When Schizophrenia Develops Early, Impairment Often More Severe

Youth with schizophrenia spectrum disorders have symptom profiles similar to, but more severe than, adults with schizophrenia.

A multicenter study of children with schizophrenia, schizoaffective disorder, and schizophreniform disorder revealed that they have very significant social and functional impairment and are liable to have had a range of psychiatric diagnoses prior to being diagnosed with a schizophrenia spectrum disorder.

Lead author Jean Frazier, M.D., told Psychiatric News that the study, which is reported in the August Journal of the American Academy of Child and Adolescent Psychiatry, provides the largest formal study of the demographic and clinical characteristics of this rare cohort of patients. Schizophrenia onset prior to age 18 occurs in approximately 0.5 percent of adolescents; very early onset (prior to age 13) occurs in 0.002 percent (or 2 per 100,000).

She said the severity of impairment revealed by the study confirms long-held clinical impressions.

“Our youths showed more impairment than what is described in the literature on adults with schizophrenia,” Frazier said. “They had significantly worse symptoms and greater functional and social impairment.”

These impairments included social, academic, and behavioral problems in school; a history of aggression and legal problems; prior hospitalizations; and a history of suicide attempts.

Frazier said that early-onset schizophrenia spectrum disorders (EOSS) in children share clinical features with other psychiatric disorders; that is, many of the children in the study had received previous diagnoses such as ADHD, major depression, and bipolar disorder and had been prescribed multiple psychotropic medications.

“The study highlights the need for a thorough evaluation by a clinician well trained in early identification of early-onset schizophrenia due to the challenges of making an accurate diagnosis.”

Early Diagnosis Means Early Treatment

Frazier also noted that the data from this study, combined with the use of structured rating instruments, can help clinicians identify those children with EOSS disorder. “A systematic approach to diagnosis and treatment should lead to more timely initiation of appropriate treatment and improved outcome,” Frazier told Psychiatric News.

She is director of the child and adolescent neuropsychiatric research program and director of child psychopharmacology, as well as co-director of the Center for Child and Adolescent Development at Cambridge Health Alliance at Harvard Medical School.

In the study, “Treatment of Early-Onset Schizophrenia Spectrum Disorders,” 119 youth with schizophrenia, schizoaffective disorder, or schizophreniform disorder were recruited at four academic sites—the University of Washington, Case Western Reserve University School of Medicine, University of North Carolina School of Medicine, and Cambridge Heath Alliance at Harvard Medical School.

The study was funded by the National Institute of Mental Health.

Subjects had to be aged 8 to 19 and had to score at least“ moderate” on one or more of the key psychosis items of the Positive and Negative Syndrome Scale (PANSS) or the Brief Psychiatric Rating Scale for Children (BPRS-C). The structured Clinical Interview for DSM-IV, Childhood Diagnoses (KID-SCID) was used to exclude other diagnoses, and children with active substance abuse were excluded.

The EOSS diagnosis was made by a board-certified or board-eligible child and adolescent psychiatrist at each site based on clinical interview, a review of records, and the KID-SCID. The mean age at enrollment was 13.

Here are some key findings from the study:

Frazier noted that one goal of the study was to compare characteristics of children with schizophrenia with those of children who have schizoaffective disorder. She and colleagues found that functional and social impairments were similar in both groups, though youth with schizophrenia had significantly poorer rapport as measured by the PANSS; children with schizoaffective disorder reported significantly more depressive symptoms on the BPRS-C.

“Early identification of these children is important, but it appears to be less important to distinguish schizophrenia from schizoaffective disorder due to the fact that they are so similar,” she said.

Among the most striking findings from the study, Frazier said, was the severity of impairment compared with adults with schizophrenia. To compare the symptom and functional profiles of the EOSS sample with those of adults suffering from the illness, Frazier and colleagues used PubMed to search for studies of adults with first-episode schizophrenia published within the past 10 years that included ratings on the PANSS, Clinical Global Impression-Severity (CGI-S), or Children's Global Assessment Scale.

They found that youth with EOSS had significantly worse overall ratings on the PANSS and on the CGI-S than reported in the literature on adults.

Frazier noted that forthcoming results from the same study will report the efficacy of treatment of youngsters with the antipsychotics olanzapine and risperidone.

“This is important because we typically base prescriptive practice on treatment studies done in adult populations,” she said. “Yet these studies typically fall short because kids are not small adults, and they respond differently to medication.

“Not only do youth with schizophrenia spectrum disorders benefit from medication but they also benefit from psychoeducation, educational support, vocational training, family and psychotherapeutic interventions, and substance abuse treatment,” Frazier said.

Development Can Complicate Diagnosis

In addition to the fact that children with EOSS can have symptoms of other psychiatric illnesses, the relative rarity of the disorder may cause clinicians to think of more common diagnoses before considering EOSS. Moreover, some of the prominent symptoms these children display—such as social withdrawal and inattention—can be nonspecific to EOSS.

In addition, there are developmental factors that complicate the diagnosis of EOSS. For instance, children are normally expected to have a rich fantasy life, but youth with EOSS have thought content that goes well beyond what is normally expected, Frazier said.

She said that children with EOSS display a gradual progression that begins in infancy with a broad spectrum of nonspecific dysfunction. By preschool, there is likely to be concern on the part of parents and teachers that something is wrong, and by school age these children will display social, behavioral and attentional impairments.

“As they grow a little older, they develop psychosis,” Frazier said. She cited a March 2002 report in JAACAP describing a diagnostic pathway to early-onset schizophrenia that typically began with a diagnosis of ADHD, then bipolar disorder, and finally schizophrenia.

Frazier noted that in that sample it was only child psychiatrists who made the distinguishing diagnosis of early-onset schizophrenia. “The important thing about our study is that it should heighten awareness that these children do exist,” she said. “Clinicians generally understand that you can have schizophrenia prior to the age of 18, but education on how to look for it and assess it is important.”

An abstract of “Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics” is posted at<www.jaacap.com/pt/re/jaacap/abstract.00004583-200708000-00009.htm>.▪