Schizophrenia. 2019. https://www.who.int/mental_health/management/schizophrenia/en/.
Elvevåg B, Goldberg TE. Cognitive impairment in schizophrenia is the core of the disorder. Crit Rev Neurobiol. 2000;14(1):21.
Harvey PD. What is the evidence for changes in cognition and functioning over the lifespan in patients with schizophrenia? J Clin Psychiatry. 2014;75(Suppl 2):34–8.
Keefe RS. The longitudinal course of cognitive impairment in schizophrenia: an examination of data from premorbid through posttreatment phases of illness. J Clin Psychiatry. 2014;75(Suppl 2):2–8.
•• Fusar-Poli P, Deste G, Smieskova R, Barlati S, Yung AR, Howes O, et al. Cognitive functioning in prodromal psychosis: a meta-analysis. Arch Gen Psychiatry. 2012;69:562–71. This is a meta-analysis of cognitive function in prodromal state.
Bora E, Murray RM. Meta-analysis of cognitive deficits in ultra-high risk to psychosis and first-episode psychosis: do the cognitive deficits progress over, or after, the onset of psychosis? Schizophr Bull. 2014;40:744–55.
Mollon J, Reichenberg A. Cognitive development prior to onset of psychosis. Psychol Med. 2018;48:392–403.
Hauser M, Zhang JP, Sheridan EM, Burdick KE, Mogil R, Kane JM, et al. Neuropsychological test performance to enhance identification of subjects at clinical high risk for psychosis and to be most promising for predictive algorithms for conversion to psychosis: a meta-analysis. J Clin Psychiatry. 2017;78:e28–40.
Bolt LK, Amminger GP, Farhall J, McGorry PD, Nelson B, Markulev C, et al. Neurocognition as a predictor of transition to psychotic disorder and functional outcomes in ultra-high risk participants: findings from the NEURAPRO randomized clinical trial. Schizophr Res. 2018;206:67–74. https://doi.org/10.1016/j.schres.2018.12.013.
Bloomfield PS, Selvaraj S, Veronese M, Rizzo G, Bertoldo A, Owen DR, et al. Microglial activity in people at ultra high risk of psychosis and in schizophrenia: an [11C]PBR28 PET brain imaging study. Am J Psychiatry. 2016;173:44–52.
Di Biase MA, Zalesky A, O’keefe G, Laskaris L, Baune BT, Weickert CS, et al. PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia. Transl Psychiatry. 2017;7:e1225.
Hafizi S, Da Silva T, Gerritsen C, Kiang M, Bagby RM, Prce I, et al. Imaging microglial activation in individuals at clinical high risk for psychosis: an in vivo PET study with [18F]FEPPA. Neuropsychopharmacology. 2017;42:2474–81.
Marques TR, Ashok AH, Pillinger T, Veronese M, Turkheimer FE, Dazzan P, et al. Neuroinflammation in schizophrenia: meta-analysis of in vivo microglial imaging studies. Psychol Med. 2018:1–11. https://doi.org/10.1017/S0033291718003057.
Laskaris LE, Di Biase MA, Everall I, Chana G, Christopoulos A, Skafidas E, et al. Microglial activation and progressive brain changes in schizophrenia. Br J Pharmacol. 2016;173:666–80.
Mendelson T, Eaton WW. Recent advances in the prevention of mental disorders. Soc Psychiatry Psychiatr Epidemiol. 2018;53:325–39.
Canetta S, Sourander A, Surcel HM, Hinkka-Yli-Salomäki S, Leiviskä J, Kellendonk C, et al. Elevated maternal C-reactive protein and increased risk of schizophrenia in a national birth cohort. Am J Psychiatry. 2014;171:960–8.
• Estes ML, McAllister AK. Maternal immune activation: implications for neuropsychiatric disorders. Science. 2016;353:772–7. This is a review article on MIA and psychiatric disorders.
•• Brown AS, Meyer U. Maternal immune activation and neuropsychiatric illness: a translational research perspective. Am J Psychiatry. 2018;175:1073–83. This is a review article on MIA and psychiatric disorders.
Boulanger-Bertolus J, Pancaro C, Mashour GA. Increasing role of maternal immune activation in neurodevelopmental disorders. Front Behav Neurosci. 2018;12:230.
Gumusoglu SB, Stevens HE. Maternal inflammation and neurodevelopmental programming: a review of preclinical outcomes and implications for translational psychiatry. Biol Psychiatry. 2019;85:107–21.
Lydholm CN, Köhler-Forsberg O, Nordentoft M, Yolken RH, Mortensen PB, Petersen L, et al. Parental infections before, during, and after pregnancy as risk factors for mental disorders in childhood and adolescence: a nationwide Danish study. Biol Psychiatry. 2019;85:317–25.
Smolders S, Notter T, Smolders SMT, Rigo JM, Brône B. Controversies and prospects about microglia in maternal immune activation models for neurodevelopmental disorders. Brain Behav Immun. 2018;73:51–65.
• Fujita Y, Ishima T, Hashimoto K. Supplementation with D-serine prevents the onset of cognitive deficits in adult offspring after maternal immune activation. Sci Rep. 2016;6:37261. This is an article showing beneficial effects of D-serine in prodromal model of schizophrenia.
•• Han M, Zhang JC, Yao W, Yang C, Ishima T, Ren Q, et al. Intake of 7,8-dihydroxyflavone during juvenile and adolescent stages prevents onset of psychosis in adult offspring after maternal immune activation. Sci Rep. 2016;6:36087. This is an article showing beneficial effects of 7,8-dihydroxyflavone (TrkB agonist) in prodromal model of schizophrenia.
Han M, Zhang JC, Huang XF, Hashimoto K. Intake of 7,8-dihydroxyflavone from pregnancy to weaning prevents cognitive deficits in adult offspring after maternal immune activation. Eur Arch Psychiatry Clin Neurosci. 2017;267:479–83.
Dabbah-Assadi F, Alon D, Golani I, Doron R, Kremer I, Beloosesky R, et al. The influence of immune activation at early vs late gestation on fetal NRG1-ErbB4 expression and behavior in juvenile and adult mice offspring. Brain Behav Immun. 2019. https://doi.org/10.1016/j.bbi.2019.02.002.
Hashimoto K, Malchow B, Falkai P, Schmitt A. Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders. Eur Arch Psychiatry Clin Neurosci. 2013;263:367–77.
Hashimoto K. Targeting of NMDA receptors in new treatments for schizophrenia. Expert Opin Ther Targets. 2014;18:1049–63.
Ohgi Y, Futamura T, Hashimoto K. Glutamate signaling in synaptogenesis and NMDA receptors as potential therapeutic targets for psychiatric disorders. Curr Mol Med. 2015;15:206–21.
Hardingham GE, Do KQ. Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis. Nat Rev Neurosci. 2016;17:125–34.
Coyle JT. Schizophrenia: basic and clinical. Adv Neurobiol. 2017;15:255–80.
Javitt DC, Lee M, Kantrowitz JT, Martinez A. Mismatch negativity as a biomarker of theta band oscillatory dysfunction in schizophrenia. Schizophr Res. 2018;191:51–60.
Kantrowitz JT, Swerdlow NR, Dunn W, Vinogradov S. Auditory system target engagement during plasticity-based interventions in schizophrenia: a focus on modulation of N-methyl-D-aspartate-type glutamate receptor function. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3:581–90.
Hashimoto K, Fukushima T, Shimizu E, Komatsu N, Watanabe H, Shinoda N, et al. 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. 2003;60:572–6.
Hashimoto K, Engberg G, Shimizu E, Nordin C, Lindström LH, Iyo M. Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients. Prog Neuro-Psychopharmacol Biol Psychiatry. 2005;29:767–9.
Guercio GD, Panizzutti R. Potential and challenges for the clinical use of D-serine as a cognitive enhancer. Front Psychiatry. 2018;9:14.
MacKay MB, Kravtsenyuk M, Thomas R, Mitchell ND, Dursun SM, Baker GB. D-Serine: Potential therapeutic agent and/or biomarker in schizophrenia and depression? Front Psychiatry. 2018;10:25.
Miya K, Inoue R, Takata Y, Abe M, Natsume R, Sakimura K, et al. Serine racemase is predominantly localized in neurons in mouse brain. J Comp Neurol. 2008;510:641–54.
Coyle JT, Balu DT. The role of serine racemase in the pathophysiology of brain disorders. Adv Pharmacol. 2018;82:35–56.
Wolosker H. The neurobiology of D-serine signaling. Adv Pharmacol. 2018;82:325–48.
Ivanov AD, Mothet JP. The plastic D-serine signaling pathway: sliding from neurons to glia and vice-versa. Neurosci Lett. 2019;689:21–5.
Perez EJ, Tapanes SA, Loris ZB, Balu DT, Sick TJ, Coyle JT, et al. Enhanced astrocytic D-serine underlies synaptic damage after traumatic brain injury. J Clin Invest. 2017;127:3114–25.
Dong C, Zhang JC, Ren Q, Ma M, Qu Y, Zhang K, et al. Deletion of serine racemase confers D-serine -dependent resilience to chronic social defeat stress. Neurochem Int. 2018;116:43–51.
Levin R, Dor-Abarbanel AE, Edelman S, Durrant AR, Hashimoto K, Javitt DC, et al. Behavioral and cognitive effects of the N-methyl-D-aspartate receptor co-agonist D-serine in healthy humans: initial findings. J Psychiatr Res. 2015;61:188–95.
Kantrowitz JT, Epstein ML, Lee M, Lehrfeld N, Nolan KA, Shope C, et al. Improvement in mismatch negativity generation during d-serine treatment in schizophrenia: correlation with symptoms. Schizophr Res. 2018;191:70–9.
Koshiyama D, Kirihara K, Tada M, Nagai T, Fujioka M, Usui K, et al. Gamma-band auditory steady-state response is associated with plasma levels of D-serine in schizophrenia: an exploratory study. Schizophr Res. 2019;208:467–9. https://doi.org/10.1016/j.schres.2019.02.012.
Panizzutti R, Fisher M, Garrett C, Man WH, Sena W, Madeira C, et al. Association between increased serum D-serine and cognitive gains induced by intensive cognitive training in schizophrenia. Schizophr Res. 2018;207:63–9. https://doi.org/10.1016/j.schres.2018.04.011.
Chang CH, Lane HY, Tseng PT, Chen SJ, Liu CY, Lin CH. Effect of N-methyl-D-aspartate-receptor-enhancing agents on cognition in patients with schizophrenia: a systematic review and meta-analysis of double-blind randomised controlled trials. J Psychopharmacol. 2019;33:436–48. https://doi.org/10.1177/0269881118822157.
Hagiwara H, Iyo M, Hashimoto K. Neonatal disruption of serine racemase causes schizophrenia-like behavioral abnormalities in adulthood: clinical rescue by D-serine. PLoS One. 2013;8:e62438.
Ryan A, Baker A, Dark F, Foley S, Gordon A, Hatherill S, et al. The efficacy of sodium benzoate as an adjunctive treatment in early psychosis - CADENCE-BZ: study protocol for a randomized controlled trial. Trials. 2017;18:165.
Han M, Zhang JC, Hashimoto K. Increased levels of C1q in the prefrontal cortex of adult offspring after maternal immune activation: prevention by 7,8-dihydroxyflavone. Clin Psychopharmacol Neurosci. 2017;15:64–7.
Shirai Y, Fujita Y, Hashimoto R, Ohi K, Yamamori H, Yasuda Y, et al. Dietary intake of sulforaphane-rich broccoli sprout extracts during juvenile and adolescence can prevent phencyclidine-induced cognitive deficits at adulthood. PLoS One. 2015;10:e0127244.
•• Matsuura A, Ishima T, Fujita Y, Iwayama Y, Hasegawa S, Kawahara-Miki R, et al. Dietary glucoraphanin prevents the onset of psychosis in the adult offspring after maternal immune activation. Sci Rep. 2018;8:2158. This is an article showing beneficial effects of dietary glucoraphanin in the prevention of psychosis in offspring after MIA.
•• Ma M, Ren Q, Yang J, Zhang K, Xiong Z, Ishima T, et al. Key role of soluble epoxide hydrolase in the neurodevelopmental disorders of offspring after maternal immune activation. Proc Natl Acad Sci U S A. 2019. https://doi.org/10.1073/pnas.1819234116. This is the first article showing the role of soluble epoxide hydrolase in neurodevelopmental disorders such as schizophrenia and ASD.
CoNCERT Pharmaceuticals Inc. 2019. https://www.concertpharma.com/product-pipeline/.
•• Lane HY, Lin CH, Green MF, Hellemann G, Huang CC, Chen PW, et al. Add-on treatment of benzoate for schizophrenia: a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor. JAMA Psychiatry. 2013;70:1267–75. This is an article showing beneficial effects of sodium benzoate in patients with schizophrenia.
Lin CH, Lin CH, Chang YC, Huang YJ, Chen PW, Yang HT, et al. Sodium benzoate, a D-amino acid oxidase inhibitor, added to clozapine for the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial. Biol Psychiatry. 2018;84:422–32.
Matsuura A, Fujita Y, Iyo M, Hashimoto K. Effects of sodium benzoate on pre-pulse inhibition deficits and hyperlocomotion in mice after administration of phencyclidine. Acta Neuropsychiatr. 2015;27:159–67.
Popiolek M, Tierney B, Steyn SJ, DeVivo M. Lack of effect of sodium benzoate at reported clinical therapeutic concentration on D-alanine metabolism in dogs. ACS Chem Neurosci. 2018;9:2832–7.
Brahmachari S, Jana A, Pahan K. Sodium benzoate, a metabolite of cinnamon and a food additive, reduces microglial and astroglial inflammatory responses. J Immunol. 2009;183:5917–27.
Nieto R, Kukuljan M, Silva H. BDNF and schizophrenia: from neurodevelopment to neuronal plasticity, learning, and memory. Front Psychiatry. 2013;4:45.
Rodrigues-Amorim D, Rivera-Baltanás T, Bessa J, Sousa N, Vallejo-Curto MC, Rodríguez-Jamardo C, et al. The neurobiological hypothesis of neurotrophins in the pathophysiology of schizophrenia: a meta-analysis. J Psychiatr Res. 2018;106:43–53.
• Yang B, Ren Q, Zhang JC, Chen QX, Hashimoto K. Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: rethinking the brain-liver axis. Transl Psychiatry. 2017;7:e1128. This is an article showing abnormalities in proBDNF, BDNF, and BDNF pro-peptide in the postmortem brain from schizophrenia.
Islam F, Mulsant BH, Voineskos AN, Rajji TK. Brain-derived neurotrophic factor expression in individuals with schizophrenia and healthy aging: testing the accelerated aging hypothesis of schizophrenia. Curr Psychiatry Rep. 2017;19:36.
Du X, Hill RA. 7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental disorders. Neurochem Int. 2015;89:170–80.
Liu C, Chan CB, Ye K. 7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders. Transl Neurodegener. 2016;5:2.
Makar TK, Nimmagadda VK, Singh IS, Lam K, Mubariz F, Judge SI, et al. TrkB agonist, 7,8-dihydroxyflavone, reduces the clinical and pathological severity of a murine model of multiple sclerosis. J Neuroimmunol. 2016;292:9–20.
Zhang JC, Yao W, Hashimoto K. Brain-derived neurotrophic factor (BDNF)-TrkB signaling in inflammation-related depression and potential therapeutic targets. Curr Neuropharmacol. 2016;14:721–31.
Ren Q, Zhang JC, Fujita Y, Ma M, Wu J, Hashimoto K. Effects of TrkB agonist 7,8-dihydroxyflavone on sensory gating deficits in mice after administration of methamphetamine. Pharmacol Biochem Behav. 2013;106:124–7.
Ren Q, Zhang JC, Ma M, Fujita Y, Wu J, Hashimoto K. 7,8-Dihydroxyflavone, a TrkB agonist, attenuates behavioral abnormalities and neurotoxicity in mice after administration of methamphetamine. Psychopharmacology. 2014;231:159–66.
Zhang JC, Wu J, Fujita Y, Yao W, Ren Q, Yang C, et al. Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation. Int J Neuropsychopharmacol. 2014;18:pyu077.
Zhang JC, Yao W, Dong C, Yang C, Ren Q, Ma M, et al. Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression. Psychopharmacology. 2015;232:4325–35.
Shirayama Y, Yang C, Zhang JC, Ren Q, Yao W, Hashimoto K. Alterations in brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain regions of a learned helplessness rat model and the antidepressant effects of a TrkB agonist and antagonist. Eur Neuropsychopharmacol. 2015;25:2449–58.
Agarwal V, Blom AM. Roles of complement C1q in pneumococcus-host interactions. Crit Rev Immunol. 2015;35:173–84.
Kouser L, Madhukaran SP, Shastri A, Saraon A, Ferluga J, Al-Mozaini M. Emerging and novel functions of complement protein C1q. Front Immunol. 2015;6:317.
• Yamamoto M, Kensler TW, Motohashi H. The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis. Physiol Rev. 2018;98:1169–203. This is an excellent review article on Keap1-Nrf2 system.
Hashimoto K. Essential role of Keap1-Nrf2 signaling in mood disorders: overview and future perspective. Front Pharmacol. 2018;9:1182.
• Yao W, Zhang JC, Ishima T, Dong C, Yang C, Ren Q, et al. Role of Keap1-Nrf2 signaling in depression and dietary intake of glucoraphanin confers stress resilience in mice. Sci Rep. 2016;6:30659. This is an article showing stress resilience in Nrf2 KO mice.
Zhang JC, Yao W, Dong C, Yang C, Ren Q, Ma M, et al. Prophylactic effects of sulforaphane on depression-like behavior and dendritic changes in mice after inflammation. J Nutr Biochem. 2017;39:134–44.
Zhang JC, Yao W, Dong C, Han M, Shirayama Y, Hashimoto K. Keap1-Nrf2 signaling pathway confers resilience versus susceptibility to inescapable electric stress. Eur Arch Psychiatry Clin Neurosci. 2018;268:865–70.
Chen H, Wu J, Zhang J, Fujita Y, Ishima T, Iyo M, et al. Protective effects of the antioxidant sulforaphane on behavioral changes and neurotoxicity in mice after the administration of methamphetamine. Psychopharmacology. 2012;222:37–45.
Shirai Y, Fujita Y, Hashimoto K. Effects of the antioxidant sulforaphane on hyperlocomotion and prepulse inhibition deficits in mice after phencyclidine administration. Clin Psychopharmacol Neurosci. 2012;10:94–8.
McNamara RK, Almeida DM. Omega-3 polyunsaturated fatty acid deficiency and progressive neuropathology in psychiatric disorders: a review of translational evidence and candidate mechanisms. Harv Rev Psychiatry. 2019;27:94–107.
Amminger GP, Schäfer MR, Papageorgiou K, Klier CM, Cotton SM, Harrigan SM, et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010;67:146–54.
McGorry PD, Nelson B, Markulev C, Yuen HP, Schäfer MR, Mossaheb N, et al. Effect of ω-3 polyunsaturated fatty acids in young people at ultrahigh risk for psychotic pisorders: the NEURAPRO randomized clinical trial. JAMA Psychiatry. 2017;74:19–27.
Davies C, Cipriani A, Ioannidis JPA, Radua J, Stahl D, Provenzani U, et al. Lack of evidence to favor specific preventive interventions in psychosis: a network meta-analysis. World Psychiatry. 2018;17:196–209.
Swardfager W, Hennebelle M, Yu D, Hammock BD, Levitt AJ, Hashimoto K, et al. Metabolic/inflammatory/vascular comorbidity in psychiatric disorders; soluble epoxide hydrolase (sEH) as a possible new target. Neurosci Biobehav Rev. 2018;87:56–66.
Hashimoto K. Role of soluble epoxide hydrolase in metabolism of PUFAs in psychiatric and neurological disorders. Front Pharmacol. 2018;10:36.
Morisseau C, Hammock BD. Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu Rev Pharmacol Toxicol. 2013;53:37–58.
Hashimoto K. Soluble epoxide hydrolase: a new therapeutic target for depression. Expert Opin Ther Targets. 2016;20:1149–51.
Wagner KM, McReynolds CB, Schmidt WK, Hammock BD. Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases. Pharmacol Ther. 2017;180:62–76.
• Ren Q, Ma M, Ishima T, Morisseau C, Yang J, Wagner KM, et al. Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress. Proc Natl Acad Sci U S A. 2016;113:E1944–52. This is the first article showing the role of soluble epoxide hydrolase in depression.
• Ren Q, Ma M, Yang J, Nonaka R, Yamaguchi A, Ishikawa KI, et al. Soluble epoxide hydrolase plays a key role in the pathogenesis of Parkinson’s disease. Proc Natl Acad Sci U S A. 2018;115:E5815–23. This is the first article showing the role of soluble epoxide hydrolase in Parkinson’s disease and dementia with Lewy body.
Schultze-Lutter F, Michel C, Schmidt SJ, Schimmelmann BG, Maric NP, Salokangas RK, et al. EPA guidance on the early detection of clinical high risk states of psychoses. Eur Psychiatry. 2015;30:405–16.