2026-01-28

107_ Drugs Capable of Remyelination and Cognitive Performance in Psychosis and Affective Disorders (Amendment 2 to 096)

Research Question and Aims

With this second amendment, we would like to indicate adjustments to the original research plan as outlined in the original proposal and the first amendment of the research project “Drugs Capable of Remyelination and Cognitive Performance in Psychosis and Affective Disorders”.
First, we initially intended to address the effects of quetiapine in patients with psychosis and affective disorders. After evaluating the available data, we need to restrict the analytical sample to patients with psychosis, i.e., schizophrenia spectrum disorder due to the following reasons: a) the sample of patients with a diagnose of Major Depression/Recurrent Depression under quetiapine treatment was too small (n = 19 at visit 1) for providing the necessary statistical power; b) antipsychotic treatment with quetiapine in patients with a diagnose of Bipolar Disorder was too predominant resulting in an unbalanced distribution of psychopharmacological drug classes between patients with and without quetiapine treatment, presumably due to the prominent role of quetiapine as antipsychotic first-line treatment in Bipolar Disorder.
Second, we already suggested to evaluate the moderating effects of cell type-specific polygenic burden scores reflecting the polygenic schizophrenia risk (Amendment 1). We wish to extend this approach by additionally evaluating the moderating effects of polygenic proxy-scores for estimating subcortical brain volumes as recently introduced by Garcia-Martins et al (PMID: 39433889).

Analytic Plan

In deviation from our original analytical plan, we intend to restrict our analyses to PsyCourse participants with schizophrenia spectrum disorder. In addition, we wish to calculate the individual polygenic proxy-scores for subcortical brain volumes of the PsyCourse patients based on the available Illumina GSA genotypes. Then, we intend to re-analyze the effects of quetiapine on cognitive function in psychotic patients by additionally including each of the polygenic proxy-scores as moderators plus a proxy-score for the intracranial brain volume as general benchmark.

Resources needed