Childhood-Onset Schizophrenia

Introduction

With symptom onset prior to 13 years of age, Childhood-onset schizophrenia (COS) is an exceptionally rare and devastating psychiatric condition, which clinically and neurobiologically resembles adult-onset schizophrenia (AOS). The etiology of schizophrenia largely remains unknown, but it is widely accepted that it is due to a combination of genetic predisposition and environmental influences. Earlier onset cases are more strongly influenced by genetic factors, less so by environmental causes, and are typically more severe in disease manifestation with an overall poorer prognosis. Because of the timing of onset and nature of the disease course, COS severely disrupts neurobiologic, cognitive, and social development, causing a significant burden of illness to the patient and the family.

From 1990 to 2017, the National Institute of Mental Health (NIMH) Child Psychiatry Branch (CPB) maintained the largest cohort of COS patients for longitudinal analysis, with inpatient observation available up to 2016. After referral and an extensive prescreen, which included a thorough records review, children and their parents underwent clinical and structural interviews. Ninety percent of prescreened patients were excluded. Patients who met inclusion criteria after screening were admitted to the NIMH inpatient unit where they participated in the inpatient phase of the study. This phase, frequently lasting up to 5 months, included observation, medication washout, diagnosis, and clinical stabilization phases.

Nearly 3500 pediatric patients were referred to the NIMH COS study. Sixty percent of those screened in person ultimately failed to meet criteria for schizophrenia. Of the 217 children admitted to the inpatient phase of the study, only 134 patients ultimately received a diagnosis of COS. Follow-up studies of COS and rule-out patients indicated excellent reliability of both the diagnosis of COS and the alternative diagnoses. Trauma, mood, anxiety, developmental, and/or behavioral disorders served as the most frequent alternative diagnoses.

Although COS is commonly associated with auditory hallucinations (94.9% of COS patients), hallucinations are neither necessary nor sufficient for the diagnosis, and diagnosis should not be based on positive symptoms alone. Hallucinations, delusions, and disordered thoughts can be seen in healthy, nonpsychotic children and typically diminish after 7 years of age. Transient visual hallucinations in preschool children are occasionally reported in conjunction with anxiety and stress, and the prognosis is generally benign. Because the prevalence of COS is so low, there is a very high probability that children presenting with hallucinations and delusions are suffering from something other than COS.

NIMH CPB researchers identified a heterogeneous subgroup of children who presented with transient psychotic symptoms and multiple developmental abnormalities. These children did not fit clearly into any existing DSM category and were ultimately referred to as “multidimensionally impaired” (MDI); the most fitting diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ( DSM-5 ) would be “psychosis not otherwise specified”. MDI patients often exhibit stress-related transient episodes of psychosis, emotional instability, impaired interpersonal skills, and information-processing deficits. This diagnostic category can be mistaken as COS and requires a multidisciplinary approach that includes physical therapy, occupational therapy, special education, and antipsychotic treatment.

Definition/Symptom Criteria

Schizophrenia, the prototype for psychotic disorders, is defined by delusions, hallucinations, disorganized thought, disorganized behavior, and/or negative symptoms. COS is neither differentiated from schizophrenia in the DSM-5 ( Table 17.1 ) nor distinguished in previous editions. In an effort to better obtain a homogenous cohort, the NIMH CPB established additional diagnostic criteria for COS to differentiate it from its later-onset counterparts, adolescent-onset and adult-onset schizophrenia:

• 1.

  Onset of psychotic symptoms before 13 years of age

• 2.

  Premorbid intelligence quotient (IQ) of 70 or above

• 3.

  Absence of significant neurologic problems

The DSM-5 definition of schizophrenia is demonstrated in Table 17.1 .

The DSM-5 did not radically alter the diagnostic criteria seen in the DSM-IV . Two changes have been made to Criterion A: (1) at least one of the two required symptoms has to be delusions, hallucinations, or disorganized thinking, and (2) bizarre delusions and special auditory hallucinations (Kurt Schneider’s first-rank symptoms in the DSM-IV ) are no longer given special consideration. Criterion F has also been altered, as pervasive developmental disorder (PDD) is now considered an autism spectrum disorder (ASD).

For schizophrenia, the majority of the changes between the two editions were seen in the dimensional categorization of symptoms and in the removal of the subtypes of schizophrenia (catatonic, disorganized, paranoid, residual, undifferentiated). Subtypes showed limited diagnostic stability, low reliability, and poor validity. The dimensional categories include delusions, hallucinations, negative symptoms, disorganized speech, cognitive impairment, motor symptoms (includes catatonia), depression, and mania. Dimensions that respond best to atypical antipsychotics are hallucinations, delusions, disorganized speech, and mania.

Despite changes in the new edition, 99.5% of patients in pre-DSM-5 clinical trials meet diagnostic criteria for schizophrenia in the DSM-5 , suggesting very little impact in the generalizability of previous research as well as in the diagnosis of schizophrenia. Many support omission of the classic subtypes of schizophrenia because of the lack of clinical value and variation in treatment response. Longitudinal studies also support the transition to a dimensional, rather than categoric, approach to psychosis.

Epidemiology

COS is an exceptionally rare psychiatric illness with an estimated incidence of less than 0.04% and a prevalence estimated between 1:30,000 and 1:40,000 children. Some studies report a COS prevalence of 1:10,000 and a prevalence of schizophrenia before the age of 15 years as 1.4:10,000. A nationwide population study in Denmark found a 1.9% prevalence rate of Early Onset Schizophrenia (EOS), higher than estimates in a Finnish study, suggesting that 4.7% of patients with schizophrenia have onset before the age of 19 years. Because of the rare nature of COS, large-scale prevalence studies based on standardized clinical assessments have not been performed. Psychotic symptoms, however, are relatively common in children—both healthy and with other psychiatric conditions—with prevalence reported up to 5%.

Screening/Diagnosis

An overall lack of systematic, evidence-based diagnostic tools and biologic markers of disease make diagnosing mental health disorders overall particularly challenging. The diagnosis of COS requires an extensive, longitudinal analysis of a patient’s clinical presentation and the incorporation of collateral information from family members, caretakers, teachers, and other members of the treatment team. Although developmental impairments are neither diagnostic nor reliable prodromal indicators of disease, they are frequently present in individuals being considered for a diagnosis of COS, and clinicians must be astute in assessing for them. Surprisingly, developmental abnormalities in language, social, and motor domains appear to be more significant in cases of COS with a later symptom onset.

Family dynamics, clinical severity, and the pressure of time to diagnose and treat children with psychotic illness are barriers to obtaining a valid, reliable diagnosis. When considering COS as a diagnosis, clinicians must not be blinded by the presence of hallucinations, as hallucinations are very common in children who are healthy, in those who have behavioral disturbances, and in various other psychiatric disorders.