Schizophrenia as a whole is beyond the scope of this article. This article is primarily concerned with childhood-onset schizophrenia.
- Schizophrenia with onset before age 18 is termed early-onset schizophrenia
- Onset before age 13 is described as childhood-onset schizophrenia (COS)
- The worldwide prevalence of schizophrenia is ~1%, with slight male predominance of approximately 1.4 to 1.
- Peak onset of schizophrenia is before age 25 in males, and somewhat later in females, with a second peak in women aged >45. (see figure)
- 25% will recover fully; 4-13% commit suicide.
- COS is rare with rates of 1 per 10,000 (schizophrenia as a whole is 1 per 100).
- Patients whose disease is of acute onset (25%), with productive schizophrenic manifestations such as hallucinations and delusions (positive manifestations), have a better prognosis than those whose disease begins insidiously (75%) and takes an unfavorable course, with depressive states and continually worsening impairment of cognitive function.
- The patient's premorbid personality plays a major role. Patients who were described as socially active, intelligent, and integrated children and adolescents before they became ill have a better prognosis than those who were intellectually impaired, timid, introverted and uncommunicative before they became ill. (1)
- The prognosis seems to be better for patients who have no family history of schizophrenia, those whose families cooperate well, and those whose condition improves rapidly during inpatient treatment.
- Visual hallucinations are common are correlate with earlier onset, lower IQ and greater clinical impairment as compared to schizophrenic children without visual hallucinations. (David CN. JAACAP 2011)
- The most common comorbidity in COS is depression (54%), followed by OCD (21%), GAD and ADHD (15% each) (NIMH)
- A 42-year longitudinal study of patients with childhood-onset schizophrenia revealed their suicide rate to be higher than that of patients with adult-onset schizophrenia.
Most often COS is persistent, non-episodic illness with poor prognosis. DSM-5 criteria can be applied to children and adolescents. It's important to rule out affective disorders, substance-induced psychosis as well as autism and PDD. Youth diagnosed with PTSD, conduct problems, depression, and those with history of abuse report higher rates of psychotic-like symptoms (McClellan JAACAP 2013).
- In preschoolers, psychosis (particularly hallucinations) are most likely caused by stress or anxiety; these are transient and benign.
- In school-age children, psychotic symptoms may be more persistent, and are more likely to be associated with drug toxicity or significant mental illness (Lewis, p. 494)
- Prescription medications that are associated with psychosis include corticosteroids, anesthetics, anticholinergics, antihistamines, and amphetamines.
- Youth with EOS exhibit significant decreases in gray matter and hippocampal volume reduction as well as enlargement of ventricular volumes compared to normal controls (Steen RG. meta-analysis, BrJPsych 2006);
- They also exhibit decreased cortical folding (McClellan J. JAACAP 2013).
Atypical antipsychotics are the mainstay of treatment in youth with schizophrenia. (McClellan J. JAACAP 2013)
- Risperidone, aripiprazole, quetiapine, paliperidone, and olanzapine are approved by the FDA dor schizophrenia in adolescents >=13 years based on effecacy in RCTs.
- Ziprasidone RCT was stopped due to lack of efficacy.
- In the only RCT of clozapine, it showed somewhat better results vs olanzapine (particularly in improving negative symptoms), but also more side effects. In the open-label follow-up most children were switched from olanzapine to clozapine. (2)
In treatment of early-onset schizophrenia spectrum disorders (TEOSS) study, (n=116), first- and second-generation antipsychotics were compared in 8-19 year-olds. Efficasy of risperidone, olanzapine, and molidone (10-140 mg/day) was comparable, but SGA's caused significant weight gain, and olanzapine was associated with hyperlipidemia. (5)
- Across all three treatments, >50% failed to achieve adequate response after 8 weeks.
Risk of relapse is significant, and antipsychotic maintenance treatment should be continued in most youth with schizophrenia to improve functioning and prevent relapse. (McClellan J. JAACAP 2013)
- Visual hallucinations are common in COS, and are associated with greater clinical impairment and greater compromise in overall brain functioning. (3)
- On imaging, COS children show progressive loss of gray matter during adolescence (this is not found in adult schizophrenics)
- Omega-3 fatty acids can delay the onset of psychosis in high-risk patients.
- NIMH identified a heterogeneous group of children with transient psychotic symptoms and multiple developmental abnormalities had been termed the Multi Dimensionally Impaired (MDI) group.
- These children have cognitive deficits, psychotic symptoms in response to stress without a thought disorder, impaired interpersonal skills, ADHD symptoms, and emotional dysregulation.
- They are at risk for developing bipolar disorder later in life. 
- For children on clozapine who develop neutropenia, lithium can be added for clozapine rechallenge [2cases:(4)]
1. Neuropsychobiology 2012;66(1):63-9 "Early-onset schizophrenia"
2. Shaw P et.al Childhood-onset schizophrenia: A double-blind, randomized clozapine-olanzapine comparison. Arch Gen Psychiatry. 2006 Jul;63(7):721-30.
3. David Cn et. al. Childhood onset schizophrenia: high rate of visual hallucinations.J Am Acad Child Adolesc Psychiatry. 2011 Jul;50(7):681-686.e3. Epub 2011 Jun 11.
4. Sporn A, et al.: Clozapine-induced neutropenia in children: Management with lithium carbonate. J Child Adolesc Psychopharmacol 13(3):401–404, 2003
5. Sikich, L., Frazier JA. et.al.: Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study. Am J Psychiatry. 2008 Nov;165(11):1420-31.
6. Nicolson R, Lenane M, Brookner F, et al. Children and adolescents with psychotic disorder not otherwise specified: a 2- to 8-year follow-up study. Compr Psychiatry. 2001;42:319-325.
7. Jon McClellan, M.D., Saundra Stock, M.D., AND AACAP Committee on Quality Issues. Practice Parameter for the Assessment and Treatment of Children and Adolescents With Schizophrenia. JAACAP, 2013;52(9):976–990
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