To assess whether the genetic architecture of this severe therapy-resistant SCZ phenotype differs from the broad DSM-based SCZ phenotype.
ID
Source
Brief title
Health condition
Genetics of clozapine use because of schizophrenia, schizo-affective disorder, schizophreniform disorder
Sponsors and support
Intervention
Outcome measures
Primary outcome
First, in a discovery cohort a case-control genome-wide association study (GWAS) will be performed on 2000 CLZ using subjects (cases) and >30,000 already available SCZ patients (controls, drawn from the most recent Psychiatric Genomics Consortium analysis, . We hereby aim to reveal potential differences in the genetic architecture between the severe CLZ-SCZ phenotype and the broad SCZ phenotype.
Secondary outcome
Second, a replication cohort of the same size as the discovery cohort (N=2,000 CLZ using subjects and the same number of controls) will be used to replicate any positive associations for each of the two GWAS analyses. Should funding allow and if replication cohorts are available elsewhere and possibly for the purpose of participation in large-scale consortia, GWAS and NGS may be performed on >2,000 CLZ users, e.g. the entire study population. In addition, we use the data with our other protocol (NTR 5257) to create a prediction model for clozapine response and side effects.
Background summary
Clozapine (CLZ) is generally prescribed if at least two trials of antipsychotic agents have not led to satisfactory clinical improvement, thereby implying that patients on CLZ generally suffer from more severe and/or persistent symptoms than patients suffering from schizophrenia spectrum disorders (SCZ) on other antipsychotic agents. Unraveling the (functional) genetic variation underlying this severe SCZ phenotype therefore has the potential to deepen our understanding of the biological underpinnings of SCZ beyond the boundaries of DSM-based consensus criteria. Such knowledge in turn has the potential to shape future pharmacotherapeutic research. We here hypothesize that targeting this phenotype in genome-wide association studies and next-generation sequencing studies will signal genetic risk loci implicated in this severe SCZ phenotype. In the future, this may lead to early detection of severe SCZ, which in turn will enable tailoring of pharmacotherapeutic strategies to such SCZ subtypes.
In addition, we use the data with our other protocol (NTR 5257) to create a prediction model for clozapine response and side effects.
Study objective
To assess whether the genetic architecture of this severe therapy-resistant SCZ phenotype differs from the broad DSM-based SCZ phenotype.
Study design
One visit
Intervention
None
Marte van der Horst
Heidelberglaan 100
Utrecht 3508 GA
The Netherlands
0887551460
mzvanderhorst@gmail.com
Marte van der Horst
Heidelberglaan 100
Utrecht 3508 GA
The Netherlands
0887551460
mzvanderhorst@gmail.com
Inclusion criteria
-he/she currently uses CLZ
-he/she has received a diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder or psychosis not otherwise specified
-his/her age must be ≥18 years old
-he/she must be able to speak and read the Dutch language
-he/she must be mentally competent and have decisional capacity with regard to a decision to participate in the current study
Exclusion criteria
- admission to a psychiatric unit involuntarily in the context of an ‘inbewaringstelling’ (IBS)
- a history of Parkinson’s disease
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL5116 |
| NTR-old | NTR5248 |
| CCMO | NL52726.041.15 |
| OMON | NL-OMON50518 |