Although the currently available antidepressants are well established in the treatment of the major depressive disorder (MDD), there is strong variability in the response of individual patients. Reliable predictors to guide treatment decisions before or in an early stage of treatment are needed. DNA-methylation has been proven a useful biomarker in different clinical conditions, but its importance for mechanisms of antidepressant response has not yet been determined. 80 MDD patients were selected out of >500 participants from the Early Medication Change (EMC) cohort with available genetic material based on their antidepressant response after four weeks and stratified into clear responders and age- and sex-matched non-responders (N = 40, each). Early improvement after two weeks was analyzed as a secondary outcome. DNA-methylation was determined using the Illumina EPIC BeadChip. Epigenome-wide association studies were performed and differentially methylated regions (DMRs) identified using the comb-p algorithm. Enrichment was tested for hallmark gene-sets and in genome-wide association studies of depression and antidepressant response. No epigenome-wide significant differentially methylated positions were found for treatment response or early improvement. Twenty DMRs were associated with response; the strongest in an enhancer region in SORBS2, which has been related to cardiovascular diseases and type II diabetes. Another DMR was located in CYP2C18, a gene previously linked to antidepressant response. Results pointed towards differential methylation in genes associated with cardiac function, neuroticism, and depression. Linking differential methylation to antidepressant treatment response is an emerging topic and represents a step towards personalized medicine, potentially facilitating the prediction of patients’ response before treatment.
Stress is an established risk factor for somatic and mental disorders. The COVID-19 pandemic and the related countermeasures severely affect the lives of families. Prenatal stress, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and genetic factors might impact the well-being of individuals. The present work is part of an ongoing birth cohort study and aims to investigate maternal perceived stress, early childhood HPA axis activity and polygenic risk scores (PRSs) as predictors of emotional well-being during the COVID-19 pandemic. All participants are part of the ongoing birth cohort study POSEIDON. Emotional well-being of children (n = 259) and mothers (n = 211) was assessed during the COVID-19 pandemic using the CRISIS questionnaire. Furthermore, associations between previously assessed maternal perceived stress (Perceived Stress Scale), children's salivary and morning urine cortisol measures at 45 months, PRSs for depression, schizophrenia, loneliness and current emotional well-being were investigated. A positive association between the child's and the mother's emotional well-being was found. A worse emotional well-being was observed in both children and mothers during the pandemic compared to before. Children's emotional well-being improved over the course of the pandemic, while mothers' well-being worsened. Maternal perceived stress, salivary and morning urine cortisol and PRSs were not significantly associated with the assessed emotional wellbeing. The present study confirms that emotional well-being of children and mothers is negatively affected by the COVID-19 pandemic, with differences in development over time. Future studies should examine which mechanisms contribute to stress-related associations and at which age they can be identified.
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