Anne Krogh Nøhr:
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Antidepressants are a first line treatment for a variety of mental disorders including major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). However, the response to antidepressant treatment varies greatly between individuals. How to select which treatment that offers the greatest benefit for the individual is still an open question. Through three papers this joint industry-academia thesis sought to identify biological and clinical factors affecting antidepressant treatment response in patients with MDD or PTSD.
The first paper examined demographic and clinical predictors and latent classes of antidepressant treatment (sertraline or paroxetine) response in patients with PTSD from a clinical trial. Using growth mixture modeling three classes with similar response trajectories were identified: fast responders, responders with low pretreatment symptom severity and responders with high pretreatment symptom severity. Class membership was predicted by time since index trauma, severity of depression, and severity of anxiety.
The second paper investigated changes and sources of variability in gene expression in peripheral blood related to antidepressant treatment (vortioxetine) and treatment response for patients suffering from recurrent MDD. The paper revealed three novel genes whose gene expression at baseline and week 8 were associated with treatment response after 8 weeks of treatment. Analysis of genome-wide expression variability showed that treatment response explains a low proportion of the gene expression variance across all genes.
The third paper examined whether polygenic risk scores (PRS) were associated with placebo and treatment response (vortioxetine) from pooled clinical trial data and self-reported vortioxetine response from a web-based survey in depressed patients. In the clinical test sample, PRS for clinically assessed treatment response was nominally associated with treatment response and placebo response. Furthermore, higher subjective well-being PRS and lower depression PRS were nominally associated with higher placebo response. In the self-reported test sample, higher schizophrenia PRS was associated with poorer self-reported response.