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Childhood Schizophrenia Brain Findings

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Childhood-Onset Schizophrenia:

Structural Brain Abnormalities

Courtney Dawson

Penn State College of Medicine

2003

Basic information regarding childhood-onset schizophrenia (COS):

Onset of psychosis by age 12 (2)
Rare à 1/50 the prevalence of later-onset disease (1)
Insidious rather than episodic onset (7)
Continuing severe illness in about ½ of the cases (7)
Psychotic symptomatology prior to the completion of normal brain maturation (9)

A retrospective study (17 subjects) conducted at the University of Colorado looked at premorbid and prodromal diagnostic features of COS (8):

65% reported problems is school as the initial symptom
59% reported 1^st sign of psychotic symptoms between 5-10 years of age
Average age of 1^st clinical diagnosis of COS or schizoaffective disorder reported as 10.5 years of age
Significant lag time between initial symptoms and a concrete clinical diagnosis

Neurodevelopmental Hypothesis of Schizophrenia: Brain “lesion” is present early in life but does not manifest itself until late in adolescence or early adulthood (6)

Underlying brain pathology presents differently at different ages:

1) Global delays in motor and possibly language development

2) Nonspecific attentional and behavioral dysfunction

3) Clinically identifiable thought disorder

4) Development of the full clinical syndrome as the brain matures

COS subjects had an increased incidence of speech and motor abnormalities prior to the onset of psychosis à possible indication of earlier brain developmental abnormalities

Current research focused on structural changes in COS: (9)

Most of the research has been conducted by Rapoport and colleagues at the National Institute of Mental Health, most are prospective studies involving 15-75 COS subjects with initial MRI scans and follow-up scans at 2-year intervals
General trend: progressive age-related changes reach an asymptote as subjects reach late adolescence or adulthood
Add to previous evidence for abnormal postnatal brain development in schizophrenia

Structural Brain Abnormalities and Clinical Correlates:

1) Total cerebral volume: 9.2% ¯ with COS (1) compared to 3% ¯ in adult-onset patients (9)à indicates that COS patients are more severely affected than their adult-onset counterparts

2) Lateral Ventricular volume: progressive with an ventricular brain ratio (1)à correlated to Premorbid Assessment Scale scores (7) and Brief Psychiatric Rating Scale scores at follow-up

3) Cortical gray matter volume: 8% ¯ with COS compared to 1.98% ¯ in healthy controls (6)à rate of loss correlated to baseline Brief Psychiatric Rating Scale scores, follows a back-to-front “wave” pattern

4) Midline thalamus volume: 17.2% ¯ with COS (1)à might explain complex symptoms involved in the psychotic process of schizophrenia, given the role of the thalamus in filtering sensory input

5) Cerebellar volume: progressive ¯ during adolescence (4) , developmental trajectories differ from controlsà possible relationship to impaired executive function and working memory, but NIMH study failed to find a correlation

6) Basal ganglia volume: progressive in caudate, putamen, and globus pallidus volumes (1)à globus pallidus volume may be related to neuroleptic exposure

7) Corpus callosum volume: focal ¯ in the splenium (posterior region) compared to a generalized volume as expected in this age group (5)à may be related to posterior gray matter changes in schizophrenia

8) Hippocampal volume: progressive ¯ (2)à correlated to Scale for Assessment of Positive Symptoms scores

Could there be a genetic trait marker for COS?

A prospective study conducted at the NIMH looked at structural brain abnormalities in healthy siblings of patients with COS (3):

· 15 full siblings of COS patients, 32 matched healthy volunteers

· Healthy siblings of COS probands have ¯ total and parietal gray matter volumes than controls

· No significant difference in white matter volumes

· No ventricular enlargement seen in siblings

· In families with a member who has schizophrenia, familial or genetic factors may contribute to shared structural brain abnormalities

Future research opportunities:

Adolescence is a unique window of opportunity to study structural brain changes in this COS population
Must look at both early and late changes and the progressive nature of the changes

References:

1) Frazier J, Giedd J, et al. Brain Anatomic Magnetic Resonance Imaging in Childhood-Onset Schizophrenia. Arch Gen Psychiatry. 1996; 53: 617-624.

2) Giedd J, Jeffries N, et al. Childhood-Onset Schizophrenia: Progressive Brain Changes during Adolescence. Biol Psychiatry. 1999; 46: 892-898.

3) Gogtay N, Sporn A, et al. Structural Brain MRI Abnormalities in Healthy Siblings of Patients with Childhood-Onset Schizophrenia. Am J Psychiatry. 2003; 160: 569-571.

4) Keller A, Castellanos F, et al. Progressive Loss of Cerebellar Volume in Childhood-Onset Schizophrenia. Am J Psychiatry. 2003; 160: 128-133.

5) Keller A, Jeffries N, et al. Corpus callosum development in childhood-onset schizophrenia. Schizophrenia Research. 2003; 62: 105-114.

6) Rapoport J, Giedd 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.

7) Rapoport J, Giedd J, et al. Childhood-Onset Schizophrenia: Progressive Ventricular Change During Adolescence. Arch Gen Psychiatry. 1997; 54: 897-903.

8) Schaeffer J, Ross R. Childhood-Onset Schizophrenia: Premorbid and Prodromal Diagnostic and Treatment Histories. J Am Acad Child Adolesc Psychiatry. 2002; 41: 538-545.

9) Sowell E, Toga A, Asarnow R. Brain Abnormalities Observed in Childhood-Onset Schizophrenia: A Review of the Structural Magnetic Resonance Imaging Literature. Mental Retardation and Developmental Disabilities Research Reviews. 2000; 6: 180-185.

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