by Leslie B. Knowlton
Psychiatric Times March 1995 Vol. XII Issue 3
Although schizophrenia has been described in children as young as 5 years, little systematic research has focused on the childhood onset and its treatment. Many clinicians misdiagnose it.
So reported Judith L. Rapoport, M.D., at the 41st annual meeting of the American Academy of Child and Adolescent Psychiatry (AACAP) in New York City.
Rapoport said one major impediment to research and diagnosis of childhood-onset schizophrenia has been its rarity, believed to have about one-sixtieth of the prevalence of the adult disorder.
Another has been the broad or unspecified criteria for childhood psychosis, which grouped schizophrenic subjects and patients with those afflicted by other problems including autism, organic mental disorders, borderline disorders and major affective disorders.
"Children have long been observed to exhibit symptoms similar to those of adults with schizophrenia," said Rapoport. "However, not only do the nature and content of symptoms vary with age, but a variety of other severe psychiatric conditions of childhood have symptoms that overlap with those of schizophrenia. The diagnosis remains confusing."
Drug treatment for children with the disease has also been problematic, she added, because there have been few controlled studies of neuroleptics on children or adolescents.
Those that have been done documented young persons' susceptibility to adverse effects-including tardive dyskinesia and withdrawal dyskinesias-and indicated only partial responsiveness.
"And when new drugs come out, the boiler-plate says 'not for children,' making children therapeutic orphans," said Rapoport. "So it's important to test drugs on this population."
Rapoport, chief of the child psychiatry branch of the National Institute of Mental Health in Bethesda, Md., has coauthored several articles on childhood-onset schizophrenia. Currently, she is working on an ongoing NIMH study that seeks biological correlates of the disorder-including phenomenology, genetics, neuropsychology, physiology, neuroimaging and biochemistry.
"Schizophrenia as defined in the DSM-III-R requires that the frequency and severity of symptoms such as hallucinations and delusions be present a significant portion of time," Rapoport said. "But this may not be readily ascertainable in children, and there are not agreed-upon standards for rating their pervasiveness in this population. We are trying to address these issues."
The study, which began about five years ago, also seeks to understand variability in age of disease onset.
Rapoport said, "Schizophrenia in adults is almost certainly a heterogeneous disorder with both genetic and environmental factors playing etiologic roles. Variability in age at onset has long been noted, but nothing is known about the cause of this variability, with no data confirming or refuting etiological continuity of childhood-onset and later-onset schizophrenia."
And if there is etiological continuity, said Rapoport, then systematic study of the childhood-onset subgroup may reveal even more marked and consistent neurobiological findings than adult studies. Why? Because earlier onset might result from a "heavier genetic load or a more potent environmental insult," she said. "And such genetic and environmental insults would likely result in more consistent findings in very young patients for whom there is less confounding by institutionalization, chronic neuroleptic treatment and substance abuse as compared to adult patients."
Additionally, the NIMH study is testing the drug clozapine (Clozaril), which has been demonstrated to be effective in 30 percent to 50 percent of treatment-resistant adult patients.
"Before our work, there had been no controlled studies of clozapine in schizophrenic children," Rapoport said.
The NIMH project thus far has screened more than 500 charts and interviewed more than 100 patients from 6 to 18 years old. Subjects-who were nationally recruited through the AACAP and the National Alliance of the Mentally Ill-were included on the basis of the DSM-III-R criteria for schizophrenia with onset of psychosis prior to age 12, with a full-scale IQ of 70 or greater. Preliminary pilot data has been completed on 23 subjects, with the following results:
Phenomenology. All subjects had severe and persistent delusions and hallucinations, and all but two had formal thought disorder. As in adults, both positive and negative symptoms were very frequent.
Genetics. About 17 percent of the patient's families had first-degree relatives with nonaffective psychotic disorders.
Smooth pursuit eye movement (SPEM). Results are similar to findings in adult schizophrenics and consistent with etiologic continuity between childhood-onset and later-onset forms of the illness.
Autonomic responsivity. Results were qualitatively similar to those obtained with adult subjects but showed a higher degree of consistency.
Magnetic resonance imaging. Subjects had an 8 percent smaller total brain volume and a larger ventricular volume than normal controls.
Clozapine. A six-week, double-blind trial using haloperidol (Haldol) and clozapine revealed a 58 percent improvement in positive symptoms and a 42 percent improvement in negative symptoms. Fifty-six percent of patients who received haloperidol and then clozapine showed a greater than 30 percent improvement in their Brief Psychiatric Rating Scale scores while taking clozapine. The drug was well-tolerated, and side effects were similar to those seen in adults, although there is some evidence of a slightly greater risk of agranulocytosis.
"The bottom line," Rapoport said, "is that very early-onset schizophrenia looks very much the same as adult onset by all patterns you can name. There also appears to be a bigger hit in the early onset as evidenced by things like more chronic unremitting course, poor early language development and in some regions, more abnormal magnetic resonance imaging."
The finding that clozapine can be "dramatically effective" is clinically very important, Rapoport added.
"Our group represents the largest systematically studied and homogenous group of schizophrenic children and adolescents treated with clozapine to date," she said. "The study supports the efficacy in schizophrenic adolescents that has been so well-documented in controlled trials with adults.
"Even though for the present," Rapoport cautioned, "clozapine appears to be promising for selected severely ill schizophrenic children, long-term monitoring is needed. Ultimately, other atypical neuroleptics without the adverse effects of clozapine will be developed for long-term use."