Early-Onset Schizophrenia
Childhood-onset schizophrenia (COS) is a rare and severe form of schizophrenia characterized by an onset of psychotic symptoms by age 12 years, believed to represent a subgroup of affected individuals with an increased heritable etiology. Children diagnosed with COS have high rates of premorbid developmental abnormalities that appear to be nonspecific markers of severe early impaired neurodevelopment. Recent imaging studies have provided data to suggest that children with COS have decreased anterior cingulated gyrus (ACG) volumes with age, unlike controls, and an absence of the normal decreased left- to right-ACG volume asymmetry. These structural differences are hypothesized to be related to abnormal neurodevelopment influencing attention and emotion regulation, which are characteristic of some cognitive impairments in psychosis. The frequency of COS is reported to be less than 1 case in 10,000 children, whereas among adolescents between the ages of 13 and 18 years, the frequency of schizophrenia is markedly increased. Schizophrenia with childhood onset has the same core phenomenological features as schizophrenia in adolescence and adulthood; however, extremely high rates of comorbid psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), depressive disorders, and separation anxiety disorder, are seen in children and adolescents with COS.
EPIDEMIOLOGY
Schizophrenia in prepubertal children is exceedingly rare; it is estimated to occur in less than 1 of 10,000 children. In adolescents, the prevalence of schizophrenia is estimated to be 50 times that in younger children, with probable rates of 1 to 2 per 1,000. Boys seem to have a slight preponderance among children diagnosed with schizophrenia, with an estimated ratio of about 1.67 boys to 1 girl. Boys often become identified at a younger age than girls. It has been estimated that 0.1 to 1 percent present before age 10 years, with 4 percent presenting before 15 years of age. The rate of onset increases sharply during adolescence. Schizophrenia rarely is diagnosed in children younger than 5 years of age. Psychotic symptoms usually emerge insidiously, and the diagnostic criteria are met gradually over time. Occasionally, the onset of schizophrenia is sudden and occurs in a previously well-functioning child. Schizophrenia also may be diagnosed in a child who has had chronic difficulties and then experiences a significant exacerbation. The prevalence of schizophrenia among the parents of children with schizophrenia is about 8 percent, which is close to twice the prevalence in the parents of patients with adult-onset schizophrenia.
Schizotypal personality disorder is similar to schizophrenia in its inappropriate affects, excessive magical thinking, odd beliefs, social isolation, ideas of reference, and unusual perceptual experiences, such as illusions. Schizotypal personality disorder, however, does not have psychotic features; still, the disorder seems to aggregate in families with adult-onset schizophrenia. Therefore, the relation between the two disorders is unclear.
ETIOLOGY
The etiology of COS has multiple contributing factors, and estimates of its heritability are as high as 80 percent. COS is a severe form of schizophrenia, which may increase its likelihood of heritability to among the highest of estimates. Genetic studies provide substantial evidence for a significant genetic basis in the development of schizophrenia. The precise mechanisms of transmission of schizophrenia are not well understood. It is known to be up to eight times more prevalent among first-degree relatives of those with schizophrenia than in the general population. Adoption studies of patients with adult-onset schizophrenia have shown that schizophrenia occurs in the biological relatives, not the adoptive relatives. Additional genetic evidence is supported by higher concordance rates for schizophrenia in monozygotic twins than in dizygotic twins. Higher rates of schizophrenia are found among relatives of those with childhood-onset schizophrenia than among relatives of those with adult-onset schizophrenia. A recent case report identified a rare genetic occurrence in which an offspring received two chromosome homologues from the same parent (uniparental isodisomy) of chromosome 5, already implicated in several linkage studies to be associated with schizophrenia in a child with COS.
Currently, no reliable method can identify persons at the highest risk for schizophrenia in a given family. Neurodevelopmental abnormalities and higher-than-expected rates of neurological soft signs and impairments in sustaining attention and in strategies for information processing appear among children at high risk. Increased rates of disturbed communication styles are found in families with a member with schizophrenia. Recent reports have documented marked neuropsychological deficits in attention, working memory, and premorbid intelligence quotient (IQ) among children who develop schizophrenia and its spectrum disorders. High expressed emotion, characterized by overly critical responses in families, has been shown to be correlated with increased relapse rates among patients with schizophrenia.
Recent studies have documented gray matter loss in the brains of children with COS that started in the parietal region and proceeded frontally to dorsolateral prefrontal and temporal cortices, including superior temporal gyri. Magnetic resonance imaging (MRI) studies of 12 children with COS at baseline, and at follow-up 5 years later, were compared with
normal controls. Children with COS showed severe bilateral frontal gray matter loss over the 5-year period that occurred in a dorsal-to-ventral pattern across the medial hemispheres. Frontal regions were most affected, whereas cingulated-limbic regions were less vulnerable, which correlates with the brain areas responsible for the cognitive and metabolic dysfunction typically observed in schizophrenia. Children and adolescents with schizophrenia are more likely to have a premorbid history of social rejection, poor peer relationships, clingy, withdrawn behavior, and academic trouble than individuals with adult-onset schizophrenia. Some children with schizophrenia first seen in middle childhood have early histories of motor milestones and delayed language acquisition that are similar to some symptoms of autistic disorder. The mechanisms of biological vulnerability and environmental influences producing manifestations of schizophrenia are under investigation.
normal controls. Children with COS showed severe bilateral frontal gray matter loss over the 5-year period that occurred in a dorsal-to-ventral pattern across the medial hemispheres. Frontal regions were most affected, whereas cingulated-limbic regions were less vulnerable, which correlates with the brain areas responsible for the cognitive and metabolic dysfunction typically observed in schizophrenia. Children and adolescents with schizophrenia are more likely to have a premorbid history of social rejection, poor peer relationships, clingy, withdrawn behavior, and academic trouble than individuals with adult-onset schizophrenia. Some children with schizophrenia first seen in middle childhood have early histories of motor milestones and delayed language acquisition that are similar to some symptoms of autistic disorder. The mechanisms of biological vulnerability and environmental influences producing manifestations of schizophrenia are under investigation.
DIAGNOSIS AND CLINICAL FEATURES
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