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Neuroimaging and the Longitudinal Course of Schizophrenia

  • Geraldo F. Busatto
  • Pedro G. P. Rosa
  • Paolo Fusar-Poli
  • Lynn E. DeLisi
Chapter

Abstract

For many decades, neuroimaging studies have consistently demonstrated the presence of brain pathological changes associated with the diagnosis of schizophrenia, more recently using magnetic resonance imaging (MRI). With several thousands of patients examined in different disease stages, MRI studies have allowed investigations of the possible patterns of progression of such brain changes over the longitudinal course of schizophrenia after the initial onset of symptoms. Overall, the available MRI data indicate that structural brain abnormalities associated with the diagnosis of schizophrenia may progress from the first psychotic episode (or even in the prodromal stage) to chronic disease states, particularly during the initial few years after illness onset. Such progressive brain changes are probably restricted to subgroups of patients with an unremitting disease course and poorer outcome. Conversely, there is some evidence from longitudinal MRI studies suggesting that brain abnormalities in cases of schizophrenia with better prognosis may be even reversible. In addition, longitudinal MRI studies also suggest that the degree of progression of brain structural abnormalities over the course of schizophrenia is likely (at least partially) to be under the influence of chronic antipsychotic usage.

References

  1. 1.
    DeLisi LE. The concept of progressive brain change in schizophrenia: implications for understanding schizophrenia. Schizophr Bull. 2008;34(2):312–21.  https://doi.org/10.1093/schbul/sbm164.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Johnstone EC, Crow TJ, Frith CD, et al. Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet. 1976;2(7992):924–6.PubMedGoogle Scholar
  3. 3.
    Weinberger DR, Torrey EF, Wyatt RJ. Cerebellar atrophy in chronic schizophrenia. Lancet. 1979;1(8118):718–9.PubMedGoogle Scholar
  4. 4.
    Weinberger DR, Torrey EF, Neophytides AN, et al. Lateral cerebral ventricular enlargement in chronic schizophrenia. Arch Gen Psychiatry. 1979;36(7):735–9.PubMedGoogle Scholar
  5. 5.
    Weinberger DR, Torrey EF, Neophytides AN, et al. Structural abnormalities in the cerebral cortex of chronic schizophrenic patients. Arch Gen Psychiatry. 1979;36(9):935–9.PubMedGoogle Scholar
  6. 6.
    Zipursky RB, Reilly TJ, Murray RM. The myth of schizophrenia as a progressive brain disease. Schizophr Bull. 2013;39(6):1363–72.  https://doi.org/10.1093/schbul/sbs135.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Eickhoff SB, Bzdok D, Laird AR, et al. Activation likelihood estimation meta-analysis revisited. NeuroImage. 2012;59(3):2349–61.  https://doi.org/10.1016/j.neuroimage.2011.09.017.PubMedGoogle Scholar
  8. 8.
    Ellison-Wright I, Glahn DC, Laird AR, et al. The anatomy of first-episode and chronic schizophrenia: an anatomical likelihood estimation meta-analysis. Am J Psychiatry. 2008;165(8):1015–23.  https://doi.org/10.1176/appi.ajp.2008.07101562.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Chan RC, Di X, McAlonan GM, et al. Brain anatomical abnormalities in high-risk individuals, first-episode, and chronic schizophrenia: an activation likelihood estimation meta-analysis of illness progression. Schizophr Bull. 2011;37(1):177–88.  https://doi.org/10.1093/schbul/sbp073.PubMedGoogle Scholar
  10. 10.
    Hajima SV, Van Haren N, Cahn W, et al. Brain volumes in schizophrenia: a meta-analysis in over 18 000 subjects. Schizophr Bull. 2013;39(5):1129–38.  https://doi.org/10.1093/schbul/sbs118.Google Scholar
  11. 11.
    Meisenzahl EM, Koutsouleris N, Bottlender R, et al. Structural brain alterations at different stages of schizophrenia: a voxel-based morphometric study. Schizophr Res. 2008;104(1–3):44–60.  https://doi.org/10.1016/j.schres.2008.06.023.PubMedGoogle Scholar
  12. 12.
    Torres US, Duran FL, Schaufelberger MS, et al. Patterns of regional gray matter loss at different stages of schizophrenia: a multisite, cross-sectional VBM study in first-episode and chronic illness. Neuroimage Clin. 2016;12:1–15.  https://doi.org/10.1016/j.nicl.2016.06.002.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Schaufelberger MS, Duran FL, Lappin JM, et al. Grey matter abnormalities in Brazilians with first-episode psychosis. Br J Psychiatry Suppl. 2007;51:s117–s22.  https://doi.org/10.1192/bjp.191.51.s117.PubMedGoogle Scholar
  14. 14.
    Häfner H, Nowotny B. Epidemiology of early-onset schizophrenia. Eur Arch Psychiatry Clin Neurosci. 1995;245(2):80–92.PubMedGoogle Scholar
  15. 15.
    Clemmensen L, Vernal DL, Steinhausen HC. A systematic review of the long-term outcome of early onset schizophrenia. BMC Psychiatry. 2012;12:150.  https://doi.org/10.1186/1471-244X-12-150.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Olabi B, Ellison-Wright I, McIntosh AM, et al. Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies. Biol Psychiatry. 2011;70(1):88–96.  https://doi.org/10.1016/j.biopsych.2011.01.032.PubMedGoogle Scholar
  17. 17.
    Chakos MH, Lieberman JA, Bilder RM, et al. Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. Am J Psychiatry. 1994;151(10):1430–6.Google Scholar
  18. 18.
    Prasad KM, Eack SM, Goradia D, et al. Progressive gray matter loss and changes in cognitive functioning associated with exposure to herpes simplex virus 1 in schizophrenia: a longitudinal study. Am J Psychiatry. 2011;168(8):822–30.  https://doi.org/10.1176/appi.ajp.2011.10101423.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Gur RE, Cowell P, Turetsky BI, et al. A follow-up magnetic resonance imaging study of schizophrenia. Relationship of neuroanatomical changes to clinical and neurobehavioral measures. Arch Gen Psychiatry. 1998;55(2):145–52.PubMedGoogle Scholar
  20. 20.
    Puri BK, Hutton SB, Saeed N, et al. A serial longitudinal quantitative MRI study of cerebral changes in first-episode schizophrenia using image segmentation and subvoxel registration. Psychiatry Res. 2001;106(2):141–50.PubMedGoogle Scholar
  21. 21.
    Boonstra G, Cahn W, Schnack HG, et al. Duration of untreated illness in schizophrenia is not associated with 5-year brain volume change. Schizophr Res. 2011;132(1):84–90.  https://doi.org/10.1016/j.schres.2011.07.018.PubMedGoogle Scholar
  22. 22.
    Clark GM, Mackay CE, Davidson ME, et al. Paracingulate sulcus asymmetry; sex difference, correlation with semantic fluency and change over time in adolescent onset psychosis. Psychiatry Res. 2010;184(1):10–5.  https://doi.org/10.1016/j.pscychresns.2010.06.012.PubMedGoogle Scholar
  23. 23.
    Palaniyappan L, Crow TJ, Hough M, et al. Gyrification of Broca’s region is anomalously lateralized at onset of schizophrenia in adolescence and regresses at 2 year follow-up. Schizophr Res. 2013;147(1):39–45.  https://doi.org/10.1016/j.schres.2013.03.028.PubMedGoogle Scholar
  24. 24.
    Tauscher-Wisniewski S, Tauscher J, Logan J, et al. Caudate volume changes in first episode psychosis parallel the effects of normal aging: a 5-year follow-up study. Schizophr Res. 2002;58(2–3):185–818.Google Scholar
  25. 25.
    Andreasen NC, Nopoulos P, Magnotta V, et al. Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia. Biol Psychiatry. 2011;70(7):672–9.  https://doi.org/10.1016/j.biopsych.2011.05.017.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Lee SH, Niznikiewicz M, Asami T, et al. Initial and progressive gray matter abnormalities in insular gyrus and temporal pole in first-episode schizophrenia contrasted with first-episode affective psychosis. Schizophr Bull. 2016;42(3):790–801.  https://doi.org/10.1093/schbul/sbv177.PubMedGoogle Scholar
  27. 27.
    Whitworth AB, Kemmler G, Honeder M, et al. Longitudinal volumetric MRI study in first- and multiple-episode male schizophrenia patients. Psychiatry Res. 2005;140(3):225–37.PubMedGoogle Scholar
  28. 28.
    Lieberman JA, Tollefson GD, Charles C, et al. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry. 2005;62(4):361–70.Google Scholar
  29. 29.
    Mamah D, Harms MP, Barch D, et al. Hippocampal shape and volume changes with antipsychotics in early stage psychotic illness. Front Psychiatry. 2012;3:96.  https://doi.org/10.3389/fpsyt.2012.00096.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Whitford TJ, Grieve SM, Farrow TF, et al. Volumetric white matter abnormalities in first-episode schizophrenia: a longitudinal, tensor-based morphometry study. Am J Psychiatry. 2007;164(7):1082–9.PubMedGoogle Scholar
  31. 31.
    Glenthoj A, Glenthoj BY, Mackeprang T, et al. Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug. Psychiatry Res. 2007;154(3):199–208.PubMedGoogle Scholar
  32. 32.
    Roiz-Santiáñez R, Ortiz-García de la Foz V, Ayesa-Arriola R, et al. No progression of the alterations in the cortical thickness of individuals with schizophrenia-spectrum disorder: a three-year longitudinal magnetic resonance imaging study of first-episode patients. Psychol Med. 2015;45(13):2861–71.  https://doi.org/10.1017/S0033291715000811.PubMedGoogle Scholar
  33. 33.
    Arango C, Rapado-Castro M, Reig S, et al. Progressive brain changes in children and adolescents with first-episode psychosis. Arch Gen Psychiatry. 2012;69(1):16–26.  https://doi.org/10.1001/archgenpsychiatry.2011.150.PubMedGoogle Scholar
  34. 34.
    Kasparek T, Prikryl R, Schwarz D, et al. Gray matter morphology and the level of functioning in one-year follow-up of first-episode schizophrenia patients. Prog Neuro-Psychopharmacol Biol Psychiatry. 2009;33(8):1438–46.  https://doi.org/10.1016/j.pnpbp.2009.07.025.Google Scholar
  35. 35.
    Mané A, Falcon C, Mateos JJ, et al. Progressive gray matter changes in first episode schizophrenia: a 4-year longitudinal magnetic resonance study using VBM. Schizophr Res. 2009;114(1–3):136–43.  https://doi.org/10.1016/j.schres.2009.07.014.PubMedGoogle Scholar
  36. 36.
    Takahashi T, Wood SJ, Yung AR, et al. Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. Arch Gen Psychiatry. 2009;66(4):366–76.  https://doi.org/10.1001/archgenpsychiatry.2009.12.PubMedGoogle Scholar
  37. 37.
    Takahashi T, Nakamura K, Ikeda E, et al. Longitudinal MRI study of the midline brain regions in first-episode schizophrenia. Psychiatry Res. 2013;212(2):150–3.  https://doi.org/10.1016/j.pscychresns.2012.12.001.PubMedGoogle Scholar
  38. 38.
    Schaufelberger MS, Lappin JM, Duran FL, et al. Lack of progression of brain abnormalities in first-episode psychosis: a longitudinal magnetic resonance imaging study. Psychol Med. 2011;41(8):1677–89.  https://doi.org/10.1017/S0033291710002163.PubMedGoogle Scholar
  39. 39.
    Rosa PG, Zanetti MV, Duran FL, et al. What determines continuing grey matter changes in first-episode schizophrenia and affective psychosis? Psychol Med. 2015;45(4):817–28.  https://doi.org/10.1017/S0033291714001895.PubMedGoogle Scholar
  40. 40.
    de Castro-Manglano P, Mechelli A, Soutullo C, et al. Longitudinal changes in brain structure following the first episode of psychosis. Psychiatry Res. 2011;191(3):166–3.  https://doi.org/10.1016/j.pscychresns.2010.10.010.PubMedGoogle Scholar
  41. 41.
    Li M, Chen Z, Deng W, et al. Volume increases in putamen associated with positive symptom reduction in previously drug-naive schizophrenia after 6 weeks antipsychotic treatment. Psychol Med. 2012;42(7):1475–83.  https://doi.org/10.1017/S0033291711002157.PubMedGoogle Scholar
  42. 42.
    Wang Q, Cheung C, Deng W, et al. White-matter microstructure in previously drug-naive patients with schizophrenia after 6 weeks of treatment. Psychol Med. 2013;43(11):2301–9.  https://doi.org/10.1017/S0033291713000238.PubMedGoogle Scholar
  43. 43.
    Lappin JM, Morgan C, Chalavi S, et al. Bilateral hippocampal increase following first-episode psychosis is associated with good clinical, functional and cognitive outcomes. Psychol Med. 2014;44(6):1279–91.  https://doi.org/10.1017/S0033291713001712.PubMedGoogle Scholar
  44. 44.
    Gutiérrez-Galve L, Chu EM, Leeson VC, et al. A longitudinal study of cortical changes and their cognitive correlates in patients followed up after first-episode psychosis. Psychol Med. 2015;45(1):205–16.  https://doi.org/10.1017/S0033291714001433.PubMedGoogle Scholar
  45. 45.
    Kawano M, Sawada K, Shimodera S, et al. Hippocampal subfield volumes in first episode and chronic schizophrenia. PLoS One. 2015;10(2):e0117785.  https://doi.org/10.1371/journal.pone.0117785.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Haukvik UK, Hartberg CB, Nerland S, et al. No progressive brain changes during a 1-year follow-up of patients with first-episode psychosis. Psychol Med. 2016;46(3):589–98.  https://doi.org/10.1017/S003329171500210X.PubMedGoogle Scholar
  47. 47.
    Jørgensen KN, Nesvåg R, Nerland S, et al. Brain volume change in first-episode psychosis: an effect of antipsychotic medication independent of BMI change. Acta Psychiatr Scand. 2017;135(2):117–26.  https://doi.org/10.1111/acps.12677.PubMedGoogle Scholar
  48. 48.
    DeLisi LE, Stritzke P, Riordan H, et al. The timing of brain morphological changes in schizophrenia and their relationship to clinical outcome. Biol Psychiatry. 1992;31(3):241–54.PubMedGoogle Scholar
  49. 49.
    DeLisi LE, Tew W, Xie S, et al. A prospective follow-up study of brain morphology and cognition in first-episode schizophrenic patients: preliminary findings. Biol Psychiatry. 1995;38(6):349–60.PubMedGoogle Scholar
  50. 50.
    DeLisi LE, Sakuma M, Tew W, et al. Schizophrenia as a chronic active brain process: a study of progressive brain structural change subsequent to the onset of schizophrenia. Psychiatry Res. 1997;74(3):129–40.PubMedGoogle Scholar
  51. 51.
    DeLisi LE, Sakuma M, Maurizio AM, et al. Cerebral ventricular change over the first 10 years after the onset of schizophrenia. Psychiatry Res. 2004;130(1):57–70.PubMedGoogle Scholar
  52. 52.
    Trzesniak C, Schaufelberger MS, Duran FL, et al. Longitudinal follow-up of cavum septum pellucidum and adhesio interthalamica alterations in first-episode psychosis: a population-based MRI study. Psychol Med. 2012;42(12):2523–34.PubMedGoogle Scholar
  53. 53.
    Ho BC, Andreasen NC, Nopoulos P, et al. Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. Arch Gen Psychiatry. 2003;60(6):585–94.PubMedGoogle Scholar
  54. 54.
    Whitford TJ, Grieve SM, Farrow TF, et al. Progressive grey matter atrophy over the first 2–3 years of illness in first-episode schizophrenia: a tensor-based morphometry study. NeuroImage. 2006;32(2):511–9.PubMedGoogle Scholar
  55. 55.
    James AC, Javaloyes A, James S, et al. Evidence for non-progressive changes in adolescent-onset schizophrenia: follow-up magnetic resonance imaging study. Br J Psychiatry. 2002;180:339–44.PubMedGoogle Scholar
  56. 56.
    James AC, James S, Smith DM, et al. Cerebellar, prefrontal cortex, and thalamic volumes over two time points in adolescent-onset schizophrenia. Am J Psychiatry. 2004;161(6):1023–9.PubMedGoogle Scholar
  57. 57.
    Nakamura M, Salisbury DF, Hirayasu Y, et al. Neocortical gray matter volume in first-episode schizophrenia and first-episode affective psychosis: a cross-sectional and longitudinal MRI study. Biol Psychiatry. 2007;62(7):773–83.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Cahn W, Hulshoff Pol HE, Lems EB, et al. Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Arch Gen Psychiatry. 2002;59(11):1002–10.PubMedGoogle Scholar
  59. 59.
    Rais M, Cahn W, Van Haren N, et al. Excessive brain volume loss over time in cannabis-using first-episode schizophrenia patients. Am J Psychiatry. 2008;165(4):490–6.  https://doi.org/10.1176/appi.ajp.2007.07071110.PubMedGoogle Scholar
  60. 60.
    Reig S, Moreno C, Moreno D, et al. Progression of brain volume changes in adolescent-onset psychosis. Schizophr Bull. 2009;35(1):233–43.  https://doi.org/10.1093/schbul/sbm160.PubMedGoogle Scholar
  61. 61.
    Suárez-Pinilla P, Roiz-Santiáñez R, de la Foz VO, et al. BDNF Val66Met variants and brain volume changes in non-affective psychosis patients and healthy controls: a 3 year follow-up study. Prog Neuro-Psychopharmacol Biol Psychiatry. 2013;45:201–6.  https://doi.org/10.1016/j.pnpbp.2013.05.014.PubMedGoogle Scholar
  62. 62.
    Ota M, Obu S, Sato N, et al. Progressive brain changes in schizophrenia: a 1-year follow-up study of diffusion tensor imaging. Acta Neuropsychiatr. 2009;21(6):301–7.  https://doi.org/10.1111/j.1601-5215.2009.00422.x.PubMedGoogle Scholar
  63. 63.
    Mitelman SA, Nikiforova YK, Canfield EL, et al. A longitudinal study of the corpus callosum in chronic schizophrenia. Schizophr Res. 2009;114(1–3):144–53.  https://doi.org/10.1016/j.schres.2009.07.021.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Sun Y, Chen Y, Lee R, et al. Disruption of brain anatomical networks in schizophrenia: a longitudinal, diffusion tensor imaging based study. Schizophr Res. 2016;171(1–3):149–57.  https://doi.org/10.1016/j.schres.2016.01.025.PubMedGoogle Scholar
  65. 65.
    Vita A, De Peri L, Deste G, et al. Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies. Transl Psychiatry. 2012;2:e190.  https://doi.org/10.1038/tp.2012.116.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Fusar-Poli P, Smieskova R, Kempton MJ, et al. Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neurosci Biobehav Rev. 2013;37(8):1680–91.  https://doi.org/10.1016/j.neubiorev.2013.06.001.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Fraguas D, Merchán-Naranjo J, del Rey-Mejías Á, et al. A longitudinal study on the relationship between duration of untreated psychosis and executive function in early-onset first-episode psychosis. Schizophr Res. 2014;158(1–3):126–33.  https://doi.org/10.1016/j.schres.2014.06.038.PubMedGoogle Scholar
  68. 68.
    van Haren NE, Cahn W, Hulshoff Pol HE, et al. Schizophrenia as a progressive brain disease. Eur Psychiatry. 2008;23(4):245–54.  https://doi.org/10.1016/j.eurpsy.2007.10.013.PubMedPubMedCentralGoogle Scholar
  69. 69.
    van Haren NE, Kahn RS. Progressive brain tissue loss in schizophrenia. Schizophr Res. 2016;173(3):121–3.  https://doi.org/10.1016/j.schres.2016.03.023.PubMedGoogle Scholar
  70. 70.
    Tanskanen P, Ridler K, Murray GK, et al. Morphometric brain abnormalities in schizophrenia in a population-based sample: relationship to duration of illness. Schizophr Bull. 2010;36(4):766–77.  https://doi.org/10.1093/schbul/sbn141.PubMedGoogle Scholar
  71. 71.
    Kasai K, Shenton ME, Salisbury DF, et al. Progressive decrease of left superior temporal gyrus gray matter volume in patients with first-episode schizophrenia. Am J Psychiatry. 2003;160(1):156–64.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Kasai K, Shenton ME, Salisbury DF, et al. Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Arch Gen Psychiatry. 2003;60(8):766–75.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Lieberman J, Chakos M, Wu H, et al. Longitudinal study of brain morphology in first episode schizophrenia. Biol Psychiatry. 2001;49(6):487–99.PubMedGoogle Scholar
  74. 74.
    Hulshoff Pol HE, Schnack HG, Mandl RC, et al. Focal gray matter density changes in schizophrenia. Arch Gen Psychiatry. 2001;58(12):1118–25.PubMedGoogle Scholar
  75. 75.
    Cahn W, Rais M, Stigter FP, et al. Psychosis and brain volume changes during the first five years of schizophrenia. Eur Neuropsychopharmacol. 2009;19(2):147–51.  https://doi.org/10.1016/j.euroneuro.2008.10.006.PubMedGoogle Scholar
  76. 76.
    Kahn RS, Sommer IE, Murray RM, et al. Schizophrenia. Nat Rev Dis Primers. 2015;1:15067.  https://doi.org/10.1038/nrdp.2015.67.PubMedGoogle Scholar
  77. 77.
    Fusar-Poli P, Meyer-Lindenberg A. Forty years of structural imaging in psychosis: promises and truth. Acta Psychiatr Scand. 2016;134(3):207–24.  https://doi.org/10.1111/acps.12619.PubMedGoogle Scholar
  78. 78.
    Keshavan MS, Haas GL, Kahn CE, et al. Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible? J Psychiatr Res. 1998;32(3–4):161–7.PubMedGoogle Scholar
  79. 79.
    Jääskeläinen E, Juola P, Kurtti J, et al. Associations between brain morphology and outcome in schizophrenia in a general population sample. Eur Psychiatry. 2014;29(7):456–62.  https://doi.org/10.1016/j.eurpsy.2013.10.006.PubMedGoogle Scholar
  80. 80.
    Wassink TH, Andreasen NC, Nopoulos P, et al. Cerebellar morphology as a predictor of symptom and psychosocial outcome in schizophrenia. Biol Psychiatry. 1999;45(1):41–8.PubMedGoogle Scholar
  81. 81.
    Staal WG, Hulshoff Pol HE, Schnack HG, et al. Structural brain abnormalities in chronic schizophrenia at the extremes of the outcome spectrum. Am J Psychiatry. 2001;158(7):1140–2.PubMedGoogle Scholar
  82. 82.
    Brickman AM, Buchsbaum MS, Ivanov Z, et al. Internal capsule size in good-outcome and poor-outcome schizophrenia. J Neuropsychiatr Clin Neurosci. 2006;18(3):364–76.Google Scholar
  83. 83.
    Mitelman SA, Brickman AM, Shihabuddin L, et al. A comprehensive assessment of gray and white matter volumes and their relationship to outcome and severity in schizophrenia. NeuroImage. 2007;37(2):449–62.PubMedPubMedCentralGoogle Scholar
  84. 84.
    Molina V, Hernández JA, Sanz J, et al. Subcortical and cortical gray matter differences between Kraepelinian and non-Kraepelinian schizophrenia patients identified using voxel-based morphometry. Psychiatry Res. 2010;184(1):16–22.  https://doi.org/10.1016/j.pscychresns.2010.06.006.PubMedGoogle Scholar
  85. 85.
    Goldman M, Tandon R, DeQuardo JR, et al. Biological predictors of 1-year outcome in schizophrenia in males and females. Schizophr Res. 1996;21(2):65–73.PubMedGoogle Scholar
  86. 86.
    DeLisi LE, Sakuma M, Ge S, et al. Association of brain structural change with the heterogeneous course of schizophrenia from early childhood through five years subsequent to a first hospitalization. Psychiatry Res. 1998;84(2–3):75–88.PubMedGoogle Scholar
  87. 87.
    van Haren NE, Cahn W, Hulshoff Pol HE, et al. Brain volumes as predictor of outcome in recent-onset schizophrenia: a multi-center MRI study. Schizophr Res. 2003;64(1):41–52.PubMedGoogle Scholar
  88. 88.
    Robinson DG, Woerner MG, McMeniman M, et al. Symptomatic and functional recovery from a first episode of schizophrenia or schizoaffective disorder. Am J Psychiatry. 2004;161(3):473–9.PubMedGoogle Scholar
  89. 89.
    Bachmann S, Bottmer C, Schröder J, et al. Compliance with medication but not structural MRI measures predict functional outcome in first-episode schizophrenia patients. Schizophr Res. 2007;90(1–3):355–6.PubMedGoogle Scholar
  90. 90.
    Koo MS, Levitt JJ, Salisbury DF, et al. A cross-sectional and longitudinal magnetic resonance imaging study of cingulate gyrus gray matter volume abnormalities in first-episode schizophrenia and first-episode affective psychosis. Arch Gen Psychiatry. 2008;65(7):746–60.  https://doi.org/10.1001/archpsyc.65.7.746.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Cahn W, van Haren NE, Hulshoff Pol HE, et al. Brain volume changes in the first year of illness and 5-year outcome of schizophrenia. Br J Psychiatry. 2006;189:381–2.PubMedGoogle Scholar
  92. 92.
    van Haren NE, Schnack HG, Cahn W, et al. Changes in cortical thickness during the course of illness in schizophrenia. Arch Gen Psychiatry. 2011;68(9):871–80.  https://doi.org/10.1001/archgenpsychiatry.2011.88.Google Scholar
  93. 93.
    Dusi N, Bellani M, Perlini C, et al. Progressive disability and prefrontal shrinkage in schizophrenia patients with poor outcome: a 3-year longitudinal study. Schizophr Res. 2017;179:104–11.  https://doi.org/10.1016/j.schres.2016.09.013.PubMedGoogle Scholar
  94. 94.
    Quarantelli M, Palladino O, Prinster A, et al. Patients with poor response to antipsychotics have a more severe pattern of frontal atrophy: a voxel-based morphometry study of treatment resistance in schizophrenia. Biomed Res Int. 2014;2014:325052.  https://doi.org/10.1155/2014/325052.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Veijola J, Guo JY, Moilanen JS, et al. Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication. PLoS One. 2014;9(7):e101689.  https://doi.org/10.1371/journal.pone.0101689.PubMedPubMedCentralGoogle Scholar
  96. 96.
    Dorph-Petersen KA, Pierri JN, Perel JM, et al. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology. 2005;30(9):1649–61.Google Scholar
  97. 97.
    Konopaske GT, Dorph-Petersen KA, Pierri JN, et al. Effect of chronic exposure to antipsychotic medication on cell numbers in the parietal cortex of macaque monkeys. Neuropsychopharmacology. 2007;32(6):1216–23.Google Scholar
  98. 98.
    Shah C, Zhang W, Xiao Y, et al. Common pattern of gray-matter abnormalities in drug-naïve and medicated first-episode schizophrenia: a multimodal meta-analysis. Psychol Med. 2017;47(3):401–13.  https://doi.org/10.1017/S0033291716002683.PubMedGoogle Scholar
  99. 99.
    Ho BC, Andreasen NC, Ziebell S, et al. Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Arch Gen Psychiatry. 2011;68(2):128–37.  https://doi.org/10.1001/archgenpsychiatry.2010.199.PubMedPubMedCentralGoogle Scholar
  100. 100.
    Théberge J, Williamson KE, Aoyama N, et al. Longitudinal grey-matter and glutamatergic losses first-episode schizophrenia. Br J Psychiatry. 2007;191:325–34.PubMedGoogle Scholar
  101. 101.
    Wood SJ, Velakoulis D, Smith DJ, et al. A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia. Schizophr Res. 2001;52(1–2):37–46.PubMedGoogle Scholar
  102. 102.
    Moncrieff J, Leo J. A systematic review of the effects of antipsychotic drugs on brain volume. Psychol Med. 2010;40(9):1409–22.  https://doi.org/10.1017/S0033291709992297.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Roiz-Santiañez R, Suarez-Pinilla P, Crespo-Facorro B. Brain structural effects of antipsychotic treatment in schizophrenia: a systematic review. Curr Neuropharmacol. 2015;13(4):422–34.PubMedPubMedCentralGoogle Scholar
  104. 104.
    Vita A, De Peri L, Deste G, et al. The effect of antipsychotic treatment on cortical gray matter changes in schizophrenia: does the class matter? A meta-analysis and meta-regression of longitudinal magnetic resonance imaging studies. Biol Psychiatry. 2015;78(6):403–12.  https://doi.org/10.1016/j.biopsych.2015.02.008.PubMedGoogle Scholar
  105. 105.
    Pantelis C, Velakoulis D, McGorry PD, et al. Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet. 2003;361(9354):281–8.PubMedGoogle Scholar
  106. 106.
    Suvisaari J, Keinänen J, Eskelinen S, et al. Diabetes and schizophrenia. Curr Diab Rep. 2016;16(2):16.  https://doi.org/10.1007/s11892-015-0704-4.PubMedGoogle Scholar
  107. 107.
    Willette AA, Kapogiannis D. Does the brain shrink as the waist expands? Ageing Res Rev. 2015;20:86–97.  https://doi.org/10.1016/j.arr.2014.03.007.PubMedGoogle Scholar
  108. 108.
    McIntyre RS, Kenna HA, Nguyen HT, et al. Brain volume abnormalities and neurocognitive deficits in diabetes mellitus: points of pathophysiological commonality with mood disorders? Adv Ther. 2010;27(2):63–80.  https://doi.org/10.1007/s12325-010-0011-z.PubMedGoogle Scholar
  109. 109.
    Poirier MF, Canceil O, Baylé F, et al. Prevalence of smoking in psychiatric patients. Prog Neuro-Psychopharmacol Biol Psychiatry. 2002;26(3):529–37.Google Scholar
  110. 110.
    Gage SH, Hickman M, Zammit S. Association between cannabis and psychosis: epidemiologic evidence. Biol Psychiatry. 2016;79(7):549–56.  https://doi.org/10.1016/j.biopsych.2015.08.001.PubMedGoogle Scholar
  111. 111.
    Murray RM, Englund A, Abi-Dargham A, et al. Cannabis-associated psychosis: neural substrate and clinical impact. Neuropharmacology. 2017;124:89–104.PubMedGoogle Scholar
  112. 112.
    Van Haren NE, Cahn W, Hulshoff Pol H, et al. Confounders of excessive brain volume loss in schizophrenia. Neurosci Biobehav Rev. 2012;37(10 Pt 1):2418–23.  https://doi.org/10.1016/j.neubiorev.2012.09.006.PubMedGoogle Scholar
  113. 113.
    French L, Gray C, Leonard G, et al. Early cannabis use, polygenic risk score for schizophrenia and brain maturation in adolescence. JAMA Psychiatry. 2015;72(10):1002–11.  https://doi.org/10.1001/jamapsychiatry.2015.1131.PubMedPubMedCentralGoogle Scholar
  114. 114.
    Gurillo P, Jauhar S, Murray RM, et al. Does tobacco use cause psychosis? Systematic review and meta-analysis. Lancet Psychiatry. 2015;2(8):718–25.  https://doi.org/10.1016/S2215-0366(15)00152-2.PubMedPubMedCentralGoogle Scholar
  115. 115.
    Van Haren NE, Koolschijn PC, Cahn W, et al. Cigarette smoking and progressive brain volume loss in schizophrenia. Eur Neuropsychopharmacol. 2010;20(7):454–8.  https://doi.org/10.1016/j.euroneuro.2010.02.009.PubMedGoogle Scholar
  116. 116.
    Harrison PJ. The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications. Psychopharmacology. 2004;174(1):151–62.PubMedGoogle Scholar
  117. 117.
    Glantz LA, Gilmore JH, Lieberman JA, et al. Apoptotic mechanisms and the synaptic pathology of schizophrenia. Schizophr Res. 2006;81(1):47–63.PubMedGoogle Scholar
  118. 118.
    Garey L. When cortical development goes wrong: schizophrenia as a neurodevelopmental disease of microcircuits. J Anat. 2010;217(4):324–33.  https://doi.org/10.1111/j.1469-7580.2010.01231.x.PubMedPubMedCentralGoogle Scholar
  119. 119.
    Adriano F, Caltagirone C, Spalletta G. Hippocampal volume reduction in first-episode and chronic schizophrenia: a review and meta-analysis. Neuroscientist. 2012;18(2):180–200.  https://doi.org/10.1177/1073858410395147.PubMedGoogle Scholar
  120. 120.
    Falkai P, Malchow B, Schmitt A. Aerobic exercise and its effects on cognition in schizophrenia. Curr Opin Psychiatry. 2017;30(3):171–5.  https://doi.org/10.1097/YCO.0000000000000326.PubMedGoogle Scholar
  121. 121.
    Muraki K, Tanigaki K. Neuronal migration abnormalities and its possible implications for schizophrenia. Front Neurosci. 2015;9:74.  https://doi.org/10.3389/fnins.2015.00074.PubMedPubMedCentralGoogle Scholar
  122. 122.
    Giedd JN, Raznahan A, Alexander-Bloch A, et al. Child psychiatry branch of the National Institute of Mental Health longitudinal structural magnetic resonance imaging study of human brain development. Neuropsychopharmacology. 2015;40(1):43–9.  https://doi.org/10.1038/npp.2014.236.PubMedGoogle Scholar
  123. 123.
    Selemon LD, Goldman-Rakic PS. The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol Psychiatry. 1999;45(1):17–25.PubMedGoogle Scholar
  124. 124.
    Cannon TD, van Erp TG, Bearden CE, et al. Early and late neurodevelopmental influences in the prodrome to schizophrenia: contributions of genes, environment, and their interactions. Schizophr Bull. 2003;29(4):653–69.PubMedGoogle Scholar
  125. 125.
    Selemon LD, Zecevic N. Schizophrenia: a tale of two critical periods for prefrontal cortical development. Transl Psychiatry. 2015;5:e623.  https://doi.org/10.1038/tp.2015.115.PubMedPubMedCentralGoogle Scholar
  126. 126.
    Dorph-Petersen KA, Delevich KM, Marcsisin MJ, et al. Pyramidal neuron number in layer 3 of primary auditory cortex of subjects with schizophrenia. Brain Res. 2009;1285:42–57.  https://doi.org/10.1016/j.brainres.2009.06.019.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Prasad KM, Burgess AM, Keshavan MS, et al. Neuropil pruning in early-course schizophrenia: immunological, clinical, and neurocognitive correlates. Biol Psychiatry Cogn Neurosci Neuroimaging. 2016;6:528–38.  https://doi.org/10.1016/j.bpsc.2016.08.007.Google Scholar
  128. 128.
    Harrison PJ. Postmortem studies in schizophrenia. Dialogues Clin Neurosci. 2000;2(4):349–57.PubMedPubMedCentralGoogle Scholar
  129. 129.
    Falkai P, Mike O, Inez MG, et al. A roadmap to disentangle the molecular etiology of schizophrenia. Eur Psychiatry. 2008;23(4):224–32.  https://doi.org/10.1016/j.eurpsy.2008.02.006.PubMedGoogle Scholar
  130. 130.
    Addington AM, Gornick M, Duckworth J, et al. GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss. Mol Psychiatry. 2005;10(6):581–8.PubMedGoogle Scholar
  131. 131.
    Poels EM, Kegeles LS, Kantrowitz JT, et al. Imaging glutamate in schizophrenia: review of findings and implications for drug discovery. Mol Psychiatry. 2014;19(1):20–9.  https://doi.org/10.1038/mp.2013.136.PubMedGoogle Scholar
  132. 132.
    DeLisi LE. Is schizophrenia a lifetime disorder of brain plasticity, growth and aging? Schizophr Res. 1997;23(2):119–29.PubMedGoogle Scholar
  133. 133.
    Schnack HG, van Haren NE, Nieuwenhuis M, et al. Accelerated brain aging in schizophrenia: a longitudinal pattern recognition study. Am J Psychiatry. 2016;173(6):607–16.  https://doi.org/10.1176/appi.ajp.2015.15070922.Google Scholar
  134. 134.
    Cropley VL, Klauser P, Lenroot RK, et al. Accelerated gray and white matter deterioration with age in schizophrenia. Am J Psychiatry. 2017;174(3):286–95.  https://doi.org/10.1176/appi.ajp.2016.16050610.PubMedGoogle Scholar
  135. 135.
    Kao HT, Cawthon RM, Delisi LE, et al. Rapid telomere erosion in schizophrenia. Mol Psychiatry. 2008;13(2):118–9.PubMedGoogle Scholar
  136. 136.
    Laskaris LE, Di Biase MA, Everall I, et al. Microglial activation and progressive brain changes in schizophrenia. Br J Pharmacol. 2016;173(4):666–80.  https://doi.org/10.1111/bph.13364.PubMedPubMedCentralGoogle Scholar
  137. 137.
    Miller BJ, Buckley P, Seabolt W, et al. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry. 2011;70(7):663–71.  https://doi.org/10.1016/j.biopsych.2011.04.013.PubMedPubMedCentralGoogle Scholar
  138. 138.
    Misiak B, Stańczykiewicz B, Kotowicz K, et al. Cytokines and C-reactive protein alterations with respect to cognitive impairment in schizophrenia and bipolar disorder: a systematic review. Schizophr Res. 2017;192:16–29.  https://doi.org/10.1016/j.schres.2017.04.015.PubMedGoogle Scholar
  139. 139.
    Dieset I, Haukvik UK, Melle I, et al. Association between altered brain morphology and elevated peripheral endothelial markers--implications for psychotic disorders. Schizophr Res. 2015;61(2–3):222–8.  https://doi.org/10.1016/j.schres.2014.11.006.Google Scholar
  140. 140.
    Pillai A, Howell KR, Ahmed AO, et al. Association of serum VEGF levels with prefrontal cortex volume in schizophrenia. Mol Psychiatry. 2016;1(5):686–92.  https://doi.org/10.1038/mp.2015.96.Google Scholar
  141. 141.
    Drakesmith M, Dutt A, Fonville L, et al. Mediation of developmental risk factors for psychosis by white matter microstructure in young adults with psychotic experiences. JAMA Psychiatry. 2016;73(4):396–406.  https://doi.org/10.1001/jamapsychiatry.2015.3375.PubMedGoogle Scholar
  142. 142.
    Camchong J, MacDonald AW 3rd, Bell C, et al. Altered functional and anatomical connectivity in schizophrenia. Schizophr Bull. 2011;37(3):640–50.PubMedGoogle Scholar
  143. 143.
    Suárez-Pinilla P, Roíz-Santiañez R, Mata I, et al. Progressive structural brain changes and NRG1 gene variants in first-episode nonaffective psychosis. Neuropsychobiology. 2015;71(2):103–11.PubMedGoogle Scholar
  144. 144.
    Suárez-Pinilla P, Roiz-Santiañez R, Ortiz-García de la Foz V, et al. Brain structural and clinical changes after first episode psychosis: focus on cannabinoid receptor 1 polymorphisms. Psychiatry Res. 2015;233(2):112–9.  https://doi.org/10.1016/j.pscychresns.2015.05.005.PubMedGoogle Scholar
  145. 145.
    Brans RG, van Haren NE, van Baal GC, et al. Longitudinal MRI study in schizophrenia patients and their healthy siblings. Br J Psychiatry. 2008;193(5):422–3.  https://doi.org/10.1192/bjp.bp.107.041467.PubMedGoogle Scholar
  146. 146.
    Hedman AM, van Haren NE, van Baal GC, et al. Heritability of cortical thickness changes over time in twin pairs discordant for schizophrenia. Schizophr Res. 2016;173(3):192–9.  https://doi.org/10.1016/j.schres.2015.06.021.PubMedGoogle Scholar
  147. 147.
    Haddad L, Schäfer A, Streit F, et al. Brain structure correlates of urban upbringing, an environmental risk factor for schizophrenia. Schizophr Bull. 2015;41(1):115–22.  https://doi.org/10.1093/schbul/sbu072.PubMedGoogle Scholar
  148. 148.
    Akdeniz C, Tost H, Streit F, et al. Neuroimaging evidence for a role of neural social stress processing in ethnic minority-associated environmental risk. JAMA Psychiatry. 2014;71(6):672–80.  https://doi.org/10.1001/jamapsychiatry.2014.35. Erratum in: JAMA Psychiatry. 2014;71(8):888.PubMedGoogle Scholar
  149. 149.
    Frissen A, van Os J, Habets P, Genetic Risk and Outcome in Psychosis (G.R.O.U.P.), et al. No evidence of association between childhood urban environment and cortical thinning in psychotic disorder. PLoS One. 2017;12(1):e0166651.  https://doi.org/10.1371/journal.pone.0166651. Erratum in: PLoS One 2017;12(5):e0178312.PubMedPubMedCentralGoogle Scholar
  150. 150.
    Hallak JE, de Paula AL, Chaves C, et al. An overview on the search for schizophrenia biomarkers. CNS Neurol Disord Drug Targets. 2015;14(8):996–1000.PubMedGoogle Scholar
  151. 151.
    Kapur S, Phillips AG, Insel TR. Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it? Mol Psychiatry. 2012;17(12):1174–9.  https://doi.org/10.1038/mp.2012.105.PubMedGoogle Scholar
  152. 152.
    Thompson PM, Stein JL, Medland SE, et al. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data. Brain Imaging Behav. 2014;8(2):153–82.  https://doi.org/10.1007/s11682-013-9269-5.PubMedPubMedCentralGoogle Scholar
  153. 153.
    Schmaal L, Hibar DP, Sämann PG, et al. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group. Mol Psychiatry. 2017;22(6):900–9.  https://doi.org/10.1038/mp.2016.60.PubMedGoogle Scholar
  154. 154.
    Okada N, Fukunaga M, Yamashita F, et al. Abnormal asymmetries in subcortical brain volume in schizophrenia. Mol Psychiatry. 2016;21(10):1460–6.  https://doi.org/10.1038/mp.2015.209.PubMedPubMedCentralGoogle Scholar
  155. 155.
    van Erp TG, Hibar DP, Rasmussen JM, et al. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Mol Psychiatry. 2016;21(4):585.  https://doi.org/10.1038/mp.2015.118.PubMedGoogle Scholar
  156. 156.
    Rathore S, Habes M, Iftikhar MA, et al. A review on neuroimaging-based classification studies and associated feature extraction methods for Alzheimer’s disease and its prodromal stages. NeuroImage. 2017;155:530–48.  https://doi.org/10.1016/j.neuroimage.2017.03.057.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Geraldo F. Busatto
    • 1
    • 2
  • Pedro G. P. Rosa
    • 1
    • 2
  • Paolo Fusar-Poli
    • 3
    • 4
  • Lynn E. DeLisi
    • 5
  1. 1.Department of Psychiatry, Faculty of MedicineUniversity of São PauloSão PauloBrazil
  2. 2.Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São PauloSão PauloBrazil
  3. 3.Early Psychosis Interventions and Clinical Detection (EPIC) Lab, Department of Psychosis StudiesInstitute of Psychiatry Psychology and Neuroscience (IoPPN), King’s College LondonLondonUK
  4. 4.Department of Brain and Behavioral SciencesUniversity of PaviaPaviaItaly
  5. 5.VA Boston Healthcare SystemHarvard Medical SchoolBrocktonUSA

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