Asian Journal of Psychiatry
Volume 4, Issue 4 , Pages 248-254 , December 2011

Neurobiology of self-awareness deficits in schizophrenia: A hypothetical model

  • Mujeeb U. Shad

      Affiliations

    • The University of Texas Health Science Center, 1421 East Road BBSB # 3118, Houston, TX 77054, United States
    • Corresponding Author InformationCorresponding author. Tel.: +1 713 486 2759; fax: +1 713 486 2753.
  • ,
  • Benjamin K. Brent

      Affiliations

    • Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA, United States
  • ,
  • Matcheri S. Keshavan

      Affiliations

    • Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA, United States

Received 11 August 2011 ,Accepted 28 September 2011.

References 

  1. Amodio DM, Frith CD. Meeting of minds: the medial frontal cortex and social cognition. Nat. Rev. Neurosci. 2006;7(4):268–277
  2. Baiano M, David A, Versace A, Churchill R, Balestrieri M, Brambilla P. Anterior cingulate volumes in schizophrenia: a systematic review and a meta-analysis of MRI studies. Schizophr. Res. 2007;93:1–12
  3. Blackwood NJ, Bentall RP, Ffytche DH, Simmons A, Murray RM, Howard RJ. Persecutory delusions and the determination of self-relevance: an fMRI investigation. Psychol. Med. 2004;34(4):591–596
  4. Brass M, Derrfuss J, Forstmann B, von Cramon DY. The role of the inferior frontal junction area in cognitive control. Trends Cogn. Sci. 2005;9:314–316
  5. Brune M, Lissek S, Fuchs N, Witthaus H, Peters S, Nicolas V, et al. An fMRI study of theory of mind in schizophrenic patients with passivity symptoms. Neuropsychologia. 2008;46:1992–2001
  6. Buchsbaum MS, Buchsbaum BR, Hazlett EA, Haznedar MM, Newmark R, Tang CY, et al. Relative glucose metabolic rate higher in white matter in patients with schizophrenia. Am. J. Psychiatry. 2007;164:1072–1081
  7. Buckner RL, Andrews-Hanna JR, Schacter DL. The brain's default network: anatomy, function, and relevance to disease. Ann. N. Y. Acad. Sci. 2008;1124:1–38
  8. Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn. Sci. 2000;4:215–222
  9. Camchong J, MacDonald AW, Bell C, Mueller BA, Lim KO. Altered functional and anatomical connectivity in schizophrenia. Schizophr. Bull. 2011;37(3):640–650
  10. Carruthers P. How we know our own minds: the relationship between mindreading and metacognition. Behav. Brain Sci. 2009;32:121–138
  11. Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain. 2006;129(Pt 3):564–583
  12. D’Argembeau A, Ruby P, Collette F, Degueldre C, Balteau E, Luxen A, et al. Distinct regions of the medial prefrontal cortex are associated with self-referential processing and perspective taking. J. Cogn. Neurosci. 2007;19:935–944
  13. Damasio AR. The Feeling of What Happens: Body and Emotion in the Making of Consciousness. Harcourt Brace; 1999;
  14. Dassa D, Boyer L, Benoit M, Bourcet S, Raymondet P, Bottai T. Factors associated with medication non-adherence in patients suffering from schizophrenia: a cross-sectional study in a universal coverage health-care system. Aust. N. Z. J. Psychiatry. 2010;44(10):921–928
  15. Devinsky O, Morrell MJ, Vogt BA. Contributions of anterior cingulate cortex to behaviour. Brain. 1995;118:279–306
  16. Dimaggio G, Lysaker PH, Carcione A, Nicolo G, Semerari A. Know yourself and you shall know the other to a certain extent: multiple paths of influence of self-reflection on mindreading. Conscious Cogn. 2008;17:778–789
  17. Fisher M, McCoy K, Poole JH, Vinogradov S. Self and other in schizophrenia: a cognitive neuroscience perspective. Am. J. Psychiatry. 2008;165:1465–1472
  18. Fossati P, Hevenor SJ, Lepage M, Graham SJ, Grady C, Keightley ML, et al. Distributed self in episodic memory: neural correlates of successful retrieval of self-encoded positive and negative personality traits. Neuroimage. 2004;22(4):1596–1604
  19. Frith CD. The Cognitive Neuropsychology of Schizophrenia. Hove, England: Erlbaum; 1992;
  20. Frith U, Frith CD. Development and neurophysiology of mentalizing. Philos. Trans. R. Soc. Lond. 2003;358:459–473
  21. Fujiwara H, Namiki C, Hirao K, Miyata J, Shimizu M, Fukuyama H, et al. Anterior and posterior cingulum abnormalities and their association with psychopathology in schizophrenia: a diffusion tensor imaging study. Schizophr. Res. 2007;95:215–222
  22. Gainotti G, Almonti S, Di Betta AM, Silveri MC. Retrograde amnesia in a patient with retrosplenial tumour. Neurocase. 1998;4:519–526
  23. Gallagher HL, Frith CD. Functional imaging of ‘theory of mind’. Trends Cogn. Sci. 2003;7:77–83
  24. Gusnard DA, Akbudak E, Shulman GL, Raichle ME. Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function. Proc. Natl. Acad. Sci. U.S.A. 2001;98:4259–4264
  25. Gusnard DA, Raichle ME. Searching for a baseline: functional imaging and the resting human brain. Nat. Rev. Neurosci. 2001;2:685–694
  26. Holt DJ, Cassidy BS, Andrews-Hanna JR, Lee SM, Coombs G, Goff DC, et al. An anterior-to-posterior shift in midline cortical activity in schizophrenia during self-reflection. Biol. Psychiatry. 2011;69(5):415–423
  27. Irani F, Platek SM, Panyavin IS, Calkins ME, Kohler C, Siegel SJ, et al. Self-face recognition and theory of mind in patients with schizophrenia and first-degree relatives. Schizophr. Res. 2006;88:151–160
  28. Kamali M, Kelly BD, Clarke M, Browne S, Gervin M, Kinsella A, et al. A prospective evaluation of adherence to medication in first episode schizophrenia. Eur. Psychiatry. 2006;21(1):29–33
  29. Kelley WM, Macrae CN, Wyland CL, Caglar S, Inati S, Heatherton TF. Finding the self? An event-related fMRI study. J. Cogn. Neurosci. 2002;14(5):785–794
  30. Kerns JG, Cohen JD, MacDonald AW, Cho RY, Stenger VA, Carter CS. Anterior cingulate conflict monitoring and adjustments in control. Science. 2004;303:1023–1026
  31. Kettle JWL, O‘Brien-Simpson L, Allen NB. Impaired theory of mind in first episode schizophrenia: comparison with community, university and depressed controls. Schizophr. Res. 2008;99:96–102
  32. Koren D, Seidman LJ, Poyurovsky M, Goldsmith M, Viksman P, Zichel S, et al. The neuropsychological basis of insight in first-episode schizophrenia: a pilot metacognitive study. Schizophr. Res. 2004;70:195–202
  33. Kreczmanski P, Schmidt-Kastner R, Heinsen H, Steinbusch HW, Hof PR, Schmitz C. Stereological studies of capillary length density in the frontal cortex of schizophrenics. Acta Neuropathol. 2005;109:510–518
  34. Kubicki M, Westin CF, Nestor PG, Wible CG, Frumin M, Maier SE, et al. Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study. Biol. Psychiatry. 2003;54:1171–1180
  35. Kumra S, Ashtari M, Cervellione KL, Henderson I, Kester H, Roofeh D, et al. White matter abnormalities in early-onset schizophrenia: a voxel-based diffusion tensor imaging study. Am. Acad. Child. Adolesc. Psychiatry. 2005;44:934–941
  36. Lee KH, Brown WH, Egleston PN, Green RD, Farrow TF, Hunter MD, et al. A functional magnetic resonance imaging study of social cognition in schizophrenia during an acute episode and after recovery. Am J. Psychiatry. 2006;163:1926–1933
  37. Lemogne C, Delaveau P, Freton M, Guionnet S, Fossati P. Medial prefrontal cortex and the self in major depression. J. Affect. Disord. 2010;[Epub ahead of print] PubMed PMID: 21185083
  38. Lysaker PH, Carcione A, Dimaggio G, Johannesen JK, Nicolò G, Procacci M, et al. Metacognition amidst narratives of self and illness in schizophrenia: associations with neurocognition, symptoms, insight and quality of life. Acta Psychiatr. Scand. 2005;112:64–71
  39. Lysaker PH, Dimaggio G, Buck KD, Carcione A, Nicolo G. Metacognition within narratives of schizophrenia: associations with multiple domains of neurocognition. Schizophr. Res. 2007;93:278–287
  40. Lysaker PH, Dimaggio G, Carcione A, Procacci M, Buck KD, Davis LW, et al. Metacognition and schizophrenia: the capacity for self-reflectivity as a predictor for prospective assessments of work performance over six months. Schizophr. Res. 2009;122:124–130
  41. Maddock RJ. The retrosplenial cortex and emotion: new insights from functional neuroimaging of the human brain. Trends Neurosci. 1999;7:310–316
  42. Materna S, Dicke PW, Thier P. The posterior superior temporal sulcus is involved in social communication not specific for the eyes. Neuropsycologia. 2008;46:59–65
  43. Mega MS, Cummings JL, Salloway S, Malloy P. The limbic system: an anatomic, phylogenetic, and clinical perspective. J. Neuropsychiatry Clin. Neurosci. 1997;9:315–330
  44. Modinos G, Renken R, Ormel J, Aleman A. Self-reflection and the psychosis-prone brain: an fMRI study. Neuropsychology. 2011;25(3):295–305
  45. Murphy ER, Brent BK, Benton M, Pruitt P, Diwadkar V, Rajarethinam RP, et al. Differential processing of metacognitive evaluation and the neural circuitry of the self and others in schizophrenia: a pilot study. Schizophr. Res. 2010;116(2-3):252–258
  46. Northoff G, Heinzel A, de Greck M, Bermpohl F, Dobrowolny H, Panksepp J. Self-referential processing in our brain—a meta-analysis of imaging studies on the self. Neuroimage. 2006;31:440–457
  47. Northoff G, Bermpohl F. Cortical midline structures and the self. Trends Cogn. Sci. 2004;8:102–107
  48. Ochsner KN, Beer JS, Robertson ER, Cooper JC, Gabrieli JD, Kihsltrom JF, et al. The neural correlates of direct and reflected self-knowledge. Neuroimage. 2005;28(4):797–814
  49. Ongur D, Price JL. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb. Cortex. 2000;10:206–219
  50. Reske M, Habel U, Kellermann T, Backes V, Jon Shah N, von Wilmsdorff M, et al. Differential brain activation during facial emotion discrimination in first-episode schizophrenia. J. Psychiatr. Res. 2009;43:592–599
  51. Sass LA, Parnas J. Schizophrenia, consciousness, and the self. Schizophr. Bull. 2003;29:427–444
  52. Saxe R, Kanwisher N. People thinking about thinking people: the role of the temporo-parietal junction in theory of mind. NeuroImage. 2003;19:1835–1842
  53. Schmitz TW, Johnson SC. Relevance to self: a brief review and framework of neural systems underlying appraisal. Neurosci. Biobehav. Rev. 2007;31(4):585–596Review
  54. Schmitz TW, Johnson SC. Self-appraisal decisions evoke dissociated dorsal–ventral aMPFC networks. Neuroimage. 2006;30(3):1050–1058
  55. Schore AN. Affect Dysregulation and Disorders of the Self. W. W. Norton; 2003;
  56. Segal D, Haznedar MM, Hazlett EA, Entis JJ, Newmark RE, Torosjan Y, et al. Diffusion tensor anisotropy in the cingulate gyrus in schizophrenia. Neuroimage. 2010;50(2):357–365
  57. Sergi MJ, Rassovsky Y, Nuechterlein KH, Green MF. Social perception as a mediator of the influence of early visual processing on functional status in schizophrenia. Am. J. Psychiatry. 2006;163:448–454
  58. Sprong M, Schothorst P, Vos E, Hox J, van EH. Theory of mind in schizophrenia: meta-analysis. Br. J. Psychiatry. 2007;191:5–13
  59. Sun Z, Wang F, Cui L, Breeze J, Du X, Wang X, et al. Abnormal anterior cingulum in patients with schizophrenia: a diffusion tensor imaging study. NeuroReport. 2003;14:1833–1836
  60. Théberge J, Bartha R, Drost DJ, Menon RS, Malla A, Takhar J, et al. Glutamate and glutamine measured with 4.0T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am. J. Psychiatry. 2002;159:1944–1946
  61. van der Meer L, Costafreda S, Aleman A, David AS. Self-reflection and the brain: a theoretical review and meta-analysis of neuroimaging studies with implications for schizophrenia. Neurosci. Biobehav. Rev. 2010;34(6):935–946Review
  62. Vogeley K. Schizophrenia as disturbance of the self-construct. In:  Kircher T,  David A editor. The Self in Neuroscience and Psychiatry. second ed.. Cambridge: Cambridge University Press; 2007;p. 361–379
  63. Vogt BA, Finch DM, Olson CR. Functional heterogeneity in cingulate cortex: the anterior executive and posterior evaluative regions. Cereb. Cortex. 1992;2:435–443
  64. Völlm BA, Taylor ANW, Richardson P, Corcoran R, Stirling J, McKie S, et al. Neuronal correlates of theory of mind and empathy: a functional magnetic resonance imaging study in a nonverbal task. NeuroImage. 2006;29:90–98
  65. Walter H, Ciaramidaro A, Adenzato M, Vasic N, Ardito RB, Erk S, et al. Dysfunction of the social brain in schizophrenia is modulated by intention type: an fMRI study. Soc. Cogn. Affect. Neurosci. 2009;4:166–176
  66. Wang F, Sun Z, Cui L, Du X, Wang X, Zhang H, et al. Anterior cingulum abnormalities in male patients with schizophrenia determined through diffusion tensor imaging. Am. J. Psychiatry. 2004;161:573–575
  67. Wang L, Hosakere M, Trein JC, Miller A, Ratnanather JT, Barch DM, et al. Abnormalities of cingulate gyrus neuroanatomy in schizophrenia. Schizophr. Res. 2007;93:66–78
  68. White T, Cullen K, Rohrer LM, Karatekin C, Luciana M, Schmidt M, et al. Limbic structures and networks in children and adolescents with schizophrenia. Schizophr. Bull. 2008;34:18–29
  69. Whitfield-Gabrieli S, Thermenos HW, Milanovic S, Tsuang MT, Faraone SV, McCarley RW, et al. Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia. Proc. Natl. Acad. Sci. U.S.A. 2009;106(4):1279–1284
  70. Wood SJ, Yucel M, Wellard RM, Harrison BJ, Clarke K, Fornito A, et al. Evidence for neuronal dysfunction in the anterior cingulate of patients with schizophrenia: a proton magnetic resonance spectroscopy study at 3T. Schizophr. Res. 2007;94:328–331
  71. Zhou Y, Liang M, Tian L, Wang K, Hao Y, Liu H, et al. Functional disintegration in paranoid schizophrenia using resting-state fMRI. Schizophr. Res. 2007;97(1-3):194–205

PII: S1876-2018(11)00115-8

doi: 10.1016/j.ajp.2011.09.002

Asian Journal of Psychiatry
Volume 4, Issue 4 , Pages 248-254 , December 2011