AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

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).¹ 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.²

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 D₂ 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.³ 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.⁴

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.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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:
• • Delusions
  • Hallucinations
  • Disorganized speech
  • Catatonia or disorganized behavior
  • 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.⁵
• • Hallucinations and delusions become more complex and elaborated with increasing age.
  • Hallucinations are usually the presenting symptom.
  • Hallucinations are reported by approximately 80% of children who receive the diagnosis. Auditory hallucinations are more common than visual hallucinations.
  • 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.
• • Caplan and associates have demonstrated that loose associations and illogical thinking can be documented reliably.^{6, 7, 8}
  • 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.
• • 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.
  • Attention and executive functioning may be impaired.
  • A subsequent decline in full-scale IQ appears to be due to failure to learn rather than to loss of function.
  • 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.⁹
• Patients with childhood-onset schizophrenia suffer from significant sleep disturbances, which are highly related to symptom severity.¹⁰

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.¹¹
• 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.¹²

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.¹³
  • In the Pittsburgh high-risk study, findings among young relatives of schizophrenia patients included the following:¹⁴
  • • 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.¹⁵
• 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.
• 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.¹⁶
  • 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.^{17, 18} 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.¹⁹
  • 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.²⁰
  • 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.²¹
• 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.²² Early adolescent cannabis use coupled with a specific genetic vulnerability may be a risk factor for the development of schizophrenia.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Psychosis secondary to epilepsy
Neurodegenerative disorders
Multidimensionally impaired syndrome (not a DSM-IV diagnosis, characterized by emotional lability, distractibility, poor social skills, brief hallucinations, and trouble distinguishing fact from fiction)
CNS tumor
Progressive organic CNS disorder (eg, sclerosing panencephalitis)
Psychosis not otherwise specified
Psychosis, single episode
Schizoaffective disorder
Chromosomal disorder - 22q11 deletion syndrome

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Laboratory studies are performed as part of an assessment for differential diagnosis.
• • Toxicology screens may be needed if substance abuse is suggested.
  • Liver function studies, copper, and ceruloplasmin are part of the workup for Wilson disease.
  • Obtain porphobilinogen for porphyria.
  • Human immunodeficiency virus (HIV) titers, Venereal Disease Research Laboratory (VDRL) testing, or heavy metal screening may be needed.
• Prior to starting psychopharmacologic therapy, perform standard laboratory studies.
• • Typical neuroleptics and risperidone have caused abnormalities in hematologic and liver functions. The atypical antipsychotics have caused glucose and lipid abnormalities; thus, glucose, cholesterol, and triglycerides need to be monitored.
  • Clozapine may cause severe leukopenia.
  • Thyroid and renal functions are required prior to starting lithium.
• If the child has mental retardation or dysmorphic features, include a karyotype in the genetic assessment. One example is the 22q11 deletion syndrome, or velocardiofacial syndrome.²³ Other preliminary reports suggest 5q involvement.

Imaging Studies

• Neuroimaging using MRI or CT scanning (if MRI is not available) should be part of the evaluation of new-onset psychosis.
• MRI helps exclude certain organic causes of psychosis.
• Demyelination is observed in the child with leukodystrophy.
• Atrophy is observed in some children with neuronal ceroid lipofuscinosis.
• Ventricular enlargement and gray matter loss are consistent with, but not diagnostic of, childhood-onset schizophrenia.

Other Tests

• Structured or semistructured interviews
• • These tests are beneficial for initial assessment and monitoring symptoms during follow-up care.
  • Initially, the recommended Mental Status Examination forms a baseline diagnostic framework.
  • Other standard instruments include the following:
  • • Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) ⁶
    • Brief psychiatric rating scale (BPRS)
    • Positive and Negative Syndrome Scale (PANSS)
• Psychological testing of cognitive function: This testing is essential for treatment planning.
• Projective tests
• • Projective tests, such as the Rorschach, may be helpful in eliciting further symptoms.
  • The Thematic Apperception Test may also be helpful in eliciting additional information.
  • However, diagnosis is confirmed by comprehensive clinical assessment.
• EEG
• • Perform an EEG if episodic symptoms or signs are present in the evaluation of a child with psychosis.
  • In children who receive clozapine, obtain an EEG because of the increased risk of seizures associated with clozapine.
• ECG
• • Obtain an ECG prior to starting a low-potency antipsychotic.
  • Perform ECG prior to starting medication and as part of follow-up care of a child who receives pimozide.

Histologic Findings

Neuropathologic studies are available for persons with later-onset schizophrenia but not for children with schizophrenia. Postmortem studies have demonstrated reduced volume of the hippocampus. Gliosis has not been found, suggesting that no active inflammatory process occurs.

TREATMENT

Section 6 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

• Pharmacotherapy
• • Pharmacotherapy is essential in the treatment of individuals with childhood-onset psychosis.
  • The first-line agents are neuroleptics.
  • Newer atypical antipsychotic agents are generally chosen as the initial drugs of choice (DOC).
  • Occasionally, the agitated child with new-onset schizophrenia may need a benzodiazepine to calm and alleviate the anxiety accompanying the experience of psychosis.
• Electroconvulsive therapy: Electroconvulsive therapy (ECT) has also been used adjunctively in rare cases.
• Psychosocial care
• • The child with schizophrenia requires multimodal care. This should include social skills training, a supportive environment, and a structured individualized special education program.
  • Supportive psychotherapy is used to encourage reality testing and to help the child monitor for warning symptoms of impending relapse.
  • Cognitive behavioral therapy has been used successfully in adults with schizophrenia and may help improve coping with schizophrenia and monitoring of beliefs and attributions.
• Family education
• • Families need to be educated about the causes, therapy, and complications of childhood-onset schizophrenia.
  • Family members need to know warning signs of impending relapse.
  • High levels of expressed emotion have been associated with an increased risk of relapse in adults with schizophrenia and can possibly contribute to problems in children with schizophrenia.

Consultations

• Psychologist
• • A psychologist is an essential part of the evaluation and treatment team.
  • Because of the expected cognitive impairments, the mental health clinician should obtain IQ and achievement testing for adequate educational planning.
  • Projective tests, such as the Rorschach or the Thematic Apperception Test, may be helpful in eliciting additional information.
  • However, their reliability and validity are not superior to a competent interview.
• Child neurologist and geneticist: These health care professionals may be needed to help evaluate for possible organic etiologies.
• Ophthalmologist: Children taking chlorpromazine and thioridazine should be checked for retinopathy and lenticular changes by an ophthalmologist.
• Multimodal care
• • Due to the pervasive problems of the child with schizophrenia, a team approach is needed.
  • Involve nursing, speech and language therapy, and occupational and physical therapy.
  • A case manager may facilitate care.

Diet

• Both typical and atypical antipsychotic medications may stimulate the appetite.
• Low-calorie snacks and limitation of total intake at meals may help prevent excess weight gain.
• Weight and body mass index (BMI) should be monitored in all patients on atypical antipsychotics.

MEDICATION

Section 7 of 11  

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• References

Drug Category: Antipsychotics, typical

Historically, typical antipsychotics are the first-line therapy for individuals with childhood-onset schizophrenia. Controlled trials of haloperidol and loxapine are available, as are single-blind trials of thioridazine and thiothixene. However, thioridazine is no longer a preferred medication because of significant cardiac toxicity and risk of death.

Although little difference in the efficacy of individual typical antipsychotics is observed, a difference in the adverse effect profile is noted. High-potency drugs (eg, haloperidol) have an increased risk of extrapyramidal adverse effects, whereas low-potency drugs cause more sedation and orthostatic hypotension. Extrapyramidal adverse effects can occur early, late, or during withdrawal.

Problems that occur early include dystonia, parkinsonism, akathisia, and neuroleptic malignant syndrome (NMS). Dystonia affects adolescent boys more often, but parkinsonism is less common in children. The late-appearing and withdrawal adverse effects include choreiform movements or, less commonly, dystonia. Other adverse effects of antipsychotics include weight gain,²⁴ photosensitivity, decreased white cell count, jaundice, blurred vision, constipation, amenorrhea, and gynecomastia.

Drug Category: Antipsychotics, atypical

Generally, atypical antipsychotics are currently chosen as first-line antipsychotic therapy. Controlled trials in childhood-onset schizophrenia are available only for clozapine. Open-label trials have been completed with risperidone and olanzapine, and the effectiveness of quetiapine has been anecdotally reported. Weight gain has been a problem with all currently available atypical antipsychotics, although weight gain may be less of a problem with ziprasidone. Extrapyramidal adverse effects are less common than those observed with the traditional antipsychotics, although they have been reported with both clozapine and risperidone. Sedation has occurred with all available atypical antipsychotics.

An ongoing study of the effectiveness of antipsychotic drugs in adults with schizophrenia found that patients stayed on olanzapine for a longer duration of time but also developed more weight gain and adverse metabolic effects on olanzapine.²⁵

Drug Category: Benzodiazepines

These agents have been used in combination with antipsychotics early in treatment of acute psychosis when sedation is needed.

Drug Category: Antiparkinsonian agents

Anticholinergics have been used to prevent and treat acute dystonia, parkinsonism, and NMS. They have also been used for tardive dyskinesia.

Drug Category: Antihistamines

Antihistamines are possibly useful for treatment of extrapyramidal adverse effects of antipsychotic agents (eg, dystonia, akathisia). They have also been used for sedation and as mild hypnotics.

Drug Category: Beta-adrenergic blockers

Beta-adrenergic blockers have been used to treat akathisia, tremor, anxiety, and aggression.

Drug Category: Dopamine agonist

NMS is an adverse effect of antipsychotic drugs and is characterized by fever, muscle rigidity, and autonomic dysfunction. NMS has been treated with dopamine agonists (eg, bromocriptine, amantadine). Other drugs used include dantrolene sodium, benztropine, and diphenhydramine.

FOLLOW-UP

Section 8 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Acute inpatient care is necessary for persons with behaviors dangerous to self or others.
• The child with schizophrenia who is severely impaired may need day treatment programs or hospitalization until the child is stabilized and not considered a danger to self or others.

Further Outpatient Care

The frequency of regular outpatient visits is determined by the presence of continuing symptoms.

• Many children with schizophrenia have a residual phase with predominantly negative symptoms that can be socially disabling.
• During residual phase or remission, monitor the child with schizophrenia for recurrence of positive symptoms (eg, hallucinations, delusions) that may signal a relapse or worsening of negative symptoms.
• Monitor for any new symptoms or episodes of mania. Approximately 15-20% of children with an initial diagnosis of schizophrenia may be found later to have bipolar disorder, schizoaffective disorder, or one of the disorders listed in the differential diagnosis (see Differentials).

In/Out Patient Meds

Repeating assessment for medication adverse effects using standard measures is essential.

• The abnormal involuntary movement scale (AIMS) is one such standard measure.
• Possibly one third of children on antipsychotics develop withdrawal dyskinesias.
• Recommendations for monitoring adults on atypical antipsychotics include checking the following:
• • Weight at baseline; 4, 8, and 12 weeks; and then quarterly
  • Blood pressure at baseline, 12 weeks, and annually
  • Fasting plasma glucose level at baseline, 12 weeks, and annually
  • Fasting lipid profile at baseline, 12 weeks, and every 5 years
• Similar recommendations are not yet available for children and adolescents, but careful monitoring of weight, blood pressure, and glucose and lipids levels seems warranted.

Deterrence/Prevention

Treatment prior to emergence of psychosis is under investigation.

• In very preliminary work, first-degree relatives of patients with schizophrenia who had suggestive symptoms and neuropsychological deficits received risperidone with a subsequent reduction in suggestive symptoms and improvement in attention and working memory.²⁶ In a randomized controlled trial that compared risperidone and cognitive behavior therapy with intervention for symptoms in individuals at very high risk for schizophrenia, fewer people in the active treatment group progressed to a first episode of psychosis.²⁷
• This preliminary finding raises the possibility that children with prodromal symptoms of schizophrenia can be treated prior to emergence of psychosis.
• Further study is required before such therapy can be recommended.

Complications

• Suicide is a major complication of schizophrenia. Approximately 10% of adults with schizophrenia commit suicide.
• Violence is a potential problem, particularly for the adolescent with paranoid ideation.
• Other complications arise from poor self-care, impulsivity leading to injury or sexually acquired diseases, and substance abuse.
• Adults with schizophrenia may not receive adequate medical care.

Prognosis

• The prognosis for childhood-onset schizophrenia and adolescent-onset schizophrenia is worse than that observed in adult-onset schizophrenia.
• As adults, these children experience the following:
• • Fewer close social relationships
  • Less academic achievement
  • More unemployment
  • Less capacity for independent living
• Patients with an onset prior to adolescence and those with an insidious onset appear to have a worse response to medication and a worse prognosis.

Patient Education

• Psychoeducation is essential for families of children with schizophrenia. They need to know symptoms of the disorder, natural history, and adverse effects of medication.
• Once children with schizophrenia are in remission, teach them to self-monitor for signs of possible relapse. Inform these children about possible adverse effects of medication.
• For excellent patient education resources, visit eMedicine's Mental Health and Behavior Center. Also, see eMedicine's patient education article Schizophrenia.

MISCELLANEOUS

Section 9 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to adequately inform the child and family about potential drug adverse effects such as tardive dyskinesia and the metabolic syndrome
• Failure to warn and to protect if suicide is a risk
• Failure to warn and to protect when aggressive or homicidal behavior is a risk

MULTIMEDIA

Section 10 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Early and late gray matter deficits in schizophrenia. Areas of gray matter loss, shown in red and yellow, spread from back-to-front (right to left) over 5 years in composite MRI scan data from 12 teens with childhood-onset schizophrenia, beginning at age 14 (left). Red and yellow denotes areas of greater loss. Source: Paul Thompson, MD, UCLA, Laboratory of Neuroimaging. NIMH media file.
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Media type:  Image

Media file 2:  Rate of gray matter loss. Composite MRI scan data showing areas of gray matter loss over 5 years, comparing 12 normal teens (left) and 12 teens with childhood-onset schizophrenia. Red and yellow denotes areas of greater loss. Front of brain is at left. Source: Paul Thompson, MD, UCLA, Laboratory of Neuroimaging. NIMH media file.
	View Full Size Image
Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
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• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4^th ed. Washington, DC: APA; 1994.
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR). 4^th ed. Washington, DC: APA; 2000.
3. Clinton SM, Haroutunian V, Davis KL. Altered transcript expression of NMDA receptor-associated postsynaptic proteins in the thalamus of subjects with schizophrenia. Am J Psychiatry. Jun 2003;160(6):1100-9. [Medline].
4. Kirkbride JB, Fearon P, Morgan C, et al. Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study. Arch Gen Psychiatry. Mar 2006;63(3):250-8. [Medline].
5. Ballageer T, Malla A, Manchanda R, et al. Is adolescent-onset first-episode psychosis different from adult onset?. J Am Acad Child Adolesc Psychiatry. Aug 2005;44(8):782-9. [Medline].
6. Caplan R, Guthrie D, Fish B, et al. The Kiddie Formal Thought Disorder Rating Scale: clinical assessment, reliability, and validity. J Am Acad Child Adolesc Psychiatry. May 1989;28(3):408-16. [Medline].
7. Caplan R, Guthrie D, Tang B, et al. Thought disorder in childhood schizophrenia: replication and update of concept. J Am Acad Child Adolesc Psychiatry. Jun 2000;39(6):771-8. [Medline].
8. Caplan R, Siddarth P, Bailey CE, Lanphier EK, Gurbani S, Donald Shields W, et al. Thought disorder: A developmental disability in pediatric epilepsy. Epilepsy Behav. Jun 2006;8(4):726-35. [Medline].
9. Gochman PA, Greenstein D, Sporn A, et al. IQ stabilization in childhood-onset schizophrenia. Schizophr Res. Sep 15 2005;77(2-3):271-7. [Medline].
10. Mattai AA, Tossell J, Greenstein DK, et al. Sleep disturbances in childhood-onset schizophrenia. Schizophr Res. Sep 2006;86 (1-3):123-9. [Medline].
11. Karp BI, Garvey M, Jacobsen LK, et al. Abnormal neurologic maturation in adolescents with early-onset schizophrenia. Am J Psychiatry. Jan 2001;158(1):118-22. [Medline].
12. Erlenmeyer-Kimling L, Hans S, Ingraham L, et al. Handedness in children of schizophrenic parents: data from three high-risk studies. Behav Genet. May 2005;35(3):351-8. [Medline].
13. Asarnow RF, Nuechterlein KH, Fogelson D, et al. Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study. Arch Gen Psychiatry. Jun 2001;58(6):581-8. [Medline].
14. Keshavan MS, Diwadkar VA, Montrose DM, Stanley JA, Pettegrew JW. Premorbid characterization in schizophrenia: the Pittsburgh High Risk Study. World Psychiatry. Oct 2004;3(3):163-8. [Medline].
15. Gogtay N, Sporn A, Clasen LS. Structural brain MRI abnormalities in healthy siblings of patients with childhood-onset schizophrenia. Am J Psychiatry. Mar