Contributions of the Catechol-O-Methyltransferase Val158Met Polymorphism to Changes in Brain Iron Across Adulthood and Their Relationships to Working Memory

Bibliographic Details
Title: Contributions of the Catechol-O-Methyltransferase Val158Met Polymorphism to Changes in Brain Iron Across Adulthood and Their Relationships to Working Memory
Authors: Jonatan Gustavsson, Goran Papenberg, Farshad Falahati, Erika J. Laukka, Grégoria Kalpouzos
Source: Frontiers in Human Neuroscience, Vol 16 (2022)
Publisher Information: Frontiers Media S.A., 2022.
Publication Year: 2022
Collection: LCC:Neurosciences. Biological psychiatry. Neuropsychiatry
Subject Terms: brain iron, COMT, working memory, longitudinal, ageing, QSM, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
More Details: Ageing is associated with excessive free brain iron, which may induce oxidative stress and neuroinflammation, likely causing cognitive deficits. Lack of dopamine may be a factor behind the increase of iron with advancing age, as it has an important role in cellular iron homoeostasis. We investigated the effect of COMT Val 158 Met (rs4680), a polymorphism crucial for dopamine degradation and proxy for endogenous dopamine, on iron accumulation and working memory in a longitudinal lifespan sample (n = 208, age 20–79 at baseline, mean follow-up time = 2.75 years) using structural equation modelling. Approximation of iron content was assessed using quantitative susceptibility mapping in striatum and dorsolateral prefrontal cortex (DLPFC). Iron accumulated in both striatum and DLPFC during the follow-up period. Greater iron accumulation in DLPFC was associated with more deleterious change in working memory. Older (age 50–79) Val homozygotes (with presumably lower endogenous dopamine) accumulated more iron than older Met carriers in both striatum and DLPFC, no such differences were observed among younger adults (age 20–49). In conclusion, individual differences in genetic predisposition related to low dopamine levels increase iron accumulation, which in turn may trigger deleterious change in working memory. Future studies are needed to better understand how dopamine may modulate iron accumulation across the human lifespan.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1662-5161
Relation: https://www.frontiersin.org/articles/10.3389/fnhum.2022.838228/full; https://doaj.org/toc/1662-5161
DOI: 10.3389/fnhum.2022.838228
Access URL: https://doaj.org/article/6a222cdfd5bb4ce5bae85c4b47f30d5c
Accession Number: edsdoj.6a222cdfd5bb4ce5bae85c4b47f30d5c
Database: Directory of Open Access Journals
More Details
ISSN:16625161
DOI:10.3389/fnhum.2022.838228
Published in:Frontiers in Human Neuroscience
Language:English