Contributed by Melissa Yates

Penn State College of Medicine

Definition:   -   Same diagnostic criteria apply to children, adolescents, and adults

-    Based on characteristic symptoms, deficits in adaptive functioning, and duration of six months

General Characteristics:    Incidence of childhood schizophrenia is less than 1/10,000 births

1.       Slight male predominance

2.       Less educated and professionally successful families

3.       Patients have low-average to average range of intelligence

4.       Patterns of behavior before a formal diagnosis:  attention/conduct problems, earlier patterns of inhibition, withdrawal and sensitivity

5.       Disease is rarely observed before age 5

6.       80% of children have auditory hallucinations; 50% have delusional beliefs

7.       Can be observed with additional conditions such as:  conduct disorder, learning disabilities, mental retardation, and autism

8.       Poor prognosis if onset before age 10 with above personality difficulties

 Since 1990 there has been an ongoing study of childhood onset schizophrenia (COS) of 49 patients at the National Institute of Mental Health (NIMH) which most of the following findings are based on.

  Findings before a Formal Diagnosis is made⁶:    based on 49 treatment refractory patients at NIMH (patients that did not respond to conventional therapy currently available for schizophrenia)

-          55% had language abnormalities

-          57% had motor abnormalities

-          55% had social abnormalities

-          63.3% either failed a grade or required placement in special education

-          overall poor neuropsychological functioning in attention, working memory and executive function (i.e. making and carrying out appropriate decisions on a day to day basis)

-          findings were more striking than those in adult patients which indicates a more severe early disruption of brain development in COS – also indicates greater familial vulnerability (possibly a greater likihood of a genetic component to the disease)

Family Characteristics⁶:

-          high rate of spectrum personality disorders (schizoaffective, schizotypal, paranoid) 45% had at least one relative with a disorder

-          increased schizophrenia in relatives (1.8%) vs. control group (0.5%)

-          77.3% of patients with family members with spectrum disorders had prediagnosis language abnormalities which was more striking than adult patients

Obstetric/Environmental Characteristics:

-          NIMH study doesn’t show an increase in obstetrical complications in COS vs. adults patients (though there have been studies that have found a link between obstetrical complications and schizophrenia in general)

-          No association of socioeconomic status, psychological trauma with an earlier age of onset

-          Study at UCLA of Finnish patients showed an increase in early onset schizophrenia with perinatal hypoxia (each event increased the risk 2 fold)²

-          No correlation has been shown b/w onset of puberty and onset of psychosis⁴

Genetic Findings:

-          NIMH study found several chromosomal abnormalities in patients such as:  Turner’s Syndrome (female patients with one X chromosome), translocation of chromosomes 1 and 7 and Velocardiofacial syndrome (deletion of 22q11) – findings were more striking than adult patients

-          No association found with ApoE4, HLA or trinucleotide repeats^3,7 (which are protein and genetic abnormalities found in diseases like Alzheimer’s and Huntington’s Disease respectively)

-          Velocardiofacial syndrome (VCFS) found in 6.4% of COS patients vs 0.025% of general population, and 2.0% of adult schizophrenic patients – causes craniofacial malformation, cardiac abnormalities, and developmental problems

-          Patients with both COS and VCFS found to have increased neurodevelopmental impairment¹¹

Smooth Pursuit Eye Movements and P50 sensory gating

-          67% of COS patients had qualitatively poor eye tracking

-          21% of relatives noted to have poor eye tracking vs. 5% of controls

-          Patients also noted to have an increased rate of anticipatory saccades⁶

-          University of Colorado study demonstrated the bilineal inheritance (inheritance from both parents) of both anticipatory saccades and P50 auditory evoked responses¹⁰

§         60% of COS had both parents with elevated anticipatory saccades vs 0% of adult onset patients

§         60% of COS also had both parents with diminished suppression of P50 auditory evoked responses (responded equally to both sounds) vs 13% of adult onset patients

§         Both responses are linked to a7 nicotinic receptor gene locus on chromosome 15q14

§         Other smooth pursuit eye movements are on chromosome 6

§         These findings continue to highlight to possibility of multiple genetic abnormalities in COS children.

Brain Morphology Findings (Different areas of the brain where found to be abnormal in these patients which correlated with some of their symptoms both with the onset of schizophrenia and as the disease progressed.

-          Increase in lateral ventricular volume with decreased cerebellar volume and midsagittal thalamic area

-          Hippocampal decrease in adolescence related to decreased ability of patients to learn new information⁶

-          Out of 24 patients, 12.5% were found to have enlarged cavum septi pellucidi  (> 6 cm) which were more severe than patients with adult onset (relates to the area of the brain in charge of emotion and memory)

§         Findings suggest more severe brain abnormalities and an earlier onset of sx⁸

-          COS patients noted to have smaller than normal amounts of regional N-acetylaspartate (NAA) (a neurotransmitter in the brain) in the hippocampus and dorsolateral prefrontal cortex¹

§         No correlation with volume losses or length of illness

-          COS patients noted to have a decreased volume of the following areas during adolescence (age 13-18):  10.9% in frontal gray matter, 8.5% in parietal gray matter, 7% in temporal gray matter (unique to COS – controls have an increase in temporal lobe)⁹

§         Controls had a decrease of 2.6% in frontal and 4.1% in parietal

§         COS patients had a mean onset of psychosis at 10.3 years so the decreases were not a trigger

§         Data coincides with MRI findings of adult patients

-          NIMH study also showed that the adolescent changes tend to level off in adulthood⁵

§         Postulate that since the hippocampal volume has been noted to be related to stress if the decrease in the size of the hippocampus during adolescence is related to the stress of the illness vs. the direct effects of schizophrenia on the body

References:

1. Bertolino, et al:  Common pattern of cortical pathology in childhood-onset and adult-onset schizophrenia as identified by proton magnetic resonance spectroscopic imaging.  American Journal of Psychiatry 1998; 155:1376-1383.

2. Cannon, et al:  Fetal hypoxia linked to early onset schizophrenia.  American Journal of Psychiatry 2000; 157:801-807.

3.Fernandez, et al:  Apolipoprotein E alleles in childhood-onset schizophrenia.  American Journal of Medical Genetics 1999; 88:211-213.

4.Frazier, et al:  Pubertal development and onset of psychosis in childhood onset schizophrenia.  Psychiatry Research 1997; 70:1-7.

5. Giedd, et al:  Childhood-onset schizophrenia:  Progressive brain changes during adolescence.  Biological Psychiatry 1999; 46:892-898.

6.Nicolson, et al:  Childhood-onset schizophrenia:  Rare but worth studying.  Biological Psychiatry 1999; 46:1418-1428.

7.  Nicolson, et al:  Lessons from childhood-onset schizophrenia.  Brain Research Reviews 2000; 31:147-156.

8. Nopoulos, et al:  Frequency and severity of enlarged cavum septi pellucidi in childhood-onset schizophrenia.  American Journal of Psychiatry 1998; 155:1074-1079.

9.  Rapoport, et al:  Progressive cortical change during adolescence in childhood-onset schizophrenia:  A longitudinal magnetic resonance imaging study.  Archives of General Psychiatry 1999; 56:649-654.

10. Ross, et al:  Evidence for bilineal inheritance of physiological indicators of risk in childhood-onset schizophrenia.  American Journal of Medical Genetics 1999; 88:188-199.

11. Usiskin, et al:  Velocardiofacial syndrome in childhood-onset schizophrenia.  Journal of the American Academy of Child and Adolescent Psychiatry 1999; 38:1536-1543.