Schizophrenia in Children and Adolescents

Although the first episode usually occurs in young adults, some contributory neurodevelopmental events and experiences occur earlier (eg, during prenatal, perinatal periods and early childhood).

These early developmental risk factors include the following (1):

• Neurodevelopmental abnormalities (impaired olfactory ability, minor physical anomalies, obstetric complications, low premorbid intelligence, winter/spring season of birth)

• Maternal infections (Toxoplasma gondii)

• Psychosocial stressors (childhood adversity, migrant status, stressful life events)

• Exposure to certain drugs or substances (eg, cannabis)

• Childhood traits of social withdrawal, anhedonia

• Race/ethnicity (Black race, minorities that reside in urban areas; associated factors include poverty, high population density, social fragmentation, and environmental pollution)

• Childhood brain injury

Sudden-onset psychosis in young children should always be treated as a medical emergency and thoroughly assessed to determine whether there is a physiologic cause of the mental status change. These causes include the following (2):

• Therapeutic drugs (eg, stimulants, glucocorticoids, anticholinergics)

• Illicit drugs (eg, cannabis)

• Central nervous system (CNS) disorders, including infection (viral, bacterial, parasitic), tumors, demyelinating diseases, injury, seizures, or migraines

• Autoimmune disorders (eg, anti-NMDA [N-methyl-D-aspartate] receptor encephalitis [3], SLE)

• Endocrinopathies (eg, hyperthyroidism, hypocortisolemia)

• Sleep disorders

• Metabolic disorders (porphyria, Wilson disease, GM2 gangliosidosis)

• Mitochondrial disorders

• Lysosomal storage diseases

• Nutritional deficiencies (magnesium and vitamins A, D, B1, B3, B12)

• Chromosomal abnormalities (4-7)

The "multi-hit" model of schizophrenia posits that the disorder arises from the cumulative and interactive effects of multiple genetic, environmental, and developmental risk factors occurring at critical periods of neurodevelopment, which together exceed a threshold for disease expression, and ultimately result in the clinical syndrome (ie, manifestations) of schizophrenia (1). A strong family history confirmed by genetic studies shows an overlap of common risk-related alleles for psychiatric disorders and neurodevelopmental disorders, with schizophrenia having the greatest overlap with childhood onset neurodevelopmental disorders, autism spectrum disorder, and ADHD (2). While schizophrenia has high heritability, it is also associated with lower fecundity; such negative selection may result from de-novo mutations or unknown mechanisms (3).

Other risk factors, which occur later (eg, disproportionate synaptic pruning in the dorsolateral frontal cortex and hippocampus during early adolescence) may contribute to the emergence of psychoses, especially in youth. These risk factors (4, 5) may then trigger the onset of schizophrenia in the presence of risk factors such as acute stress and substance use that show up earlier in pathogenesis. In postmortem brain studies, patients with schizophrenia and bipolar disorder had fewer neuronal synapses and a higher number of mitochondrial copy deletions compared to controls) (6).

Childhood-onset (also called very early onset) schizophrenia usually presents with more severe symptoms than schizophrenia that occurs later in life. Hallucinations are more common than delusions. These are often auditory, accompanied by visual and tactile hallucinations. Manifestations of childhood-onset schizophrenia are usually similar to those in adolescents and adults, but delusions and visual hallucinations (which may be more common among children) may be less elaborate.

Additional characteristics also help distinguish childhood-onset schizophrenia from the adolescent/young adult form (1):

• More severe symptoms

• Increased prevalence of genetic abnormalities, developmental abnormalities (eg, pervasive developmental disorder, intellectual disability), and motor abnormalities

• Increased prevalence of premorbid social difficulties

• Insidious onset

• Cognitive deterioration or decline

• Neuroanatomic changes (progressive loss of cortical gray matter volume, increase in ventricular volume)

• Suicidal attempts

• Psychiatric assessment

• Diagnostic and Statistical Manual of Mental Disorders, Fifth edition, Text Revision (DSM-5-TR) criteria

Early onset, and especially, very early onset schizophrenia are rare diagnoses in children.

According to the DSM-5-TR (1), the diagnosis of schizophrenia in children and adolescents requires all of the following:

• Characteristic symptoms: ≥ 2 characteristic symptoms (delusions, hallucinations, disorganized speech, disorganized behavior, negative symptoms) for at least a 1-month period (symptoms must include at least 1 of the following: delusions, hallucinations, or disorganized speech)

• Social/occupational dysfunction: Decline in self care, social or occupational functioning, or self-care markedly below the level prior to onset (or a failure to achieve an expected level of functioning).

• Duration: Continuous signs of the illness for at least 6 months.

The same diagnostic criteria used in adults apply to children, but assessment must also exclude other psychiatric (eg, schizoaffective disorders, mood disorders with psychosis), developmental, and (organic) medical conditions. Because of the potential for misdiagnosis at onset, structured interviews with both the child and family, review of previous medical records, and longitudinal follow-up are essential components of the diagnosis.

• Multi-modal care

• Pharmacotherapy

Treatment of schizophrenia in children and adolescents often necessitates multi-modal care including a supportive environment, structured individualized educational programs, cognitive remediation therapy, social skills training (eg, individual resiliency training, supported education/employment), and pharmacotherapy (1). The rationale for this approach is to optimize both mental and physical health outcomes, minimize adverse effects, and support recovery through comprehensive care. Day treatment programs or hospitalization may be appropriate when behaviors that are dangerous to self or others are present. Substance abuse programs are important for individuals with substance use symptoms. Referral to a child and adolescent psychiatrist is strongly recommended.

Pharmacotherapy of schizophrenia in children and adolescents centers on the use of antipsychotic medications (2). Second-generation antipsychotics are considered first-line. These include aripiprazole, lurasidone, olanzapine, paliperidone, quetiapine, and risperidone, all of which are recommended for ages ≥ 13 years (). Second-generation antipsychotics are considered first-line. These include aripiprazole, lurasidone, olanzapine, paliperidone, quetiapine, and risperidone, all of which are recommended for ages ≥ 13 years (3). Medication selection should be individualized based on adverse effect profiles, patient and family preference, and logistical considerations (eg, cost, availability). Dosing generally follows a slow stepwise approach, with close monitoring for adverse effects. Antipsychotics have the potential to cause weight gain and metabolic syndrome; therefore, nutritional counseling and monitoring weight, BMI, lipid profile, and HbA1C are important. Monitoring for abnormal movements (AIMS scale) is also recommended (see Abnormal Involuntary Movement Scale in the American Academy of Child and Adolescent Psychiatry Toolbox of Forms).

Electroconvulsive therapy (ECT) can be an effective treatment; however, only limited studies have its safety and efficacy in children and adolescents (4). See table Selected Medications for Bipolar Disorder and Schizophrenia.

The prognosis of schizophrenia in children and adolescents is generally poor, with most patients experiencing persistent symptoms and significant functional impairment into adulthood (1). Early onset schizophrenia (prior to age 18) and very early childhood onset schizophrenia (prior to age 13) have been particularly associated with poor prognoses when compared to schizophrenia of adult onset. However, these findings are based on earlier studies, which were limited by small samples and methodological issues such as heterogeneity in study design. Data from subsequent studies are mixed, with some studies suggesting that onset before age 18 is not universally associated with poor outcomes. For example, in one 10-year longitudinal cohort study of early-onset schizophrenia, long-term functional outcomes were more favorable than previously thought, and age at onset did not predict clinical outcome (2). However, in another population-based longitudinal cohort, patients with an age of onset between 18 and 22 years had worse long-term social and clinical outcomes than those with onset before age 18 (3).

Successful long-term outcomes are dependent on continuous treatment engagement. In addition, successful transitioning from pediatric to adult care requires careful planning, early preparation, and collaboration between pediatric and adult clinicians (4).