Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-10T15:56:51.841Z Has data issue: false hasContentIssue false
  • English
  • Français

Genetics of HPA-axis, depression and suicidality

Published online by Cambridge University Press:  16 April 2020

D. Wasserman ,
J. Wasserman  and
M. Sokolowski
D. Wasserman*
Affiliation:
The National Swedish Prevention of Suicide and Mental Ill-Health (NASP), Department of Public Health Sciences, Karolinska Institute (KI), Box 230, 171 77, Stockholm, Sweden
J. Wasserman
Affiliation:
The National Swedish Prevention of Suicide and Mental Ill-Health (NASP), Department of Public Health Sciences, Karolinska Institute (KI), Box 230, 171 77, Stockholm, Sweden
M. Sokolowski
Affiliation:
The National Swedish Prevention of Suicide and Mental Ill-Health (NASP), Department of Public Health Sciences, Karolinska Institute (KI), Box 230, 171 77, Stockholm, Sweden
*
*Corresponding author. Tel.: +46 8 52 48 69 37; fax: +46 8 30 64 39. E-mail address: Danuta.Wasserman@ki.se (D. Wasserman)
Get access

Abstract

The ultimate consequence of mental ill-health, suicidal behavior (SB), is a significant problem in most societies of the world. Suicide causes about one million deaths worldwide each year, and 10–20 times more people attempt suicide. The causes of why certain people engage in SB are complex, involving for e.g., both environmental and genetic factors, and interactions in-between. Well-established environmental risk factors are events causing significant psychological stress, which are particularly difficult to cope with, e.g. exposure to physical and sexual abuse. Excessive stress have the potential to induce unfavorable effects in a variety of higher brain-functions, incurred as side-effects to maladaptive responses in the genetically controlled stress-responsive neurosystems, e.g. the hypothalamic-pituitary-adrenal (HPA) axis; a major and systemic stress-modulator, which is mainly controlled by the regulatory corticotrophin releasing hormone receptor 1 (CRHR1) gene. Variation in-between individuals in such stress-regulatory genes such as CRHR1, may underlie the causes of the increased susceptibility of certain individuals towards SB. Here we review some of the current knowledge on what is known about the roles of the HPA axis in SB, with a focus on CRHR1.

Keywords

SuicidalityHPACRHR1StressDepressionReview
Type
Original article
Information
European Psychiatry , Volume 25 , Issue 5: The role of genetics in promoting suicide prevention and the mental health of the population - Nobel Conference: The role of genetics in promoting suicide prevention and the mental health of the population , June 2010 , pp. 278 - 280
Copyright
Copyright © Elsevier Masson SAS 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aguilera, G, Nikodemova, M, Wynn, PC, Catt, KJCorticotropin releasing hormone receptors: two decades later. Peptides 2004;25:319–329.10.1016/j.peptides.2004.02.002CrossRefGoogle ScholarPubMed
Binder, EB, Kunzel, HE, Nickel, T, Kern, N, Pfennig, A, Majer, Met al.HPA-axis regulation at in-patient admission is associated with antidepressant therapy outcome in male but not in female depressed patients. Psychoneuroendocrinology 2009;34:99–109.10.1016/j.psyneuen.2008.08.018CrossRefGoogle ScholarPubMed
Blomeyer, D, Treutlein, J, Esser, G, Schmidt, MH, Schumann, G, Laucht, MInteraction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use. Biol Psychiatry 2008;63:146–151.10.1016/j.biopsych.2007.04.026CrossRefGoogle ScholarPubMed
Bradley, R, Binder, E, Epstein, M, Tang, Y, Nair, H, Liu, Wet al.Influence of child abuse on adult depression. Arch Gen Psych 2008;65:190–200.10.1001/archgenpsychiatry.2007.26CrossRefGoogle ScholarPubMed
Coryell, W, Schlesser, MCombined biological tests for suicide prediction. Psychiatry Res 2007;150:187–191.10.1016/j.psychres.2006.01.021CrossRefGoogle ScholarPubMed
De Luca, V, Tharmalingam, S, Kennedy, JAssociation study between the corticotropin-releasing hormone receptor 2 gene and suicidality in bipolar disorder. Eur Psychiatry 2007;22:282–287.10.1016/j.eurpsy.2006.12.001CrossRefGoogle ScholarPubMed
De Luca, V, Tharmalingam, S, Zai, C, Potapova, N, Strauss, J, Vincent, Jet al.Association of HPA axis genes with suicidal behaviour in schizophrenia. J Psychopharmacol 2008. 10.1177/0269881108097817Google Scholar
Gallagher, JP, Orozco-Cabal, LF, Liu, J, Shinnick-Gallagher, PSynaptic physiology of central CRH system. Eur J Pharmacol 2008;583:215–225.10.1016/j.ejphar.2007.11.075CrossRefGoogle ScholarPubMed
Goldstein, DS, Kopin, IJEvolution of concepts of stress. Stress 2007;10:109–120.10.1080/10253890701288935CrossRefGoogle ScholarPubMed
Handwerger, KDifferential patterns of HPA activity and reactivity in adult posttraumatic stress disorder and major depressive disorder. Harv Rev Psychiatry 2009;17:184–205.10.1080/10673220902996775CrossRefGoogle ScholarPubMed
Heinrichs, SC, Koob, GFCorticotropin-releasing factor in brain: a role in activation, arousal, affect, regulation. J Pharmacol Exp Ther 2004;311:427–440.10.1124/jpet.103.052092CrossRefGoogle ScholarPubMed
Joels, M, Baram, TZThe neurosymphony of stress. Nat Rev Neurosci 2009;10:459–466.10.1038/nrn2632CrossRefGoogle ScholarPubMed
Licinio, J, O’Kirwan, F, Irizarry, K, Merriman, B, Thakur, S, Jepson, Ret al.Association of a corticotropin-releasing hormone receptor 1 haplotype and antidepressant treatment response in Mexican-Americans. Mol Psychiatry 2004;9:1075–1082.10.1038/sj.mp.4001587CrossRefGoogle ScholarPubMed
Liu, Z, Zhu, F, Wang, G, Xiao, Z, Tang, J, Liu, Wet al.Association study of corticotropin-releasing hormone receptor1 gene polymorphisms and antidepressant response in major depressive disorders. Neurosci Lett 2007;414:155–158.10.1016/j.neulet.2006.12.013CrossRefGoogle ScholarPubMed
Liu, Z, Zhu, F, Wang, G, Xiao, Z, Wang, H, Tang, Jet al.Association of corticotropin-releasing hormone receptor1 gene SNP and haplotype with major depression. Neurosci Lett 2006;404:358–362.10.1016/j.neulet.2006.06.016CrossRefGoogle ScholarPubMed
Lupien, SJ, McEwen, BS, Gunnar, MR, Heim, CEffects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 2009;10:434–445.10.1038/nrn2639CrossRefGoogle ScholarPubMed
Mann, JJ, Arango, VA, Avenevoli, S, Brent, DA, Champagne, FA, Clayton, Pet al.Candidate endophenotypes for genetic studies of suicidal behavior. Biol Psychiatry 2009;65:556–563.10.1016/j.biopsych.2008.11.021CrossRefGoogle ScholarPubMed
Mann, JJ, Currier, DA review of prospective studies of biological predictors of suicidal behavior in mood disorders. Arch Suicide Res 2007;11:3–16.10.1080/13811110600993124CrossRefGoogle Scholar
Merali, Z, Du, L, Hrdina, P, Palkovits, M, Faludi, G, Poulter, MOet al.Dysregulation in the suicide brain: mRNA expression of corticotropin-releasing hormone receptors and GABA(A) receptor subunits in frontal cortical brain region. J Neurosci 2004;24:1478–1485.10.1523/JNEUROSCI.4734-03.2004CrossRefGoogle ScholarPubMed
Merali, Z, Kent, P, Du, L, Hrdina, P, Palkovits, M, Faludi, Get al.Corticotropin-releasing hormone, arginine vasopressin, gastrin-releasing peptide, and neuromedin B alterations in stress-relevant brain regions of suicides and control subjects. Biol Psychiatry 2006;59:594–602.10.1016/j.biopsych.2005.08.008CrossRefGoogle ScholarPubMed
Nemeroff, CB, Owens, MJ, Bissette, G, Andorn, AC, Stanley, MReduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Arch Gen Psychiatry 1988;45:577–579.10.1001/archpsyc.1988.01800300075009CrossRefGoogle ScholarPubMed
Orozco-Cabal, L, Liu, J, Pollandt, S, Schmidt, K, Shinnick-Gallagher, P, Gallagher, JPDopamine and corticotropin-releasing factor synergistically alter basolateral amygdala-to-medial prefrontal cortex synaptic transmission: functional switch after chronic cocaine administration. J Neurosci 2008;28:529–542.10.1523/JNEUROSCI.2666-07.2008CrossRefGoogle ScholarPubMed
Papiol, S, Arias, B, Gasto, C, Gutierrez, B, Catalan, R, Fananas, LGenetic variability at HPA axis in major depression and clinical response to antidepressant treatment. J Affect Disord 2007;104:83–90.10.1016/j.jad.2007.02.017CrossRefGoogle ScholarPubMed
Schmid, B, Blomeyer, D, Treutlein, J, Zimmermann, US, Buchmann, AF, Schmidt, MHet al.Interacting effects of CRHR1 gene and stressful life events on drinking initiation and progression among 19-year-olds. Int J Neuropsychopharmacol 2009;17:1–12.Google Scholar
Touma, C, Bunck, M, Glasl, L, Nussbaumer, M, Palme, R, Stein, Het al.Mice selected for high versus low stress reactivity: a new animal model for affective disorders. Psychoneuroendocrinology 2008;33:839–862.10.1016/j.psyneuen.2008.03.013CrossRefGoogle ScholarPubMed
Treutlein, J, Kissling, C, Frank, J, Wiemann, S, Dong, L, Depner, Met al.Genetic association of the human corticotropin releasing hormone receptor 1 (CRHR1) with binge drinking and alcohol intake patterns in two independent samples. Mol Psychiatry 2006 594–602.10.1038/sj.mp.4001813CrossRefGoogle ScholarPubMed
Tyrka, AR, Price, LH, Gelernter, J, Schepker, C, Anderson, GM, Carpenter, LLInteraction of childhood maltreatment with the corticotropin-releasing hormone receptor gene: Effects on hypothalamic-pituitary-adrenal axis reactivity. Biol Psychiatry 2009;66:681–685.10.1016/j.biopsych.2009.05.012CrossRefGoogle ScholarPubMed
Valentino, RJ, Commons, KGPeptides that fine-tune the serotonin system. Neuropeptides 2005;39:39455.10.1016/j.npep.2004.09.005CrossRefGoogle ScholarPubMed
Valentino, RJ, Van Bockstaele, EConvergent regulation of locus coeruleus activity as an adaptive response to stress. Eur J Pharmacol 2008;583:194–203.10.1016/j.ejphar.2007.11.062CrossRefGoogle ScholarPubMed
Wasserman, D, Sokolowski, M, Rozanov, V, Wasserman, JThe CRHR1 gene - a marker for suicidality in depressed males exposed to low stress. Genes Brain Behav 2008;7:14–19.Google ScholarPubMed
Wasserman, D, Wasserman, C, Oxford Textbook of Suicidology - The Five Continents Perspective. Oxford, UK: Oxford University Press; 2009.10.1093/med/9780198570059.001.0001CrossRefGoogle Scholar
Wasserman, D, Wasserman, J, Rozanov, V, Sokolowski, MDepression in suicidal males: genetic risk-variants in the CRHR1 gene. Genes Brain Behav 2009;8:72–79.10.1111/j.1601-183X.2008.00446.xCrossRefGoogle ScholarPubMed
Willour, V, Chen, H, Toolan, J, Belmonte, P, Cutler, D, Goes, Fet al.Family-based association of FKBP5 in bipolar disorder. Mol Psychiatry 2008;14:261–268.10.1038/sj.mp.4002141CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.