Schizophrenia and Other Psychoses
Childhood-onset schizophrenia is a severe form of psychotic disorder that occurs at age 12 years or younger and is often chronic and persistently debilitating. The definition of childhood schizophrenia has evolved over time and is now believed to be a virulent childhood version of the same disorder exhibited in adolescents and adults. However, in the first 2 editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM), autistic disorder and childhood-onset schizophrenia were not differentiated as distinct disorders; instead, they were listed together as childhood psychoses.
In the third edition of the DSM (DSM-III), autism was listed separately, and childhood-onset schizophrenia was incorporated under the general heading of schizophrenia. According to the fourth edition of the DSM (DSM-IV), the criteria for childhood-onset schizophrenia and adult schizophrenia are synonymous, except for one potential modification for children (ie, in childhood-onset schizophrenia, the failure to meet expected social or academic milestones may be present, rather than a deterioration in functioning). According to the text revision of the fourth edition of the DSM (DSM-IV-TR), the criterion of social/occupational dysfunction in childhood or adolescent-onset schizophrenia can consist of a failure to achieve expected level of interpersonal, academic, or occupational achievement.
Pathophysiology
Most psychological, pharmacologic, and neuroimaging studies of childhood-onset schizophrenia have suggested dysfunction in the prefrontal cortex and limbic system. The neurotransmitter implicated in the pathophysiology of schizophrenia is dopamine.
Drugs that increase dopaminergic activity may induce a schizophreniform psychosis, and drugs that block postsynaptic D 2 receptors help alleviate symptoms of schizophrenia. Other neurotransmitters may also be involved in the pathophysiology of schizophrenia. Glutamate has been implicated based, in part, on the production of psychotic symptoms by phencyclidine and the presence of N -methyl-D-aspartate (NMDA) receptor dysfunction. Serotonin may be important. The new atypical antipsychotic drugs have prominent serotonergic effects. Preliminary studies suggest gamma-aminobutyric acid (GABA) may be important.
Frequency
United States
Childhood-onset schizophrenia is rare. In preadolescents, estimated prevalence is less than 1 case per 10,000 population. The number of new cases significantly increases during late adolescence, reaching an approximate prevalence of 1% for later-onset schizophrenia.
International
No studies of prevalence of childhood-onset schizophrenia in underdeveloped countries are available. Schizophrenia with an onset later in life appears to have an equal prevalence in countries around the world, with a possible increase in prevalence in urban populations.
Mortality/Morbidity
An increased risk of death from suicide is present in patients with schizophrenia. In larger follow-up studies of childhood-onset schizophrenia, the mortality rate from suicide is 5-11%. In follow-up studies, more than one half of children with schizophrenia have persistent severe impairment in social skills and limitations in academic and occupational achievement.
Race
No studies of childhood-onset schizophrenia that allow comparisons based on race or ethnicity are available nor are studies about the prevalence in underdeveloped nations. The 2006 Aetiology and Ethnicity in Schizophrenia and Other Psychoses Study (AESOP), a large, population-based case-control study conducted over 2 years in 3 study centers in England in adults, reported all psychoses were more common in the black and minority ethnic group compared with the white British group.
Sex
Most studies demonstrate a male-to-female ratio averaging 1.5-2:1.
Age
In a child younger than 13 years, the onset of schizophrenia is rare and is generally insidious, carrying a worse prognosis. Onset of the disorder in the adolescent years is more common and may have an acute or insidious onset. In general, the earlier the onset of schizophrenia, the poorer the outcome.
History
Most children who develop schizophrenia have disturbances of behavior and cognition prior to the onset of characteristic symptoms of psychosis. Delays in speech and language and delays in acquisition of motor milestones are noted in approximately one half of these children. Children who develop schizophrenia have higher rates of impaired social skills and school achievement prior to presenting signs of schizophrenia. Approximately one third of the children develop symptoms of inattention, hyperactivity, aggression, or rage.
One half of these children have received prior diagnoses, including pervasive developmental disorders (PDDs), attention deficit hyperactivity disorder (ADHD), and internalizing disorders (eg, bipolar disorder, depression, anxiety disorders). In one study, psychotic symptoms appeared, on average, 2.5 years after initial clinical presentation, and the diagnosis of schizophrenia was made a mean of 2 years after the onset of psychosis.
- The DSM-IV-TR criteria for schizophrenia require at least 2 of the following characteristic symptoms present for most of a 1-month period:
o Delusions
o Hallucinations
o Disorganized speech
o Catatonia or disorganized behavior
o Negative symptoms, such as blunting of affect - The child fails to achieve expected level of interpersonal, academic, or occupational achievement or demonstrates significant deterioration of functioning.
- Impairment should have lasted at least 6 months, including one month when characteristic symptoms are present.
- Diagnosis requires the exclusion of mood disorders with psychotic features (bipolar disorder), substance-induced psychotic disorder, and psychosis due to a medical condition.
- If the child has a prior diagnosis of a PDD, a period of at least one month must pass, during which the child experiences hallucinations or delusions.
- All of the characteristic symptoms of schizophrenia have been described in persons with childhood-onset schizophrenia. Ballageer et al found that bizarre behavior and negative symptoms were more common in individuals with adolescent-onset schizophrenia compared with those with onset during the adult years.
o Hallucinations and delusions become more complex and elaborated with increasing age.
o Hallucinations are usually the presenting symptom.
o Hallucinations are reported by approximately 80% of children who receive the diagnosis. Auditory hallucinations are more common than visual hallucinations.
o Delusions are present in approximately 60% of patients. - Approximately one half of children with schizophrenia have a formal thought disorder, although assessment may be more difficult in children than in adults.
o Caplan and associates have demonstrated that loose associations and illogical thinking can be documented reliably.
o Poverty of speech was not documented. - Compared with adults with schizophrenia, children with schizophrenia have catatonia less often.
- Changes in affect are common, with blunting or inappropriate affect observed in approximately two thirds of children with schizophrenia.
- Cognitive functioning is often impaired at the onset of childhood schizophrenia.
o In most series of children with schizophrenia, the average full-scale intelligence quotients (IQs) have been in the 80s, with particular deficits in verbal comprehension, language, and short-term memory.
o Attention and executive functioning may be impaired.
o A subsequent decline in full-scale IQ appears to be due to failure to learn rather than to loss of function.
o Gochman et al reported that long-term trajectory of IQ measures appears stable and level cognitive functioning extends 13 years or longer after the onset of psychosis, despite chronic illness and concomitant, progressive loss of cortical gray matter. - Patients with childhood-onset schizophrenia suffer from significant sleep disturbances, which are highly related to symptom severity.
Physical
- Abnormalities in the neurologic examination are observed in as many as one half of adults with new-onset schizophrenia. In one study, Karp et al found significantly more signs of neurologic dysfunction in adolescents with earlier-onset schizophrenia.
- The most common abnormalities in individuals with adult schizophrenia are soft signs, including incoordination, persistence of developmental reflexes, and impaired ocular pursuit movements.
- Adolescents with earlier-onset schizophrenia have persistence of primitive reflexes. Compared with a healthy control group, the number of primitive reflexes does not decrease with advancing age in adolescents with schizophrenia. Children with schizophrenia are commonly reported to have delayed motor development and impaired coordination.
- Formal measurements of ocular smooth pursuit have demonstrated abnormalities in individuals with childhood-onset schizophrenia.
- Research on handedness and schizophrenia has remained replete with inconsistencies.
Causes
No definite single etiology of schizophrenia has been identified. Most theories accept both genetic and environmental contributions for the causation of childhood-onset schizophrenia. Compared with the usual onset of schizophrenia in late adolescence or early adulthood, the emergence of earlier-onset schizophrenia during childhood may be due to increased genetic loading for schizophrenia or early CNS damage due to an environmental factor.
- Several factors suggest a genetic risk.
- First-degree relatives of children with schizophrenia have a higher prevalence rate of schizophrenia and schizophrenia spectrum disorders.
- In the Pittsburgh high-risk study, findings among young relatives of schizophrenia patients included the following:
+ High proportions of axis I psychopathology, especially ADHD and conduct disorder
+ Increased expressed emotion among relatives
+ A trend for more psychopathology in offspring of relatives with high expressed emotion
+ Impaired attention, spatial working memory, and executive functions
+ Increased soft neurological signs
+ Volume reductions in the amygdala, hippocampus, and superior temporal gyrus
+ Decreased slow-wave sleep - First-degree relatives of individuals with schizophrenia have impairment in ocular smooth pursuit movements similar to that found on examination of patients with schizophrenia. One study found that healthy siblings of patients with childhood-onset schizophrenia had decreased cerebral gray matter in the same pattern as was seen in the patients.
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Several studies have described complications during pregnancy and delivery in adults who subsequently develop schizophrenia. The combination of genetic risk and evidence of acquired damage has suggested a neurodevelopmental theory with early CNS abnormalities that contribute to an increased vulnerability to schizophrenia later in life.
- An increase in minor dysmorphic features has suggested prenatal-onset problems.
- An increase in hypoxia-associated complications was demonstrated to increase the odds of developing earlier-onset schizophrenia.
- An increase in minor dysmorphic features has suggested prenatal-onset problems.
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The neurobiologic substrate of persons with childhood-onset schizophrenia has been examined by neuroimaging.
- As in adults with schizophrenia, the most consistent finding has been enlargement of the lateral ventricles.
- Although static in adults, the abnormalities in brain morphology evolve during adolescence. The possibility of a neurodegenerative process has been raised but also questioned.
- Rapoport et al demonstrated that adolescents with schizophrenia have significantly greater decreases in frontal and temporal gray matter volumes than those observed in healthy age-matched controls. They additionally found the children with schizophrenia to have more cortical gray matter loss than children with transient psychosis. Subsequent studies from this group have also shown reduced cerebral volume and gray matter in healthy siblings of patients with childhood-onset schizophrenia.
- The Edinburgh high-risk study suggested that, in high-risk subjects (defined as subjects who had at least 2 close relatives with schizophrenia), the change from vulnerability to psychosis may be preceded by reduction in size and deteriorating function of the temporal lobe.
- In a systematic review and meta-analysis of 66 papers comparing brain volume in patients with a first psychotic episode with volume in healthy controls, meta-analysis suggested that the whole brain and hippocampal volume are reduced and that ventricular volume is increased in these patients relative to healthy controls.
- Greenstein et al reported that cortical thickness loss in childhood-onset schizophrenia appears to localize with age to prefrontal and temporal regions that are seen in patients with adult-onset schizophrenia regardless of medication.
- As in adults with schizophrenia, the most consistent finding has been enlargement of the lateral ventricles.
- Evidence from 6 longitudinal studies in 5 countries shows that regular cannabis use predicts an increased risk of a schizophrenia diagnosis or of reporting symptoms of psychosis. Early adolescent cannabis use coupled with a specific genetic vulnerability may be a risk factor for the development of schizophrenia.
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Author: Rajkumar K Kalapatapu, MD, Fellow in Child/Adolescent Psychiatry, Department of Psychiatry, Indiana University School of Medicine
Coauthor(s): David W Dunn, MD, Program Director, Child and Adolescent Psychiatry, Professor, Departments of Psychiatry and Neurology, Indiana University