Childhood Schizophrenia Brain Findings

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.