Pathomechanisms and Signatures in the Longitudinal Course of Psychosis

13.01.2015

2020-01-15

024_ Preparatory work for the MulioBio project

Research Question and Aims

Despite many years of research and many promising candidates there are no validated and reliable biomarkers (BM) in clinical use for schizophrenia or other major psychoses (MP). In the MulioBio project, we postulate that phenotype definition is the reason BM couldn't be discovered. To resolve this, we intent to classify patients of the longitudinal PsyCourse cohort, that show the same behavioral profiles over time, into three to four transdiagnostic groups. Then, the PsyCourse patients will be re-contacted, PBMCs will be obtained from them under the auspices of the MulioBio study, and a multi-level BM screening of molecular phenotypes will be performed. Eventually, we plan to use an integrative approach of longitudinal patient information, cellular and molecular phenotypes with serum protein to define robust BM which will later be validated in an independent validation cohort.
To find phenotypic groups within the PsyCourse cohort, we will use the RShiny app PhenEndo. This toolbox, developed in cooperation with The Helmholtz Center of Computational Biology, is able to divide the PsyCourse individuals into clusters that show different trajectories over time.
Here, we plan to use PsyCourse data as an exercise to identify challenges and pitfalls when using PhenoEndo, which is still acitvely developed. We will also explore to which extend this approach can benefit from the addition of genomic data.

Analytic Plan

For this purpose, we will use the phenotype data that were also used to demonstrate a use case for PhenEndo (PsyCourse proposal 021_Providing a use case of longitudinal data for the manuscript "Phenendo: a tool for clustering of cross-sectional and longitudinal phenotye data", plus some additional variables). Only participants with a DSM-IV diagnosis of schizophrenia and data at all four study visits will be included (n=76). We will also use genotype data of the PsyCourse cohort to prepare for the main research question stated above.

Resources needed

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idsc_itm1
idsc_itm10
idsc_itm15
idsc_itm16
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idsc_itm19
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idsc_itm8
idsc_itm9
idsc_11_12
idsc_13_14
panss_n1
panss_n2
panss_n3
panss_n4
panss_n5
panss_n6
panss_n7
bdi2_itm1
bdi2_itm10
bdi2_itm11
bdi2_itm12
bdi2_itm13
bdi2_itm14
bdi2_itm15
bdi2_itm16
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v1_id
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sex
ageBL
idsc_sum
panss_sum_neg
bdi2_sum
v1_dur_illness
v1_evr_ill_drg

Biological data: Imputed SNP genotype data of all available PsyCourse participants