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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores genetic and immune system factors that may cause psychosis in children and teens. Researchers will use advanced genome sequencing techniques to study the DNA and proteins of young patients admitted with psychotic symptoms or schizophrenia. The goal is to identify new genetic or autoimmune causes of psychosis, potentially leading to better treatments in the future. This study suits kids and teens experiencing their first episode of psychosis and admitted to Rady Children's Hospital's psychiatric service. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could enhance future treatments for psychosis.

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 prior data suggests that these diagnostic technologies are safe for youth?

Research has shown that genomic sequencing, as used in this trial, is generally safe and manageable for participants. It involves examining a person's DNA to identify changes that might lead to certain health conditions. This process does not require medication or any procedure that alters the body.

Past studies have enhanced understanding of mental health conditions like schizophrenia and autism through genomic sequencing. No reports have indicated harmful effects from the sequencing itself. However, learning about genetic information can sometimes be emotionally stressful, as some individuals might worry about discovering their genetic risks.

Overall, genomic sequencing serves as a way to gather information without directly impacting the body, making it a low-risk option in clinical research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using genomic sequencing for youth psychosis because it offers a personalized approach by diving deep into each individual's genetic makeup. Unlike current treatments that often rely on medication and therapy to manage symptoms, genomic sequencing aims to uncover specific genetic changes and antibodies associated with psychosis. This could lead to more targeted interventions that address the root causes rather than just the symptoms, potentially transforming how we understand and treat psychosis in young people.

What evidence suggests that genomic sequencing is effective for understanding youth psychosis?

Research has shown that analyzing a person's DNA can identify genetic factors related to early-onset psychosis. By examining DNA, scientists can discover genes linked to mental health disorders. This knowledge could enhance understanding of the causes and aid in developing new treatments. In this trial, participants will undergo whole genome sequencing (WGS) and Phage ImmunoPrecipitation sequencing (PhIP-Seq) to identify specific genetic changes and antibodies (proteins that help fight disease) potentially connected to psychosis in young people. Studies have demonstrated that similar DNA research has enhanced understanding of mental health conditions. ^{1 6 7 8 9}

Who Is on the Research Team?

Aaron Besterman, MD

Principal Investigator

Rady Pediatric Genomics & Systems Medicine Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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]

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]

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