Abstract
Suicide is a significant public health crisis, with 800,000 people dying annually. Most people completing suicide have previous psychiatric conditions, and those with psychotic and mood disorders are particularly vulnerable. Unfortunately, there are currently no biomarkers available for accurately detecting suicidal ideation. Given the genetic and environmental factors that play a role in suicidal ideation, we attempted to determine epigenetic modifications, specifically DNA methylation, in response to changes in suicidal ideation. Using a longitudinal study design, 31 participants with schizophrenia spectrum disorders were interviewed at a baseline visit and again at a follow-up visit 3–12 months later. Current suicidal ideation was recorded at both visits with the Columbia Suicide Severity Rating Scale and the Beck Scale for Suicide Ideation, and whole blood was collected for methylation analysis. Our analysis shows a significant negative correlation between cg26910920 methylation and increasing Columbia Suicide Severity Rating Scale scores and a positive correlation between cg13673029 methylation and increasing Beck Scale for Suicide Ideation scores. This pilot study indicates that there is the possibility that DNA methylation can respond to changes in suicidal ideation over time and potentially be used as a biomarker of suicidal ideation in the future.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The data related to this study are available for sharing upon reasonable request to the corresponding author.
References
Aryee MJ, Jaffe AE, Corrada-Bravo H, Ladd-Acosta C, Feinberg AP, Hansen KD, Irizarry RA (2014) Minfi: a flexible and comprehensive bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics 30(10):1363–1369. https://doi.org/10.1093/bioinformatics/btu049
Bai W, Liu ZH, Jiang YY, Zhang QE, Rao WW, Cheung T, Hall BJ, Xiang YT (2021) Worldwide prevalence of suicidal ideation and suicide plan among people with schizophrenia: a meta-analysis and systematic review of epidemiological surveys. Transl Psychiatry 11(1):552. https://doi.org/10.1038/s41398-021-01671-6
Beck AT, Kovacs M, Weissman A (1979) Assessment of suicidal intention: the scale for suicide ideation. J Consult Clin Psychol 47:343–352. https://doi.org/10.1037/0022-006X.47.2.343
Bergstedt J, Azzou SAK, Tsuo K, Jaquaniello A, Urrutia A, Rotival M, Lin DTS, MacIsaac JL, Kobor MS, Albert ML, Duffy D, Patin E, Quintana-Murci L (2022) The immune factors driving DNA methylation variation in human blood. Nat Commun 13(1):5895 https://doi.org/10.1038/s41467-022-33511-6
Dada O, Qian J, Al-Chalabi N, Kolla NJ, Graff A, Zai C, Gerretsen P, De Luca V (2021) Epigenetic studies in suicidal ideation and behavior. Psychiatr Genet 31(6):205–215. https://doi.org/10.1097/YPG.0000000000000298
Dwivedi Y (2012) The neurobiological basis of suicide. CRC Press, Boca Raton
Fagerström K-O (1978) Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment. Addict Behav 3(3):235–241. https://doi.org/10.1016/0306-4603(78)90024-2
First MB (2015) Structured clinical interview for the DSM (SCID). The encyclopedia of clinical psychology. Wiley, New York, pp 1–6. https://doi.org/10.1002/9781118625392.wbecp351
Fortin J-P, Triche TJ, Hansen KD (2017) Preprocessing, normalization and integration of the Illumina HumanMethylationEPIC array with minfi. Bioinformatics (oxford, England) 33(4):558–560. https://doi.org/10.1093/bioinformatics/btw691
Guidotti A, Dong E, Gavin DP, Veldic M, Zhao W, Bhaumik DK, Pandey SC, Grayson DR (2013) DNA methylation/demethylation network expression in psychotic patients with a history of alcohol abuse. Alcohol Clin Exp Res 37(3):417–424. https://doi.org/10.1111/j.1530-0277.2012.01947.x
Guo AY, Sun J, Riley BP, Thiselton DL, Kendler KS, Zhao Z (2009) The dystrobrevin-binding protein 1 gene: features and networks. Mol Psychiatry 14(1):18–29. https://doi.org/10.1038/mp.2008.88
Ho AM-C, Winham SJ, McCauley BM, Kundakovic M, Robertson KD, Sun Z, Ordog T, Webb LM, Frye MA, Veldic M (2021) Plasma cell-free DNA methylomics of bipolar disorder with and without rapid cycling. Front Neurosci 15:774037. https://doi.org/10.3389/fnins.2021.774037
Jia Y-F, Choi Y, Ayers-Ringler JR, Biernacka JM, Geske JR, Lindberg DR, McElroy SL, Frye MA, Choi D-S, Veldic M (2017) Differential SLC1A2 promoter methylation in bipolar disorder with or without addiction. Front Cell Neurosci 11:217. https://doi.org/10.3389/fncel.2017.00217
Kang H-J, Kim J-M, Lee J-Y, Kim S-Y, Bae K-Y, Kim S-W, Shin I-S, Kim H-R, Shin M-G, Yoon J-S (2013) BDNF promoter methylation and suicidal behavior in depressive patients. J Affect Disord 151(2):679–685. https://doi.org/10.1016/j.jad.2013.08.001
Kim J-M, Kang H-J, Bae K-Y, Kim S-W, Shin I-S, Kim H-R, Shin M-G, Yoon J-S (2014) Association of BDNF promoter methylation and genotype with suicidal ideation in elderly Koreans. Am J Geriatr Psychiatry off J Am Assoc Geriatr Psychiatry 22(10):989–996. https://doi.org/10.1016/j.jagp.2014.02.011
Laursen TM (2019) Causes of premature mortality in schizophrenia: a review of literature published in 2018. Curr Opin Psychiatry 32(5):388–393. https://doi.org/10.1097/YCO.0000000000000530
Mansell G, Gorrie-Stone TJ, Bao Y, Kumari M, Schalkwyk LS, Mill J, Hannon E (2019) Guidance for DNA methylation studies: Statistical insights from the Illumina EPIC array. BMC Genom 20(1):366. https://doi.org/10.1186/s12864-019-5761-7
Moore DS (2013) Behavioral genetics, genetics, and epigenetics. The Oxford handbook of developmental psychology, vol 1. Body and mind. Oxford University Press, Oxford, pp 91–128
Mullins N, Bigdeli TB, Børglum AD, Coleman JRI, Demontis D, Mehta D, Power RA, Ripke S, Stahl EA, Starnawska A, Anjorin A, Corvin A, Sanders AR, Forstner AJ, Reif A, Koller AC, Świątkowska B, Baune BT, Müller-Myhsok B et al (2019) GWAS of suicide attempt in psychiatric disorders and association with major depression polygenic risk scores. Am J Psychiatry 176(8):651–660. https://doi.org/10.1176/appi.ajp.2019.18080957
Nock MK, Banaji MR (2007) Assessment of self-injurious thoughts using a behavioral test. Am J Psychiatry 164(5):820–823. https://doi.org/10.1176/ajp.2007.164.5.820
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ (2011) The Columbia-suicide severity rating scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry 168(12):1266–1277. https://doi.org/10.1176/appi.ajp.2011.10111704
Prata DP, Costa-Neves B, Cosme G, Vassos E (2019) Unravelling the genetic basis of schizophrenia and bipolar disorder with GWAS: a systematic review. J Psychiatr Res 114:178–207. https://doi.org/10.1016/j.jpsychires.2019.04.007
Price EM, Robinson WP (2018) Adjusting for batch effects in DNA methylation microarray data, a lesson learned. Front Genet 9:83. https://doi.org/10.3389/fgene.2018.00083
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK (2015) Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucl Acids Res 43(7):e47. https://doi.org/10.1093/nar/gkv007
Roy B, Shelton RC, Dwivedi Y (2017) DNA methylation and expression of stress related genes in PBMC of MDD patients with and without serious suicidal ideation. J Psychiatr Res 89:115–124. https://doi.org/10.1016/j.jpsychires.2017.02.005
Saunders JB, Aasland OG, Babor TF, De La Fuente JR, Grant M (1993) Development of the alcohol use disorders identification test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption-II. Addiction 88(6):791–804. https://doi.org/10.1111/j.1360-0443.1993.tb02093.x
Sher L, Kahn RS (2019) Suicide in schizophrenia: an educational overview. Medicina (kaunas) 55(7):361. https://doi.org/10.3390/medicina55070361
Touleimat N, Tost J (2012) Complete pipeline for Infinium(®) Human Methylation 450K BeadChip data processing using subset quantile normalization for accurate DNA methylation estimation. Epigenomics 4(3):325–341. https://doi.org/10.2217/epi.12.21
WHO Collaborating Centre for Drug Statistics Methodology (2022) Guideline for ATC classification and DDD assignment. World Health Organization. https://www.whocc.no/filearchive/publications/2023_guidelines_web.pdf
World Health Organization (2019) Suicide in the world: global health estimates (WHO/MSD/MER/19.3). World Health Organization. https://apps.who.int/iris/handle/10665/326948
Xie C, Leung Y-K, Chen A, Long D-X, Hoyo C, Ho S-M (2019) Differential methylation values in differential methylation analysis. Bioinformatics 35(7):1094–1097. https://doi.org/10.1093/bioinformatics/bty778
Ziller MJ, Hansen KD, Meissner A, Aryee MJ (2015) Coverage recommendations for methylation analysis by whole-genome bisulfite sequencing. Nat Methods 12(3):230–232. https://doi.org/10.1038/nmeth.3152
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Al-Chalabi, N., Qian, J., Gerretsen, P. et al. Dynamic change in genome-wide methylation in response to increased suicidal ideation in schizophrenia spectrum disorders. J Neural Transm 130, 1303–1313 (2023). https://doi.org/10.1007/s00702-023-02661-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-023-02661-2