Feifel D, Reza TL, Wustrow DJ, Davis MD. Novel antipsychotic-like effects on prepulse inhibition of startle produced by a neurotensin agonist. J Pharmacol Exp Ther 1999; 288(2): 710-3.
[PMID: 9918579]
[147]
Cáceda R, Kinkead B, Nemeroff CB. Neurotensin: role in psychiatric and neurological diseases. Peptides 2006; 27(10): 2385-404.
[http://dx.doi.org/10.1016/j.peptides.2006.04.024] [PMID: 16891042]
[148]
Woodworth HL, Brown JA, Batchelor HM, Bugescu R, Leinninger GM. Determination of neurotensin projections to the ventral tegmental area in mice. Neuropeptides 2018; 68: 57-74.
[http://dx.doi.org/10.1016/j.npep.2018.02.003] [PMID: 29478718]
[149]
Servonnet A, Minogianis EA, Bouchard C, et al. Neurotensin in the nucleus accumbens reverses dopamine supersensitivity evoked by antipsychotic treatment. Neuropharmacology 2017; 123: 10-21.
[http://dx.doi.org/10.1016/j.neuropharm.2017.05.015] [PMID: 28522313]
[150]
Kost NV, Meshavkin VK, Khashaba EY, et al. Neurotensin-like peptides as potential antipsychotics: modulation of the serotonin system. Bull Exp Biol Med 2014; 157(6): 738-41.
[http://dx.doi.org/10.1007/s10517-014-2656-0] [PMID: 25339589]

© 2024 Bentham Science Publishers | Privacy Policy