Epigenetic changes in the CYP2D6 gene are related to severity of suicide attempt: A cross-sectional study of suicide attempters

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Boström, Adrian Desai E.Umeå universitet,Psykiatri,Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health/Neuropediatrics, Karolinska Institutet, Stockholm, Sweden,Umeå Univ, Dept Clin Sci Psychiat, Umeå, Sweden.;Karolinska Inst, Karolinska Univ Hosp, Ctr Psychiat Res, Dept Clin Neurosci, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm Hlth Care Serv, Reg Stockholm, SE-17176 Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth Neuropediat, Stockholm, Sweden. (författare)

Epigenetic changes in the CYP2D6 gene are related to severity of suicide attempt : A cross-sectional study of suicide attempters

Artikel/kapitelEngelska2023

Förlag, utgivningsår, omfång ...

Elsevier,2023
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:umu-205637
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-205637URI
https://doi.org/10.1016/j.jpsychires.2023.02.025DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-500011URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:152150180URI

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Språk:engelska
Sammanfattning på:engelska

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Background: The ability to accurately estimate risk of suicide deaths on an individual level remains elusive.Methods: This study reports on a case-control study set-up from a well-characterized cohort of 88 predominantly female suicide attempters (SA), stratified into low- (n = 57) and high-risk groups (n = 31) based on reports of later death by suicide, as well as degree of intent-to-die and lethality of SA method. We perform an unbiased analysis of 12,930 whole-blood derived CpG-sites (Illumina Infinium EPIC BeadChip) previously demonstrated to be more conciliable with brain-derived variations. The candidate site was validated by pyrosequencing. External replication was performed in (1) relation to age at index suicide attempt in 97 women with emotionally unstable personality disorder (whole-blood) and (2) death by suicide in a mixed group of 183 prefrontal-cortex (PFC) derived samples who died by suicide or from non-psychiatric etiologies.Results: CYP2D6-coupled CpG-site cg07016288 was hypomethylated in severe suicidal behavior (p < 10E-06). Results were validated by pyrosequencing (p < 0.01). Replication analyses demonstrate hypomethylation of cg07016288 in relation to age at index SA in females (p < 0.05) and hypermethylation in PFC of male suicide completers (p < 0.05). Limitations: Genotyping of CYP2D6 was not performed and CpG-site associations to gene expression were not explored.Conclusions: CYP2D6-coupled epigenetic markers are hypomethylated in females in dependency of features known to confer increased risk of suicide deaths and hypermethylated in PFC of male suicide completers. Further elucidating the role of CYP2D6 in severe suicidality or suicide deaths hold promise to deduce clinically meaningful results.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Psykiatri hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Psychiatry hsv//eng
cg07016288
CYP2D6
DNA methylation
Psychiatry
Suicide
Suicide prevention

Biuppslag (personer, institutioner, konferenser, titlar ...)

Jamshidi, EsmailUmeå universitet,Psykiatri,Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden,Umeå Univ, Dept Clin Sci Psychiat, Umeå, Sweden.;Reg Stockholm, Stockholm Hlth Care Serv, Stockholm, Sweden.(Swepub:umu)esja0010 (författare)
Manu, Diana-MariaUppsala universitet,Institutionen för kirurgiska vetenskaper,Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden(Swepub:uu)diaci119 (författare)
Kular, LaraKarolinska Institutet,Department of Clinical Neruoscience/Neuro, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden (författare)
Schiöth, Helgi B.Uppsala universitet,Funktionell farmakologi och neurovetenskap,Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden(Swepub:uu)helgschi (författare)
Åsberg, MarieKarolinska Institutet,Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden (författare)
Jokinen, JussiKarolinska Institutet,Umeå universitet,Psykiatri,Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden,Umeå Univ, Dept Clin Sci Psychiat, Umeå, Sweden.;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.(Swepub:umu)jujo0022 (författare)
Umeå universitetPsykiatri (creator_code:org_t)

Sammanhörande titlar

Ingår i:Journal of Psychiatric Research: Elsevier160, s. 217-2240022-39561879-1379

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Av författaren/redakt...: Boström, Adrian ...; Jamshidi, Esmail; Manu, Diana-Mari ...; Kular, Lara; Schiöth, Helgi B ...; Åsberg, Marie; visa fler...; Jokinen, Jussi; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Psykiatri

Artiklar i publikationen: Journal of Psych ...

Av lärosätet: Umeå universitet; Uppsala universitet; Karolinska Institutet

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