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. 2023 Feb 14;26(2):116-124.
doi: 10.1093/ijnp/pyac085.

Effect of MAOA DNA Methylation on Human in Vivo Protein Expression Measured by [11C]harmine Positron Emission Tomography

Patricia A Handschuh  1 , Matej Murgaš  1 , Chrysoula Vraka  2 , Lukas Nics  2 , Annette M Hartmann  1 , Edda Winkler-Pjrek  1 , Pia Baldinger-Melich  1 , Wolfgang Wadsak  2   3 , Dietmar Winkler  1 , Marcus Hacker  2 , Dan Rujescu  1 , Katharina Domschke  4   5 , Rupert Lanzenberger  1 , Marie Spies  1
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Effect of MAOA DNA Methylation on Human in Vivo Protein Expression Measured by [11C]harmine Positron Emission Tomography

Patricia A Handschuh et al. Int J Neuropsychopharmacol. .

Abstract

Background: Epigenetic modifications like DNA methylation are understood as an intermediary between environmental factors and neurobiology. Cerebral monoamine oxidase A (MAO-A) levels are altered in depression, as are DNA methylation levels within the MAOA gene, particularly in the promoter/exon I/intron I region. An effect of MAOA methylation on peripheral protein expression was shown, but the extent to which methylation affects brain MAO-A levels is not fully understood.

Methods: Here, the influence of MAOA promoter/exon I/intron I region DNA methylation on global MAO-A distribution volume (VT), an index of MAO-A density, was assessed via [11C]harmine positron emission tomography in 22 patients (14 females) suffering from seasonal affective disorder and 30 healthy controls (17 females).

Results: No significant influence of MAOA DNA methylation on global MAO-A VT was found, despite correction for health status, sex, season, and MAOA variable number of tandem repeat genotype. However, season affected average methylation in women, with higher levels in spring and summer (Puncorr = .03). We thus did not find evidence for an effect of MAOA DNA methylation on brain MAO-A VT.

Conclusions: In contrast to a previous study demonstrating an effect of methylation of a MAOA promoter region located further 5' on brain MAO-A, MAOA methylation of the region assessed here appears to affect brain protein levels to a limited extent at most. The observed effect of season on methylation levels is in accordance with extensive evidence for seasonal effects within the serotonergic system.

Clinicaltrials.gov identifier: NCT02582398 (https://clinicaltrials.gov/ct2/show/NCT02582398).

Keywords: MAOA; DNA methylation; monoamine oxidase A; positron emission tomography; seasonal affective disorder.

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Figures

Figure 1.
Figure 1.
Lower average MAOA promoter/exon I/intron I region DNA methylation in autumn and winter compared with spring and summer within the female participant group (all women, 2-sided Mann–Whitney U test, Puncorr = .030).
See this image and copyright information in PMC

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References

    1. Alvarado S, Fernald RD, Storey KB, Szyf M (2014) The dynamic nature of DNA methylation: a role in response to social and seasonal variation. Integr Comp Biol 54:68–76. - PMC - PubMed
    1. Attwells S, Setiawan E, Wilson AA, Rusjan PM, Mizrahi R, Miler L, Xu C, Richter MA, Kahn A, Kish SJ, Houle S, Ravindran L, Meyer JH (2017) Inflammation in the neurocircuitry of obsessive-compulsive disorder. JAMA Psychiatry 74:833–840. - PMC - PubMed
    1. Azzi A, Dallmann R, Casserly A, Rehrauer H, Patrignani A, Maier B, Kramer A, Brown SA (2014) Circadian behavior is light-reprogrammed by plastic DNA methylation. Nat Neurosci 17:377–382. - PubMed
    1. Bacher I, Houle S, Xu X, Zawertailo L, Soliman A, Wilson AA, Selby P, George TP, Sacher J, Miler L, Kish SJ, Rusjan P, Meyer JH (2011) Monoamine oxidase A binding in the prefrontal and anterior cingulate cortices during acute withdrawal from heavy cigarette smoking. Arch Gen Psychiatry 68:817–826. - PubMed
    1. Baldinger-Melich P, Gryglewski G, Philippe C, James GM, Vraka C, Silberbauer L, Balber T, Vanicek T, Pichler V, Unterholzner J, Kranz GS, Hahn A, Winkler D, Mitterhauser M, Wadsak W, Hacker M, Kasper S, Frey R, Lanzenberger R (2019) The effect of electroconvulsive therapy on cerebral monoamine oxidase A expression in treatment-resistant depression investigated using positron emission tomography. Brain Stimul 12:714–723. - PubMed

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