Advertisement

Current Psychiatry Reports

, Volume 2, Issue 5, pp 410–415 | Cite as

Update on childhood-onset schizophrenia

  • Judith L. Rapoport
  • Gale Inoff-Germain
Article

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.

Keywords

Schizophrenia Aripiprazole Acad Child Adolesc Psychiatry Magnetic Resonance Spectroscopic Imaging Onset Schizophrenia 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Childs B, Scriver CR: Age at onset and causes of disease. Perspect Biol Med 1986, 29:437–460.PubMedGoogle Scholar
  2. 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. 3.
    Gordon CT, Frazier JA, McKenna K, et al.: Childhood-onset schizophrenia: an NIMH study in progress. Schizophr Bull 1994, 20:697–712.PubMedGoogle Scholar
  4. 4.
    Jacobsen LK, Rapoport JL: Research update: childhood-onset schizophrenia: implications of clinical and neurobiological research. J Child Psychol Psychiatry 1998, 39:101–113.PubMedCrossRefGoogle Scholar
  5. 5.
    Nicolson R, Rapoport JL: Childhood-onset schizophrenia: rare but worth studying. Biol Psychiatry 1999, 46:1418–1428.PubMedCrossRefGoogle Scholar
  6. 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. 7.
    Kolvin I: Studies in the childhood psychoses: I. Diagnostic criteria and classification. Br J Psychiatry 1971, 118:381–384.PubMedGoogle Scholar
  8. 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.PubMedGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 12.
    Asarnow RF, Asamen J, Granholm E, et al.: Cognitive/neuropsychological studies of children with a schizophrenic disorder. Schizophr Bull 1994, 20:647–669.PubMedGoogle Scholar
  13. 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.Google Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.Google Scholar
  18. 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.PubMedGoogle Scholar
  19. 19.
    Jacobsen LK, Giedd JN, Vaituzis AC, et al.: Temporal lobe morphology in childhood-onset schizophrenia. Am J Psychiatry 1996, 153:355–361.PubMedGoogle Scholar
  20. 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.PubMedGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 22.
    Jacobsen LK, Hamburger SD, Van Horn JD, et al.: Cerebral glucose metabolism in childhood onset schizophrenia. Psychiatry Res 1997, 75:131–144.PubMedCrossRefGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 24.
    Nicolson R, Malaspina D, Giedd JN, et al.: Obstetrical complications and childhood-onset schizophrenia. Am J Psychiatry 1999, 156:1650–1652.PubMedGoogle Scholar
  25. 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.PubMedGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 29.
    Russell AT, Bott L, Sammons C: The phenomenology of schizophrenia occurring in childhood. J Am Acad Child Adolesc Psychiatry 1989, 28:399–407.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 31.
    Hollis C: Child and adolescent (juvenile onset) schizophrenia. A case control study of premorbid developmental impairments. Br J Psychiatry 1995, 166:489–495.PubMedGoogle Scholar
  32. 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. 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.PubMedCrossRefGoogle Scholar
  34. 34.
    Clark AF, Lewis SW: Practitioner review: treatment of schizophrenia in childhood and adolescence. J Child Psychol Psychiat 1998, 39:1071–1081.PubMedCrossRefGoogle Scholar
  35. 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.PubMedGoogle Scholar
  36. 36.
    Toren P, Laor N, Weizman A: Use of atypical neuroleptics in child and adolescent psychiatry. J Clin Psychiatry 1998, 59:644–656.PubMedGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.Google Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 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.CrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.PubMedGoogle Scholar
  44. 44.
    Rapoport JL, Giedd JN, Kumra S, et al.: Childhood-onset schizophrenia. Progressive ventricular change during adolescence. Arch Gen Psychiatry 1997, 54:897–903.PubMedGoogle Scholar
  45. 45.
    Giedd JN, Jeffries NO, Blumenthal J, et al.: Childhood-onset schizophrenia: progressive brain changes during adolescence. Biol Psychiatry 1999, 46:892–898.PubMedCrossRefGoogle Scholar
  46. 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.PubMedCrossRefGoogle Scholar
  47. 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.PubMedGoogle Scholar
  48. 48.
    Karp BI, Garvey M, Jacobsen LK, et al.: Abnormal neurologic maturation in very early-onset schizophrenia. Am J Psychiatry 2000, in press.Google Scholar
  49. 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.PubMedCrossRefGoogle Scholar
  50. 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.PubMedCrossRefGoogle Scholar
  51. 51.
    Huttenlocher PR, Dabholkar AS: Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 1997, 387:167–178.PubMedCrossRefGoogle Scholar
  52. 52.
    Glantz LA, Lewis DA: Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry 2000, 57:65–73.PubMedCrossRefGoogle Scholar
  53. 53.
    Selemon LD, Goldman-Rakic PS: The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol Psychiatry 1999, 45:17–25.PubMedCrossRefGoogle Scholar
  54. 54.
    Woods BT: Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenetic mechanism. Am J Psychiatry 1998, 155:1661–1670.PubMedGoogle Scholar
  55. 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.PubMedCrossRefGoogle Scholar
  56. 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.PubMedGoogle Scholar
  57. 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.Google Scholar
  58. 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.Google Scholar
  59. 59.
    Weickert CS, Weinberger DR: A candidate molecule approach to defining developmental pathology in schizophrenia. Schizophr Bull 1998, 24:303–316.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2000

Authors and Affiliations

  • Judith L. Rapoport
    • 1
  • Gale Inoff-Germain
    • 1
  1. 1.Child Psychiatry Branch (Building 10, Room 3N202)National Institute of Mental HealthBethesdaUSA

Personalised recommendations