{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:04:03Z","timestamp":1791259443484,"version":"4.1.0"},"reference-count":136,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2015,12,17]],"date-time":"2015-12-17T00:00:00Z","timestamp":1450310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although the dopamine D2 receptor (DRD2) has been a main target of antipsychotic pharmacotherapy for the treatment of schizophrenia, the standard treatment does not offer sufficient relief of symptoms to 20%\u201330% of patients suffering from this disorder. Moreover, over 80% of patients experience relapsed psychotic episodes within five years following treatment initiation. These data strongly suggest that the continuous blockade of DRD2 by antipsychotic(s) could eventually fail to control the psychosis in some point during long-term treatment, even if such treatment has successfully provided symptomatic improvement for the first-episode psychosis, or stability for the subsequent chronic stage. Dopamine supersensitivity psychosis (DSP) is historically known as a by-product of antipsychotic treatment in the manner of tardive dyskinesia or transient rebound psychosis. Numerous data in psychopharmacological studies suggest that the up-regulation of DRD2, caused by antipsychotic(s), is likely the mechanism underlying the development of the dopamine supersensitivity state. However, regardless of evolving notions of dopamine signaling, particularly dopamine release, signal transduction, and receptor recycling, most of this research has been conducted and discussed from the standpoint of disease etiology or action mechanism of the antipsychotic, not of DSP. Hence, the mechanism of the DRD2 up-regulation or mechanism evoking clinical DSP, both of which are caused by pharmacotherapy, remains unknown. Once patients experience a DSP episode, they become increasingly difficult to treat. Light was recently shed on a new aspect of DSP as a treatment-resistant factor. Clarification of the detailed mechanism of DSP is therefore crucial, and a preventive treatment strategy for DSP or treatment-resistant schizophrenia is urgently needed.<\/jats:p>","DOI":"10.3390\/ijms161226228","type":"journal-article","created":{"date-parts":[[2015,12,17]],"date-time":"2015-12-17T10:47:37Z","timestamp":1450349257000},"page":"30144-30163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Alterations of Dopamine D2 Receptors and Related Receptor-Interacting Proteins in Schizophrenia: The Pivotal Position of Dopamine Supersensitivity Psychosis in Treatment-Resistant Schizophrenia"],"prefix":"10.3390","volume":"16","author":[{"given":"Yasunori","family":"Oda","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhisa","family":"Kanahara","sequence":"additional","affiliation":[{"name":"Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaomi","family":"Iyo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1517\/14728222.10.4.515","article-title":"Targeting the dopamine D2 receptor in schizophrenia","volume":"10","author":"Seeman","year":"2006","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1176\/appi.ajp.162.3.441","article-title":"Remission in schizophrenia: Proposed criteria and rationale for consensus","volume":"162","author":"Andreasen","year":"2005","journal-title":"Am. J. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.schres.2008.09.018","article-title":"Course of illness in a sample of 265 patients with first-episode psychosis-five-year follow-up of the Danish OPUS trial","volume":"107","author":"Bertelsen","year":"2009","journal-title":"Schizophr. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1001\/archpsyc.1988.01800330013001","article-title":"Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine","volume":"45","author":"Kane","year":"1988","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_5","first-page":"58","article-title":"Gender aspect in schizophrenia: Bridging the border between social and biological psychiatry","volume":"407","year":"2000","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1176\/ajp.154.4.475","article-title":"Age at onset and gender of schizophrenic patients in relation to neuroleptic resistance","volume":"154","author":"Meltzer","year":"1997","journal-title":"Am. J. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1097\/00004714-199804001-00002","article-title":"Predictors of outcome in schizophrenia","volume":"18","author":"Murray","year":"1998","journal-title":"J. Clin. Psychophamacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1001\/archpsyc.62.9.975","article-title":"Association between duration of untreated psychosis and outcome in cohorts of first-episode patients. A systematic review","volume":"62","author":"Marshall","year":"2005","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1176\/appi.ajp.162.10.1785","article-title":"Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: A critical review and meta-analysis","volume":"162","author":"Perkins","year":"2005","journal-title":"Am. J. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1017\/S0033291799002627","article-title":"Social disability in schizophrenia: Its development and prediction over 15 years in incidence cohorts in six European centers","volume":"30","author":"Wiersma","year":"2000","journal-title":"Psychol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1001\/archpsyc.1993.01820170047006","article-title":"Time course and biologic correlates of treatment response in first-episode schizophrenia","volume":"50","author":"Lieberman","year":"1993","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1176\/ajp.156.4.544","article-title":"Predictors of treatment response from a first episode of schizophrenia or schizoaffective disorder","volume":"156","author":"Robinson","year":"1999","journal-title":"Am. J. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/hup.2469","article-title":"Rate and predictors of non-response to first-line antipsychotic treatment in first-episode schizophrenia","volume":"30","author":"Chiliza","year":"2015","journal-title":"Hum. Psychopharmacol. Clin. Exp."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1176\/ajp.135.11.1409","article-title":"Neuroleptic-induced supersensitivity psychosis","volume":"135","author":"Chouinard","year":"1978","journal-title":"Am. J. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1176\/ajp.135.11.1321","article-title":"Withdrawal syndromes associated with antipsychotic drugs","volume":"135","author":"Gardos","year":"1978","journal-title":"Am. J. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1176\/ajp.137.1.16","article-title":"Neuroleptic-induced supersensitivity psychosis: Clinical and pharmacological characteristics","volume":"137","author":"Chouinard","year":"1980","journal-title":"Am. J. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0920-9964(91)90050-2","article-title":"Severe cases of neuroleptic-induced supersensitivity psychosis. Diagnostic criteria for the disorder and its treatment","volume":"5","author":"Chouinard","year":"1991","journal-title":"Schizophr. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1097\/JCP.0b013e31828ea95c","article-title":"Optimal extent of dopamine D2 receptor occupancy by antipsychotics for treatment of dopamine supersensitivity psychosis and late-onset psychosis","volume":"33","author":"Iyo","year":"2013","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1600-0447.2006.00787.x","article-title":"Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersenstivity psychosis) and withdrawal-related relapse","volume":"114","author":"Moncrieff","year":"2006","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1097\/00005053-199204000-00009","article-title":"The concept of supersensitivity psychosis","volume":"180","author":"Kirkpatrick","year":"1992","journal-title":"J. Nerv. Ment. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1177\/0269881109359097","article-title":"A naturalistic controlled study of relapsing schizophrenic patients with tardive dyskinesia and supersensitivity psychosis","volume":"25","author":"Fallon","year":"2011","journal-title":"J. Psychopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1177\/0269881115570083","article-title":"Dopamine supersensitivity psychosis and dopamine partial agonist: A retrospective survey of failure of switching to aripiprazole in schizophrenia","volume":"29","author":"Takase","year":"2015","journal-title":"J. Psychopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1001\/archpsyc.1995.03950240089014","article-title":"Conversions from clozapine to other antipsychotic drugs","volume":"52","author":"Baldessarini","year":"1995","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1176\/ajp.156.6.876","article-title":"Rapid release of antipsychotic drugs from dopamine D2 receptors: An explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine","volume":"156","author":"Seeman","year":"1999","journal-title":"Am. J. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.schres.2014.02.022","article-title":"A prospective comparative study of risperidone long-acting injectable for treatment-resistant schizophrenia with dopamine supersensitivity psychosis","volume":"155","author":"Kimura","year":"2014","journal-title":"Schizophr. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1097\/00004714-198105000-00002","article-title":"Drug withdrawal in chronic schizophrenic patients: In search of neuroleptic-induced supersensitivity psychosis","volume":"1","author":"Weinberger","year":"1981","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_27","first-page":"891","article-title":"Neuroleptic-induced psychological supersensitivity syndromes: Are these syndromes myth or reality?","volume":"22","author":"Chouinard","year":"1986","journal-title":"Psychopharmacol. Bull."},{"key":"ref_28","first-page":"319","article-title":"Neuroleptic withdrawal in patients meeting criteria for supersensitivity psychosis","volume":"51","author":"Singh","year":"1990","journal-title":"J. Clin. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1177\/2045125311431105","article-title":"Drug-induced supersensitivity psychosis revisited: Characteristics of relapse in treatment-compliant patients","volume":"2","author":"Fallon","year":"2012","journal-title":"Ther. Adv. Psychopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1159\/000112883","article-title":"Atypical antipsychotics. CATIE study, drug-induced movement disorder and resulting iatrogenic psychiatric-like symptoms, supersensitivity rebound psychosis and withdrawal discontinuation syndromes","volume":"77","author":"Chouinard","year":"2008","journal-title":"Psychother. Psychosom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.psychres.2015.02.021","article-title":"Dopamine supersensitivity psychosis as a pivotal factor in treatment-resistant schizophrenia","volume":"227","author":"Suzuki","year":"2015","journal-title":"Psychiatr. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"147","DOI":"10.4088\/PCC.08r00612","article-title":"Partial adherence to antipsychotic medication impacts the course of illness in patients with schizophrenia: A review","volume":"11","author":"Masand","year":"2009","journal-title":"Prim. Care Companion J. Clin. Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.encep.2010.01.003","article-title":"Iatrogenic psychiatric-like symptoms recognition","volume":"36","author":"Demily","year":"2010","journal-title":"Encephale"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0304-3940(94)90248-8","article-title":"A new animal model of dopamine supersensitivity using s.c. implantation of haloperidol releasing polymers","volume":"170","author":"Augusatin","year":"1994","journal-title":"Neurosci. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0197-0186(96)00093-9","article-title":"Effects of chronic neuroleptic treatments on dopamine D1 and D2 receptors: Homogenate binding and autoradiographic studies","volume":"30","author":"Huang","year":"1997","journal-title":"Neurochem. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0014-2999(96)00920-X","article-title":"Aripiprazole, a novel antipsychotic drug, inhibits quinpirole-evoked GTPase activity but does not up-regulate dopamine D2 receptor following repeated treatment in the rat striatum","volume":"321","author":"Inoue","year":"1997","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0376-6357(03)00028-7","article-title":"Effects of haloperidol on rat behavior and density of dopaminergic D2-like receptors","volume":"63","author":"Vasconcelos","year":"2003","journal-title":"Behav. Process."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1523\/JNEUROSCI.5416-06.2007","article-title":"\u201cBreakthrough\u201d dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time","volume":"27","author":"Samaha","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1093\/schbul\/sbr006","article-title":"Chronic treatment with aripiprazole prevents development of dopamine supersensitivity and potentially supersensitivity psychosis","volume":"38","author":"Tadokoro","year":"2011","journal-title":"Schizophr. Bull."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/syn.10139","article-title":"Amphetamine-sensitized animals show a marked increase in dopamine D2HIGH receptors occupied by endogenous dopamine, even in the absence of acute challenges","volume":"46","author":"Seeman","year":"2002","journal-title":"Synapse"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3513","DOI":"10.1073\/pnas.0409766102","article-title":"Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis","volume":"102","author":"Seeman","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1126\/science.6147018","article-title":"Bimodal distribution of dopamine receptor densities in brains of schizophrenics","volume":"225","author":"Seeman","year":"1984","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s002130000532","article-title":"Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: A clinical PET study","volume":"152","author":"Silvestri","year":"2000","journal-title":"Psychopharmacology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1192\/bjp.171.6.574","article-title":"Altered dopaminergic function and negative symptoms in drug-free patients with schizophrenia. [123I]-iodobenzamide SPECT study","volume":"171","author":"Knable","year":"1997","journal-title":"Br. J. Psychiatry"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s00213-003-1644-2","article-title":"Striatal dopamine D2 receptor density in neuroleptic-naive and in neuroleptic-free schizophrenic patients: An 123I-IBZM-SPECT study","volume":"172","author":"Catafau","year":"2004","journal-title":"Psychopharmacology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1097\/00004647-200003000-00001","article-title":"Imaging synaptic neurotransmission with in vivo binding competition techniques: A critical review","volume":"20","author":"Laruelle","year":"2000","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/syn.20498","article-title":"Dopamine D2High receptors moderately elevated by sertindole","volume":"62","author":"Seeman","year":"2008","journal-title":"Synapse"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0920-9964(98)00041-3","article-title":"Dopamine D2 densities and the schizophrenic brain","volume":"32","author":"Zakzanis","year":"1998","journal-title":"Schizophr. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1001\/archgenpsychiatry.2012.169","article-title":"The nature of dopamine dysfunction in schizophrenia and what this means for treatment","volume":"69","author":"Howes","year":"2012","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/npp.2008.199","article-title":"The dopamine D2 receptors in high-affinity state and D3 receptors in schizophrenia: A clinical [11C]-(+)-PHNO PET study","volume":"34","author":"Mizrahi","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1001\/archgenpsychiatry.2009.43","article-title":"The effect of antipsychotics on the high-affinity state of D2 and D3 receptors","volume":"66","author":"Mamo","year":"2009","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0006-3223(99)00067-0","article-title":"Increased dopamine transmission in schizophrenia: Relationship to illness phases","volume":"46","author":"Laruelle","year":"1999","journal-title":"Biol. Psychiatry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8104","DOI":"10.1073\/pnas.97.14.8104","article-title":"Increased baseline occupancy of D2 receptors by dopamine in schizophrenia","volume":"97","author":"Rodenhiser","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1001\/archgenpsychiatry.2010.10","article-title":"Increased synaptic dopamine function in associative regions of the striatum in schizophrenia","volume":"67","author":"Kegeles","year":"2010","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1176\/appi.ajp.2012.12010144","article-title":"Dopamine synthesis capacity in patients with treatment-resistant schizophrenia","volume":"169","author":"Demjaha","year":"2012","journal-title":"Am. J. Psychiatry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/humu.20039","article-title":"Identification and characterization of ANKK1: A novel kinase gene closely linked to DRD2 on chromosome band 11q23.1","volume":"23","author":"Neville","year":"2004","journal-title":"Hum. Mutat."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/sj.mp.4000350","article-title":"The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers","volume":"3","author":"Pohjalainen","year":"1998","journal-title":"Mol. Psychiatry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/sj.mp.4000532","article-title":"Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers","volume":"4","author":"Jonsson","year":"1999","journal-title":"Mol. Psychiatry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1126\/science.281.5381.1285h","article-title":"DRD2 gene and alcoholism","volume":"281","author":"Noble","year":"1998","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/00008571-199712000-00006","article-title":"D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: Reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele","volume":"7","author":"Thompson","year":"1997","journal-title":"Pharmacogenetics"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1093\/hmg\/6.4.577","article-title":"A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia","volume":"6","author":"Arinami","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1176\/appi.ajp.158.5.802","article-title":"Association of short-term response to haloperidol treatment with a polymorphism in the dopamine D2 receptor gene","volume":"158","author":"Rujescu","year":"2001","journal-title":"Am. J. Psychiatry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neulet.2004.11.014","article-title":"Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients","volume":"376","author":"Wu","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1176\/appi.ajp.163.3.529","article-title":"DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients","volume":"163","author":"Lencz","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1176\/appi.ajp.2009.09040598","article-title":"D2 receptor genetic variation and clinical response to antipsychotic drug treatment: A meta-analysis","volume":"167","author":"Zhang","year":"2010","journal-title":"Am. J. Psychiatry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/S0278-5846(03)00151-9","article-title":"Combination of dopamine D2 receptor gene polymorphisms as a possible predictor of treatment-resistance to dopamine antagonists in schizophrenic patients","volume":"27","author":"Kondo","year":"2003","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/j.1440-1819.2007.01633.x","article-title":"Dopamine D2 receptor gene polymorphisms predict well the response to dopamine antagonists at therapeutic dosages in patients with schizophrenia","volume":"61","author":"Sakumoto","year":"2007","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.tips.2007.02.006","article-title":"The AKT-GSK-3 signaling cascade in the actions of dopamine","volume":"28","author":"Beaulieu","year":"2007","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5099","DOI":"10.1073\/pnas.0307921101","article-title":"Lithium antagonizes dopamine-dependent behaviors mediated by an AKT\/glycogen synthase kinase 3 signaling cascade","volume":"101","author":"Beaulieu","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.cellsig.2005.01.002","article-title":"Pathophysiological roles of G-protein-coupled receptor kinases","volume":"17","author":"Metaye","year":"2005","journal-title":"Cell Signal."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.bbamem.2006.09.019","article-title":"The G protein-coupled receptor kinase (GRK) interactome: Role of GRKs in GPCR regulation and signaling","volume":"1768","author":"Ribas","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1124\/pr.110.002642","article-title":"The physiology, signaling, and pharmacology of dopamine receptors","volume":"63","author":"Beaulieu","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/mp.2011.123","article-title":"Hypothesis review: Are clathrin-mediated endocytosis and clathrin-dependent membrane and protein trafficking core pathophysiological processes in schizophrenia and bipolar disorder?","volume":"17","author":"Schubert","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/310503a0","article-title":"DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1","volume":"310","author":"Hemmings","year":"1984","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1146\/annurev.pharmtox.44.101802.121415","article-title":"DARPP-32: An integrator of neurotransmission","volume":"44","author":"Svenningsson","year":"2004","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8147","DOI":"10.1523\/JNEUROSCI.17-21-08147.1997","article-title":"Bidirectional regulation of DARPP-32 phosphorylation by dopamine","volume":"17","author":"Nishi","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/cne.903230206","article-title":"Immunocytochemical localization of DARPP-32, a dopamine and cyclic-AMP-regulated phosphoprotein, in the primate brain","volume":"323","author":"Ouimet","year":"1992","journal-title":"J. Comp. Neurol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1523\/JNEUROSCI.04-01-00111.1984","article-title":"DARPP-32, a dopamine- and adenosine 3\u2019,5\u2019-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. III. Immunocytochemical localization","volume":"4","author":"Ouimet","year":"1984","journal-title":"J. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1126\/science.1089681","article-title":"Diverse psychotomimetics act through a common signaling pathway","volume":"302","author":"Svenningsson","year":"2003","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1126\/science.281.5378.838","article-title":"DARPP-32: Regulator of the efficacy of dopaminergic neurotransmission","volume":"281","author":"Fiengerg","year":"1998","journal-title":"Science"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1172\/JCI30413","article-title":"Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition","volume":"117","author":"Straub","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/mp.2012.174","article-title":"Revisiting DARPP-32 in postmortem human brain: Changes in schizophrenia and bipolar disorder and genetic associations with t-DARPP-32 expression","volume":"19","author":"Kunii","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.schres.2007.10.028","article-title":"Genetic analysis of the gene coding for DARPP-32 (PPP1R1B) in Japanese patients with schizophrenia or bipolar disorder","volume":"100","author":"Yoshimi","year":"2008","journal-title":"Schizophr. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1146\/annurev.biochem.67.1.653","article-title":"G protein-coupled receptor kinases","volume":"67","author":"Picher","year":"1998","journal-title":"Annu. Rev. Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0006-8993(01)03046-3","article-title":"Distribution of G-protein-coupled receptor kinase (GRK) isoforms 2, 3, 5 and 6 mRNA in the rat brain","volume":"95","author":"Mayer","year":"2001","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0896-6273(03)00192-2","article-title":"Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice","volume":"38","author":"Gainetdinov","year":"2003","journal-title":"Neuron"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/syn.20303","article-title":"Psychosis pathways converge via D2HIGH dopamine receptors","volume":"60","author":"Seeman","year":"2006","journal-title":"Synapse"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"28ra28","DOI":"10.1126\/scitranslmed.3000664","article-title":"Lentiviral overexpression of GRK6 alleviates l-DOPA-induced dyskinesia in experimental Parkinson\u2019s disease","volume":"2","author":"Ahmed","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1002\/hup.2375","article-title":"Association study of common variants within the G protein-coupled receptor kinase 6 gene and schizophrenia susceptibility in Han Chinese","volume":"29","author":"Tang","year":"2014","journal-title":"Hum. Psychopharmacol."},{"key":"ref_90","first-page":"1845","article-title":"Genetic association between G protein-coupled receptor kinase 6\/\u03b2-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia","volume":"11","author":"Oda","year":"2015","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.schres.2014.07.040","article-title":"Increased G protein-coupled receptor kinase (GRK) expression in the anterior cingulate cortex in schizophrenia","volume":"159","author":"Funk","year":"2014","journal-title":"Schizophr. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.nbd.2011.07.009","article-title":"Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder","volume":"44","author":"Bychkov","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/383447a0","article-title":"\u03b2-Arrestin acts as a clathrin adaptor in endocytosis of the \u03b22-adrenergic receptor","volume":"383","author":"Goodman","year":"1996","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"35518","DOI":"10.1074\/jbc.M405878200","article-title":"Differential kinetic and spatial patterns of \u03b2-arrestin and G protein-mediated ERK activation by the angiotensin II receptor","volume":"279","author":"Ahn","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.pharmthera.2008.11.005","article-title":"Physiological and pharmacological implications of \u03b2-arrestin regulation","volume":"121","author":"Schmid","year":"2009","journal-title":"Pharmacol. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1083\/jcb.145.5.927","article-title":"Heptahelical receptor signaling: Beyond the G protein paradigm","volume":"145","author":"Hall","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.cell.2005.05.012","article-title":"An Akt\/\u03b2-arrestin 2\/PP2A signaling complex mediates dopaminergic neurotransmission and behavior","volume":"122","author":"Beaulieu","year":"2005","journal-title":"Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"18488","DOI":"10.1073\/pnas.1104807108","article-title":"Discovery of \u03b2-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy","volume":"108","author":"Allen","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1601-183X.2006.00237.x","article-title":"Possible association of \u03b2-arrestin 2 gene with methamphetamine use disorder, but not schizophrenia","volume":"6","author":"Ikeda","year":"2007","journal-title":"Genes Brain Behav."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1111\/j.1468-1331.2008.02316.x","article-title":"The coding-synonymous polymorphism rs1045280 (Ser280Ser) in b-arrestin2 (ARRB2) gene is associated with tardive dyskinesia in Chinese patients with schizophrenia","volume":"15","author":"Liou","year":"2008","journal-title":"Eur. J. Neurol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.pnpbp.2013.07.006","article-title":"Are dopamine D2 receptors out of control in psychosis?","volume":"46","author":"Seeman","year":"2013","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1177\/0269881115593903","article-title":"G protein-coupled receptor kinase 6\/\u03b2-arrestin 2 system in a rat model of dopamine supersensitivity psychosis","volume":"29","author":"Oda","year":"2015","journal-title":"J. Psychopharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/ng1296","article-title":"Convergent evidence for impaired AKT1-GSK3\u03b2 signaling in schizophrenia","volume":"36","author":"Emamian","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s00213-013-2997-9","article-title":"Electrophysiological and behavioral responses to ketamine in mice with reduced Akt1 expression","volume":"227","author":"Featherstone","year":"2013","journal-title":"Psychopharmacology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neuroscience.2010.09.056","article-title":"Behavioral phenotyping of v-akt murine thymoma viral oncogene homolog 1-deficient mice reveals a sex-specific prepulse inhibition deficit in females that can be partially alleviated by glycogen synthase kinase-3 inhibitors but not by antipsychotics","volume":"174","author":"Chen","year":"2011","journal-title":"Neuroscience"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.biopsych.2004.07.023","article-title":"Association of AKT1 with schizophrenia confirmed in a Japanese population","volume":"56","author":"Ikeda","year":"2004","journal-title":"Biol. Psychiatry"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/ajmg.b.30291","article-title":"Association of AKT1 haplotype with the risk of schizophrenia in Iranian population","volume":"141B","author":"Bajestan","year":"2006","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.4088\/JCP.v68n0906","article-title":"Association of AKT1 gene polymorphisms with risk of schizophrenia and with response to antipsychotics in the Chinese population","volume":"68","author":"Xu","year":"2007","journal-title":"J. Clin. Psychiatry"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.biopsych.2007.06.005","article-title":"AKT1 is associated with schizophrenia across multiple symptom dimensions in the Irish study of high density schizophrenia families","volume":"63","author":"Thiselton","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.psychres.2013.05.017","article-title":"No association between AKT1 gene variants and schizophrenia: A Malaysian case-control study and meta-analysis","volume":"209","author":"Loh","year":"2013","journal-title":"Psychiatry Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1038\/npp.2011.141","article-title":"AKT1 moderation of cannabis-induced cognitive alterations in psychotic disorder","volume":"36","author":"Simons","year":"2011","journal-title":"Neuropsychopharmacology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.biopsych.2012.06.020","article-title":"Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users","volume":"72","author":"Iyegbe","year":"2012","journal-title":"Biol. Psychiatry"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.brainres.2012.06.032","article-title":"The possible role of the Akt signaling pathway in schizophrenia","volume":"1470","author":"Zheng","year":"2012","journal-title":"Brain Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1002\/j.1460-2075.1990.tb07419.x","article-title":"Molecular cloning and expression of glycogen synthase kinase-3\/factor A","volume":"9","author":"Woodgett","year":"1990","journal-title":"EMBO. J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1046\/j.1471-4159.1994.63010245.x","article-title":"Localization and developmental changes of tau protein kinase I\/glycogen synthase kinase-3\u03b2 in rat brain","volume":"63","author":"Takahashi","year":"1994","journal-title":"J. Neurochem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1016\/j.euroneuro.2014.07.004","article-title":"Reduced striatal dopamine DA D2 receptor function in dominant-negative GSK-3 transgenic mice","volume":"24","author":"Bortolozzi","year":"2014","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.schres.2012.01.024","article-title":"Inhibition of glycogen synthase kinase-3 attenuates psychotomimetic effects of ketamine","volume":"136","author":"Chan","year":"2012","journal-title":"Schizophr. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.tins.2007.02.002","article-title":"Schizophrenia as a GSK-3 dysregulation disorder","volume":"30","author":"Lovestone","year":"2007","journal-title":"Trends Neurosci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3389\/fnmol.2012.00033","article-title":"AKT\/GSK3 signaling pathway and schizophrenia","volume":"5","author":"Emamian","year":"2012","journal-title":"Front. Mol. Neurosci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.neubiorev.2010.08.001","article-title":"GSK-3\u03b2 activity and hyperdopamine-dependent behaviors","volume":"35","author":"Li","year":"2011","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1176\/appi.ajp.2009.08121873","article-title":"Roles of the Akt\/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action","volume":"167","author":"Freuberg","year":"2010","journal-title":"Am. J. Psychiatry"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.biopsych.2013.08.035","article-title":"Glycogen synthase kinase-3 overexpression replicates electroretinogram anomalies of offspring at high genetic risk for schizophrenia and bipolar disorder","volume":"76","author":"Lavoie","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neuropharm.2013.05.012","article-title":"Altered GSK3\u03b2 signaling in an infection-based mouse model of developmental neuropsychiatric disease","volume":"73","author":"Willi","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.biopsych.2004.11.036","article-title":"Antipsychotics alter the protein expression levels of \u03b2-catenin and GSK-3 in the rat medial prefrontal cortex and striatum","volume":"57","author":"Alimohamad","year":"2005","journal-title":"Biol. Psychiatry"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s00213-008-1193-9","article-title":"Association study of GSK3 gene polymorphisms with schizophrenia and clozapine response","volume":"200","author":"Souza","year":"2008","journal-title":"Psychopharmacology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.schres.2011.09.013","article-title":"Genetic association and identification of a functional SNP at GSK3\u03b2 for schizophrenia susceptibility","volume":"133","author":"Li","year":"2011","journal-title":"Schizophr. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1176\/appi.ajp.2012.12070908","article-title":"Association of GSK-3\u03b2 genetic variation with GSK-3\u03b2 expression, prefrontal cortical thickness, prefrontal physiology, and schizophrenia","volume":"170","author":"Blasi","year":"2013","journal-title":"Am. J. Psychiatry"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1007\/s12035-013-8414-x","article-title":"GSK-3\u03b2 polymorphism discriminates bipolar disorder and schizophrenia: A systematic meta-analysis","volume":"48","author":"Tang","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1176\/appi.ajp.157.5.831","article-title":"Low GSK-3\u03b2 immunoreactivity in postmortem frontal cortex of schizophrenic patients","volume":"157","author":"Kozlovsky","year":"2000","journal-title":"Am. J. Psychiatry"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1007\/s00702-004-0166-3","article-title":"Reduced GSK-3\u03b2 mRNA levels in postmortem dorsolateral prefrontal cortex of schizophnirec patients","volume":"111","author":"Kozlovsky","year":"2004","journal-title":"J. Neural. Transm."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1111\/j.1460-9568.2006.05023.x","article-title":"Internalization of D2 dopamine receptors is clathrin-dependent and select to dendro-axonic appositions in primate prefrontal cortex","volume":"24","author":"Paspalas","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s12017-010-8142-6","article-title":"CALM, a clathrin assembly protein, influences cell surface GluR2 abundance","volume":"13","author":"Harel","year":"2011","journal-title":"Neuromol. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"7972","DOI":"10.1523\/JNEUROSCI.20-21-07972.2000","article-title":"Constitutive endocytosis of GABAA receptors by an association with the adaptin AP2 complex modulates inhibitory synaptic currents in hippocampal neurons","volume":"20","author":"Kittler","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"3S","DOI":"10.1097\/00004714-198808001-00002","article-title":"Antipsychotic drug binding in the substantia nigra: An examination of high metoclopramide binding in the brains of normal, Alzheimer\u2019s disease, Huntington\u2019s disease, and Multiple Sclerosis patients, and its relation to tardive dyskinesia","volume":"8","author":"Seeman","year":"1988","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/syn.20825","article-title":"Cell membrane lytic action of metoclopramide and its relation to tardive dyskinesia","volume":"65","author":"Chen","year":"2011","journal-title":"Synapse"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/syn.21504","article-title":"Tardive dyskinesia, dopamine receptors, and neuroleptic damage to cell membranes","volume":"66","author":"Lai","year":"2012","journal-title":"Synapse"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/12\/26228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:54:18Z","timestamp":1760216058000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/12\/26228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,17]]},"references-count":136,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2015,12]]}},"alternative-id":["ijms161226228"],"URL":"https:\/\/doi.org\/10.3390\/ijms161226228","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,17]]}}}