An interventional study of genetic and phenotypic profile in Schizophrenia and Dissociative Disorders, sponsored by Fondation Lenval. Completed at 1 site in France. Open to participants aged 7 Years to 18 Years. Per ClinicalTrials.gov, last updated 2023-09-29.
Sponsored by Fondation Lenval · Not applicable, Interventional, and Diagnostic
Early onset schizophrenia "early dissociative disorder" is a rare disorder with a low incidence of approximately (1/5000 to 1/20000). Its link with autism spectrum disorders remains unknown although both are serious neurodevelopmental diseases. As part of the 2011-2013 Interregional hospital Clinical Research program, University Department of Child and Adolescent Psychiatry Pediatric Hospitals of CHU de Nice Lenval identified patients with a complex phenotype characterized by an early schizophrenia associated with autism spectrum disorders and developmental disabilities in mild to moderate. This phenotype could be a new syndrome.
The goal of our project is to define the genetic causes of this phenotype. The technique of high throughput sequencing will be used to obtain the sequence of exomes of these patients and their families. This study will therefore be important to give an accurate diagnosis for patients and their families. Moreover, we believe that this project will identify new genes involved allowing a better understanding of the pathophysiology. Recent studies show the involvement of mutations in several genes (eg NRXN1 and UPF3B) in these different clinical phenotypes. However, the genetic basis of the childhood and early onset schizophrenia are much less well known than those of autism spectrum disorder
Introduction: Early-onset Schizophrenia (EOS) is a rare and severe condition displaying early dissociative disorder (i.e., age of onset \< 18 years). A higher rate of neurodevelopmental abnormalities is observed in EOS compared to adult onset schizophrenia (AOS). Thus, patients affected by EOS typically present intellectual, learning, communication or neuromotor impairments, as well as attention deficit hyperactivity disorder. Early signs of autism spectrum disorders (ASD) are also found in 30% of patients with EOS.
Cytogenetics abnormalities, including copy number variations (CNVs), are frequent in neurodevelopmental disorders and have been linked to ASD physiopathology. Implicated genes encode proteins playing a role in brain development, synaptic morphology, plasticity and neurogenesis. In addition, an increasing number of genetic abnormalities are shared by EOS and ASD, suggesting that schizophrenia can be considered a neurodevelopmental disorder.
The main objective of the present study is to identify mutations in genes involved in neurodevelopmental pathways in our cohort of patients affected by both EOS and ASD.
Method and analysis: We describe here a multicenter study in a pediatric population named "Exploration and characterization of genetic and phenotypic profile of the 'early dissociative disorder' associated with autism spectrum disorder (GenAuDiss)". The study started in April 2014. The inclusion criteria are: age 7 to 22 years, diagnoses of EOS with co-morbid ASD and IQ > 50; as well as parents and siblings of the included patients.
We perform standardized psychiatric assessments (MINI, K-SADS-PL, PANSS, SANS, TCI 226, and AQ) and neurocognitive evaluations (IQ, TMT A/B, and verbal fluency). Then, we study variants of the coding part of the DNA (exome), using next generation sequencing (NGS) process on trio (mother, father, and child). Divers bio-informatics tools such as RVIS and PolyPhen-2 will be used to prioritize the potential candidate genes. The inclusion period of this study will end in November 2019.
Ethics and dissemination: The study protocol was approved by the Ethics Committee 'Sud Méditerrané V' (number 14.002) and by the French National Agency for Medicines and Health Products Safety (ANSM 2013-A01699-36). All patients, their parents and siblings signed informed consent upon enrolment in the study.
Results of the present study should help to unravel the molecular pathology of EOS, paving the way for an early therapeutic intervention
3,563 studies on the registry are indexed under Schizophrenia; 491 are open to participants now.
This study's enrollment of 111 is above the median of 71 across 2,944 interventional studies indexed under Schizophrenia.
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Of the child:
Brothers and sisters:
Parents:
Exclusion Criteria:
Of the child:
Brothers and sisters:
Parents:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
blood sample, clinical and neurocognitive assessment
Other: genetic and phenotypic profile
Genetic and phenotypic profile, clinical and neurocognitive assessment for child with Schizophrenia and autism, their parents and brotherhood
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing standard karyotype
A standard karyotype at a resolution of 300 to 400 bands per haploid lot. It can diagnose numerical anomalies and certain structural abnormalities such as reciprocal translocations, inversions, deletions. A standard karyotype at a resolution of 300 to 400 bands per haploid lot is established initially. It can diagnose numerical anomalies and certain structural abnormalities such as reciprocal translocations, inversions, deletions Big. The pathological nature of these mutations will be stutied on the gene function and reaches its pattern of expression.
Time frame: inclusion visit
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing search CGG
A search of the CGG expansion hypermethylated in the 5 'UTR of the FMR1 gene mutation that causes Fragile X syndrome.
Time frame: inclusion visit
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing whole exome sequencing
Whole Exome Sequencing on trio (mother, father and child); This technology has demonstrated its power in recent years to determine the genetic causes of many rare diseases (Ropers, HH., 2012).
Time frame: inclusion visit
Intensity of positive symptoms of schizophrenia
Evaluation of the intensity of positive and negative symptoms, general psychopathology and subtypes of schizophrenia by using positive and negative syndrome scale (PANSS)
Time frame: inclusion visit
Co-morbid psychiatric diagnosis
Evaluation of clinical profile: by using K-SADS-PL scale for DSM IV-TR / DSM-5 co-morbid psychiatric diagnosis of patients and minor siblings and by using MINI assessments for DSM IV-TR / DSM 5 psychiatric diagnosis of parents and major siblings.
Time frame: inclusion visit
Evaluation of executive and attentional by the verbal fluency test
Evaluation of executive and attentional functions of patients using Trail Making Test (TMT) A and B and verbal fluency;
Time frame: inclusion visit
Clinical evaluation of autistic symptoms
Clinical evaluation of autistic symptoms by using AQ (Baron-Cohen) in siblings and parents
Time frame: inclusion visit
Neurocognitive profile
Evaluation of cognitive functioning by Wechsler Intelligence Scale for Children Scale IV (WISC IV).full version in patient and WISC IV abridged version in minor siblings; Wechsler Adult Intelligence Scale-III (WAIS III) in a short form in adult siblings and parents
Time frame: inclusion visit
Personality dimensional test
Personality dimensional test using computerized version of TCI 226 (Cloninger) in parents
Time frame: inclusion visit
This study is completed, as verified in Sep 2023. You cannot join it, but the record below documents what was studied.
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