Cutting-Edge Diagnostic Technologies for Youth Psychosis

Overseen By Corrine Blucher, BS

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Rady Pediatric Genomics & Systems Medicine Institute

Disqualifiers: Prior genome sequencing, Informed consent, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

15 Participants Needed

Trial Summary

What is the purpose of this trial?

Rady Children's Institute for Genomic Medicine seeks to understand the genomes and immune systems in 15 children and adolescents who are admitted to Rady Children's Hospital Child and Adolescent Psychiatry Service with psychotic symptoms or schizophrenia. Cutting-edge genome and protein sequencing technology will be used to better understand how immunological and genetic assessments may improve our ability to identify the cause of psychosis and impact care. The investigator also hopes to identify new genetic and/or autoimmune causes of psychosis that may inform new treatment for future patients.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Genomic sequencing for youth psychosis?

Research shows that whole genome sequencing (WGS) can help identify genetic factors in schizophrenia and other psychotic disorders, which may guide treatment and genetic counseling. In some studies, WGS and whole exome sequencing (WES) have been used to find genetic variants that could influence treatment decisions and improve understanding of these conditions. ^{1 2 3 4 5}

Is genomic sequencing safe for use in humans?

The research does not provide specific safety data for genomic sequencing, but it is generally used in clinical settings for genetic counseling and research without reported safety concerns. ^{2 3 6 7 8}

How is this treatment for youth psychosis different from other treatments?

This treatment is unique because it uses cutting-edge diagnostic technologies like whole-genome sequencing (WGS) to rapidly identify genetic factors in youth psychosis, allowing for more precise and individualized treatment plans. Unlike traditional methods, this approach can quickly provide detailed genetic information, potentially leading to faster and more accurate diagnoses. ^{3 9 10 11 12}

Research Team

Aaron Besterman, MD

Principal Investigator

Rady Pediatric Genomics & Systems Medicine Institute

Eligibility Criteria

This trial is for children and adolescents with first break psychosis admitted to Rady Children's Hospital. Biological parents can also join for genetic testing. It excludes those who've had prior genome sequencing, cannot give consent, or are protected research subjects.

Inclusion Criteria

I am the biological parent of a child in this study and presumed genetically related.

I am a child/adolescent experiencing my first episode of psychosis.

Exclusion Criteria

I am a child/adolescent patient who meets all the required criteria for the study.

Family members are ineligible for participation in this study if: They are known to not be genetically related to the child/adolescent patient participant

Family members are ineligible for participation in this study if: They are a member of a protected research population.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genomic and Immunological Assessment

Participants undergo whole genome sequencing and Phage ImmunoPrecipitation sequencing to identify genetic changes and novel antibodies associated with psychosis

2 years

Follow-up

Participants are monitored for safety and effectiveness after genomic and immunological assessments

4 weeks

Treatment Details

Interventions

• Genomic sequencing

Trial Overview The study uses advanced genomic and protein sequencing technologies to understand the genetic and immune factors in youth with psychosis. The goal is to find new causes of psychosis that could lead to better treatments.

Participant Groups

Group I: Enrollees - WGS Experimental Treatment 2 Interventions

These participants will be subject to whole genome sequencing and Phage ImmunoPrecipiation sequencing (PhIP-Seq) to identify genetic changes and novel antibodies associated with psychosis.

Who Is Running the Clinical Trial?

Rady Pediatric Genomics & Systems Medicine Institute

Lead Sponsor

Trials

10

Recruited

214,000+

Findings from Research

Current research on schizophrenia highlights the potential of advanced genetic technologies like whole-exome sequencing (WES) and whole-genome sequencing (WGS) to uncover genetic variations associated with the disorder.

Identifying these genetic factors could pave the way for developing new therapeutic targets, offering hope for more effective treatments for schizophrenia, which currently has no cure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-generation sequencing in schizophrenia and other neuropsychiatric disorders. Schreiber, M., Dorschner, M., Tsuang, D.[2020]

In a study involving 251 families with schizophrenia and related disorders, whole genome sequencing (WGS) identified clinically significant genetic variants in 6.4% of cases, suggesting a potential diagnostic benefit for genetic analysis in these conditions.

The research also revealed an enrichment of rare loss-of-function variants in key schizophrenia-related genes and provided pharmacogenomic insights, which could help tailor antipsychotic treatments based on individual genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The benefit of diagnostic whole genome sequencing in schizophrenia and other psychotic disorders. Alkelai, A., Greenbaum, L., Docherty, AR., et al.[2023]

This study identified two male patients with childhood onset psychosis who carry rare genetic variants in the L1CAM gene, suggesting a potential link between these variants and the development of psychosis in children.

The findings indicate that L1CAM variants, previously associated with intellectual disabilities, may also contribute to childhood onset psychosis, highlighting the need for further research into genetic interactions that could influence this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemizygous mutations in L1CAM in two unrelated male probands with childhood onset psychosis. Sato, MS., Kyriakopoulos, M., James, A., et al.[2022]

In a study of 37 Israeli Jewish families with childhood-onset schizophrenia (COS), diagnostic exome sequencing identified clinically significant genetic variants in 19% of the probands, suggesting a genetic component to the disorder.

COS patients showed a significant enrichment of rare loss of function variants in genes associated with developmental diseases compared to 4721 healthy controls, highlighting the potential role of these genetic factors in COS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic insights into childhood-onset schizophrenia: The yield of clinical exome sequencing. Alkelai, A., Greenbaum, L., Shohat, S., et al.[2023]

Whole exome sequencing (WES) can lead to significant changes in medical management for patients with complex neuropsychiatric conditions, as demonstrated in a case study of a male adolescent with autism spectrum disorder and psychosis.

The findings from WES directly informed the pharmacologic treatment plan for the patient, highlighting the potential of genomic testing to tailor interventions based on individual genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole Exome Sequencing Guides Pharmacotherapy for an Adolescent With Autism Spectrum Disorder and Psychosis. Wigby, K., Nicolas, S., Carpinello, M., et al.[2022]

DNA testing has empowered patients and families to make more informed healthcare decisions, particularly in the context of understanding conditions like schizophrenia, due to the rapid advancements in genetic technology.

While direct-to-consumer DNA testing offers valuable insights, it raises ethical concerns and discussions among experts regarding the implications of genetic information, especially when it comes to predicting serious health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ethical issues in the use of genetic testing of patients with schizophrenia and their families. DeLisi, LE.[2014]

The study identified two rare missense variations in the PDCD11 gene from whole-exome sequencing of three families, but these variations were not found to be significantly associated with schizophrenia in a larger case-control study of 1357 patients and 1394 controls.

Overall, the research suggests that rare variations in the PDCD11 gene do not confer a substantial risk for developing schizophrenia in the Japanese population, indicating that other genetic factors may be more influential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rare PDCD11 variations are not associated with risk of schizophrenia in Japan. Hoya, S., Watanabe, Y., Hishimoto, A., et al.[2018]

Psychiatric genomics has the potential to enhance risk prediction, diagnosis, and treatment in mental health, but there are significant structural and clinical challenges that need to be addressed for its effective integration into practice.

To maximize the benefits of psychiatric genomics, there is a need for improved training for clinicians, the establishment of practice guidelines, and a focus on patient engagement and informed consent in genomic testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating Genomics into Psychiatric Practice: Ethical and Legal Challenges for Clinicians. Ward, ET., Kostick, KM., Lázaro-Muñoz, G.[2020]

TORMES is a user-friendly pipeline designed for whole genome sequencing (WGS) analysis of bacteria, making it accessible for researchers without specialized bioinformatics skills.

The pipeline automates essential WGS steps, such as quality filtering and genome annotation, and produces interactive reports that facilitate easy sharing and collaboration among researchers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TORMES: an automated pipeline for whole bacterial genome analysis. Quijada, NM., Rodríguez-Lázaro, D., Eiros, JM., et al.[2020]

Rapid whole-genome sequencing (WGS) can sequence an infant's genome in just 26 hours, enabling quick diagnosis and tailored management of genetic diseases.

This technology has the potential to reduce costs and minimize the time to diagnosis, which can alleviate pain and suffering for infants in the NICU, but it also raises important ethical considerations that need to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ethical Implications of Rapid Whole-Genome Sequencing in Neonates. Bell, SG.[2018]

In a study involving 142 children over five years, rapid next-generation sequencing (NGS) achieved a diagnostic yield of 39%, significantly impacting clinical management decisions in acute pediatric care.

Rapid genome sequencing (rGS) identified 7% of diagnoses that would not have been detected by the targeted NGS panel (RapSeq), highlighting the importance of using comprehensive sequencing methods for accurate diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating use of changing technologies for rapid next-generation sequencing in pediatrics. Palmquist, R., Jenkins, SM., Bentley, D., et al.[2023]

A comprehensive whole-genome sequencing (WGS) pipeline for diagnosing genetic disorders was developed and validated using 45 samples with known variants, demonstrating its effectiveness in detecting various genetic alterations.

The pipeline includes advanced bioinformatics tools for identifying multiple types of genetic variants, ensuring a robust approach to genetic testing that can improve clinical diagnostics for genetic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Test development, optimization and validation of a WGS pipeline for genetic disorders. Yang, Z., Yang, X., Sun, Y., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Next-generation sequencing in schizophrenia and other neuropsychiatric disorders. [2020]

2. England pubmed.ncbi.nlm.nih.gov

The benefit of diagnostic whole genome sequencing in schizophrenia and other psychotic disorders. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Hemizygous mutations in L1CAM in two unrelated male probands with childhood onset psychosis. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Genetic insights into childhood-onset schizophrenia: The yield of clinical exome sequencing. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Whole Exome Sequencing Guides Pharmacotherapy for an Adolescent With Autism Spectrum Disorder and Psychosis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Ethical issues in the use of genetic testing of patients with schizophrenia and their families. [2014]

7. Australia pubmed.ncbi.nlm.nih.gov

Rare PDCD11 variations are not associated with risk of schizophrenia in Japan. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Integrating Genomics into Psychiatric Practice: Ethical and Legal Challenges for Clinicians. [2020]

9. England pubmed.ncbi.nlm.nih.gov

TORMES: an automated pipeline for whole bacterial genome analysis. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Ethical Implications of Rapid Whole-Genome Sequencing in Neonates. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Evaluating use of changing technologies for rapid next-generation sequencing in pediatrics. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Test development, optimization and validation of a WGS pipeline for genetic disorders. [2023]