Brain anatomic magnetic resonance imaging in childhood-onset schizophrenia.

BACKGROUND Early-onset schizophrenia (first psychotic symptoms by age 12 years) has been the subject of a small number of studies, and its biological continuity with later-onset disorder has not been established. In this study quantitative anatomic brain magnetic resonance images of children and adolescents with early-onset schizophrenia were compared with those of matched controls. Brain abnormalities in childhood-onset schizophrenia were examined in relation to those reported for later-onset schizophrenics. METHODS Anatomic brain magnetic resonance imaging scans were obtained for 21 patients (mean +/- SD age, 14.6 +/- 2.1 years; range, 10 to 18 years) with childhood-onset schizophrenia (13 males, eight females) and 33 age-, sex-, height-, and weight-matched normal controls. Quantitative measurements were obtained for the cerebrum, anterior frontal region, lateral ventricles, thalamus, caudate, putamen, and globus pallidus. RESULTS Total cerebral volume and midsagittal thalamic area were smaller in the patients (analysis of variance, P = .002, and analysis of covariance, P = .03, respectively); the caudate, putamen, and globus pallidus were larger in the patients (analysis of covariance, P = .05, P = .007, and P < .001, respectively); and the lateral ventricles tended to be larger in the patients (analysis of covariance, P = .06). Globus pallidus enlargement correlated with neuroleptic exposure and with age of onset of psychosis. The magnitude of abnormalities compared with controls was similar to that reported in adult studies, although there was a trend toward relatively smaller cerebral volumes for the childhood-onset group compared with controls. CONCLUSION Brain anatomic abnormalities in childhood-onset schizophrenia are similar to those reported for adult populations, indicating overall continuity between these rare childhood cases and the adult schizophrenia populations.

[1]  F. Volkmar,et al.  Phenomenology and classification of the childhood psychoses , 1988, Psychological Medicine.

[2]  J. Lieberman,et al.  Brain morphology, dopamine, and eye-tracking abnormalities in first-episode schizophrenia. Prevalence and clinical correlates. , 1993, Archives of general psychiatry.

[3]  B. Bogerts,et al.  Recent advances in the neuropathology of schizophrenia. , 1993, Schizophrenia bulletin.

[4]  J. Lieberman,et al.  Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. , 1994, The American journal of psychiatry.

[5]  Denckla Mb,et al.  Revised Neurological Examination for Subtle Signs (1985). , 1985 .

[6]  B. Fish Neurobiologic antecedents of schizophrenia in children. Evidence for an inherited, congenital neurointegrative defect. , 1977, Archives of general psychiatry.

[7]  J. Kleinman,et al.  Cerebral ventricular enlargement in chronic schizophrenia. An association with poor response to treatment. , 1980, Archives of general psychiatry.

[8]  D L Braff,et al.  Magnetic resonance imaging abnormalities in lenticular nuclei and cerebral cortex in schizophrenia. , 1991, Archives of general psychiatry.

[9]  J. Ehrhardt,et al.  Structural abnormalities in the frontal system in schizophrenia. A magnetic resonance imaging study. , 1986, Archives of general psychiatry.

[10]  Joseph E. Schwartz,et al.  Brain morphology in first-episode schizophrenic-like psychotic patients: A quantitative magnetic resonance imaging study , 1991, Biological Psychiatry.

[11]  G. Eisenhauer,et al.  CT Scan and MRI Findings in a Child With Schizophrenia , 1987, Journal of child neurology.

[12]  C. Tamminga,et al.  Ultrastructural correlates of haloperidol‐induced oral dyskinesias in rat striatum , 1995, Synapse.

[13]  R. Buchanan,et al.  Brain morphology and schizophrenia. A magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures. , 1992, Archives of general psychiatry.

[14]  C. Gordon,et al.  Childhood-onset schizophrenia: The severity of premorbid course , 1995, Biological Psychiatry.

[15]  J. Rapoport,et al.  Quantitative morphology of the caudate nucleus in attention deficit hyperactivity disorder. , 1994, The American journal of psychiatry.

[16]  Francine M. Benes,et al.  The effects of haloperidol on synaptic patterns in the rat striatum , 1985, Brain Research.

[17]  J. Ehrhardt,et al.  Magnetic resonance imaging of the brain in schizophrenia. The pathophysiologic significance of structural abnormalities. , 1990, Archives of general psychiatry.

[18]  R. Murray,et al.  A neurodevelopmental approach to the classification of schizophrenia. , 1992, Schizophrenia bulletin.

[19]  P. Huttenlocher Synaptic density in human frontal cortex - developmental changes and effects of aging. , 1979, Brain research.

[20]  Manzar Ashtari,et al.  Caudate nuclei volumes in schizophrenic patients treated with typical antipsychotics or clozapine , 1995, The Lancet.

[21]  Tyrone D. Cannon,et al.  Fetal Neural Development and Adult Schizophrenia , 1991 .

[22]  A. Russell,et al.  The phenomenology of schizophrenia occurring in childhood. , 1989, Journal of the American Academy of Child and Adolescent Psychiatry.

[23]  W T Carpenter,et al.  Structural abnormalities in deficit and nondeficit schizophrenia. , 1993, The American journal of psychiatry.

[24]  M Ashtari,et al.  Absence of regional hemispheric volume asymmetries in first-episode schizophrenia. , 1994, The American journal of psychiatry.

[25]  I. Gottesman Schizophrenia Genesis: The Origins of Madness , 1990 .

[26]  J. Lieberman,et al.  Prospective study of psychobiology in first-episode schizophrenia at Hillside Hospital. , 1992, Schizophrenia bulletin.

[27]  J. Lieberman,et al.  Qualitative assessment of brain morphology in acute and chronic schizophrenia. , 1992, The American journal of psychiatry.

[28]  Philip Seeman,et al.  Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine , 1991, Nature.

[29]  B. Bogerts,et al.  Basal Ganglia and Limbic System Pathology in Schizophrenia: A Morphometric Study of Brain Volume and Shrinkage , 1985 .

[30]  D. Hommer,et al.  Childhood-onset schizophrenia: an NIMH study in progress. , 1994, Schizophrenia bulletin.

[31]  U. Ungerstedt,et al.  Regional specific effects of clozapine and haloperidol on GABA and dopamine release in rat basal ganglia. , 1990, European journal of pharmacology.

[32]  W. Reich,et al.  Reliability, validity, and parent-child agreement studies of the Diagnostic Interview for Children and Adolescents (DICA). , 1987, Journal of the American Academy of Child and Adolescent Psychiatry.

[33]  F. Benes,et al.  Haloperidol-induced plasticity of axon terminals in rat substantia nigra. , 1983, Science.

[34]  J. Ehrhardt,et al.  Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. , 1994, Science.

[35]  D. Weinberger,et al.  CEREBRAL VENTRICULAR SIZE: A BIOLOGICAL MARKER FOR SUB-TYPING CHRONIC SCHIZOPHRENIA , 1982 .

[36]  J. Stevens Clinicopathologic correlations in schizophrenia. , 1986, Archives of general psychiatry.

[37]  S. Anderson,et al.  Is schizophrenia due to excessive synaptic pruning in the prefrontal cortex? The Feinberg hypothesis revisited. , 1994, Journal of psychiatric research.

[38]  I. Feinberg,et al.  Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? , 1982, Journal of psychiatric research.

[39]  J. Ehrhardt,et al.  Intelligence and brain structure in normal individuals. , 1993, The American journal of psychiatry.

[40]  H. Meltzer,et al.  Biological studies in schizophrenia. , 1987, Schizophrenia bulletin.

[41]  M. LeMay,et al.  Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. , 1992, The New England journal of medicine.

[42]  F. Bloom,et al.  Advancing a neurodevelopmental origin for schizophrenia. , 1993, Archives of general psychiatry.

[43]  David A. Hamburg,et al.  Methods for Reliable Longitudinal Observation of Behavior: Development of a Method for Systematic Observation of Emotional Behavior on Psychiatric Wards , 1963 .

[44]  S. Heckers,et al.  Cortex, white matter, and basal ganglia in schizophrenia: A volumetric postmortem study , 1991, Biological Psychiatry.

[45]  D. Weinberger Implications of normal brain development for the pathogenesis of schizophrenia. , 1987, Archives of general psychiatry.

[46]  R. Murray,et al.  Is schizophrenia a neurodevelopmental disorder? , 1987, British medical journal.

[47]  R. Hamer,et al.  Ventricular enlargement in teenage patients with schizophrenia spectrum disorder. , 1983, The American journal of psychiatry.

[48]  J. Overall,et al.  The Brief Psychiatric Rating Scale , 1962 .

[49]  C. Ounsted,et al.  II. the Phenomenology of Childhood Psychoses , 1971, British Journal of Psychiatry.

[50]  T. Crow,et al.  The two-syndrome concept: origins and current status. , 1985, Schizophrenia bulletin.

[51]  B. Pakkenberg,et al.  Stereological quantitation of human brains from normal and schizophrenic individuals , 1992, Acta neurologica Scandinavica. Supplementum.

[52]  I. Feinberg Cortical pruning and the development of schizophrenia. , 1990, Schizophrenia bulletin.

[53]  J N Giedd,et al.  Childhood-onset schizophrenia: brain MRI rescan after 2 years of clozapine maintenance treatment. , 1996, The American journal of psychiatry.

[54]  R. Asarnow,et al.  Symptom development in childhood onset schizophrenia. , 1988, Journal of child psychology and psychiatry, and allied disciplines.

[55]  J. Stevens An anatomy of schizophrenia? , 1973, Archives of general psychiatry.

[56]  J. Rapoport,et al.  Childhood-onset schizophrenia: timely neurobiological research. , 1994, Journal of the American Academy of Child and Adolescent Psychiatry.

[57]  H. Loos,et al.  Synaptogenesis in human visual cortex — evidence for synapse elimination during normal development , 1982, Neuroscience Letters.

[58]  M Ashtari,et al.  Volumes of ventricular system subdivisions measured from magnetic resonance images in first-episode schizophrenic patients. , 1992, Archives of general psychiatry.

[59]  J L Rapoport,et al.  Looking for childhood-onset schizophrenia: the first 71 cases screened. , 1994, Journal of the American Academy of Child and Adolescent Psychiatry.

[60]  J. Rapoport,et al.  An open trial of clozapine in 11 adolescents with childhood-onset schizophrenia. , 1994, Journal of the American Academy of Child and Adolescent Psychiatry.

[61]  Douglas G. Altman,et al.  Practical statistics for medical research , 1990 .

[62]  Magnetic resonance imaging of severely disturbed children--a preliminary study. , 1991, Journal of the American Academy of Child and Adolescent Psychiatry.

[63]  Jagath C. Rajapakse,et al.  Quantitative Magnetic Resonance Imaging of Human Brain Development: Ages 4–18 , 1996 .

[64]  R. Buchanan,et al.  Basal ganglia pathology in schizophrenia and tardive dyskinesia: an MRI quantitative study. , 1994, The American journal of psychiatry.

[65]  J. Werry Child and adolescent (early onset) schizophrenia: A review in light of DSM-III-R , 1992, Journal of autism and developmental disorders.

[66]  N. Andreasen The mechanisms of schizophrenia , 1994, Current Opinion in Neurobiology.

[67]  James C. Ehrhardt,et al.  Subcortical and temporal structures in affective disorder and schizophrenia: A magnetic resonance imaging study , 1992, Biological Psychiatry.

[68]  Daniel R. Weinberger,et al.  Medial temporal lobe structures in schizophrenia: relationship of size to duration of illness , 1994, Schizophrenia Research.