Millan MJ, Agid Y, Brüne M, Bullmore ET, Carter CS, Clayton NS, Connor R, Davis S, Deakin B, DeRubeis RJ, Dubois B, Geyer MA, Goodwin GM, Gorwood P, Jay TM, Joëls M, Mansuy IM, Meyer-Lindenberg A, Murphy D, Rolls E, Saletu B, Spedding M, Sweeney J, Whittington M, Young LJ (2012) Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov 11(2):141–168. https://doi.org/10.1038/nrd3628

Article  CAS  PubMed  Google Scholar 

Gebreegziabhere Y, Habatmu K, Mihretu A, Cella M, Alem A (2022) Cognitive impairment in people with schizophrenia: an umbrella review. Eur Arch Psychiatry Clin Neurosci 272(7):1139–1155. https://doi.org/10.1007/s00406-022-01416-6

Article  PubMed  PubMed Central  Google Scholar 

Kriesche D, Woll CFJ, Tschentscher N, Engel RR, Karch S (2022) Neurocognitive deficits in depression: a systematic review of cognitive impairment in the acute and remitted state. Eur Arch Psychiatry Clin Neurosci. https://doi.org/10.1007/s00406-022-01479-5

Article  PubMed  Google Scholar 

Yoshida T, Suga M, Arima K, Muranaka Y, Tanaka T, Eguchi S, Lin C, Yoshida S, Ishikawa M, Higuchi Y, Seo T, Ueoka Y, Tomotake M, Kaneda Y, Darby D, Maruff P, Iyo M, Kasai K, Higuchi T, Sumiyoshi T, Ohmori T, Takahashi K, Hashimoto K (2011) Criterion and construct validity of the CogState Schizophrenia Battery in Japanese patients with schizophrenia. PLoS One 6(5):e20469. https://doi.org/10.1371/journal.pone.0020469

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yoshida T, Ishikawa M, Niitsu T, Nakazato M, Watanabe H, Shiraishi T, Shiina A, Hashimoto T, Kanahara N, Hasegawa T, Enohara M, Kimura A, Iyo M, Hashimoto K (2012) Decreased serum levels of mature brain-derived neurotrophic factor (BDNF), but not its precursor proBDNF, in patients with major depressive disorder. PLoS One 7(8):e42676. https://doi.org/10.1371/journal.pone.0042676

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kitchen H, Rofail D, Herton L, Sacco P (2012) Cognitive impairment associated with schizophrenia: a review of the humanistic burden. Adv Ther 29(2):148–162. https://doi.org/10.1007/s12325-012-0001-4

Article  PubMed  Google Scholar 

Aquila R, Citrome L (2015) Cognitive impairment in schizophrenia: the great unmet need. CNS Spectr 20(Suppl 1):35–39. https://doi.org/10.1017/S109285291500070X

Article  PubMed  Google Scholar 

Keefe RS (2016) Treating cognitive impairment in depression: an unmet need. Lancet Psychiatry 3(5):392–393. https://doi.org/10.1016/S2215-0366(16)00095-X

Article  PubMed  Google Scholar 

Hashimoto K (2019) Recent advances in the early intervention in schizophrenia: future direction from preclinical findings. Curr Psychiatry Rep 21(8):75. https://doi.org/10.1007/s11920-019-1063-7

Article  PubMed  Google Scholar 

Javitt DC, Zukin SR (1991) Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 148(10):1301–1308. https://doi.org/10.1176/ajp.148.10.1301

Article  CAS  PubMed  Google Scholar 

Neill JC, Barnes S, Cook S, Grayson B, Idris NF, McLean SL, Snigdha S, Rajagopal L, Harte MK (2010) Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism. Pharmacol Ther 128(3):419–432. https://doi.org/10.1016/j.pharmthera.2010.07.004

Article  CAS  PubMed  Google Scholar 

Domino EF, Luby ED (2012) Phencyclidine/schizophrenia: one view toward the past, the other to the future. Schizophr Bull 38(5):914–919. https://doi.org/10.1093/schbul/sbs011

Article  PubMed  PubMed Central  Google Scholar 

Javitt DC, Zukin SR, Heresco-Levy U, Umbricht D (2012) Has an angel shown the way? Etiological and therapeutic implications of the PCP/NMDA model of schizophrenia. Schizophr Bull 38(5):958–966. https://doi.org/10.1093/schbul/sbs069

Article  PubMed  PubMed Central  Google Scholar 

Hashimoto K, Malchow B, Falkai P, Schmitt A (2013) Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders. Eur Arch Psychiatry Clin Neurosci 263(5):367–377. https://doi.org/10.1007/s00406-013-0399-y

Article  PubMed  Google Scholar 

Wiescholleck V, Manahan-Vaughan D (2013) Long-lasting changes in hippocampal synaptic plasticity and cognition in an animal model of NMDA receptor dysfunction in psychosis. Neuropharmacology 74:48–58. https://doi.org/10.1016/j.neuropharm.2013.01.001

Article  CAS  PubMed  Google Scholar 

Hashimoto K (2014) Targeting of NMDA receptors in new treatments for schizophrenia. Expert Opin Ther Targets 18(9):1049–1063. https://doi.org/10.1517/14728222.2014.934225

Article  CAS  PubMed  Google Scholar 

Cadinu D, Grayson B, Podda G, Harte MK, Doostdar N, Neill JC (2018) NMDA receptor antagonist rodent models for cognition in schizophrenia and identification of novel drug treatments, an update. Neuropharmacology 142:41–62. https://doi.org/10.1016/j.neuropharm.2017.11.045

Article  CAS  PubMed  Google Scholar 

Javitt DC (2023) Cognitive impairment associated with schizophrenia: toward novel therapeutics. Annu Rev Pharmacol Toxicol 63:119–141. https://doi.org/10.1146/annurev-pharmtox-051921-093250

Article  CAS  PubMed  Google Scholar 

Hashimoto K, Fukushima T, Shimizu E, Komatsu N, Watanabe H, Shinoda N, Nakazato M, Kumakiri C, Okada S, Hasegawa H, Imai K, Iyo M (2003) Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia. Arch Gen Psychiatry 60(6):572–576. https://doi.org/10.1001/archpsyc.60.6.572

Article  CAS  PubMed  Google Scholar 

Hashimoto K, Engberg G, Shimizu E, Nordin C, Lindström LH, Iyo M (2005) Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry 29(5):767–769. https://doi.org/10.1016/j.pnpbp.2005.04.023

Article  CAS  PubMed  Google Scholar 

Yamada K, Ohnishi T, Hashimoto K, Ohba H, Iwayama-Shigeno Y, Toyoshima M, Okuno A, Takao H, Toyota T, Minabe Y, Nakamura K, Shimizu E, Itokawa M, Mori N, Iyo M, Yoshikawa T (2005) Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and D-serine levels. Biol Psychiatry 57(12):1493–1503. https://doi.org/10.1016/j.biopsych.2005.03.018

Article  CAS  PubMed  Google Scholar 

Maekawa M, Ohnishi T, Hashimoto K, Watanabe A, Iwayama Y, Ohba H, Hattori E, Yamada K, Yoshikawa T (2010) Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia. J Neurochem 115(6):1374–1385. https://doi.org/10.1111/j.1471-4159.2010.07039.x

Article  CAS  PubMed  Google Scholar 

Merritt K, McGuire PK, Egerton A, 1H-MRS in Schizophrenia Investigators, Aleman A, Block W, Bloemen OJN, Borgan F, Bustillo JR, Capizzano AA, Coughlin JM, De la Fuente-Sandoval C, Demjaha A, Dempster K, Do KQ, Du F, Falkai P, Galinska-Skok B, Gallinat J, Gasparovic C, Ginestet CE, Goto N, Graff-Guerrero A, Ho BC, Howes OD, Jauhar S, Jeon P, Kato T, Kaufmann CA, Kegeles LS, Keshavan M, Kim SY, Kunugi H, Lauriello J, Liemburg EJ, Mcilwain ME, Modinos G, Mouchlianitis ED, Nakamura J, Nenadic I, Öngür D, Ota M, Palaniyappan L, Pantelis C, Plitman E, Posporelis S, Purdon SE, Reichenbach JR, Renshaw PF, Russell BR, Sawa A, Schaefer M, Shungu DC, Smesny S, Stanley JA, Stone JM, Szulc A, Taylor R, Thakkar K, Théberge J, Tibbo PG, van Amelsvoort T, Walecki J, Williamson PC, Wood SJ, Xin L, Yamasue H (2021) Association of age, antipsychotic medication, and symptom severity in schizophrenia with proton magnetic resonance spectroscopy brain glutamate level: a mega-analysis of individual participant-level data. JAMA Psychiat 78(6):667–681. https://doi.org/10.1001/jamapsychiatry.2021.0380

Article  Google Scholar 

Hashimoto K, Sawa A, Iyo M (2007) Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry 62(11):1310–1316. https://doi.org/10.1016/j.biopsych.2007.03.017

Article  CAS  PubMed  Google Scholar 

Hashimoto K (2009) Emerging role of glutamate in the pathophysiology of major depressive disorder. Brain Res Rev 61(2):105–123. https://doi.org/10.1016/j.brainresrev.2009.05.005

Article  CAS  PubMed  Google Scholar 

Tokita K, Yamaji T, Hashimoto K (2012) Roles of glutamate signaling in preclinical and/or mechanistic models of depression. Pharmacol Biochem Behav 100(4):688–704. https://doi.org/10.1016/j.pbb.2011.04.016

Article  CAS  PubMed  Google Scholar 

Ohgi Y, Futamura T, Hashimoto K (2015) Glutamate signaling in synaptogenesis and NMDA receptors as potential therapeutic targets for psychiatric disorders. Curr Mol Med 15(3):206–221. https://doi.org/10.2174/1566524015666150330143008

Article  CAS  PubMed  Google Scholar 

Hashimoto K, Yoshida T, Ishikawa M, Fujita Y, Niitsu T, Nakazato M, Watanabe H, Sasaki T, Shiina A, Hashimoto T, Kanahara N, Hasegawa T, Enohara M, Kimura A, Iyo M (2016) Increased serum levels of serine enantiomers in patients with depression. Acta Neuropsychiatr 28(3):173–178. https://doi.org/10.1017/neu.2015.59

Article  PubMed  Google Scholar 

Hashimoto K, Bruno D, Nierenberg J, Marmar CR, Zetterberg H, Blennow K, Pomara N (2016) Abnormality in glutamine-glutamate cycle in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder: a 3-year follow-up study. Transl Psychiatry 6(3):e744. https://doi.org/10.1038/tp.2016.8

Article  CAS  PubMed  PubMed Central  Google Scholar 

Moriguchi S, Takamiya A, Noda Y, Horita N, Wada M, Tsugawa S, Plitman E, Sano Y, Tarumi R, ElSalhy M, Katayama N, Ogyu K, Miyazaki T, Kishimoto T, Graff-Guerrero A, Meyer JH, Blumberger DM, Daskalakis ZJ, Mimura M, Nakajima S (2019) Glutamatergic neurometabolite levels in major depressive disorder: a systematic review and meta-analysis of proton magnetic resonance spectroscopy studies. Mol Psychiatry 24(7):952–964. https://doi.org/10.1038/s41380-018-0252-9

Article  CAS  PubMed  Google Scholar 

Chabert J, Allauze E, Pereira B, Chassain C, De Chazeron I, Rotgé JY, Fossati P, Llorca PM, Samalin L (2022) Glutamatergic and N-acetylaspartate metabolites in bipolar disorder: a systematic review and meta-analysis of proton magnetic resonance spectroscopy studies. Int J Mol Sci 23(16):8974. https://doi.org/10.3390/ijms23168974

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shirayama Y, Takahashi M, Osone F, Hara A, Okubo T (2017) Myo-inositol, glutamate, and glutamine in the prefrontal cortex, hippocampus, and amygdala in major depression. Biol Psychiatry Cogn Neurosci Neuroimaging 2(2):196–204.