Brief Report: Association of Sex Chromosome Anomalies With Childhood-Onset Psychotic Disorders

doi:10.1097/00004583-199803000-00014

Journal of the American Academy of Child & Adolescent Psychiatry

Volume 37, Issue 3, March 1998, Pages 292-296

https://doi.org/10.1097/00004583-199803000-00014 Get rights and content

ABSTRACT

Objective

An apparent excess of sex chromosome aneuploidies (XXY, XXX, and possibly XYY) has been reported in patients with adult-onset schizophrenia and with unspecified psychoses. This study describes the results of cytogenetic screening carried out for pediatric patients meeting DSM-III-R criteria for childhood-onset schizophrenia (COS) and a subgroup of patients with childhood-onset psychotic disorder not otherwise specified, provisionally labeled by the authors as multidimensionally impaired (MDI).

Method

From August 1990 to July 1997, karyotypes were determined for 66 neuroleptic-nonresponsive pediatric patients (28 MDI, 38 COS), referred to the National Institute of Mental Health for an inpatient treatment trial of clozapine.

Results

Four (6.1%) of 66 patients (3 MDI, 1 COS) were found to have sex chromosome anomalies (mosaic 47,XXY; 47,XXY; 47,XYY; mosaic 45,XO, respectively), which is higher than the expected rate of 1 per 426 children or 2.34 per 1,000 in the general population (4/66 versus 1/426, X² = 19.2, df= 1, p = .00001). All cases had been previously undiagnosed.

Conclusions

These findings lend support to a hypothesis that a loss of balance of gene products on the sex chromosomes may predispose affected individuals to susceptibility to additional genetic and environmental insults that result in childhood-onset psychotic disorders. Karyotyping of children with psychotic disorders should be routine. J. Am. Acad. Child Adolesc. Psychiatry, 1998, 37(3):292–296.

REFERENCES (22)

J Alaghband-Rad et al.
Early-onset schizophrenia: mental retardation in siblings (letter)
J Am Acad Child Adolesc Pychiatry
(1998)
J Alaghband-Rad et al.
Childhood-onset schizophrenia: the severity of premorbid course
J Am Acad Child Adolesc Psychiatry
(1995)
TJ Crow
Sexual selection, Machiavellian intelligence, and the origins of psychosis
Lancet
(1993)
S Kumra et al.
“Multidimensionally impaired disorder”: is it a variant of very early-onset schizophrenia?
J Am Acad Child Adolcsc Pychiatry
(1998)
K McKenna et al.
Looking for childhood-onset schizophrenia: the first 71 cases screened
J Am Acad Child Adolcsc Psychiatry
(1994)
G Turner
Intelligence and the X chromosome
Lancer
(1996)
BG Bender et al.
Verbal and spatial processing efficiency in 32 children with sex chromosome abnormalities
Pediatr
(1989)
BG Bender et al.
Environment and developmental risk in children with sex chromosome abnormalities
J Am Acad Child Adolesc Psychiatry
(1996)
LE DeLisi et al.
Schizophrenia and sex chromosome anomalies
Schizophr Bull
(1994)
P Franke et al.
Fragile-X carrier females: evidence for a distinct psychopathological phenotype?
Am J Med Genet
(1996)

CT Gordon et al.

Brief report: translocation involving chromosomes 1 and 7 in a boy with childhood-onset schizophrenia

J Autism Dev Disord

(1994)

Cited by (40)

"Autism-plus" Spectrum Disorders. Intersection with Psychosis and the Schizophrenia Spectrum.
2013, Child and Adolescent Psychiatric Clinics of North America
Citation Excerpt :
They also had no evidence of formal thought disorder. These patients were initially labeled as having MDI syndrome,48,65,66,73 although later reports identified their diagnosis as psychotic disorder not otherwise specified67–72,74 (See article in this issue by Driver, Gogtay, and Rapoport: Childhood Onset Schizophrenia and Early Onset Schizophrenia Spectrum Disorders). Although the NIMH researchers did not consider these individuals to be associated with ASDs,48 the surface resemblance of domains of dysfunction in MDI compared with MCDD is striking (see Table 1).
Cryoglobulins as indicators of upregulated immune response in schizophrenia
2008, Clinical Biochemistry
In the present work the concentration of abnormal immune complexes, cryoglobulins (Cgs), in the blood of schizophrenic patients was determined, and immunochemical composition of these complexes was studied.
Eighty multiple-episode schizophrenia-affected subjects (55 medicated, 25 drug-free) and 40 healthy controls were involved in the study. Cgs were isolated by exposure of blood serum samples to precipitation at low temperature followed by extensive washings of Cg-enriched pellets. The immunochemical composition of Cgs was analyzed using different electrophoretic and immunoblotting systems.
Significantly increased blood serum levels of type III Cgs were detected in all schizophrenia-affected subjects, as compared to controls. We also revealed the presence of C1q and C3 complement proteins and their activation products in Cgs isolated from the blood of schizophrenic patients.
The results of the present study suggest that Cgs are involved in schizophrenia-associated upregulated immune response by binding the complement proteins, activating the complement cascade and triggering aberrant apoptosis.
Fragile X syndrome and very early onset schizophrenia: A female case study
2005, Archives de Pediatrie
L'étude du phénotype psychopathologique des femmes adultes porteuses de la mutation et de la prémutation pour l'X fragile suggère l'existence d'une association préférentielle avec le spectre schizo-affectif. Chez l'enfant, seuls quelques traits comportementaux et non des troubles mentaux définis par des critères diagnostiques consensuels, ont été étudiés parmi les filles porteuses de la mutation complète. C'est pourquoi, la coexistence d'une mutation complète pour l'X fragile avec une schizophrénie à début très précoce chez une fille de neuf ans, dont la mère est porteuse de la prémutation pour l'X fragile et d'une personnalité pathologique schizotypique, nous a paru intéressante à rapporter. Cette association entre le syndrome de l'X fragile et le spectre schizophrénique pourrait avoir d'importantes implications dans la compréhension de la génétique de la schizophrénie, comme du phénotype psychopathologique du syndrome de l'X fragile.
Genotype-phenotype relationship studies for psychiatric disorders in females carrying fragile X syndrome full mutation and premutation underline association with schizo-affective disorders. In female children with X fragile full mutation, only behavioural symptoms and no standardised psychiatric disorders have been systematically explored. Therefore, we report the case of a nine-year-old girl carrying the fragile X syndrome full mutation with a comorbid childhood onset schizophrenia (COS), and of her mother carrying the fragile X syndrome premutation and a comorbid schizotypal personality disorder. The impact of these associations is discussed regarding the recent literature in chromosome anomalies in COS.
Cytogenetic Abnormalities in Attention-Deficit/Hyperactivity Disorder
2002, Journal of the American Academy of Child and Adolescent Psychiatry
To systematically assess the prevalence of fragile X syndrome, velocardiofacial syndrome, and other cytogenetic abnormalities in a group of children with attention-deficit/hyperactivity disorder (ADHD).
Blood samples were obtained from 100 children (64 boys) with combined type ADHD and normal intelligence and analyzed for the presence of fragile X mutation expansions, the 22q11.2 microdeletion associated with velocardiofacial syndrome, and cytogenetic abnormalities that would be detected with high resolution chromosomal banding.
One girl with ADHD had a sex chromosome aneuploidy (47,XXX). One boy had a premutation-sized allele for fragile X; no subjects showed the full mutation. Testing for 22q11.2 microdeletion was negative for all subjects with ADHD screened. None of these differences exceeded those expected by chance.
In the absence of clinical signs or positive family history, these relatively expensive laboratory assessments are not clinically indicated for children with ADHD and normal intelligence, and are not recommended as a component of other genetic investigations of this disorder.
Karyotype analysis of 161 unrelated schizophrenics: No increased rates of X chromosome mosaicism or inv(9), using ethnically matched and age-stratified controls
2001, Schizophrenia Research
Chromosomal aberrations have long been studied in an effort to identify susceptibility genes in schizophrenia. The two most frequently detected abnormalities are X chromosome mosaicism in female patients and pericentric inversions of chromosome 9 [inv(9)]. Chromosome X aneuploidies are known to be age dependent but differences due to ethnicity remain undetermined. In the case of inv(9), its prevalence in the general population varies with ethnicity. To evaluate the importance of these karyotypic changes in schizophrenia, cytogenetic analysis was performed on 161 unrelated schizophrenics of Japanese origin. We observed an increase in the incidence of X chromosome mosaicism in female schizophrenics with age. However, when compared with age matched female controls (92 individuals), no significant differences between patient and control samples were detected. Moreover, this study showed that there is no significant difference in the incidence of X chromosome loss between Japanese and Caucasian populations. The four cases with inv(9) (2.5%) detected in this study, did not differ significantly from the reported incidence of between 1.7 and 2.1% seen in the general Japanese population. We also observed a small number of additional karyotypic changes, none of which were recurrent. This is the first report to examine the comparative rates of X mosaicism in female schizophrenics and age matched controls.
Psychological features
2020, Trends in Andrology and Sexual Medicine

View all citing articles on Scopus

: The authors thank Drs. Bruce Bender and Stanley Walzer for their suggestions.

View full text

ARTICLESBrief Report: Association of Sex Chromosome Anomalies With Childhood-Onset Psychotic Disorders

ABSTRACT

Objective

Method

Results

Conclusions

J Am Acad Child Adolesc Pychiatry

J Am Acad Child Adolesc Psychiatry

Lancet

J Am Acad Child Adolcsc Pychiatry

J Am Acad Child Adolcsc Psychiatry

Lancer

Verbal and spatial processing efficiency in 32 children with sex chromosome abnormalities

Pediatr

Environment and developmental risk in children with sex chromosome abnormalities

J Am Acad Child Adolesc Psychiatry

Schizophrenia and sex chromosome anomalies

Schizophr Bull

Fragile-X carrier females: evidence for a distinct psychopathological phenotype?

Am J Med Genet

Brief report: translocation involving chromosomes 1 and 7 in a boy with childhood-onset schizophrenia

J Autism Dev Disord

ARTICLES
Brief Report: Association of Sex Chromosome Anomalies With Childhood-Onset Psychotic Disorders