Ignite Creation Date:
2024-05-05 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00161109
Status:
UNKNOWN
Last Update Posted:
2006-10-13
First Post:
2005-09-08
Brief Title:
Genetics and Psychopathology in the 22q11 Deletion Syndrome
Sponsor:
UMC Utrecht
Organization:
UMC Utrecht
Study Overview
Official Title:
Genetics and Psychopathology in the 22q11 Deletion Syndrome
Status:
UNKNOWN
Status Verified Date:
2004-10
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purposes of this study are to
1 study the nature and longitudinal course of psychiatric symptoms in children with the 22q112 deletion syndrome and
2 identify genes that contribute to the occurrence of these symptoms
1 study the nature and longitudinal course of psychiatric symptoms in children with the 22q112 deletion syndrome and
2 identify genes that contribute to the occurrence of these symptoms
Detailed Description:
The study of genes that are implicated in various mental diseases is increasingly relevant The association between a gene and a disease can provide valuable information on how the neurobiology of the brain is altered by studying the function of the protein encoded by the gene This information is important for the development of new treatments
However the identification of these disease genes is difficult due to the complexity of human behavior and the interaction of multiple genes Moreover the human genome consists of approximately 35000 genes further complicating the matter
The situation is simplified when a psychiatric disorder and a genetic anomaly co-occur assuming a causative relation one can focus on the implicated genetic region
The 22q11-deletion syndrome 22q11DS is an example of this type this syndrome is caused by a disappearance deletion of 20-30 genes in a well-defined region on chromosome 22 People with 22q11DS have a high risk of autism and psychosis therefore one or more genes in the 22q11DS region must be associated with these disorders
In this study we aim to identify these genes by carefully studying psychiatric symptoms and additional parameters of brain functioning in a large sample of 22q11DS children and subsequently statistically correlate these findings to specific genes within the 22q11DS region If genes associated with autism andor psychosis in the 22q11DS population can be found they may help to understand the underlying neurobiology that cause these diseases not only in 22q11DS patients but in the general population as well
The aims of this study are
1 STUDY NATURE AND DEVELOPMENTAL COURSE OF PSYCHIATRIC SYMPTOMS To perform a prospective longitudinal follow up study of a sample of children with the 22q112 deletion syndrome with specific attention to a possible predictors for psychosis in psychiatric and neuropsychological profile and b a possible correlation between autistic symptoms and psychosis
2 ASSESS THE CORRELATION OF 22q112 DELETIONS WITH THE PSYCHOSIS AUTISTIC PHENOTYPE AND ASSOCIATED ENDOPHENOTYPES To evaluate whether the size of the deletion and or polymorphisms at selected candidate genes within the 22q112 deleted region contribute to the psychosis and or autistic phenotype or to related psychophysiologic neuropsychological impairments in 22q11DS
METHODS
With regard to aim 1
A large sample a final sample size of 100-120 is anticipated of children with 22q11DS aged 10 - 20 year is broadly phenotyped using standard psychiatric assessment methods intelligence and selected neuropsychological tests as well as psychophysiological assessments Approximately 4 years after the initial assessment a follow up assessment is planned Age and IQ matched children without the deletion or any other apparent genetic abnormality are used as a control group
With regard to aim 2
Phenotypes Individuals with a certain endophenotype cases eg the presence of autistic symptoms or a decreased Pre Pulse Inhibition or impaired performance on executive tasks will be compared to children without that particular phenotype controls
Genetic analysis
Genotyping consists of
1 assessment of the size of the deletion and
2 genotyping single nucleotide polymorphisms SNPs across the deleted genomic region Genotyping will be performed using approximately 75 previously characterized SNPs with an increased density of SNPs in the target candidate genes 3-5 SNPs per candidate gene In order to determine whether a haplotype andor variants of genes within region 22q112 contribute to the autistic phenotype and related neuro-psychological impairments in patients with the deletion we will identify DNA polymorphisms using existing databases We will then genotype patients with the 22q112 deletion for the selected polymorphisms and compare the allele frequencies and haplotype combinations in 22q11DS patients with the phenotype cases to those deleted patients without these findings controls applying chi-square Fishers exact test and other statistical genetic methods as appropriate
However the identification of these disease genes is difficult due to the complexity of human behavior and the interaction of multiple genes Moreover the human genome consists of approximately 35000 genes further complicating the matter
The situation is simplified when a psychiatric disorder and a genetic anomaly co-occur assuming a causative relation one can focus on the implicated genetic region
The 22q11-deletion syndrome 22q11DS is an example of this type this syndrome is caused by a disappearance deletion of 20-30 genes in a well-defined region on chromosome 22 People with 22q11DS have a high risk of autism and psychosis therefore one or more genes in the 22q11DS region must be associated with these disorders
In this study we aim to identify these genes by carefully studying psychiatric symptoms and additional parameters of brain functioning in a large sample of 22q11DS children and subsequently statistically correlate these findings to specific genes within the 22q11DS region If genes associated with autism andor psychosis in the 22q11DS population can be found they may help to understand the underlying neurobiology that cause these diseases not only in 22q11DS patients but in the general population as well
The aims of this study are
1 STUDY NATURE AND DEVELOPMENTAL COURSE OF PSYCHIATRIC SYMPTOMS To perform a prospective longitudinal follow up study of a sample of children with the 22q112 deletion syndrome with specific attention to a possible predictors for psychosis in psychiatric and neuropsychological profile and b a possible correlation between autistic symptoms and psychosis
2 ASSESS THE CORRELATION OF 22q112 DELETIONS WITH THE PSYCHOSIS AUTISTIC PHENOTYPE AND ASSOCIATED ENDOPHENOTYPES To evaluate whether the size of the deletion and or polymorphisms at selected candidate genes within the 22q112 deleted region contribute to the psychosis and or autistic phenotype or to related psychophysiologic neuropsychological impairments in 22q11DS
METHODS
With regard to aim 1
A large sample a final sample size of 100-120 is anticipated of children with 22q11DS aged 10 - 20 year is broadly phenotyped using standard psychiatric assessment methods intelligence and selected neuropsychological tests as well as psychophysiological assessments Approximately 4 years after the initial assessment a follow up assessment is planned Age and IQ matched children without the deletion or any other apparent genetic abnormality are used as a control group
With regard to aim 2
Phenotypes Individuals with a certain endophenotype cases eg the presence of autistic symptoms or a decreased Pre Pulse Inhibition or impaired performance on executive tasks will be compared to children without that particular phenotype controls
Genetic analysis
Genotyping consists of
1 assessment of the size of the deletion and
2 genotyping single nucleotide polymorphisms SNPs across the deleted genomic region Genotyping will be performed using approximately 75 previously characterized SNPs with an increased density of SNPs in the target candidate genes 3-5 SNPs per candidate gene In order to determine whether a haplotype andor variants of genes within region 22q112 contribute to the autistic phenotype and related neuro-psychological impairments in patients with the deletion we will identify DNA polymorphisms using existing databases We will then genotype patients with the 22q112 deletion for the selected polymorphisms and compare the allele frequencies and haplotype combinations in 22q11DS patients with the phenotype cases to those deleted patients without these findings controls applying chi-square Fishers exact test and other statistical genetic methods as appropriate
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None