When does structural brain change appear in schizophrenia and is it clinically relevant?

  • Lynn E. Delisi


Despite Kraepelin’s descriptions in the early 1900’s of structural brain pathology at the cellular level in patients with dementia praecox (Kraepelin 1919), little acceptance of this notion was present among 20thcentury psychiatrists who were focused on perfecting psychoanalytic techniques even for schizophrenia (Fromm-Reichmann 1943). Great care was taken to separate psychoses into those that were “organic” (i.e. a brain disease) and those that were functional (i.e. due to psychological factors; Davison 1987). Although early pneumoencephalographic studies clearly showed evidence that brain ventricular enlargement was present in patients with chronic schizophrenia (Haug et al. 1963, 1982; Huber 1957, 1979; Jacobi and Winkler 1927), it was not until Johnstone et al. (1976) and then Weinberger et al. (1979) demonstrated with CT that this finding was widely present in populations of patients with schizophrenia, that researchers began to accept its presence and attempt to uncover its relevance. When magnetic resonance imaging was available for human medical imaging, numerous brain scans of subjects with schizophrenia were examined further for both cortical and subcortical structural changes, and a large array of findings about brain structure, other than ventricular enlargement, emerged (reviewed in Shenton et al. 2001). Without any clear indication that duration of illness or any treatments had an effect on these findings, various brain developmental hypotheses about schizophrenia were proposed (Weinberger 1987; Murray et al. 1991; Feinberg 1982/83) and consideration was also given to a lifetime trajectory of deviant brain change that is likely to be genetically controlled (DeLisi 1997), or at least have both a developmental and degenerative component (Woods 1998; Waddington et al. 1997). In addition, what has emerged relatively consistently across studies is that some changes are asymmetrical and sometimes only relate to differences in asymmetry rather than absolute differences in one side of the brain, leading Crow and colleagues (1989) to propose that the primary defect in schizophrenia relates to the anomalous development of normal cerebral asymmetries.


Brain Change Chronic Schizophrenia Ventricular Enlargement Biological Psychiatry Structural Brain Change 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Cahn W, Hulshoff P, Hilleke E, Lems EBTE, van Haren NEM, Schnack HG, van der Linden JA, Schothorst PF, van Egeland H, Kahn RS (2002) Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Archives General Psychiatry 59:1002–1010CrossRefGoogle Scholar
  2. Crow TJ, Ball J, Bloom SR, Brown R, Bruton CJ, Colter N, Frith CD, Johnstone EC, Owens DG, Roberts GW (1989) Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease. Archives of General Psychiatry 46(12):1145–1150PubMedCrossRefGoogle Scholar
  3. Davis KL, Buchsbaum MS, Shihabuddin L, Spiegel-Cohen J, Metzger M, Frecska E, Keefe RS, Powchick P (1998) Ventricular enlargement in poor-outcome schizophrenia. Biological Psychiatry 43:783–793PubMedCrossRefGoogle Scholar
  4. Davison K (1987) Organic and toxic concomitants of schizophrenia: association or chance? In: Helmchen H, Henn FA (eds) Biological Perspectives of Schizophrenia. Life Sciences Research Reports 40. John Wiley and Sons, Chichester New York, pp 139–161Google Scholar
  5. DeGreef G, Ashtari M, Wu H, Borenstein M, Geisler S, Lieberman J (1991) Follow-up MRI study in first-episode schizophrenia. Schizophrenia Research 5:204–206PubMedCrossRefGoogle Scholar
  6. DeLisi LE (1999a) Defining the course of brain structural growth and plasticity in schizophrenia. Psychiatry Research, Neuroimaging 92(1):1–9CrossRefGoogle Scholar
  7. DeLisi LE (1999b) Regional brain volume change over the life-time course of schizophrenia. Journal of Psychiatric Research 33:535–541CrossRefGoogle Scholar
  8. DeLisi LE (1997) Is schizophrenia a lifetime disorder of brain plasticity, growth and aging? Schizophrenia Research 23:119–129PubMedCrossRefGoogle Scholar
  9. DeLisi LE, Grimson R, Sakuma M, Tew W, Kushner M, Hoff AL (1997) Schizophrenia as a chronic active brain process: a study of progressive brain structural change subsequent to the onset of schizophrenia. Psychiatry Research (Neuroimaging) 74:129–140CrossRefGoogle Scholar
  10. DeLisi LE, Sakuma M, Kushner M (1998) Association of brain structural change with the heterogeneous course of schizophrenia from early childhood through five years subsequent to a first hospitalization. Psychiatry Research (Neuroimaging) 84:75–88CrossRefGoogle Scholar
  11. DeLisi LE, Sakuma M, Maurizio A, Relja M, Hoff AL (2003) Structural Brain Changes over the first 10 years after the onset of Schizophrenia. (Submitted for publication)Google Scholar
  12. DeLisi LE, Schwartz CC, Targum SD, Byrnes SM, Cannon-Spoor E, Weinberger DR, Wyatt RJ (1983) Prediction of outcome in acute schizophreniform disorder. Psychiatry Research 9:169–171PubMedCrossRefGoogle Scholar
  13. DeLisi LE, Tew W, Xie S-H, Hoff AL, Sakuma M, Kushner M, Lee G, Shedlack K, Smith AM, Grimson R (1995) A prospective follow-up study of brain morphology and cognition in 1stepisode schizophrenic patients. Biological Psychiatry 38:349–360PubMedCrossRefGoogle Scholar
  14. DeLisi LE, Sakuma M, Maurizio A, Hoff AL (2004) Ten year follow-up of ventricular enlargement in first-episode patients with schizophrenia. Psychiatry Research, Neuroimaging (in press)Google Scholar
  15. Feinberg I (1982/1983) Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J Psychiatric Research 17:319–334CrossRefGoogle Scholar
  16. Fromm-Reichmann F (1943) Psychoanalytic psychotherapy with psychotics; the influence of the modifications in technique on present trends in psychoanalysis. Journal for the Study of Interpersonal Processes 6 (1943):277–279Google Scholar
  17. Garver DL, Nair TR, Christensen JD, Holcomb JA, Kingsbury SJ (2000) Brain and ventricle instability during psychotic episodes of the schizophrenias. Schizophrenia Research 44(1):11–23PubMedCrossRefGoogle Scholar
  18. Giedd JN, Jeffries NO, Blumenthal J, Castellanos FX, Vaituzis AC, Fernandez T, Hamburger SD, Liu H, Nelson J, Bedwell J, Tran L, Lenane M, Nicolson R, Rapoport JL (1999) Childhood-onset schizophrenia: progressive brain changes during adolescence. Biological Psychiatry 46(7):892–898PubMedCrossRefGoogle Scholar
  19. Gur RE, Cowell P, Turetsky BI, Gallacher F, Cannon T, Bilker W, Gur RC (1998) A follow-up magnetic resonance imaging study of schizophrenia. Relationship of neuroanatomical changes to clinical and neurobehavioral measures. Archives of General Psychiatry 55(2):145–152PubMedCrossRefGoogle Scholar
  20. Haug JO (1963) Pneumoencephalographic studies in mental disease. Acta Psych and Neurol Scand Suppl 165, 38:11–104Google Scholar
  21. Haug JO (1982) Pneumoencephalographic evidence of brain atrophy in acute and chronic schizophrenic patients. Acta Psychiatrica Scandinavica 66(5):374–383PubMedCrossRefGoogle Scholar
  22. Huber G (1957) Pneumoencephalographische and psychopathologische Bilder bei endogen Psychosen. Springer, BerlinCrossRefGoogle Scholar
  23. Huber G (1979) Pure defect and its meaning for a somatosis hypothesis of schizophrenia. In: Obiols J, Ballus C, Gonzales E, Pugol J (eds) Biological Psychiatry Today. Elsevier, Amsterdam, pp 345–350Google Scholar
  24. Illowski BP, Juliano DM, Bigelow LBG, Weinberger DR (1988) Stability of C.T. scan findings in schizophrenia: results of an 8 year follow-up study. Journal of Neurology, Neurosurgery and Psychiatry 51:209–213CrossRefGoogle Scholar
  25. Jacobi W, Winkler H (1927) Encephalographische Studien an chronische Schizophrenen. Archiv Psychiat Nervenkrankheiten 81:299–332CrossRefGoogle Scholar
  26. Jacobsen LK, Giedd JN, Castellanos X, Vaituzis AC, Hamberger SD, Kumra S, Lenane MC, Rapoport JL (1998) Progressive reduction of temporal lobe structures in childhood-onset schizophrenia. American J of Psychiatry 155:678–685Google Scholar
  27. James AC, Javaloyes A, James S, Smith DM (2002) Evidence for non-progressive changes in adolescent-onset schizophrenia: follow-up magnetic resonance imaging study. British Journal of Psychiatry 180:339–344PubMedCrossRefGoogle Scholar
  28. Jaskiw GE, Juliano DM, Goldberg TE, Hertzman M, Urow-Hamell E, Weinberger DR (1994) Cerebral ventricular enlargement in schizophreniform disorder does not progress: a seven year follow-up study. Schizophrenia Research 14:23–28PubMedCrossRefGoogle Scholar
  29. Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L (1976) Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet 2:924–926PubMedCrossRefGoogle Scholar
  30. Johnstone EC, Lawrie SM, Cosway R (2002) What does the Edinburgh high-risk study tell us about schizophrenia? Am J of Medical Genetics (Neuropsychiatric Genetics) 114:906–912CrossRefGoogle Scholar
  31. Kasai K, Shenton ME, Salisbury DF, Hirayasu Y, Lee CU, Ciszewski AA, YurgelunTodd D, Kikinis R, Jolesz FA, McCarley RW (2003) Progressive decrease of left superior temporal gyrus gray matter volume in patients with first-episode schizophrenia. Am J Psychiatry 160(1):156–164PubMedCrossRefGoogle Scholar
  32. Kemali D, Maj M, Galderisi S, Milici N, Salvati A (1989) Ventricle-to-brain ratio in schizophrenia: a controlled follow-up study. Biological Psychiatry 26:753–756CrossRefGoogle Scholar
  33. Kraepelin E (1919) Dementia Praecox and Paraphrenia. Barclay RM (trans) 1971 edition. Krieger, New YorkGoogle Scholar
  34. Lawrie SM, Whalley H, Kestelman JN, Abukmeil SS, Byrne M, Hodges A, Rimmington JE, Best JJ, Owens DG, Johnstone EC (1999) Magnetic resonance imaging of brain in people at high risk of developing schizophrenia. Lancet 353(9146):30–33PubMedCrossRefGoogle Scholar
  35. Lawrie SM, Whalley HC, Abukmeil SS, Kestelman JN, Miller P, Best JJ, Owens DG, Johnstone EC (2002) Temporal lobe volume changes in people at high risk of schizophrenia with psychotic symptoms. British Journal of Psychiatry 181:138–143PubMedGoogle Scholar
  36. Lieberman JA (1999) Is schizophrenia a neurodegenerative disorder? A clinical and neurobiological perspective. Biological Psychiatry 46(6):729–739PubMedCrossRefGoogle Scholar
  37. Lieberman JA, Chakos M, Wu H, Alvir J, Hoffman E, Robinson D, Bilder R (2001) Longitudinal study of brain morphology in first episode schizophrenia. Biol Psychiatry 49(6):487–499PubMedCrossRefGoogle Scholar
  38. Mathalon DH, Sullivan EV, Lim KO, Pfefferbaum A (2001) Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study. Arch Gen Psychiatry 58(2):148–157PubMedCrossRefGoogle Scholar
  39. Moore MD, Nathan AR, Elliot G, Laubach (1935) Encephalographic studies in mental disease. Am J of Psychiatry 92:43–67Google Scholar
  40. Murray RM, Jones P, O’Callaghan E (1991) Fetal brain development and later schizophrenia. Ciba Foundation Symposium 156:155–163PubMedGoogle Scholar
  41. Nair TR, Christensen JD, Kingsbury SJ, Kumar NG, Terry WM, Garver DL (1997) Progression of cerebral ventricular enlargement and the subtyping of schizophrenia. Psychiatry Research 74:141–150PubMedCrossRefGoogle Scholar
  42. Nasrallah HA, Olson SC, McCalley-Whitters M, Chapman S, Jacoby CG (1986) Cerebral ventricular enlargement in schizophrenia: a preliminary follow-up study. Archives General Psychiatry 43:157–159CrossRefGoogle Scholar
  43. Pantelis C, Velakoulis D, McGorry PD, Wood SJ, Suckling J, Phillips LJ, Yung AR, Bullmore ET, Brewer W, Soulsby B, Desmond P, McGuire PK (2003) Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 361(9354):281–288PubMedCrossRefGoogle Scholar
  44. Rapoport JL, Giedd JN, Kumra S, Jacobsen L, Smith A, Lee P, Nelson J, Hamberger S (1997) Childhood schizophrenia: progressive ventricular change during adolescence. Archives General Psychiatry 54:897–903CrossRefGoogle Scholar
  45. Shenton ME, Dickey CC, Frumin M, McCarley RW (2001) A review of MRI findings in schizophrenia. Schizophrenia Research 49(1/2):1–52PubMedCrossRefGoogle Scholar
  46. Sponheim SR, Iacono WG, Beiser M (1991) Stability of ventricular size after the onset of psychosis in schizophrenia. Psychiatry Research (Neuroimaging) 40:21–29CrossRefGoogle Scholar
  47. Vita A, Giobbio GM, Dieci M, Garbarini M, Morganti C, Comazzi M, Invernizzi G (1994) Stability of cerebral ventricular size from the appearance of the first psychotic symptoms to the later diagnosis of schizophrenia. Biological Psychiatry 35:960–962PubMedCrossRefGoogle Scholar
  48. Vita A, Sacchetti E, Valvassori G, Cazullo CL (1988) Brain morphology in schizophrenia: a 2–5 year CT scan follow-up study. Acta Psychiatrica Scandinavica 78: 618–621PubMedCrossRefGoogle Scholar
  49. Waddington JL, Scully PJ, Youssef HA (1997) Developmental trajectory and disease progression in schizophrenia: the conundrum, and insights from a 12-year prospective study in the Monaghan 101. Schizophrenia Research 23(2):107–118PubMedCrossRefGoogle Scholar
  50. Weinberger DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Archives General Psychiatry 44:660–669CrossRefGoogle Scholar
  51. Weinberger DR, Torrey EF, Neophytides A, Wyatt RJ (1979) Lateral cerebral ventricular enlargement in chronic schizophrenia. Archives General Psychiatry 36:735–738CrossRefGoogle Scholar
  52. Wood SJ, Velakoulis D, Smith DJ, Bond D, Stuart GW, McGorry PD, Brewer WJ, Bridle N, Eritaia J, Desmond P, Singh B, Copolov D, Pantelis C (2001) A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia. Schizophr Res 52(112):37–46PubMedCrossRefGoogle Scholar
  53. Woods BT (1998) Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenetic mechanism. American Journal of Psychiatry 155(12):1661–1667PubMedGoogle Scholar
  54. Woods BT, Yurgelun-Todd D, Benes FM, Frankenburg FR, Pope HC, McSparren J (1990) Progressive ventricular enlargement in schizophrenia: comparison to bipolar affective disorder and correlation to clinical course. Biological Psychiatry 27:341–352PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • Lynn E. Delisi
    • 1
  1. 1.Department of PsychiatryNew York UniversityNew YorkUSA

Personalised recommendations