1932

Abstract

Cognitive impairment is a core feature of schizophrenia and a major contributor to poor functional outcomes. Methods for assessment of cognitive dysfunction in schizophrenia are now well established. In addition, there has been increasing appreciation in recent years of the additional role of social cognitive impairment in driving functional outcomes and of the contributions of sensory-level dysfunction to higher-order impairments. At the neurochemical level, acute administration of -methyl--aspartate receptor (NMDAR) antagonists reproduces the pattern of neurocognitive dysfunction associated with schizophrenia, encouraging the development of treatments targeted at both NMDAR and its interactome. At the local-circuit level, an auditory neurophysiological measure, mismatch negativity, has emerged both as a veridical index of NMDAR dysfunction and excitatory/inhibitory imbalance in schizophrenia and as a critical biomarker for early-stage translational drug development. Although no compounds have yet been approved for treatment of cognitive impairment associated with schizophrenia, several candidates are showing promise in early-phase testing.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-051921-093250
2023-01-20
2024-12-06
Loading full text...

Full text loading...

/deliver/fulltext/pharmtox/63/1/annurev-pharmtox-051921-093250.html?itemId=/content/journals/10.1146/annurev-pharmtox-051921-093250&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Donde C, Avissar M, Weber MM, Javitt DC. 2019. A century of sensory processing dysfunction in schizophrenia. Eur. Psychiatry 59:77–79
    [Google Scholar]
  2. 2.
    Javitt DC, Zukin SR. 1991. Recent advances in the phencyclidine model of schizophrenia. Am. J. Psychiatry 148:1301–8
    [Google Scholar]
  3. 3.
    Flor-Henry P. 1990. Neuropsychology and psychopathology: a progress report. Neuropsychol. Rev. 1:103–23
    [Google Scholar]
  4. 4.
    Heinrichs RW, Zakzanis KK. 1998. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 12:426–45
    [Google Scholar]
  5. 5.
    Green MF, Nuechterlein KH, Gold JM, Barch DM, Cohen J et al. 2004. Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria. Biol. Psychiatry 56:301–7
    [Google Scholar]
  6. 6.
    Kern RS, Nuechterlein KH, Green MF, Baade LE, Fenton WS et al. 2008. The MATRICS Consensus Cognitive Battery, part 2: co-norming and standardization. Am. J. Psychiatry 165:214–20
    [Google Scholar]
  7. 7.
    Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM et al. 2008. The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. Am. J. Psychiatry 165:203–13
    [Google Scholar]
  8. 8.
    Green MF, Horan WP, Lee J. 2019. Nonsocial and social cognition in schizophrenia: current evidence and future directions. World Psychiatry 18:146–61This review provides a comprehensive summary of the current state of clinical research in social and nonsocial cognition.
    [Google Scholar]
  9. 9.
    Keefe RS, Harvey PD, Goldberg TE, Gold JM, Walker TM et al. 2008. Norms and standardization of the Brief Assessment of Cognition in Schizophrenia (BACS). Schizophr. Res. 102:108–15
    [Google Scholar]
  10. 10.
    Moore TM, Reise SP, Gur RE, Hakonarson H, Gur RC. 2015. Psychometric properties of the Penn Computerized Neurocognitive Battery. Neuropsychology 29:235–46
    [Google Scholar]
  11. 11.
    Gold R, Butler P, Revheim N, Leitman DI, Hansen JA et al. 2012. Auditory emotion recognition impairments in schizophrenia: relationship to acoustic features and cognition. Am. J. Psychiatry 169:424–32
    [Google Scholar]
  12. 12.
    Kantrowitz JT, Hoptman MJ, Leitman DI, Moreno-Ortega M, Lehrfeld JM et al. 2015. Neural substrates of auditory emotion recognition deficits in schizophrenia. J. Neurosci. 35:14909–21
    [Google Scholar]
  13. 13.
    Gur RC, Gur RE. 2016. Social cognition as an RDoC domain. Am. J. Med. Genet. B Neuropsychiatr. Genet. 171:132–41
    [Google Scholar]
  14. 14.
    Martinez A, Tobe R, Dias EC, Ardekani BA, Veenstra-VanderWeele J et al. 2019. Differential patterns of visual sensory alteration underlying face emotion recognition impairment and motion perception deficits in schizophrenia and autism spectrum disorder. Biol. Psychiatry 86:557–67
    [Google Scholar]
  15. 15.
    Martinez A, Tobe RH, Gaspar PA, Malinsky D, Dias EC et al. 2021. Disease-specific contribution of pulvinar dysfunction to impaired emotion recognition in schizophrenia. Front. Behav. Neurosci. 15:787383This study provides a critical discussion of the role played by subcortical and cortical mechanisms in face emotion recognition and social cognition.
    [Google Scholar]
  16. 16.
    Pinkham AE, Harvey PD, Penn DL. 2017. Social cognition psychometric evaluation: results of the final validation study. Schizophr. Bull. 44:737–48
    [Google Scholar]
  17. 17.
    Patel GH, Arkin SC, Ruiz-Betancourt DR, DeBaun HM, Strauss NE et al. 2021. What you see is what you get: visual scanning failures of naturalistic social scenes in schizophrenia. Psychol. Med. 51:2923–32
    [Google Scholar]
  18. 18.
    Patel GH, Arkin SC, Ruiz-Betancourt DR, Plaza FI, Mirza SA et al. 2021. Failure to engage the temporoparietal junction/posterior superior temporal sulcus predicts impaired naturalistic social cognition in schizophrenia. Brain 144:1898–910This study provides a critical discussion of the role played by superior temporal sulcus in social cognition.
    [Google Scholar]
  19. 19.
    Javitt DC, Rabinowicz E, Silipo G, Dias EC. 2007. Encoding versus retention: differential effects of cue manipulation on working memory performance in schizophrenia. Schizophr. Res. 91:159–68
    [Google Scholar]
  20. 20.
    Wylie GR, Clark EA, Butler PD, Javitt DC. 2010. Schizophrenia patients show task switching deficits consistent with N-methyl-d-aspartate system dysfunction but not global executive deficits: implications for pathophysiology of executive dysfunction in schizophrenia. Schizophr. Bull. 36:585–94
    [Google Scholar]
  21. 21.
    Breton F, Plante A, Legauffre C, Morel N, Ades J et al. 2011. The executive control of attention differentiates patients with schizophrenia, their first-degree relatives and healthy controls. Neuropsychologia 49:203–8
    [Google Scholar]
  22. 22.
    Fuller R, Nopoulos P, Arndt S, O'Leary D, Ho BC, Andreasen NC. 2002. Longitudinal assessment of premorbid cognitive functioning in patients with schizophrenia through examination of standardized scholastic test performance. Am. J. Psychiatry 159:1183–89
    [Google Scholar]
  23. 23.
    Reichenberg A, Weiser M, Rabinowitz J, Caspi A, Schmeidler J et al. 2002. A population-based cohort study of premorbid intellectual, language, and behavioral functioning in patients with schizophrenia, schizoaffective disorder, and nonpsychotic bipolar disorder. Am. J. Psychiatry 159:2027–35
    [Google Scholar]
  24. 24.
    Revheim N, Corcoran CM, Dias E, Hellmann E, Martinez A et al. 2014. Reading deficits in schizophrenia and individuals at high clinical risk: relationship to sensory function, course of illness, and psychosocial outcome. Am. J. Psychiatry 171:949–59
    [Google Scholar]
  25. 25.
    Donde C, Martinez A, Sehatpour P, Patel GH, Kraut R et al. 2019. Neural and functional correlates of impaired reading ability in schizophrenia. Sci. Rep. 9:16022
    [Google Scholar]
  26. 26.
    Reichenberg A, Caspi A, Harrington H, Houts R, Keefe RS et al. 2010. Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: a 30-year study. Am. J. Psychiatry 167:160–69
    [Google Scholar]
  27. 27.
    MacCabe JH, Wicks S, Lofving S, David AS, Berndtsson A et al. 2013. Decline in cognitive performance between ages 13 and 18 years and the risk for psychosis in adulthood: a Swedish longitudinal cohort study in males. JAMA Psychiatry 70:261–70
    [Google Scholar]
  28. 28.
    Seidman LJ, Giuliano AJ, Meyer EC, Addington J, Cadenhead KS et al. 2010. Neuropsychology of the prodrome to psychosis in the NAPLS consortium: relationship to family history and conversion to psychosis. Arch. Gen. Psychiatry 67:578–88
    [Google Scholar]
  29. 29.
    Seidman LJ, Shapiro DI, Stone WS, Woodberry KA, Ronzio A et al. 2016. Association of neurocognition with transition to psychosis: baseline functioning in the second phase of the North American Prodrome Longitudinal Study. JAMA Psychiatry 73:1239–48
    [Google Scholar]
  30. 30.
    Sheffield JM, Karcher NR, Barch DM. 2018. Cognitive deficits in psychotic disorders: a lifespan perspective. Neuropsychol. Rev. 28:509–33
    [Google Scholar]
  31. 31.
    Holzman PS, Proctor LR, Hughes DW. 1973. Eye-tracking patterns in schizophrenia. Science 181:179–81
    [Google Scholar]
  32. 32.
    Saccuzzo DP, Braff DL. 1981. Early information processing deficit in schizophrenia. New findings using schizophrenic subgroups and manic control subjects. Arch. Gen. Psychiatry 38:175–79
    [Google Scholar]
  33. 33.
    Javitt DC, Liederman E, Cienfuegos A, Shelley AM. 1999. Panmodal processing imprecision as a basis for dysfunction of transient memory storage systems in schizophrenia. Schizophr. Bull. 25:763–75
    [Google Scholar]
  34. 34.
    Javitt DC, Sweet RA. 2015. Auditory dysfunction in schizophrenia: integrating clinical and basic features. Nat. Rev. Neurosci. 16:535–50This review provides a comprehensive discussion of postmortem and physiological findings relating to impaired early auditory processing in schizophrenia.
    [Google Scholar]
  35. 35.
    Javitt DC, Freedman R. 2015. Sensory processing dysfunction in the personal experience and neuronal machinery of schizophrenia. Am. J. Psychiatry 172:17–31
    [Google Scholar]
  36. 36.
    Strous RD, Cowan N, Ritter W, Javitt DC. 1995. Auditory sensory (“echoic”) memory dysfunction in schizophrenia. Am. J. Psychiatry 152:1517–19
    [Google Scholar]
  37. 37.
    Dondé C, Martinez A, Kantrowitz JT, Silipo G, Dias EC et al. 2019. Bimodal distribution of tone-matching deficits indicates discrete pathophysiological entities within the syndrome of schizophrenia. Transl. Psychiatry 9:221
    [Google Scholar]
  38. 38.
    Kraus MS, Walker TM, Jarskog LF, Millet RA, Keefe RSE. 2019. Basic auditory processing deficits and their association with auditory emotion recognition in schizophrenia. Schizophr. Res. 204:155–61
    [Google Scholar]
  39. 39.
    Yang L, Chen S, Chen CM, Khan F, Forchelli G, Javitt DC. 2012. Schizophrenia, culture and neuropsychology: sensory deficits, language impairments and social functioning in Chinese-speaking schizophrenia patients. Psychol. Med. 42:1485–94
    [Google Scholar]
  40. 40.
    Fisher M, Loewy R, Carter C, Lee A, Ragland JD et al. 2015. Neuroplasticity-based auditory training via laptop computer improves cognition in young individuals with recent onset schizophrenia. Schizophr. Bull. 41:250–58
    [Google Scholar]
  41. 41.
    Medalia A, Saperstein AM, Qian M, Javitt DC. 2019. Impact of baseline early auditory processing on response to cognitive remediation for schizophrenia. Schizophr. Res. 208:397–405
    [Google Scholar]
  42. 42.
    Kantrowitz JT, Scaramello N, Jakubovitz A, Lehrfeld JM, Laukka P et al. 2014. Amusia and protolanguage impairments in schizophrenia. Psychol. Med. 44:2739–48
    [Google Scholar]
  43. 43.
    Schnakenberg Martin AM, Bartolomeo L, Howell J, Hetrick WP, Bolbecker AR et al. 2018. Auditory feature perception and auditory hallucinatory experiences in schizophrenia spectrum disorder. Eur. Arch. Psychiatry Clin. Neurosci. 268:653–61
    [Google Scholar]
  44. 44.
    Chaturvedi R, Kraus M, Keefe RSE. 2020. A new measure of authentic auditory emotion recognition: application to patients with schizophrenia. Schizophr. Res. 222:450–54
    [Google Scholar]
  45. 45.
    Sehatpour P, Molholm S, Javitt DC, Foxe JJ. 2006. Spatiotemporal dynamics of human object recognition processing: an integrated high-density electrical mapping and functional imaging study of “closure” processes. Neuroimage 29:605–18
    [Google Scholar]
  46. 46.
    Solomon SG. 2021. Retinal ganglion cells and the magnocellular, parvocellular, and koniocellular subcortical visual pathways from the eye to the brain. Handb. Clin. Neurol. 178:31–50
    [Google Scholar]
  47. 47.
    Butler PD, Schechter I, Zemon V, Schwartz SG, Greenstein VC et al. 2001. Dysfunction of early-stage visual processing in schizophrenia. Am. J. Psychiatry 158:1126–33
    [Google Scholar]
  48. 48.
    Samani NN, Proudlock FA, Siram V, Suraweera C, Hutchinson C et al. 2017. Retinal layer abnormalities as biomarkers of schizophrenia. Schizophr. Bull 44:4876–85
    [Google Scholar]
  49. 49.
    Martinez A, Hillyard SA, Dias EC, Hagler DJ Jr., Butler PD et al. 2008. Magnocellular pathway impairment in schizophrenia: evidence from functional magnetic resonance imaging. J. Neurosci. 28:7492–500
    [Google Scholar]
  50. 50.
    Chen Y, Palafox GP, Nakayama K, Levy DL, Matthysse S, Holzman PS. 1999. Motion perception in schizophrenia. Arch. Gen. Psychiatry 56:149–54
    [Google Scholar]
  51. 51.
    Kim D, Wylie G, Pasternak R, Butler PD, Javitt DC. 2006. Magnocellular contributions to impaired motion processing in schizophrenia. Schizophr. Res. 82:1–8
    [Google Scholar]
  52. 52.
    Martinez A, Gaspar PA, Hillyard SA, Andersen SK, Lopez-Calderon J et al. 2018. Impaired motion processing in schizophrenia and the attenuated psychosis syndrome: etiological and clinical implications. Am. J. Psychiatry 175:1243–54
    [Google Scholar]
  53. 53.
    Butler PD, Zemon V, Schechter I, Saperstein AM, Hoptman MJ et al. 2005. Early-stage visual processing and cortical amplification deficits in schizophrenia. Arch. Gen. Psychiatry 62:495–504
    [Google Scholar]
  54. 54.
    Schechter I, Butler PD, Zemon VM, Revheim N, Saperstein AM et al. 2005. Impairments in generation of early-stage transient visual evoked potentials to magno- and parvocellular-selective stimuli in schizophrenia. Clin. Neurophysiol. 116:2204–15
    [Google Scholar]
  55. 55.
    Dias EC, Butler PD, Hoptman MJ, Javitt DC. 2011. Early sensory contributions to contextual encoding deficits in schizophrenia. Arch. Gen. Psychiatry 68:654–64
    [Google Scholar]
  56. 56.
    Hoptman MJ, Parker EM, Nair-Collins S, Dias EC, Ross ME et al. 2018. Sensory and cross-network contributions to response inhibition in patients with schizophrenia. NeuroImage Clin 18:31–39
    [Google Scholar]
  57. 57.
    Sehatpour P, Bassir Nia A, Adair D, Wang Z, DeBaun HM et al. 2020. Multimodal computational modeling of visual object recognition deficits but intact repetition priming in schizophrenia. Front. Psychiatry 11:547189
    [Google Scholar]
  58. 58.
    Butler PD, Abeles IY, Silverstein SM, Dias EC, Weiskopf NG et al. 2013. An event-related potential examination of contour integration deficits in schizophrenia. Front. Psychol. 4:132
    [Google Scholar]
  59. 59.
    Martinez A, Revheim N, Butler PD, Guilfoyle DN, Dias EC, Javitt DC. 2012. Impaired magnocellular/dorsal stream activation predicts impaired reading ability in schizophrenia. NeuroImage Clin 2:8–16
    [Google Scholar]
  60. 60.
    Dias EC, Sheridan H, Martinez A, Sehatpour P, Silipo G et al. 2021. Neurophysiological, oculomotor, and computational modeling of impaired reading ability in schizophrenia. Schizophr. Bull. 47:97–107
    [Google Scholar]
  61. 61.
    Jerotic S, Ignjatovic Z, Silverstein SM, Maric NP. 2020. Structural imaging of the retina in psychosis spectrum disorders: current status and perspectives. Curr. Opin. Psychiatry 33:476–83
    [Google Scholar]
  62. 62.
    Joshi YB, Thomas ML, Braff DL, Green MF, Gur RC et al. 2021. Anticholinergic medication burden-associated cognitive impairment in schizophrenia. Am. J. Psychiatry 178:838–47
    [Google Scholar]
  63. 63.
    Rosenbaum G, Cohen BD, Luby ED, Gottlieb JS, Yelen D. 1959. Comparison of sernyl with other drugs: simulation of schizophrenic performance with sernyl, LSD-25, and amobarbital (amytal) sodium; I. Attention, motor function, and proprioception. AMA Arch. Gen. Psychiatry 1:651–56
    [Google Scholar]
  64. 64.
    Luby ED, Gottlieb JS, Cohen BD, Rosenbaum G, Domino EF. 1962. Model psychoses and schizophrenia. Am. J. Psychiatry 119:61–67
    [Google Scholar]
  65. 65.
    Javitt DC. 1987. Negative schizophrenic symptomatology and the PCP (phencyclidine) model of schizophrenia. Hillside J. Clin. Psychiatry 9:12–35
    [Google Scholar]
  66. 66.
    Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R et al. 1994. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch. Gen. Psychiatry 51:199–214
    [Google Scholar]
  67. 67.
    Malhotra AK, Pinals DA, Weingartner H, Sirocco K, Missar CD et al. 1996. NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Neuropsychopharmacology 14:301–7
    [Google Scholar]
  68. 68.
    Maxwell CR, Ehrlichman RS, Liang Y, Trief D, Kanes SJ et al. 2006. Ketamine produces lasting disruptions in encoding of sensory stimuli. J. Pharmacol. Exp. Ther. 316:315–24
    [Google Scholar]
  69. 69.
    Driesen NR, McCarthy G, Bhagwagar Z, Bloch MH, Calhoun VD et al. 2013. The impact of NMDA receptor blockade on human working memory-related prefrontal function and connectivity. Neuropsychopharmacology 38:2613–22
    [Google Scholar]
  70. 70.
    Blackman RK, Macdonald AW 3rd, Chafee MV. 2013. Effects of ketamine on context-processing performance in monkeys: a new animal model of cognitive deficits in schizophrenia. Neuropsychopharmacology 38:2090–100
    [Google Scholar]
  71. 71.
    Umbricht D, Schmid L, Koller R, Vollenweider FX, Hell D, Javitt DC. 2000. Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia. Arch. Gen. Psychiatry 57:1139–47
    [Google Scholar]
  72. 72.
    Stoet G, Snyder LH. 2006. Effects of the NMDA antagonist ketamine on task-switching performance: evidence for specific impairments of executive control. Neuropsychopharmacology 31:1675–81
    [Google Scholar]
  73. 73.
    Cheng WJ, Chen CH, Chen CK, Huang MC, Pietrzak RH et al. 2018. Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia. Schizophr. Res. 199:313–18
    [Google Scholar]
  74. 74.
    Singh T, Poterba T, Curtis D, Akil H, Al Eissa M et al. 2022. Rare coding variants in ten genes confer substantial risk for schizophrenia. Nature 604:509–16
    [Google Scholar]
  75. 75.
    Timms AE, Dorschner MO, Wechsler J, Choi KY, Kirkwood R et al. 2013. Support for the N-methyl-d-aspartate receptor hypofunction hypothesis of schizophrenia from exome sequencing in multiplex families. JAMA Psychiatry 70:582–90
    [Google Scholar]
  76. 76.
    Seet D, Allameen NA, Tay SH, Cho J, Mak A. 2021. Cognitive dysfunction in systemic lupus erythematosus: immunopathology, clinical manifestations, neuroimaging and management. Rheumatol. Ther. 8:651–79
    [Google Scholar]
  77. 77.
    Wollmuth LP, Chan K, Groc L 2021. The diverse and complex modes of action of anti-NMDA receptor autoantibodies. Neuropharmacology 194:108624
    [Google Scholar]
  78. 78.
    Moghaddam B, Krystal JH. 2012. Capturing the angel in “angel dust”: twenty years of translational neuroscience studies of NMDA receptor antagonists in animals and humans. Schizophr. Bull. 38:942–49
    [Google Scholar]
  79. 79.
    Ishchenko Y, Carrizales MG, Koleske AJ. 2021. Regulation of the NMDA receptor by its cytoplasmic domains: (How) is the tail wagging the dog?. Neuropharmacology 195:108634
    [Google Scholar]
  80. 80.
    Benke TA, Park K, Krey I, Camp CR, Song R et al. 2021. Clinical and therapeutic significance of genetic variation in the GRIN gene family encoding NMDARs. Neuropharmacology 199:108805
    [Google Scholar]
  81. 81.
    Amin JB, Moody GR, Wollmuth LP. 2021. From bedside-to-bench: what disease-associated variants are teaching us about the NMDA receptor. J. Physiol. 599:397–416
    [Google Scholar]
  82. 82.
    Goes FS, McGrath J, Avramopoulos D, Wolyniec P, Pirooznia M et al. 2015. Genome-wide association study of schizophrenia in Ashkenazi Jews. Am. J. Med. Genet. B Neuropsychiatr. Genet. 168:649–59
    [Google Scholar]
  83. 83.
    Feinberg I. 1990. Cortical pruning and the development of schizophrenia. Schizophr. Bull. 16:567–70
    [Google Scholar]
  84. 84.
    Johnson MB, Hyman SE. 2022. A critical perspective on the synaptic pruning hypothesis of schizophrenia pathogenesis. Biol. Psychiatry 92:440–42
    [Google Scholar]
  85. 85.
    Eyo UB, Bispo A, Liu JT, Sabu S, Wu R et al. 2018. The GluN2A subunit regulates neuronal NMDA receptor-induced microglia-neuron physical interactions. Scientific Rep. 8:828
    [Google Scholar]
  86. 86.
    Petit-Pedrol M, Groc L. 2021. Regulation of membrane NMDA receptors by dynamics and protein interactions. J. Cell Biol. 220:e202006101This study provides an important discussion of the NMDAR interactome.
    [Google Scholar]
  87. 87.
    Gulsuner S, Stein DJ, Susser ES, Sibeko G, Pretorius A et al. 2020. Genetics of schizophrenia in the South African Xhosa. Science 367:569–73
    [Google Scholar]
  88. 88.
    Hall LS, Medway CW, Pain O, Pardinas AF, Rees EG et al. 2020. A transcriptome-wide association study implicates specific pre- and post-synaptic abnormalities in schizophrenia. Hum. Mol. Genet. 29:159–67
    [Google Scholar]
  89. 89.
    Hall J, Bray NJ. 2021. Schizophrenia genomics: convergence on synaptic development, adult synaptic plasticity, or both?. Biol. Psychiatry 91:709–17
    [Google Scholar]
  90. 90.
    Kegeles LS, Abi-Dargham A, Frankle WG, Gil R, Cooper TB et al. 2010. Increased synaptic dopamine function in associative regions of the striatum in schizophrenia. Arch. Gen. Psychiatry 67:231–39
    [Google Scholar]
  91. 91.
    Veronese M, Santangelo B, Jauhar S, D'Ambrosio E, Demjaha A et al. 2021. A potential biomarker for treatment stratification in psychosis: evaluation of an [18F]FDOPA PET imaging approach. Neuropsychopharmacology 46:1122–32
    [Google Scholar]
  92. 92.
    Cassidy CM, Zucca FA, Girgis RR, Baker SC, Weinstein JJ et al. 2019. Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain. PNAS 116:5108–17
    [Google Scholar]
  93. 93.
    McCutcheon RA, Krystal JH, Howes OD. 2020. Dopamine and glutamate in schizophrenia: biology, symptoms and treatment. World Psychiatry 19:15–33This review provides a comprehensive discussion of current information regarding dopamine and glutamate models of schizophrenia.
    [Google Scholar]
  94. 94.
    Potvin S, Pelletier J, Grot S, Hebert C, Barr AM, Lecomte T. 2018. Cognitive deficits in individuals with methamphetamine use disorder: a meta-analysis. Addict. Behav. 80:154–60
    [Google Scholar]
  95. 95.
    Andrianarivelo A, Saint-Jour E, Pousinha P, Fernandez SP, Petitbon A et al. 2021. Disrupting D1-NMDA or D2-NMDA receptor heteromerization prevents cocaine's rewarding effects but preserves natural reward processing. Sci. Adv. 7:eabg5970
    [Google Scholar]
  96. 96.
    Javitt DC, Steinschneider M, Schroeder CE, Arezzo JC. 1996. Role of cortical N-methyl-d-aspartate receptors in auditory sensory memory and mismatch negativity generation: implications for schizophrenia. PNAS 93:11962–67
    [Google Scholar]
  97. 97.
    Escera C, Leung S, Grimm S. 2014. Deviance detection based on regularity encoding along the auditory hierarchy: electrophysiological evidence in humans. Brain Topogr. 27:527–38
    [Google Scholar]
  98. 98.
    Lakatos P, O'Connell MN, Barczak A, McGinnis T, Neymotin S et al. 2020. The thalamocortical circuit of auditory mismatch negativity. Biol. Psychiatry 87:770–80
    [Google Scholar]
  99. 99.
    Lee M, Balla A, Sershen H, Sehatpour P, Lakatos P, Javitt DC. 2018. Rodent mismatch negativity/theta neuro-oscillatory response as a translational neurophysiological biomarker for N-methyl-d-aspartate receptor-based new treatment development in schizophrenia. Neuropsychopharmacology 43:571–82
    [Google Scholar]
  100. 100.
    Avissar M, Xie S, Vail B, Lopez-Calderon J, Wang Y, Javitt DC 2018. Meta-analysis of mismatch negativity to simple versus complex deviants in schizophrenia. Schizophr. Res. 191:25–34
    [Google Scholar]
  101. 101.
    Lee M, Sehatpour P, Dias EC, Silipo GS, Kantrowitz JT et al. 2018. A tale of two sites: differential impairment of frequency and duration mismatch negativity across a primarily inpatient versus a primarily outpatient site in schizophrenia. Schizophr. Res. 191:10–17
    [Google Scholar]
  102. 102.
    Gaebler AJ, Zweerings J, Koten JW, Konig AA, Turetsky BI et al. 2020. Impaired subcortical detection of auditory changes in schizophrenia but not in major depression. Schizophr. Bull. 46:193–201
    [Google Scholar]
  103. 103.
    Thomas ML, Green MF, Hellemann G, Sugar CA, Tarasenko M et al. 2017. Modeling deficits from early auditory information processing to psychosocial functioning in schizophrenia. JAMA Psychiatry 74:37–46
    [Google Scholar]
  104. 104.
    Javitt DC, Schroeder CE, Steinschneider M, Arezzo JC, Vaughan HG Jr. 1992. Demonstration of mismatch negativity in the monkey. Electroencephalogr. Clin. Neurophysiol. 83:87–90
    [Google Scholar]
  105. 105.
    Gil-da-Costa R, Stoner GR, Fung R, Albright TD. 2013. Nonhuman primate model of schizophrenia using a noninvasive EEG method. PNAS 110:15425–30
    [Google Scholar]
  106. 106.
    Schuelert N, Dorner-Ciossek C, Brendel M, Rosenbrock H. 2018. A comprehensive analysis of auditory event-related potentials and network oscillations in an NMDA receptor antagonist mouse model using a novel wireless recording technology. Physiol. Rep. 6:e13782
    [Google Scholar]
  107. 107.
    Umbricht D, Schmid L, Koller R, Vollenweider FX, Hell D, Javitt DC. 2000. Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia. Arch. Gen. Psychiatry 57:1139–47
    [Google Scholar]
  108. 108.
    Rosburg T, Kreitschmann-Andermahr I. 2016. The effects of ketamine on the mismatch negativity (MMN) in humans: a meta-analysis. Clin. Neurophysiol. 127:1387–94
    [Google Scholar]
  109. 109.
    Ehrlichman RS, Maxwell CR, Majumdar S, Siegel SJ. 2008. Deviance-elicited changes in event-related potentials are attenuated by ketamine in mice. J. Cogn. Neurosci. 20:1403–14
    [Google Scholar]
  110. 110.
    Javitt DC, Lee M, Kantrowitz JT, Martinez A. 2018. Mismatch negativity as a biomarker of theta band oscillatory dysfunction in schizophrenia. Schizophr. Res. 191:51–60
    [Google Scholar]
  111. 111.
    Javitt DC, Siegel SJ, Spencer KM, Mathalon DH, Hong LE et al. 2020. A roadmap for development of neuro-oscillations as translational biomarkers for treatment development in neuropsychopharmacology. Neuropsychopharmacology 45:1411–22This review provides an important discussion of potential excitatory-inhibitory mechanisms involved in mismatch negativity generation.
    [Google Scholar]
  112. 112.
    Ross JM, Hamm JP. 2020. Cortical microcircuit mechanisms of mismatch negativity and its underlying subcomponents. Front. Neural Circuits 14:13
    [Google Scholar]
  113. 113.
    Abs E, Poorthuis RB, Apelblat D, Muhammad K, Pardi MB et al. 2018. Learning-related plasticity in dendrite-targeting layer 1 interneurons. Neuron 100:684–99.e6
    [Google Scholar]
  114. 114.
    Studer F, Barkat TR. 2021. Inhibition in the auditory cortex. Neurosci. Biobehav. Rev. 132:61–75This review provides a comprehensive summary of excitatory-inhibitory mechanisms related to local-circuit processing in auditory cortex.
    [Google Scholar]
  115. 115.
    Kullander K, Topolnik L. 2021. Cortical disinhibitory circuits: cell types, connectivity and function. Trends Neurosci 44:643–57
    [Google Scholar]
  116. 116.
    Van Derveer AB, Bastos G, Ferrell AD, Gallimore CG, Greene ML et al. 2021. A role for somatostatin-positive interneurons in neuro-oscillatory and information processing deficits in schizophrenia. Schizophr. Bull. 47:1385–98
    [Google Scholar]
  117. 117.
    Sehatpour P, Javitt DC, De Baun HM, Carlson M, Beloborodova A et al. 2022. Mismatch negativity as an index of target engagement for excitation/inhibition-based treatment development: a double-blind, placebo-controlled, randomized, single-dose cross-over study of the serotonin type-3 receptor antagonist CVN058. Neuropsychopharmacology 47:711–18
    [Google Scholar]
  118. 118.
    Korostenskaja M, Kicic D, Kahkonen S. 2008. The effect of methylphenidate on auditory information processing in healthy volunteers: a combined EEG/MEG study. Psychopharmacology 197:475–86
    [Google Scholar]
  119. 119.
    Umbricht D, Vollenweider FX, Schmid L, Grubel C, Skrabo A et al. 2003. Effects of the 5-HT2A agonist psilocybin on mismatch negativity generation and AX-continuous performance task: implications for the neuropharmacology of cognitive deficits in schizophrenia. Neuropsychopharmacology 28:170–81
    [Google Scholar]
  120. 120.
    Heekeren K, Daumann J, Neukirch A, Stock C, Kawohl W et al. 2008. Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis. Psychopharmacology 199:77–88
    [Google Scholar]
  121. 121.
    Bravermanová A, Viktorinová M, Tylš F, Novák T, Androvičová R et al. 2018. Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing—study on P300 and mismatch negativity in healthy volunteers. Psychopharmacology 235:491–503
    [Google Scholar]
  122. 122.
    Hamilton HK, Roach BJ, Bachman PM, Belger A, Carrion RE et al. 2019. Association between P300 responses to auditory oddball stimuli and clinical outcomes in the psychosis risk syndrome. JAMA Psychiatry 76:1187–97
    [Google Scholar]
  123. 123.
    Leitman DI, Sehatpour P, Higgins BA, Foxe JJ, Silipo G, Javitt DC. 2010. Sensory deficits and distributed hierarchical dysfunction in schizophrenia. Am. J. Psychiatry 167:818–27
    [Google Scholar]
  124. 124.
    Spencer KM, Salisbury DF, Shenton ME, McCarley RW. 2008. γ-Band auditory steady-state responses are impaired in first episode psychosis. Biol. Psychiatry 64:369–75
    [Google Scholar]
  125. 125.
    Thune H, Recasens M, Uhlhaas PJ. 2016. The 40-Hz auditory steady-state response in patients with schizophrenia: a meta-analysis. JAMA Psychiatry 73:1145–53
    [Google Scholar]
  126. 126.
    Koshiyama D, Thomas ML, Miyakoshi M, Joshi YB, Molina JL et al. 2021. Hierarchical pathways from sensory processing to cognitive, clinical, and functional impairments in schizophrenia. Schizophr. Bull. 47:373–85
    [Google Scholar]
  127. 127.
    Rosburg T, Boutros NN, Ford JM. 2008. Reduced auditory evoked potential component N100 in schizophrenia—a critical review. Psychiatry Res 161:259–74
    [Google Scholar]
  128. 128.
    Teichert T. 2017. Loudness- and time-dependence of auditory evoked potentials is blunted by the NMDA channel blocker MK-801. Psychiatry Res 256:202–6
    [Google Scholar]
  129. 129.
    Javitt DC, Kantrowitz JT. 2022. The glutamate/N-methyl-d-aspartate receptor (NMDAR) model of schizophrenia at 35: on the path from syndrome to disease. Schizophr. Res. 242:56–61
    [Google Scholar]
  130. 130.
    Singh SP, Singh V. 2011. Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia. CNS Drugs 25:859–85
    [Google Scholar]
  131. 131.
    Goh KK, Wu TH, Chen CH, Lu ML. 2021. Efficacy of N-methyl-d-aspartate receptor modulator augmentation in schizophrenia: a meta-analysis of randomised, placebo-controlled trials. J. Psychopharmacol. 35:236–52
    [Google Scholar]
  132. 132.
    Kantrowitz JT, Malhotra AK, Cornblatt B, Silipo G, Balla A et al. 2010. High dose D-serine in the treatment of schizophrenia. Schizophr. Res. 121:125–30
    [Google Scholar]
  133. 133.
    Kantrowitz JT, Epstein ML, Beggel O, Rohrig S, Lehrfeld JM et al. 2016. Neurophysiological mechanisms of cortical plasticity impairments in schizophrenia and modulation by the NMDA receptor agonist D-serine. Brain 139:3281–95This study provides an important discussion of potential benefits of combined pharmacological and behavioral approaches related to d-serine.
    [Google Scholar]
  134. 134.
    Fleischhacker WW, Podhorna J, Groschl M, Hake S, Zhao Y et al. 2021. Efficacy and safety of the novel glycine transporter inhibitor BI 425809 once daily in patients with schizophrenia: a double-blind, randomised, placebo-controlled phase 2 study. Lancet Psychiatry 8:191–201
    [Google Scholar]
  135. 135.
    Harvey PD, Bowie CR, McDonald S, Podhorna J. 2020. Evaluation of the efficacy of BI 425809 pharmacotherapy in patients with schizophrenia receiving computerized cognitive training: methodology for a double-blind, randomized, parallel-group trial. Clin. Drug Investig. 40:377–85
    [Google Scholar]
  136. 136.
    Murthy V, Hanson E, DeMartinis N, Asgharnejad M, Dong C et al. 2021. Luvadaxistat, an investigational D-amino acid oxidase inhibitor was associated with schizophrenia but not negative symptoms: results from the INTERACT study. Neuropsychopharmacology 46:374–75
    [Google Scholar]
  137. 137.
    O'Donnell P, Dong C, Murty VP, Asgharnejad M, Du X et al. 2021. Luvadaxistat, a D-amino acid oxidase inhibitor, improves mismatch negativity in patients with schizophrenia Paper presented at the Annual Meeting of the American College of Neuropsychopharmacology San Juan, PR: Dec. 5
    [Google Scholar]
  138. 138.
    Buchanan RW, Keefe RS, Lieberman JA, Barch DM, Csernansky JG et al. 2011. A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia. Biol. Psychiatry 69:442–49
    [Google Scholar]
  139. 139.
    Zheng W, Cai DB, Zhang QE, He J, Zhong LY et al. 2019. Adjunctive ondansetron for schizophrenia: a systematic review and meta-analysis of randomized controlled trials. J. Psychiatr. Res. 113:27–33
    [Google Scholar]
  140. 140.
    Tsitsipa E, Rogers J, Casalotti S, Belessiotis-Richards C, Zubko O et al. 2022. Selective 5HT3 antagonists and sensory processing: a systematic review. Neuropsychopharmacology 47:880–90
    [Google Scholar]
  141. 141.
    Korostenskaja M, Nikulin VV, Kicic D, Nikulina AV, Kahkonen S. 2007. Effects of NMDA receptor antagonist memantine on mismatch negativity. Brain Res. Bull. 72:275–83
    [Google Scholar]
  142. 142.
    Swerdlow NR, Bhakta S, Chou HH, Talledo JA, Balvaneda B, Light GA. 2016. Memantine effects on sensorimotor gating and mismatch negativity in patients with chronic psychosis. Neuropsychopharmacology 41:419–30
    [Google Scholar]
  143. 143.
    Zheng W, Zhu XM, Zhang QE, Cai DB, Yang XH et al. 2019. Adjunctive memantine for major mental disorders: a systematic review and meta-analysis of randomized double-blind controlled trials. Schizophr. Res. 209:12–21
    [Google Scholar]
  144. 144.
    Lieberman JA, Papadakis K, Csernansky J, Litman R, Volavka J et al. 2009. A randomized, placebo-controlled study of memantine as adjunctive treatment in patients with schizophrenia. Neuropsychopharmacology 34:1322–29
    [Google Scholar]
  145. 145.
    Bhakta SG, Chou HH, Rana B, Talledo JA, Balvaneda B et al. 2016. Effects of acute memantine administration on MATRICS Consensus Cognitive Battery performance in psychosis: testing an experimental medicine strategy. Psychopharmacology 233:2399–410
    [Google Scholar]
  146. 146.
    Swerdlow NR, Bhakta SG, Talledo J, Kotz J, Roberts BZ et al. 2020. Memantine effects on auditory discrimination and training in schizophrenia patients. Neuropsychopharmacology 452180–88This study provides an important discussion of the potential benefits of combined pharmacological and behavioral treatment approaches relative to memantine.
    [Google Scholar]
  147. 147.
    Zarate CA Jr., Singh JB, Quiroz JA, De Jesus G, Denicoff KK et al. 2006. A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am. J. Psychiatry 163:153–55
    [Google Scholar]
  148. 148.
    Johnson JW, Glasgow NG, Povysheva NV. 2015. Recent insights into the mode of action of memantine and ketamine. Curr. Opin. Pharmacol. 20:54–63
    [Google Scholar]
  149. 149.
    Castner SA, Williams GV, Goldman-Rakic PS. 2000. Reversal of antipsychotic-induced working memory deficits by short-term dopamine D1 receptor stimulation. Science 287:2020–22
    [Google Scholar]
  150. 150.
    Girgis RR, Van Snellenberg JX, Glass A, Kegeles LS, Thompson JL et al. 2016. A proof-of-concept, randomized controlled trial of DAR-0100A, a dopamine-1 receptor agonist, for cognitive enhancement in schizophrenia. J. Psychopharmacol. 30:428–35
    [Google Scholar]
  151. 151.
    Abi-Dargham A, Javitch JA, Slifstein M, Anticevic A, Calkins ME et al. 2022. Dopamine D1R receptor stimulation as a mechanistic pro-cognitive target for schizophrenia. Schizophr. Bull. 48:199–210
    [Google Scholar]
  152. 152.
    Recio-Barbero M, Segarra R, Zabala A, Gonzalez-Fraile E, Gonzalez-Pinto A, Ballesteros J. 2021. Cognitive enhancers in schizophrenia: a systematic review and meta-analysis of alpha-7 nicotinic acetylcholine receptor agonists for cognitive deficits and negative symptoms. Front. Psychiatry 12:631589
    [Google Scholar]
  153. 153.
    Matosin N, Newell KA, Quide Y, Andrews JL, Teroganova N et al. 2018. Effects of common GRM5 genetic variants on cognition, hippocampal volume and mGluR5 protein levels in schizophrenia. Brain Imaging Behav 12:509–17
    [Google Scholar]
  154. 154.
    Marder SR. 2006. Drug initiatives to improve cognitive function. J. Clin. Psychiatry 67:Suppl. 931–35
    [Google Scholar]
  155. 155.
    Sehatpour P, Avissar M, Kantrowitz JT, Corcoran CM, De Baun HM et al. 2020. Deficits in pre-attentive processing of spatial location and negative symptoms in subjects at clinical high risk for schizophrenia. Front. Psychiatry 11:629144
    [Google Scholar]
  156. 156.
    Schobel SA, Lewandowski NM, Corcoran CM, Moore H, Brown T et al. 2009. Differential targeting of the CA1 subfield of the hippocampal formation by schizophrenia and related psychotic disorders. Arch. Gen. Psychiatry 66:938–46
    [Google Scholar]
  157. 157.
    Li A, Zalesky A, Yue W, Howes O, Yan H et al. 2020. A neuroimaging biomarker for striatal dysfunction in schizophrenia. Nat. Med. 26:558–65
    [Google Scholar]
/content/journals/10.1146/annurev-pharmtox-051921-093250
Loading
/content/journals/10.1146/annurev-pharmtox-051921-093250
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error