Plasticity of Functional MAOA Gene Methylation in Acrophobia
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Epigenetic mechanisms have been proposed to mediate fear extinction in animal models. Here, MAOA methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells before and after a 2-week exposure therapy in a sample of n = 28 female patients with acrophobia as well as in n = 28 matched healthy female controls. Clinical response was measured using the Acrophobia Questionnaire and the Attitude Towards Heights Questionnaire. The functional relevance of altered MAOA methylation was investigated by luciferase-based reporter gene assays. MAOA methylation was found to be significantly decreased in patients with acrophobia compared with healthy controls. Furthermore, MAOA methylation levels were shown to significantly increase after treatment and correlate with treatment response as reflected by decreasing Acrophobia Questionnaire/Attitude Towards Heights Questionnaire scores. Functional analyses revealed decreased reporter gene activity in presence of methylated compared with unmethylated pCpGfree_MAOA reporter gene vector constructs. The present proof-of-concept psychotherapy-epigenetic study for the first time suggests functional MAOA methylation changes as a potential epigenetic correlate of treatment response in acrophobia and fosters further investigation into the notion of epigenetic mechanisms underlying fear extinction.
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In candidate gene studies in anxiety disorders, the evidence points at a pattern of MAO-A hypomethylation, as shown in acrophobia and OCD.
“in candidate gene studies in anxiety disorders, the evidence points at a pattern of hypomethylation (Ziegler et al., 2016) as shown in acrophobia (Schiele et al., 2018) and obsessive compulsive disorder (OCD) (Domschke et al., 2012).”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Schiele et al., 2018
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Oxytocin receptor gene methylation: converging multilevel evidence for a role in social anxiety
Ziegler, C., Dannlowski, U., Bräuer, D., Stevens, S., Laeger, I., Wittmann, H., Kugel, H., Dobel, C., Hurlemann, R., Reif, A., et al. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.2 · Cited by 193 · see citing works
Self-citationTadić, A., Müller-Engling, L., Schlicht, K. F., Kotsiari, A., Dreimüller, N., Kleimann, A., Bleich, S., Lieb, K., & Frieling, H. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.58 · Cited by 175 · see citing works
Hpa axis related genes and response to psychological therapies: Genetics and epigenetics
Roberts, S., Keers, R., Lester, K. J., Coleman, J. R. I., Breen, G., Arendt, K., Blatter‐Meunier, J., Cooper, P., Creswell, C., Fjermestad, K., et al. (2015) · Depression and Anxiety · doi:10.1002/da.22430 · Cited by 107 · see citing works
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Research works printed but not linked: 21
- Abelson JL, Curtis GC(1989) Cardiac and neuroendocrine responses to exposure therapy in height phobics: Desynchrony within the “physiological response system.” Behav Res Ther 27: 561– 567. 2573337
- Brenet F, Moh M, Funk P, Feierstein E, Viale AJ, Socci ND, Scandura JM(2011) DNA methylation of the first exon is tightly linked to transcriptional silencing. PLoS One 6: e14524. 21267076 PMC3022582
- Checknita D, Maussion G, Labonté B, Comai S, Tremblay RE, Vitaro F, Turecki N, Bertazzo A, Gobbi G, Côté G, Turecki G(2015) Monoamine oxidase A gene promoter methylation and transcriptional downregulation in an offender population with antisocial personality disorder. Br J Psychiatry 206: 216– 222. 25497297
- Domschke K, Tidow N, Kuithan H, Schwarte K, Klauke B, Ambrée O, Reif A, Schmidt H, Arolt V, Kersting A, Zwanzger P, Deckert J(2012) Monoamine oxidase A gene DNA hypomethylation - a risk factor for panic disorder? Int J Neuropsychopharmacol 15: 1217– 1228. 22436428
- Domschke K, Tidow N, Schrempf M, Schwarte K, Klauke B, Reif A, Kersting A, Arolt V, Zwanzger P, Deckert J(2013) Epigenetic signature of panic disorder: a role of glutamate decarboxylase 1 (GAD1) DNA hypomethylation? Prog Neuropsychopharmacol Biol Psychiatry 46: 189– 196. 23906988
- Domschke K, Tidow N, Schwarte K, Deckert J, Lesch KP, Arolt V, Zwanzger P, Baune BT(2014) Serotonin transporter gene hypomethylation predicts impaired antidepressant treatment response. Int J Neuropsychopharmacol 17: 1167– 1176. 24679990
- Domschke K, Tidow N, Schwarte K, Ziegler C, Lesch KP, Deckert J, Arolt V, Zwanzger P, Baune BT(2015) Pharmacoepigenetics of depression: no major influence of MAO-A DNA methylation on treatment response. J Neural Transm 122: 99– 108. 24809685
- Dubrovina NI, Popova NK, Gilinskii MA, Tomilenko RA, Seif I(2006) Acquisition and extinction of a conditioned passive avoidance reflex in mice with genetic knockout of monoamine oxidase A. Neurosci Behav Physiol 36: 335– 339. 16583159
- Herrmann MJ, Katzorke A, Busch Y, Gromer D, Polak T, Pauli P, Deckert J(2016) Medial prefrontal cortex stimulation accelerates therapy response of exposure therapy in acrophobia. Brain Stimul 10: 291– 297. 27931887
- Hotamisligil GS, Breakefield XO(1991) Human monoamine oxidase A gene determines levels of enzyme activity. Am J Hum Genet. 49: 383– 392. 1678250 PMC1683299
- Lattal KM, Wood MA(2013) Epigenetics and persistent memory: implications for reconsolidation and silent extinction beyond the zero. Nat Neurosci 16: 124– 129. 23354385 PMC3740093
- Lewin J, Schmitt AO, Adorján P, Hildmann T, Piepenbrock C(2004) Quantitative DNA methylation analysis based on four-dye trace data from direct sequencing of PCR amplificates. Bioinformatics 20: 3005– 3012. 15247106
- Reif A, Weber H, Domschke K, Klauke B, Baumann C, Jacob CP, Ströhle A, Gerlach AL, Alpers GW, Pauli P, Hamm A, Kircher T, Arolt V, Wittchen HU, Binder EB, Erhardt A, Deckert J(2012) Meta-analysis argues for a female-specific role of MAOA-uVNTR in panic disorder in four European populations. Am J Med Genet B Neuropsychiatr Genet 159B: 786– 793. 22911667
- Roberts S, Lester KJ, Hudson JL, Rapee RM, Creswell C, Cooper PJ, Thirlwall KJ, Coleman JRI, Breen G, Wong CCY, Eley TC(2014) Serotonin transporter [corrected] methylation and response to cognitive behaviour therapy in children with anxiety disorders. Transl Psychiatry 4: 444. PMC4203012 25226553
- Samochowiec J, Hajduk A, Samochowiec A, Horodnicki J, Stepień G, Grzywacz A, Kucharska-Mazur J(2004) Association studies of MAO-A, COMT, and 5-HTT genes polymorphisms in patients with anxiety disorders of the phobic spectrum. Psychiatry Res 128: 21– 26. 15450911
- Schiele MA, Domschke K(2018) Epigenetics at the crossroads between genes, environment and resilience in anxiety disorders. Genes Brain Behav 17:e12423. 28873274
- Shumay E, Logan J, Volkow ND, Fowler JS(2012) Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men. Epigenetics 7: 1151– 1160. 22948232 PMC3469457
- Stafford JM, Lattal KM(2011) Is an epigenetic switch the key to persistent extinction? Neurobiol Learn Mem 96: 35– 40. 21536141 PMC3111857
- Whittle N, Singewald N(2014) HDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: where do we stand? Biochem Soc T 42: 569– 581. PMC3961057 24646280
- Ziegler C, Richter J, Mahr M, Gajewska A, Schiele MA, Gehrmann A, Schmidt B, Lesch K-P, Lang T, Helbig-Lang S, Pauli P Kircher T, Reif A, Rief W, Vossbeck-Elsebusch AN, Arolt V, Wittchen H-U, Hamm AO, Deckert J, Domschke K(2016) MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy. Transl Psychiatry 6: e773. PMC4872399 27045843
- Ziegler C, et al(2018) Monoamine oxidase A gene methylation and its role in posttraumatic stress disorder - first evidence from the South Eastern Europe (SEE)-PTSD study. Int J Neuropsychopharmacol 21:423–432. PMC5932467 29186431
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Schiele, M. A., Gottschalk, M. G., & Domschke, K. (2020) · Clinical Psychology Review · doi:10.1016/j.cpr.2020.101830 · Cited by 156 · see citing works
Self-citationKolla, N. J., & Bortolato, M. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101875 · Cited by 138 · see citing works
Epigenetic signature of MAOA and MAOB genes in mental disorders
Ziegler, C., & Domschke, K. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1929-6 · Cited by 72 · see citing works
Self-citationCan epigenetics shine a light on the biological pathways underlying major mental disorders?
Alameda, L., Trotta, G., Quigley, H., Rodriguez, V., Gadelrab, R., Dwir, D., Dempster, E., Wong, C. C. Y., & Forti, M. D. (2022) · Psychological Medicine · doi:10.1017/s0033291721005559 · Cited by 60 · see citing works
“…et al. (2016) Candidate gene Blood BD/Borderline PD CA → ↑5-HT3A-R → clinical severity A MAOA ↓ Ziegler et al. (2016) Candidate gene Blood Panic disorder ↑ → Better response to CBT in agoraphobic symptpms ↓Schiele et al. (2018) Candidate gene Blood Agoraphobia ↓Domschke et al. (2012) Candidate…”
BackgroundInfluentialThe DNA methylome in panic disorder: A case-control and longitudinal psychotherapy-epigenetic study
Ziegler, C., Grundner-Culemann, F., Schiele, M. A., Schlosser, P., Kollert, L., Mahr, M., Gajewska, A., Lesch, K.-P., Deckert, J., Köttgen, A., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0648-6 · Cited by 47 · see citing works
Schiele, M. A., Kollert, L., Lesch, K.-P., Arolt, V., Zwanzger, P., Deckert, J., Ziegler, C., & Domschke, K. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2019.07.131 · Cited by 26 · see citing works
Self-citationPellicano, G. R., Daniela, S., Chiara, C., Arianna, G., Paola, A., & Carlo, L. (2022) · Journal of Affective Disorders Reports · doi:10.1016/j.jadr.2022.100310 · Cited by 6 · see citing works
- Authors
- Schiele, M. A., Ziegler, C., Kollert, L., Katzorke, A., Schartner, C., Busch, Y., Gromer, D., Reif, A., Pauli, P., Deckert, J., Herrmann, M. J., & Domschke, K.
- Affiliations
- University of Freiburg (DE)
- University of Würzburg (DE)
- University of California, San Francisco (US)
- Goethe University Frankfurt (DE)
- Corresponding author
- Domschke, Katharina
- ORCID
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-05-31
- Volume
- 21
- Issue
- 9
- Pages
- 822-827
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC6119289
- OpenAlex
- W2807182490
- Cited by
- 43
- References
- 3
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 13 · 2019: 6 · 2018: 3
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by-nc)
- Funders
- German Research Foundation (SFB-TRR-58)
- German Ministry of Research and Education (01EE1402F)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- acrophobia, monoamine oxidase A, DNA methylation, epigenetics, fear extinction, exposure therapy, treatment response, psychotherapy response, CpG methylation, luciferase reporter assay, female patients, fear of heights
- MeSH terms
- Adult, Anxiety, Extinction, Psychological, Female, Humans, Implosive Therapy, Middle Aged, Monoamine Oxidase, Phobic Disorders, Treatment Outcome, CpG Islands, DNA Methylation, Epigenesis, Genetic
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