Trial lecture - time and place
12.05.2023, 10.15, Auditorium 3, Kristine Bonnevies hus
Importance of pharmacoepigenetics and pharmacogenetics for improving diagnosis and treatment of neuropsychiatric disorders
Conferral summary
Flere studier finner en sammenheng mellom eksponering for legemidler i fosterlivet og utviklingsforstyrrelser i barnets hjerne, og én mulig underliggende mekanisme er endringer i DNA metylering: merkelapper festes på arvematerialet vårt (DNA-et) og angir om genene skal skrus av eller på. I denne avhandlingen fant vi ingen sammenheng mellom eksponering for verken paracetamol eller antidepressivet escitalopram i fosterlivet og metylering, derimot var det en sammenheng mellom metylering i gener viktige for at hjernen skal utvikle seg normalt og forsinket språklig og motorisk utvikling hos barna. Vi fant også at det foreløpig er få robuste funn innen fagfeltet, men fokuset på videreutvikling av metoder og teknologi vil kunne bidra til resultater av økt klinisk verdi i nær framtid.
Main research findings
Illustration 1. Overview of the main aim of the present doctoral thesis: exploring the relationship between prenatal medication exposure, DNA methylation and child brain development. Note that the arrows suggest one possible mechanism, other relations between medication, DNA methylation and brain development are also plausible, as is explored in the present thesis. Created with BioRender.com.
Approximately 4 in 5 women use medication(s) during pregnancy. Yet, women also report concerns about the fetal safety of medications, as studies find associations between medication exposure before birth (i.e., prenatally) and abnormal brain development in the child. Understanding the mechanisms underlying these associations is important: it may guide the development of novel therapeutics and identify prognostic markers of brain developmental conditions. One suggested mechanism includes DNA methylation (DNAm), whereby small molecules attach to our DNA, and may turn genes on or off.
To this end, this thesis explored the relationship between prenatal exposure to paracetamol or the antidepressant escitalopram, DNAm in umbilical cord blood and brain development. We found no association of exposure to medications with DNAm. However, DNAm at birth was associated with delayed child language and motor development, suggesting that DNAm may support early risk detection of developmental conditions. When we systematically reviewed the literature, we identified no overlapping findings between studies, albeit methodological differences made comparisons challenging. Additionally, we uncovered discrepancies in measured DNAm levels between technologies, potentially impacting findings. In conclusion, the research field faces challenges, but improvements of methodologies and technologies hold promise for more robust results of clinical value in the near future.
Read more (in Norwegian)
- Gena styrer korleis medisinbruken til mora påverkar fosteret (Titan, May 31, 2021)
- Forskjellige teknologiar gav vidt forskjellige forskingsresultat (forskning.no, September 1, 2022)
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Medisinbruk under svangerskapet, epigenetikk og ADHD (April 18, 2023)