Skip to main content

Advertisement

SpringerLink
Log in

Update on childhood-onset schizophrenia

  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

Abstract

Updated findings from the ongoing National Institute of Mental Health Child Psychiatry Branch longitudinal study of childhood-onset schizophrenia (COS) are presented, along with replications from collaborators at other sites. Clinical and neurobiologic continuities of COS with poor-outcome adult-onset schizophrenia suggests that their underlying pathophysiology is the same. However, these early-onset cases appear to have more striking genetic contributions to their etiology. Updated findings involve risk factors (birth complications, cytogenic abnormalities, early language and motor problems, and familial psychopathology), treatment trials, and brain magnetic resonance imaging studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Childs B, Scriver CR: Age at onset and causes of disease. Perspect Biol Med 1986, 29:437–460.

    PubMed  CAS  Google Scholar 

  2. Rapoport JL: Childhood Onset of “Adult” Psychopathology. Clinical and Research Advances. Washington, DC: American Psychiatric Press; 2000. Provides an overview of genetics and discusses the significance of age of onset in terms of individual variability and course of disease. Reviews the literature and provides insight into the etiology, progression, and prevention and treatment of very early forms of schizophrenia, depression, anxiety, criminality, and alcoholism.

    Google Scholar 

  3. Gordon CT, Frazier JA, McKenna K, et al.: Childhood-onset schizophrenia: an NIMH study in progress. Schizophr Bull 1994, 20:697–712.

    PubMed  CAS  Google Scholar 

  4. Jacobsen LK, Rapoport JL: Research update: childhood-onset schizophrenia: implications of clinical and neurobiological research. J Child Psychol Psychiatry 1998, 39:101–113.

    Article  PubMed  CAS  Google Scholar 

  5. Nicolson R, Rapoport JL: Childhood-onset schizophrenia: rare but worth studying. Biol Psychiatry 1999, 46:1418–1428.

    Article  PubMed  CAS  Google Scholar 

  6. Nicholson R, Rapoport JL: Childhood-onset schizophrenia: what can it teach us? In Childhood Onset of “Adult” Psychopathology. Clinical and Research Advances. Edited by Rapoport, JL. Washington, DC: American Psychiatric Press; 2000.

    Google Scholar 

  7. Kolvin I: Studies in the childhood psychoses: I. Diagnostic criteria and classification. Br J Psychiatry 1971, 118:381–384.

    PubMed  CAS  Google Scholar 

  8. Kolvin I, Ounsted C, Humphrey M, McNay A: Studies in childhood psychoses: II. The phenomenology of childhood psychoses. Br J Psychiatry 1971, 118:385–395.

    PubMed  CAS  Google Scholar 

  9. McKenna K, Gordon CT, Lenane M, et al.: Looking for childhood-onset schizophrenria: the first 71 cases screened. J Am Acad Child Adolesc Psychiatry 1994, 33:636–644.

    Article  PubMed  CAS  Google Scholar 

  10. Alaghband-Rad J, McKenna K, Gordon CT, et al.: Childhoodonset schizophrenia: the severity of premorbid course. J Am Acad Child Adolesc Psychiatry 1995, 34:1273–1283.

    Article  PubMed  CAS  Google Scholar 

  11. Nicolson R, Lenane M, Singaracharlu S, et al.: Premorbid speech and language impairments in childhood onset schizophrenia: association with risk factors. Am J Psychiatry 2000, 157:794–800.

    Article  PubMed  CAS  Google Scholar 

  12. Asarnow RF, Asamen J, Granholm E, et al.: Cognitive/neuropsychological studies of children with a schizophrenic disorder. Schizophr Bull 1994, 20:647–669.

    PubMed  CAS  Google Scholar 

  13. Kumra S, Wiggs E, Bedwell J, et al.: Neuropsychological deficits in pediatric patients with childhood-onset schizophrenia and psychotic disorders not otherwise specified. Schizophr Res 2000, in press.

  14. Zahn TP, Jacobsen LK, Gordon CT, et al.: Autonomic nervous system markers of psychopathology in childhood-onset schizophrenia. Arch Gen Psychiatry 1997, 54:904–912.

    PubMed  CAS  Google Scholar 

  15. Jacobsen LK, Hong WL, Hommer DW, et al.: Smooth pursuit eye movements in childhood onset schizophrenia: comparison with ADHD and normal controls. Biol Psychiatry 1996, 40:1144–1154.

    Article  PubMed  CAS  Google Scholar 

  16. Kumra S, Jacobsen LK, Lenane M, et al.: “Multidimensionally impaired disorder”: is it a variant of very early-onset schizophrenia? J Am Acad Child Adolesc Psychiatry 1998, 37:91–99.

    Article  PubMed  CAS  Google Scholar 

  17. Kumra S, Giedd JN, Vaituzis AC, et al.: Childhood-onset psychotic disorders: magnetic resonance imaging of volumetric differences in brain structure. Am J Psychiatry 2000, in press.

  18. Frazier JA, Giedd JN, Hamburger SD, et al.: Brain anatomic magnetic resonance imaging in childhood-onset schizophrenia. Arch Gen Psychiatry 1996, 53:617–624.

    PubMed  CAS  Google Scholar 

  19. Jacobsen LK, Giedd JN, Vaituzis AC, et al.: Temporal lobe morphology in childhood-onset schizophrenia. Am J Psychiatry 1996, 153:355–361.

    PubMed  CAS  Google Scholar 

  20. Jacobsen LK, Giedd JN, Berquin PC, et al.: Quantitative morphology of the cerebellum and fourth ventricle in childhoodonset schizophrenia. Am J Psychiatry 1997, 154:1663–1669.

    PubMed  CAS  Google Scholar 

  21. Jacobsen LK, Giedd JN, Rajapakse JC, et al.: Quantitative magnetic resonance imaging of the corpus callosum in childhood onset schizophrenia. Psychiatry Res 1997, 68:77–86.

    Article  PubMed  CAS  Google Scholar 

  22. Jacobsen LK, Hamburger SD, Van Horn JD, et al.: Cerebral glucose metabolism in childhood onset schizophrenia. Psychiatry Res 1997, 75:131–144.

    Article  PubMed  CAS  Google Scholar 

  23. Bertolino A, Kumra S, Callicott JH, et al.: Common pattern of cortical pathology in childhood-onset and adult-onset schizophrenia as identified by proton magnetic resonance spectroscopic imaging. Am J Psychiatry 1998, 155:1376–1383.

    PubMed  CAS  Google Scholar 

  24. Nicolson R, Malaspina D, Giedd JN, et al.: Obstetrical complications and childhood-onset schizophrenia. Am J Psychiatry 1999, 156:1650–1652.

    PubMed  CAS  Google Scholar 

  25. Nicolson R, Giedd JN, Lenane M, et al.: Clinical and neurobiological correlates of cytogenetic abnormalities in childhoodonset schizophrenia. Am J Psychiatry 1999, 156:1575–1579.

    PubMed  CAS  Google Scholar 

  26. Kumra S, Wiggs E, Krasnewich D, et al.: Brief report: association of sex chromosome anomalies with childhood-onset psychotic disorders. J Am Acad Child Adolesc Psychiatry 1998, 37:292–296.

    Article  PubMed  CAS  Google Scholar 

  27. Frazier JA, Alaghband-Rad J, Jacobsen L, et al.: Pubertal development and onset of psychosis in childhood onset schizophrenia. Psychiatry Res 1997, 70:1–7.

    Article  PubMed  CAS  Google Scholar 

  28. Karayiorgou M, Morris MA, Morrow B, et al.: Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proc Natl Acad Sci U S A 1995, 92:7612–7616.

    Article  PubMed  CAS  Google Scholar 

  29. Russell AT, Bott L, Sammons C: The phenomenology of schizophrenia occurring in childhood. J Am Acad Child Adolesc Psychiatry 1989, 28:399–407.

    Article  PubMed  CAS  Google Scholar 

  30. Green WH, Padron-Gayol M, Hardesty AS, Bassiri M: Schizophrenia with childhood onset: a phenomenological study of 38 cases. J Am Acad Child Adolesc Psychiatry 1992, 31:968–976.

    Article  PubMed  CAS  Google Scholar 

  31. Hollis C: Child and adolescent (juvenile onset) schizophrenia. A case control study of premorbid developmental impairments. Br J Psychiatry 1995, 166:489–495.

    PubMed  CAS  Google Scholar 

  32. Asarnow RF: Neurocognitive impairments in schizophrenia: a piece of the epigenetic puzzle. Eur Child Adolesc Psychiatry 1999, 8(suppl 1):15–18.

    Google Scholar 

  33. Kolvin I, Garside RF, Kidd JS: Studies in the childhood psychoses. IV. Parental personality and attitude and childhood psychoses. Br J Psychiatry 1971, 118:403–406.

    Article  PubMed  CAS  Google Scholar 

  34. Clark AF, Lewis SW: Practitioner review: treatment of schizophrenia in childhood and adolescence. J Child Psychol Psychiat 1998, 39:1071–1081.

    Article  PubMed  CAS  Google Scholar 

  35. Lewis R: Typical and atypical antipsychotics in adolescent schizophrenia: efficacy, tolerability, and differential sensitivity to extrapyramidal symptoms. Can J Psychiatry 1998, 43:596–604.

    PubMed  CAS  Google Scholar 

  36. Toren P, Laor N, Weizman A: Use of atypical neuroleptics in child and adolescent psychiatry. J Clin Psychiatry 1998, 59:644–656.

    PubMed  CAS  Google Scholar 

  37. Wudarsky M, Nicolson R, Hamburger SD, et al.: Elevated prolactin in pediatric patients on typical and atypical antipsychotics. J Child Adolesc Psychopharmacol 1999, 9:239–245.

    Article  PubMed  CAS  Google Scholar 

  38. Sikich L, Williamson K, Malekpour A, et al.: Double-blind comparison of haloperidol, risperidone and olanzapine in psychotic youth. Talk presented at the 46th Annual Meeting of the American Academy of Child and Adolescent Psychiatry. Chicago, IL: October 19–24, 1999.

  39. Lawler CP, Prioleau C, Lewis MM, et al.: Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes. Neuropsychopharmacology 1999, 20:612–627.

    Article  PubMed  CAS  Google Scholar 

  40. Castner SA, Williams GV, Goldman-Rakic PS: Reversal of antipsychotic-induced working memory deficits by shortterm dopamine D1 receptor stimulation. Science 2000, 287:2020–2022. Chronic blockade of D2 receptors, a common mechanism of action for antipsychotic drugs, down-regulates D1 receptors in the prefrontal cortex and produces severe working memory deficits. These deficits were reversed in monkeys by short-term coadministration of a D1 agonist, with improvements sustained for greater than 1 year after cessation of D1 treatment.

    Article  PubMed  CAS  Google Scholar 

  41. Keshavan MS: Development, disease and degeneration in schizophrenia: a unitary pathophysiological model. J Psychiatric Res 1999, 33:513–521. Examines how mechanizms from early and late brain neurodevelopment and post-illness onset neurodegenerative models may interact cumulatively during successive critical windows of vulnerability during brain development and during the early course of the illness to lead to the clinical manifestations of schizophrenia.

    Article  CAS  Google Scholar 

  42. Thomas MA, Ke Y, Levitt J, et al.: Preliminary study of frontal lobe 1H MR spectroscopy in childhood-onset schizophrenia. J Magn Reson Imaging 1998, 8:841–846.

    Article  PubMed  CAS  Google Scholar 

  43. Jacobsen LK, Giedd JN, Castellanos FX, et al.: Progressive reduction of temporal lobe structures in childhood onset schizophrenia. Am J Psychiatry 1998, 155:678–685.

    PubMed  CAS  Google Scholar 

  44. Rapoport JL, Giedd JN, Kumra S, et al.: Childhood-onset schizophrenia. Progressive ventricular change during adolescence. Arch Gen Psychiatry 1997, 54:897–903.

    PubMed  CAS  Google Scholar 

  45. Giedd JN, Jeffries NO, Blumenthal J, et al.: Childhood-onset schizophrenia: progressive brain changes during adolescence. Biol Psychiatry 1999, 46:892–898.

    Article  PubMed  CAS  Google Scholar 

  46. Rapoport JL, Giedd JN, Blumenthal J, et al.: Progressive cortical change during adolescence in childhood-onset schizophrenia. A longitudinal magnetic resonance imaging study. Arch Gen Psychiatry 1999, 56:649–654. Childhood-onset patients had both a four-fold greater decrease in cortical gray matter volume during adolescence and a disease-specific pattern of change.

    Article  PubMed  CAS  Google Scholar 

  47. Bedwell JS, Keller B, Smith AK, et al.: Why does postpsychotic IQ decline in childhood-onset schizophrenia? Am J Psychiatry 1999, 156:1996–1997.

    PubMed  CAS  Google Scholar 

  48. Karp BI, Garvey M, Jacobsen LK, et al.: Abnormal neurologic maturation in very early-onset schizophrenia. Am J Psychiatry 2000, in press.

  49. McGlashan TH, Hoffman RE: Schizophrenia as a disorder of developmentally reduced synaptic connectivity. Arch Gen Psychiatry 2000, 57:637–648. Proposes and describes evidence for a pathophysiologic model of reduced synaptic connectivity arising from disturbances of brain development active during perinatal and adolescent periods. Reviews computer simulation data depicting elimination of synaptic connections that model normal development and psychotic symptom formation. Discusses how the model’s parameters could account for important aspects of schizophrenia.

    Article  PubMed  CAS  Google Scholar 

  50. Giedd JN, Blumenthal J, Jeffries NO, et al.: Cerebral cortical gray matter changes during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 1999, 2:861–863.

    Article  PubMed  CAS  Google Scholar 

  51. Huttenlocher PR, Dabholkar AS: Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 1997, 387:167–178.

    Article  PubMed  CAS  Google Scholar 

  52. Glantz LA, Lewis DA: Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry 2000, 57:65–73.

    Article  PubMed  CAS  Google Scholar 

  53. Selemon LD, Goldman-Rakic PS: The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol Psychiatry 1999, 45:17–25.

    Article  PubMed  CAS  Google Scholar 

  54. Woods BT: Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenetic mechanism. Am J Psychiatry 1998, 155:1661–1670.

    PubMed  CAS  Google Scholar 

  55. Selemon LD, Lidow MS, Goldman-Rakic PS: Increased volume and glial density in primate prefrontal cortex associated with chronic antipsychotic drug exposure. Biol Psychiatry 1999, 46:161–172.

    Article  PubMed  CAS  Google Scholar 

  56. Gur RE, Maany V, Mozley PD, et al.: Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. Am J Psychiatry 1998, 155:1711–1717.

    PubMed  CAS  Google Scholar 

  57. Nicholson R, Lenane M, Brookner F, et al.: Children and adolescents with psychotic disorder not otherwise specified: A two to eight year follow-up. Compr Psychiatry 2000, in press.

  58. Nicholson R, Giedd JN, Blumenthal J, et al.: Lack of progressive cortical gray matter loss in children and adolescents with nonschizophrenic psychotic disorder. Submitted for publication.

  59. Weickert CS, Weinberger DR: A candidate molecule approach to defining developmental pathology in schizophrenia. Schizophr Bull 1998, 24:303–316.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Child Psychiatry Branch (Building 10, Room 3N202), National Institute of Mental Health, 10 Center Drive, MSC 1600, 20892-1600, Bethesda, MD, USA

    Judith L. Rapoport MD & Gale Inoff-Germain

Authors
  1. Judith L. Rapoport MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gale Inoff-Germain
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rapoport, J.L., Inoff-Germain, G. Update on childhood-onset schizophrenia. Curr Psychiatry Rep 2, 410–415 (2000). https://doi.org/10.1007/s11920-000-0024-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11920-000-0024-4

Keywords

Search

Navigation