Pervasive developmental disorder and childhood-onset schizophrenia: comorbid disorder or a phenotypic variant of a very early onset illness?

doi:10.1016/j.biopsych.2004.01.019

Biological Psychiatry

Volume 55, Issue 10, 15 May 2004, Pages 989-994

https://doi.org/10.1016/j.biopsych.2004.01.019 Get rights and content

Abstract

Background

Childhood-onset schizophrenia (COS) is a severe form of the adult-onset disorder with a high rate of premorbid developmental abnormalities. Early symptoms of pervasive developmental disorder (PDD) have been reported in five independent studies of COS. In this study, we compared evidence for premorbid PDD as a nonspecific manifestation of impaired neurodevelopment seen in schizophrenia, or as an independent risk factor for COS.

Methods

Diagnosis of past or current autism or PDD was made according to the DSM-IV criteria. COS patients with and without PDD were compared with respect to neuropsychological, clinical, and neurobiological measures. Several candidate genes for autism were examined in the entire COS sample and the subgroup with PDD using the Transmission Disequilibrium Test (TDT) and Quantitative TDT (QTDT).

Results

Nineteen (25%) of COS probands had a lifetime diagnosis of PDD: one met criteria for autism, two for Asperger's disorder, and 16 for PDD not otherwise specified. Premorbid social impairment was most common feature for COS-PDD subjects. The PDD group did not differ from the rest of the COS sample with respect to age of onset, IQ, response to medications, and rate of familial schizotypy. Unexpectedly, two siblings of COS-PDD probands met criteria for nuclear autism. There was no difference between PDD and non-PDD groups with respect to initial brain magnetic resonance imaging (MRI) measures. However, rate of gray matter loss was greater for PDD (n = 12) than for the non-PDD (n = 27) subgroup (−19.5 ± 11.3 mL/year vs. −9.6 ± 15.3 mL/year; p = .05). None of eight candidate genes for autism were associated with COS or COS-PDD.

Conclusions

Premorbid PDD in COS is more likely to be a nonspecific marker of severe early abnormal neurodevelopment. However, the occurrence of two siblings of COS-PDD probands (17%) with nuclear autism remains to be understood.

Section snippets

Subjects

Accrual of subjects for the NIMH childhood-onset schizophrenia study has been described elsewhere (Nicolson and Rapoport 1999). Briefly, children ages 6–18 meeting DSM-III-R/DSM-IV criteria for schizophrenia with onset of psychosis before their 13th birthday were recruited nationally. Diagnostic process was extensive and included detailed review of medical and school records and full-day, in-person interviews with children and their parents using the Schedule for Affective Disorders and

Results

Of 75 COS probands, 19 had a lifetime diagnosis of PDD (25%), of whom 1 met criteria for autism (past and current), 2 for Asperger's disorder (past and current), and 16 for PDD not otherwise specified. Demographic and clinical data for COS patients with and without PDD are presented in Table 2.

In 12 of 19 cases (63%), the diagnosis of PDD was made before patients entered the NIMH study. In most cases (15 of 19; 79%), PDD symptoms had been present before age 3 years; however, four patients had

Discussion

Counter to our expectations, a comorbid lifetime diagnosis of PDD or autism did not predict early age of onset, lower cognitive performance, or poor long-term outcome. In addition, COS-PDD subgroup did not differ from the rest of the COS sample on any of the clinical and neuropsychological measures. Thus, our clinical data do not support a prediction that an autistic subgroup has a unique clinical pattern.

Neurobiologically, the data are complex. The predicted profile of brain abnormalities

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Original articlePervasive developmental disorder and childhood-onset schizophrenia: comorbid disorder or a phenotypic variant of a very early onset illness?

Abstract

Background

Methods

Results

Conclusions

Section snippets

Subjects

Results

Discussion

J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

Biol Psychiatry

J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

Biol Psychiatry

J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

Biol Psychiatry

Diagnostic and Statistical Manual of Mental Disorders

Scale for the Assessment of Negative Symptoms

Scale for the Assessment of Positive Symptoms

Children with schizophrenia spectrum and depressive disorders: a comparative study of premorbid adjustment, onset pattern and severity of impairment

Childhood-onset schizophreniaEditors' introduction

Schizophr Bull

Autism screening questionnaireDiagnostic validity

Br J Psychiatry

Measurement of premorbid adjustment in chronic schizophrenia

Schizophr Bull

Childhood schizophreniaPresent but not accounted for

Am J Psychiatry

Pervasive developmental disorders and psychoses in adult life

Br J Psychiatry

Evidence of brain overgrowth in the first year of life in autism

JAMA

Unusual brain growth patterns in early life in patients with autistic disorderAn MRI study

Neurology

A diagnostic interviewThe schedule for affective disorders and schizophrenia

Arch Gen Psychiatry

Brain development during childhood and adolescenceA longitudinal MRI study

Nat Neurosci

Clinical Global Impressions, ECDEU Assessment Manual for Psychopharmacology

Schizophrenia with childhood onset: a phenomenological study of 38 cases

Original article
Pervasive developmental disorder and childhood-onset schizophrenia: comorbid disorder or a phenotypic variant of a very early onset illness?