Childhood-Onset Schizophrenia: Diagnostic and Treatment Challenges


Persons with childhood-onset schizophrenia appear to have the poorest outcome among those in whom schizophrenia is diagnosed.

February 2007, Vol. XXIV, No. 2

As a consequence of its premorbid impairments, insidious onset, and relative treatment resistance, childhood-onset schizophrenia (COS) presents clinicians with a number of diagnostic dilemmas and treatment challenges. COS occurs in fewer than 1 in 10,000 children1 and fewer than 1% of patients with schizophrenia receive this diagnosis in childhood.2 The ages and rates at onset are similar in boys and girls.3

Characterized by the onset of psychosis before the age of 13 years, COS is typically preceded by behavioral and cognitive symptoms that overlap with features of autism spectrum disorders, affective and disruptive behavior disorders, and speech and language disorders.1,3 Premorbid and comorbid psychiatric disorders make the diagnosis of COS a challenge and its treatment complicated. Persons with COS appear to have the poorest outcome among those in whom schizophrenia is diagnosed,4,5 so early detection of and intervention for COS may be important to maximize the impact of treatment for children and their families.

DIAGNOSING COS Premorbid precursors
Children in whom schizophrenia develops commonly show aberrant social and cognitive development in the very early stages, before the onset of psychosis. Precursors of COS include high rates of soft neurologic signs (minor neurologic abnormalities that are not associated with a specific neurologic disorder), significant delays in language and motor development, and social withdrawal.2Table 1 identifies behavioral precursors of COS and common premorbid childhood psychiatric disorders.

The lack of a well-defined period of normal development in children with COS may obscure the delineation of illness onset, making accurate diagnosis more difficult. Compared with adolescent- and adult-onset schizophrenia, the rates of insidious onset in COS are considerably higher, 71%6 compared with about 61% in adolescent and adult cases.7

Clinical assessment and differential diagnosis
COS is 50 times less likely to occur than adolescent-onset schizophrenia.2 The diagnosis of COS requires the presence of persistent hallucinations or delusions, disorganized speech and behavior (positive symptoms), and/or lack of developmentally appropriate affect and goal-directed behaviors (negative symptoms) for at least 1 month, and enduring impairment for at least 6 months. The current criteria in DSM-IV-TR for the diagnosis of COS are identical to those for a diagnosis of schizophrenia in adults with only one modification, namely, a child's failure to achieve an expected level of interpersonal, academic, or occupational achievement, which may replace a deterioration in function. There is no minimum age requirement for COS, and therefore, it can be diagnosed in very young children who meet the above criteria. However, it is rarely diagnosed before preschool age.

Optimal strategies for assessing and diagnosing COS include a structured or semistructured interview with the child and parent, in addition to a clinical interview and observation. A well-accepted semistructured interview is the Schedule for Affective Disorders and Schizophrenia–Present and Lifetime Versions.8

Because of the frequent preexisting thought and language dysfunction, COS is often more challenging to diagnose than schizophrenia in adolescents. For example, delusions or hallucinations may not be easily distinguished from the odd and idiosyncratic thinking in developmental disorders. In addition, a child's report of auditory hallucinations is frequently not pathognomonic of schizophrenia, since most children who report hallucinations do not have schizophrenia and many do not have psychotic disorders9-these hallucinations may simply be hypnagogic or hypnopompic.

Delusions in childhood exceed exaggerated magic beliefs, and these “fixed false beliefs” are often frightening and may drive a child to take an irrational action in an attempt to counteract them. For example, a child with a delusion that a sibling has AIDS and is trying to infect him or her might seek to “protect” himself or herself by wearing boots in the shower and hiding from the sibling at home. Similar counteractive protective behaviors may be observed in children with obsessive-compulsive disorder; however, delusions are often more bizarre than obsessions, and in general, delusional children do not believe that the danger diminishes as a result of their own responses (ie, compulsive rituals do not neutralize the fears).

True psychotic symptoms must be differentiated from children's reports of psychotic-like phenomena surrounding the idiosyncratic thinking and perceptions associated with pervasive developmental disorders (PDD), psychotic-like symptoms that may arise in children with posttraumatic stress syndrome, or anxiety-related transient “phobic” hallucinations. Psychotic symptoms in adolescents, compared with those of young children, are often more clearly described because of the increased developmental abilities of teens to articulate their inner experiences, which helps make the diagnosis of schizophrenia more clear-cut.

The comorbidity and overlap between PDD and COS sometimes makes these 2 disorders difficult to distinguish. Children with PDD may have more idiosyncratic, poorly formulated, peculiar thoughts that may shift or evolve over time. Like children with COS, children with PDD may also have odd beliefs-for example, that they are able to communicate with valued inanimate objects. Phobic hallucinations usually occur in the context of anxiety, such as a child “seeing” a frightening face in the window when it is dark, but which may not trouble the child during the day when the anxiety is muted.

Children with COS often fail to acquire the necessary social skills to fit in with same-age peers and frequently end up isolated. Significant rejection from peers, isolation from sports and other social activities, and generalized confusion and fear may emerge and permeate daily life.

Comorbid diagnoses
The relationship of COS to PDD has been of interest given their frequent coexistence. In a sample of children with COS, 34% had pervasive developmental symptomatology and 60% met criteria for a speech and/or language disorder.10 Sporn and colleagues11 found that 25% of children with COS had a lifetime diagnosis of PDD and those with comorbid PDD did not differ from the COS-only group in age at COS onset, cognitive performance, neuropsychological measures, or overall long-term outcome.

In a recent review of COS and childhood-onset schizoaffective disorder, 99% of those with either disorder were found to have at least 1 comorbid diagnosis: 84% had attention-deficit/hyperactivity disorder (ADHD), 43% had oppositional defiant disorder, 30% had depression, and 25% had separation anxiety disorder.12 Depression, anxiety,13 and eating disorders14 have been found to be comorbid with schizophrenia. Many comorbid disorders of COS, such as PDD, ADHD, and speech and language disorders, have their onset before COS.

Treatment strategies focus on alleviating positive and negative symptoms, reducing long-term morbidity, and preventing relapse. Clinical experience supports a combination of psychopharmacologic and psychosocial interventions to address the treatment needs in COS.3,15

Psychopharmacologic interventions
The available studies, as well as anecdotal clinical experience, suggest that response to antipsychotics in children with COS is less robust than in adolescents or adults with schizophrenia. Current pharmacologic research for COS is focused on identifying antipsychotic agents that provide optimal efficacy without significant adverse events. Atypical antipsychotics, including risperidone, olanzapine, and clozapine, have been shown in randomized clinical trials and open trials to be efficacious in the treatment of COS16-21; however, significant adverse effects, including weight gain, extrapyramidal adverse effects, and metabolic abnormalities, have occurred. Table 2 summarizes several recent psychopharmacologic trials for COS.

The superiority of clozapine over typical and atypical antipsychotics was shown in 2 randomized clinical trials for the treatment of COS; however, the use of clozapine was associated with serious adverse events such as tachycardia, hypertension, cardiac and lipid abnormalities, agranulocytosis, seizures, and nocturnal enuresis.16,17

In a 1-year open-label trial of olanzapine for the treatment of COS, positive symptoms improved after 6 weeks and negative symptoms showed improvement after 1 year of treatment.22 Adverse effects included increased appetite and weight gain,23 sedation,24 GI symptoms, headaches, agitation, liver function abnormalities, and sustained tachycardia.25

Pharmacologic treatment for COS remains an area of active research with 2 large ongoing multisite trials. The Early Onset Schizophrenia Study is investigating newer atypical antipsychotic agents. Preliminary open-label data suggest that ziprasidone was beneficial in approximately 13 of the 40 patients with COS after 12 weeks of treatment, with a mean final dosage of 118 mg/d. In over 1 year of this study, 50% of patients gained weight but no significant ECG changes occurred. The preliminary data suggest that ziprasidone may be useful in the treatment of COS.26 Another ongoing double-blind trial (Treatment of Early Onset Schizophrenia Spectrum Disorders) compares molindone, risperidone, and olanzapine.26

Psychosocial interventions
Psychosocial interventions address social, family, and peer relationship distress and developmental sequelae associated with COS.27 Social skills training is geared toward improving the patient's strategies for dealing with conflict and avoidance, enhancing communication within the family, and improving socialization and vocational skills. Psychoeducation helps the patient and his family understand the illness, the treatment options, and the prognosis for developing strategies to cope with the symptoms.3 Family psychoeducation and cognitive-behavioral therapy have been shown to reduce relapse in adolescents and adults with schizophrenia,15 and it is conceivable that a similar gain may occur in patients with COS.

Outcome studies ranging from several years to up to 42 years after diagnosis of COS indicate that the long-term functioning of patients with COS is poor compared with that of patients who have adolescent- or adult-onset schizophrenia.6,7,27 In general, the earlier the onset of COS, the poorer the prognosis. Variables indicative of better prognoses among children with COS are higher premorbid intelligence, more positive than negative symptoms of schizophrenia, and cooperation of family in treatment.2 Outcome variables in COS are detailed in Table 3.

Follow-up data indicate that close to two thirds of children with onset of schizophrenia between the ages of 6 and 14 years will be chronically ill.27,28 While outcomes are most grave for children with onset of illness before 13 years of age, findings from long-term outcome studies of adolescents with schizophrenia indicate that the illness has a negative impact on their academic success.29 For example, compared with the general population, adolescents with schizophrenia are about one third as likely to graduate from secondary school.29

With respect to occupational functioning, the findings from a 3-year outcome study of schizophrenia in children and adolescents showed that fewer than one fifth were able to function in academic or work settings at the level of same-age peers in the general population.30 Long-term follow-up of individuals with COS and adolescent-onset schizophrenia over 6 to 40 years indicates that significant impairment persists into adulthood; only 7% of the sample were able to maintain a stable relationship, and 59% were unmarried and living alone. Although 73% had some form of employment, 27% were unable to work.31 Clearly, the burden of schizophrenia lingers over the years.

While COS and adolescent-onset schizophrenia are the same disorder, their relationship is highlighted by a poorer prognosis in youth who meet diagnostic criteria before age 14 years.28 Children with COS are at significantly increased risk for having bor-derline intellectual function or mild mental retardation,32 and they are more likely to have speech and language disorders33 and a history of PDD34 compared with those who have adolescent-onset schizophrenia.

Given the challenge of finding successful multimodal interventions for COS, available psychopharmacologic agents have shown some evidence of effectiveness, although all are still limited by serious adverse effects. Future investigations of combined psychosocial and pharmacologic treatments are needed to provide a broader range of effective interventions to improve long-term function of patients with COS.

Dr Khurana and Dr Aminzadeh are first-year child and adolescent psychiatry fellows at the Los Angeles County–University of Southern California (USC) Child and Adolescent Psychiatry Fellowship Program. Dr Bostic is director of school psychiatry at Massachusetts General Hospital in Boston and McLean Hospital in Belmont, Mass. Dr Pataki is director of residency training in child psychiatry at the USC Keck School of Medicine in Los Angeles.

Dr Khurana and Dr Aminzadeh report that they have no conflicts of interest concerning the subject matter of this article. Dr Bostic has received grant support and/or honoraria from Abbott, Forest, GlaxoSmithKline, Eli Lilly, and Pfizer; he is on the speakers' bureau for Forest and a consultant for GlaxoSmithKline. Dr Pataki has received research support from Eli Lilly, Pfizer, Novartis, and Shire.

Drugs Mentioned in This Article
Clozapine (Clozaril)
Haloperidol (Haldol)
Molindone (Moban)
Olanzapine (Zyprexa)
Risperidone (Risperdal)
Ziprasidone (Geodon)

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Evidence-Based References

  • Remschmidt H, Martin M, Fleischhaker C, et al. Forty-two-years later: the outcome of childhood-onset schizophrenia. J Neural Transm. 2006 Aug 10; [Epub ahead of print].
  • Shaw P, Sporn A, Gogtay N, et al. Childhood-onset schizophrenia. A double-blind, randomized clozapine-olanzapine comparison. Arch Gen Psychiatry. 2006;63:721-730.


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