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Stress, genetics and epigenetic effects on the neurobiology of suicidal behavior and depression
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Alterations in a number of neurobiological systems have been associated with suicidal behavior including the serotonergic and noradrenergic systems and the hypothalamic-pituitary-adrenal axis. Altered functioning of these systems may stem from both genetic and developmental causes. Adversity in early-life has developmental consequences on these systems that persist into adulthood. Genetic differences may also contribute to alterations in functioning of neurobiological systems. Moreover, the interaction of early-life experiences of adversity and genetic vulnerability is increasingly thought to play a role, including via epigenetic mechanisms.
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“These results are in line with the widely perceived notion that complex genetic and environmental interactions have substantial effects on suicidality in MDD (Mann and Currier, 2010).”
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“During the past decade, an epigenetic approach has gained support to describe the joint action of genes and environment and its impact on adult health (Fiori & Turecki, 2016; McGowan et al., 2009; Teicher & Samson, 2013) and specifically on MDD (Bao & Swaab, 2014; Mann & Currier, 2010).”
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“Therefore, it is likely that pathologies of suicide behaviours are not associated with any specific psychiatric diagnosis (Mann and Currier, 2010) and postmortem studies appear to include clinically biased samples of severely”
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“Suicide risk is most likely mediated by a genetic diathesis interacting with environmental and psychosocial risk factors as well as epigenetic mechanisms that alter the function of neuronal circuits early in life, and exert effects persisting throughout adulthood [11,12,13].”
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“This might suggest that unlike violent suicide attempts and their correlation to serotonin pathways (Mann and Currier, 2010; van Heeringen et al., 2003), the dopaminergic system of the brain could possibly be the mediator of impulsivity as well as nonviolent suicide attempts.”
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Baek, J. H., Kim, K., Hong, J. P., Cho, M. J., D, M. F. M., Mischoulon, D., Chang, S. M., Kim, J., Cho, H., & Jeon, H. J. (2018) · PLoS ONE · doi:10.1371/journal.pone.0198192 · Cited by 22
Posner, K., Subramany, R., Amira, L., & Mann, J. J. (2014) · Springer eBooks · doi:10.1007/978-3-319-09964-4_4 · Cited by 24
Self-citationBielau, H., Brisch, R., Bernard-Mittelstaedt, J., Dobrowolny, H., Gos, T., Baumann, B., Mawrin, C., Bernstein, H., Bogerts, B., & Steiner, J. (2012) · Brain Research · doi:10.1016/j.brainres.2012.04.022 · Cited by 17
Aggression among 216 patients with a first-psychotic episode of bipolar I disorder
Khalsa, H.-M. K., Baldessarini, R. J., Tohen, M. F., & Salvatore, P. (2018) · International Journal of Bipolar Disorders · doi:10.1186/s40345-018-0126-8 · Cited by 20
“…of candidate endophenotypes of vulnerability to suicide, including impulsive aggression as well as disadvantageous decision making and deficits in risk assessment, with possibly related disturbances in prefrontal cortical functioning (Mann and Currier 2010; Courtet and Guillaume 2011).”
BackgroundEndophenotypes as a measure of suicidality
Chistiakov, D. A., Kekelidze, Z. I., & Chekhonin, V. P. (2012) · Journal of Applied Genetics · doi:10.1007/s13353-012-0113-1 · Cited by 22
Sher, L., Flory, J. D., Bierer, L. M., Makotkine, I., & Yehuda, R. (2018) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12897 · Cited by 19
“Considerable evidence suggests that suicidal behaviour is associated with hyperactivity of the HPA axis (47, 48).”
BackgroundZhang, Q., Hong, S., Cao, J., Zhou, Y., Xu, X., Ai, M., & Kuang, L. (2021) · BioMed Research International · doi:10.1155/2021/5524846 · Cited by 18
“Although it was originally regarded as an extreme outcome of MDD and then as a potential confounding factor in studies ofmood disorder neurobiology, suicide is increasingly thought to have its own unique neurobiological mechanisms [3, 4].”
BackgroundOverlapping genetic effects between suicidal ideation and neurocognitive functioning
Brick, L. A. D., Marraccini, M. E., Micalizzi, L., Benca‐Bachman, C. E., Knopik, V. S., & Palmer, R. H. C. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.02.003 · Cited by 19
“It is possible that ideation, behavior, attempts, and completion may represent related, but distinct constructs and therefore may be differentially heritable (Mann et al., 2009; Mann and Currier, 2010; Zai et al., 2012).”
BackgroundCabello-Arreola, A., Ho, A. M., Özerdem, A., Barboza, A. B. C., Küçüker, M. U., Heppelmann, C. J. H., Charlesworth, M. C., Ceylan, D., Stockmeier, C. A., Rajkowska, G., et al. (2020) · Genes · doi:10.3390/genes11030256 · Cited by 20
“In the search for candidate genes involved in suicide and attempted suicide, previous studies have examined genes implicated in neurotransmitter systems, including the GABAergic, glutamatergic, serotonergic, noradrenergic, and dopaminergic systems [9,10].”
BackgroundBody Composition, Sarcopenia, and Suicidal Ideation in Elderly Koreans: Hallym Aging Study
Kim, J. H., Kim, D.-H., & Park, Y. S. (2016) · Journal of Korean Medical Science · doi:10.3346/jkms.2016.31.4.604 · Cited by 18
“Serotonergic dysfunction, such as low levels of the serotonin metabolite in cerebrospinal fluid or altered serotonin receptor and transporter binding, has been extensively studied in adults as a possible biological marker of suicide (30).”
BackgroundKim, H., Jeon, H. J., Bae, J. N., Cho, M. J., Cho, S. J., Lee, H., & Hong, J. P. (2018) · Psychiatry Investigation · doi:10.30773/pi.2017.06.28 · Cited by 18
Fröding, E., Gäre, B. A., Westrin, Å., & Ros, A. (2021) · BMJ Open · doi:10.1136/bmjopen-2020-044068 · Cited by 20
War Duration and the Micro-Dynamics of Decision Making under Stress
Stanley, E. A. (2018) · Polity · doi:10.1086/696359 · Cited by 16
Impulsivity and Saliva Cortisol in Patients with Suicide Attempt and Controls
Lewitzka, U., Bauer, M., Ripke, B., Bronisch, T., & Günther, L. (2017) · Neuropsychobiology · doi:10.1159/000484664 · Cited by 16
Cadeddu, R., Ibba, M., Sadile, A. G., & Carboni, E. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3335-y · Cited by 16
Impulsivity, aggression, and impulsive aggression in suicidality
Moore, F. R., Allott, C., & O’Connor, R. C. (2022) · Personality and Individual Differences · doi:10.1016/j.paid.2022.111971 · Cited by 15
“…with models in which physical aggression and impulsivity are treated as a single phenotype in relation to suicide (e.g. Mann et al., 1999; Mann & Currier, 2010; Seroczynski et al., 1999), and we argue that aggression should be targeted in suicide intervention, further work is required to…”
BackgroundFurther Evidence ofDepdc7Dna Hypomethylation in Depression: a Study in Adult Twins
Córdova‐Palomera, A., Fatjó‐Vilas, M., Palma‐Gudiel, H., Blasco-Fontecilla, H., Kébir, O., & Fañanás, L. (2015) · European Psychiatry · doi:10.1016/j.eurpsy.2015.04.001 · Cited by 15
“into the genome via DNA methylation changes, which may ultimately lead to gene expression disruptions that increase the risk for depressive psychopathology [21,24].”
BackgroundBehavioral Epigenetics: Perspectives Based on Experience-Dependent Epigenetic Inheritance
Pang, Y.-Y., Lu, R. J.-H., & Chen, P. (2019) · Epigenomes · doi:10.3390/epigenomes3030018 · Cited by 18
“As a result, aberrant epigenetic regulation can disrupt the HPA axis activity, leading to an increased risk of suicide [9].”
BackgroundBenedetti, S., Bucciarelli, S., Canestrari, F., Catalani, S., Mandolini, S., Marconi, V., Mastrogiacomo, A. R., Silvestri, R., Tagliamonte, M. C., Venanzini, R., et al. (2014) · Open Journal of Depression · doi:10.4236/ojd.2014.32011 · Cited by 13
“…as well as different ways to highlight biological markers of suicide have been tried (Turecki, Ernst, Jollant et al., 2012; Pandey & Dwivedi, 2012; Pandey, 2011; Mann & Currier, 2010; Donati, Dwivedi, Roberts et al., 2008; Mann, 2003; Turecki, 2001; Stanley & Stanley, 1989; Stanley et al., 1986).”
BackgroundEpigenetic Clues to the Biological Embedding of Early Life Adversity
McGowan, P. O. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.04.017 · Cited by 14
“Early-life adversity in the form of physical and sexual abuse or severe neglect is well recognized to increase the risk of suicide (3).”
BackgroundThe potential of microRNAs as putative biomarkers in major depressive disorder and suicidal behavior
Serafini, G., Trabucco, A., Corsini, G. P., Escelsior, A., Amerio, A., Aguglia, A., Nasrallah, H. A., & Amore, M. (2021) · Biomarkers in Neuropsychiatry · doi:10.1016/j.bionps.2021.100035 · Cited by 14
Kukoyi, O. B., Orok, E. N., Oluwafemi, F. S., Oni, O. I., Oluwadare, T., Ojo, T. F., Bamitale, T. D., Jaiyesimi, B., & Iyamu, D. (2023) · Middle East Current Psychiatry · doi:10.1186/s43045-022-00274-1 · Cited by 21
Fudalej, S., Klimkiewicz, A., Mach, A., Jakubczyk, A., Fudalej, M., Wasilewska, K., Podgórska, A., Krajewski, P., Płoski, R., & Wojnar, M. (2017) · American Journal on Addictions · doi:10.1111/ajad.12571 · Cited by 12
“The majority of previous research on the genetic vulnerability to suicidal behavior focused on the serotonergic system, the noradrenergic system and the hypothalamic– pituitary–adrenal axis.(3) The results of the previous studies are often inconsistent and require further clarification.”
BackgroundClinical correlates and prognostic impact of binge-eating symptoms in major depressive disorder
Olgiati, P., Fanelli, G., Atti, A. R., Ronchi, D. D., & Serretti, A. (2022) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000422 · Cited by 15
MicroRNAs as novel peripheral markers for suicidality in patients with major depressive disorder
Stapel, B., Xiao, K., Gorinski, N., Schmidt, K., Pfanne, A., Fiedler, J., Richter, I., Vollbrecht, A.-L., Thum, T., Kahl, K. G., et al. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1020530 · Cited by 10
“Accordingly, it is generally thought that vulnerability to suicidal behavior is mediated partly by an underlying genetic predisposition, which interacts with environmental and probable epigenetic factors (39), and might be reflected by changes in miRNA expression.”
BackgroundUnderwood, M. D., Galfalvy, H., Hsiung, S., Liu, Y., Simpson, N. R., Bakalian, M. J., Rosoklija, G. B., Dwork, A. J., Arango, V., & Mann, J. J. (2023) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyad025 · Cited by 10
“These same brain regions are reported to have neurochemical and morphologic alterations in suicide and ELA (Mann and Currier, 2010; van Heeringen and Mann, 2014; Underwood et al., 2019).”
BackgroundSelf-citationChenthamara, D., Prasathkumar, M., Robert, B., Anisha, S., Sadhasivam, S., Essa, M. M., Chidambaram, S. B., Al-Balushi, B., Guillemin, G. J., & Qoronfleh, M. W. (2020) · International Journal of Tryptophan Research · doi:10.1177/1178646920978243 · Cited by 10
López-Moríñigo, J.-D., Boldrini, M., Ricca, V., Oquendo, M. A., & Baca‐García, E. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10143057 · Cited by 9
Multiple tissue methylation analysis of HTR2A exon I in suicidal behavior
Bani‐Fatemi, A., Strauss, J., Zai, C. C. H., Wong, A. H. C., & Luca, V. D. (2017) · Psychiatric Genetics · doi:10.1097/ypg.0000000000000183 · Cited by 10
Completed Suicide in An Autopsy-Confirmed Case of Early Onset Alzheimer’s Disease
Hartzell, J. W., Geary, R., Gyure, K. A., Chivukula, V. R., & Haut, M. W. (2018) · Neurodegenerative Disease Management · doi:10.2217/nmt-2017-0045 · Cited by 9
“Neurobiological abnormalities in the brains of suicide victims, particularly within the serotonergic system, have also been identified and explored through molecular genetics research [30,31].”
BackgroundParental Psychopathology and Offspring Suicidality in Mexico
Borges, G. L. G., Borges-Monroy, R., Mora, M.-E. M., Benjet, C. L., & Nock, M. K. (2013) · Archives of Suicide Research · doi:10.1080/13811118.2013.776449 · Cited by 8
“These abnormalities could be caused by the interaction of genotypes and=or early-life experiences (Caspi et al., 2003; Mann & Currier, 2010).”
BackgroundРоль генома в суицидальном поведении (обзор литературы)
Kozlov, V. A., Голенков, А. В., & Sapozhnikov, S. P. (2021) · Суицидология · doi:10.32878/suiciderus.21-12-01(42)-3-22 · Cited by 8
Lamontagne, S. J., Ballard, E. D., & Zarate, C. A. (2022) · Neurobiology of Stress · doi:10.1016/j.ynstr.2022.100450 · Cited by 10
“with suicidal behaviors, particularly reduced concentrations of extracellular 5-HT and its metabolite, 5-HIAA (Mann et al., 1989).”
Background
Metadata
- Authors
- Mann, J. J., & Currier, D. M.
- Affiliations
- Columbia University (US)
- Corresponding author
- Mann, J.J.
- Venue
- European Psychiatry
- Publisher
- Cambridge University Press (CUP)
- Published
- 2010-06
- Volume
- 25
- Issue
- 5
- Pages
- 268-271
- ISSN
- 0924-9338 (ISSN-L)
- 1778-3585
- PMC
- PMC2896004
- OpenAlex
- W2034761715
- Cited by
- 169
- References
- 29
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 4 · 2023: 6 · 2022: 11 · 2021: 16 · 2020: 4 · 2019: 9 · 2018: 14 · 2017: 13 · 2016: 13 · 2015: 13 · 2014: 20 · 2013: 11 · 2012: 16
- FWCI
- 12.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH 62185, R10MH056390, MH48514, R01MH082041, MH56390, R01MH048514, MH82041, R01MH056390, P50MH062185)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- suicidal behavior, depression, stress, epigenetics, genetics, neurobiology, serotonergic system, noradrenergic system, hypothalamic-pituitary-adrenal axis, childhood adversity, genetic susceptibility, gene-environment interaction
- MeSH terms
- Depressive Disorder, Humans, Stress, Psychological, Suicide, Epigenesis, Genetic
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