Suicide takes a heavy toll on society but can often be avoided through adequate treatment. However, societal normalities and taboos often make it difficult for individuals who experience suicidal ideation or aspects of suicidal behaviour to seek help before it is too late.
Many factors contribute to suicidal behaviour and these can be globally classified as distal factors, which increase predisposition to suicide, and proximal factors, which precipitate a suicidal act.
Distal factors comprise a family history of suicide, indicating a genetic predisposition, genetic variation between individuals and experiences of early-life adversity. Early-life adversity can result in stable changes to gene expression, which results in increased lifetime susceptibility to suicidal behaviour.
Early-life adversity epigenetically regulates stress response systems and neuronal plasticity, which are associated with emotional and behavioural changes.
Behavioural and emotional traits are known mediators of suicide risk, with impulsive aggressive and anxiety traits being intimately linked to suicidal behaviour.
Proximal factors are associated with precipitation of the suicidal act and can be linked to changes in neurotransmitter levels, inflammation in the CNS and glial, notably astrocytic, dysfunction.
Suicide ranks among the leading causes of death around the world and takes a heavy emotional and public health toll on most societies. Both distal and proximal factors contribute to suicidal behaviour. Distal factors — such as familial and genetic predisposition, as well as early-life adversity — increase the lifetime risk of suicide. They alter responses to stress and other processes through epigenetic modification of genes and associated changes in gene expression, and through the regulation of emotional and behavioural traits. Proximal factors are associated with the precipitation of a suicidal event and include alterations in key neurotransmitter systems, inflammatory changes and glial dysfunction in the brain. This Review explores the key molecular changes that are associated with suicidality and discusses some promising avenues for future research.
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Mann, J. J. et al. Suicide prevention strategies: a systematic review. JAMA 294, 2064–2074 (2005).
Duffy, A. M., The quiet epidemic. The Ottawa Citizen, Supplement on Suicide (2003).
Silverman, M. M. The language of suicidology. Suicide Life Threat. Behav. 36, 519–532 (2006).
Kapur, N., Cooper, J., O'Connor, R. C. & Hawton, K. Non-suicidal self-injury v. attempted suicide: new diagnosis or false dichotomy? Br. J. Psychiatry 202, 326–328 (2013).
Brezo, J. et al. Identifying correlates of suicide attempts in suicidal ideators: a population-based study. Psychol. Med. 37, 1551–1562 (2007).
Arsenault-Lapierre, G., Kim, C. & Turecki, G. Psychiatric diagnoses in 3275 suicides: a meta-analysis. BMC Psychiatry 4, 37 (2004).
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 5th edn (American Psychiatric Publishing, 2013).
Dumais, A. et al. Risk factors for suicide completion in major depression: a case-control study of impulsive and aggressive behaviors in men. Am. J. Psychiatry 162, 2116–2124 (2005). This study clearly shows that when depressive psychopathology is controlled for, impulsive aggressive traits are strongly associated with suicide, particularly among young suicide completers.
McGirr, A. et al. Impulsive-aggressive behaviours and completed suicide across the life cycle: a predisposition for younger age of suicide. Psychol. Med. 38, 407–417 (2008).
Beautrais, A. L. Suicide and serious suicide attempts in youth: a multiple-group comparison study. Am. J. Psychiatry 160, 1093–1099 (2003).
Dalca, I. M., McGirr, A., Renaud, J. & Turecki, G. Gender-specific suicide risk factors: a case-control study of individuals with major depressive disorder. J. Clin. Psychiatry 74, 1209–1216 (2013).
O'Connor, R. C., Platt, S. & Gordon, J. (eds) International Handbook of Suicide Prevention: Research, Policy and Practice (John Wiley & Sons, 2011).
Moscicki, E. K. Gender differences in completed and attempted suicides. Ann. Epidemiol. 4, 152–158 (1994).
Mann, J. J. Neurobiology of suicidal behaviour. Nature Rev. Neurosci. 4, 819–828 (2003).
Tidemalm, D. et al. Familial clustering of suicide risk: a total population study of 11.4 million individuals. Psychol. Med. 41, 2527–2534 (2011).
Baldessarini, R. J. & Hennen, J. Genetics of suicide: an overview. Harv. Rev. Psychiatry 12, 1–13 (2004).
Turecki, G. Suicidal behavior: is there a genetic predisposition? Bipolar Disord. 3, 335–349 (2001).
Brent, D. What family studies teach us about suicidal behavior: implications for research, treatment, and prevention. Eur. Psychiatry 25, 260–263 (2010).
Brent, D. A., Bridge, J., Johnson, B. A. & Connolly, J. Suicidal behavior runs in families. A controlled family study of adolescent suicide victims. Arch. Gen. Psychiatry 53, 1145–1152 (1996). This is an important study that convincingly shows that familial aggregation of suicide is not exclusively explained by psychopathology.
Lieb, R., Bronisch, T., Hofler, M., Schreier, A. & Wittchen, H. U. Maternal suicidality and risk of suicidality in offspring: findings from a community study. Am. J. Psychiatry 162, 1665–1671 (2005).
Blum, R., Sudhinaraset, M. & Emerson, M. R. Youth at risk: suicidal thoughts and attempts in Vietnam, China, and Taiwan. J. Adolesc. Health 50, S37–S44 (2012).
Kim, C. D. et al. Familial aggregation of suicidal behavior: a family study of male suicide completers from the general population. Am. J. Psychiatry 162, 1017–1019 (2005).
McGirr, A. et al. Familial aggregation of suicide explained by cluster B traits: a three-group family study of suicide controlling for major depressive disorder. Am. J. Psychiatry 166, 1124–1134 (2009).
Ernst, C., Mechawar, N. & Turecki, G. Suicide neurobiology. Prog. Neurobiol. 89, 315–333 (2009).
von Borczyskowski, A., Lindblad, F., Vinnerljung, B., Reintjes, R. & Hjern, A. Familial factors and suicide: an adoption study in a Swedish National Cohort. Psychol. Med. 41, 749–758 (2011).
Mann, J. J. The serotonergic system in mood disorders and suicidal behaviour. Phil. Trans. R. Soc. B 368, 20120537 (2013).
Bach, H. & Arango, V. in The Neurobiological Basis of Suicide (ed. Dwivedi, Y.) (CRC Press, 2012).
Brezo, J., Klempan, T. & Turecki, G. The genetics of suicide: a critical review of molecular studies. Psychiatr. Clin. North Am. 31, 179–203 (2008).
Laje, G. et al. Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients. Pharmacogenet. Genom. 19, 666–674 (2009).
Menke, A. et al. Genome-wide association study of antidepressant treatment-emergent suicidal ideation. Neuropsychopharmacology 37, 797–807 (2012).
Perlis, R. H. et al. Genome-wide association study of suicide attempts in mood disorder patients. Am. J. Psychiatry 167, 1499–1507 (2010).
Perroud, N. et al. Genome-wide association study of increasing suicidal ideation during antidepressant treatment in the GENDEP project. Pharmacogenom. J. 12, 68–77 (2012).
Schosser, A. et al. Genomewide association scan of suicidal thoughts and behaviour in major depression. PLoS ONE 6, e20690 (2011).
Willour, V. L. et al. A genome-wide association study of attempted suicide. Mol. Psychiatry 17, 433–444 (2012).
Galfalvy, H. et al. A pilot genome wide association and gene expression array study of suicide with and without major depression. World J. Biol. Psychiatry 14, 574–582 (2013).
Perlis, R. H., Ruderfer, D., Hamilton, S. P. & Ernst, C. Copy number variation in subjects with major depressive disorder who attempted suicide. PLoS ONE 7, e46315 (2012).
Fergusson, D. M., Woodward, L. J. & Horwood, L. J. Risk factors and life processes associated with the onset of suicidal behaviour during adolescence and early adulthood. Psychol. Med. 30, 23–39 (2000).
Angst, J., Degonda, M. & Ernst, C. The Zurich Study: XV. Suicide attempts in a cohort from age 20 to 30. Eur. Arch. Psychiatry Clin. Neurosci. 242, 135–141 (1992).
Afifi, T. O. et al. Population attributable fractions of psychiatric disorders and suicide ideation and attempts associated with adverse childhood experiences. Am. J. Publ. Health 98, 946–952 (2008).
Gilbert, R. et al. Burden and consequences of child maltreatment in high-income countries. Lancet 373, 68–81 (2009).
Collishaw, S. et al. Resilience to adult psychopathology following childhood maltreatment: Evidence from a community sample. Child Abuse Neglect 31, 211–229 (2007).
Lansford, J. E. et al. A 12-year prospective study of the long-term effects of early child physical maltreatment on psychological, behavioral, and academic problems in adolescence. Arch. Pediatr. Adolescent Med. 156, 824–830 (2002).
Fanous, A. H., Prescott, C. A. & Kendler, K. S. The prediction of thoughts of death or self-harm in a population-based sample of female twins. Psychol. Med. 34, 301–312 (2004).
Brezo, J. et al. Predicting suicide attempts in young adults with histories of childhood abuse. Br. J. Psychiatry 193, 134–139 (2008).
Brezo, J. et al. Natural history of suicidal behaviors in a population-based sample of young adults. Psychol. Med. 37, 1563–1574 (2007).
Lopez-Castroman, J. et al. Suicidal phenotypes associated with family history of suicidal behavior and early traumatic experiences. J. Affect Disord. 142, 193–199 (2012).
Lopez-Castroman, J. et al. Early childhood sexual abuse increases suicidal intent. World Psychiatry 12, 149–154 (2013).
Cole, P. M., Michel, M. K. & Teti, L. O. The development of emotion regulation and dysregulation: a clinical perspective. Monogr. Soc. Res. Child Dev. 59, 73–100 (1994).
Malatesta, C. Z. The role of emotions in the development and organization of personality. Nebr. Symp. Motiv. 36, 1–56 (1988).
Smith, P. N. et al. The relationships of attachment style and social maladjustment to death ideation in depressed women with a history of childhood sexual abuse. J. Clin. Psychol. 68, 78–87 (2012).
Hertzman, C. Putting the concept of biological embedding in historical perspective. Proc. Natl Acad. Sci. USA 109 (Suppl. 2), 17160–17167 (2012).
Raison, C. L. & Miller, A. H. When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am. J. Psychiatry 160, 1554–1565 (2003).
Heim, C., Shugart, M., Craighead, W. E. & Nemeroff, C. B. Neurobiological and psychiatric consequences of child abuse and neglect. Dev. Psychobiol 52, 671–690 (2010).
McGowan, P. O. et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neurosci. 12, 342–348 (2009). This study shows for the first time in humans that adversity in childhood can induce brain methylation changes in crucial genes.
Conradt, E., Lester, B. M., Appleton, A. A., Armstrong, D. A. & Marsit, C. J. The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior. Epigenetics 8, 1321–1329 (2013).
Perroud, N. et al. Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Transl. Psychiatry 1, e59 (2011).
Labonte, B. et al. Genome-wide epigenetic regulation by early-life trauma. Arch. Gen. Psychiatry 69, 722–731 (2012). This study is the first genome-wide study that examines the effect of early-life trauma on methylation in the brains of suicide completers.
van der Knaap, L. J. et al. Glucocorticoid receptor gene (NR3C1) methylation following stressful events between birth and adolescence. The TRAILS study. Transl. Psychiatry 4, e381 (2014).
Perroud, N. et al. Childhood maltreatment and methylation of the glucocorticoid receptor gene NR3C1 in bipolar disorder. Br. J. Psychiatry 204, 30–35 (2014).
Melas, P. A. et al. Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities. Int. J. Neuropsychopharmacol 16, 1513–1528 (2013).
Davies, M. N. et al. Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biol. 13, R43 (2012).
Binder, E. B. et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 299, 1291–1305 (2008).
Mehta, D. et al. Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: evidence from endocrine and gene expression studies. Arch. Gen. Psychiatry 68, 901–910 (2011).
Willour, V. L. et al. Family-based association of FKBP5 in bipolar disorder. Mol. Psychiatry 14, 261–268 (2009).
Supriyanto, I. et al. Association of FKBP5 gene haplotypes with completed suicide in the Japanese population. Prog. Neuropsychopharmacol. Biol. Psychiatry 35, 252–256 (2011).
Leszczynska-Rodziewicz, A. et al. Possible association between haplotypes of the FKBP5 gene and suicidal bipolar disorder, but not with melancholic depression and psychotic features, in the course of bipolar disorder. Neuropsychiatr. Dis. Treat. 10, 243–248 (2014).
Brent, D. et al. Association of FKBP5 polymorphisms with suicidal events in the Treatment of Resistant Depression in Adolescents (TORDIA) study. Am. J. Psychiatry 167, 190–197 (2010).
Perroud, N. et al. Clinical and genetic correlates of suicidal ideation during antidepressant treatment in a depressed outpatient sample. Pharmacogenomics 12, 365–377 (2011).
Roy, A., Gorodetsky, E., Yuan, Q., Goldman, D. & Enoch, M. A. Interaction of FKBP5, a stress-related gene, with childhood trauma increases the risk for attempting suicide. Neuropsychopharmacology 35, 1674–1683 (2010).
Roy, A., Hodgkinson, C. A., Deluca, V., Goldman, D. & Enoch, M. A. Two HPA axis genes, CRHBP and FKBP5, interact with childhood trauma to increase the risk for suicidal behavior. J. Psychiatr. Res. 46, 72–79 (2012).
Klengel, T. et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nature Neurosci. 16, 33–41 (2013).
Labonte, B. et al. Genome-wide methylation changes in the brains of suicide completers. Am. J. Psychiatry 170, 511–520 (2013).
Weder, N. et al. Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry. J. Am. Acad. Child Adolesc. Psychiatry 53, 417–424 (2014).
Roth, T. L., Lubin, F. D., Funk, A. J. & Sweatt, J. D. Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol. Psychiatry 65, 760–769 (2009).
Roth, T. L., Zoladz, P. R., Sweatt, J. D. & Diamond, D. M. Epigenetic modification of hippocampal BDNF DNA in adult rats in an animal model of post-traumatic stress disorder. J. Psychiatr. Res. 45, 919–926 (2011).
Uchida, S. et al. Epigenetic status of Gdnf in the ventral striatum determines susceptibility and adaptation to daily stressful events. Neuron 69, 359–372 (2011).
Dwivedi, Y. et al. Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch. Gen. Psychiatry 60, 804–815 (2003).
Pandey, G. N. et al. Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims. Int. J. Neuropsychopharmacol. 11, 1047–1061 (2008).
Ernst, C. et al. Alternative splicing, methylation state, and expression profile of tropomyosin-related kinase B in the frontal cortex of suicide completers. Arch. Gen. Psychiatry 66, 22–32 (2009).
Maussion, G. et al. Functional DNA methylation in a transcript specific 3′UTR region of TRKB associates with suicide. Epigenetics 9, 1061–1070 (2014).
Keller, S. et al. Increased BDNF promoter methylation in the Wernicke area of suicide subjects. Arch. Gen. Psychiatry 67, 258–267 (2010).
Banerjee, R., Ghosh, A. K., Ghosh, B., Bhattacharyya, S. & Mondal, A. C. Decreased mRNA and protein expression of BDNF, NGF, and their receptors in the hippocampus from suicide: an analysis in human postmortem brain. Clin. Med. Insights Pathol. 6, 1–11 (2013).
Zhang, X. et al. Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis. Cell 126, 1189–1201 (2006).
Fuchikami, M. et al. DNA methylation profiles of the brain-derived neurotrophic factor (BDNF) gene as a potent diagnostic biomarker in major depression. PLoS ONE 6, e23881 (2011).
Kang, H. J. et al. BDNF promoter methylation and suicidal behavior in depressive patients. J. Affect. Disord. 151, 679–685 (2013).
Kim, J. M. et al. Association of BDNF promoter methylation and genotype with suicidal ideation in elderly Koreans. Am. J. Geriatr. Psychiatry 22, 989–996 (2014).
Michels, K. B. et al. Recommendations for the design and analysis of epigenome-wide association studies. Nature Methods 10, 949–955 (2013). This article outlines the key considerations for future genome-wide studies, focusing on epigenetic regulation; these recommendations will help to strengthen the data gathered from such large-scale studies.
Yang, B. Z. et al. Child abuse and epigenetic mechanisms of disease risk. Am. J. Prev. Med. 44, 101–107 (2013).
Turecki, G., Ernst, C., Jollant, F., Labonte, B. & Mechawar, N. The neurodevelopmental origins of suicidal behavior. Trends Neurosci. 35, 14–23 (2012).
Wanner, B., Vitaro, F., Tremblay, R. E. & Turecki, G. Childhood trajectories of anxiousness and disruptiveness explain the association between early-life adversity and attempted suicide. Psychol. Med. 42, 2373–2382 (2012). Through trajectory analyses, this study gathers longitudinal data to describe the behavioural phenotypes that link ELA to suicide attempts.
Courtet, P., Gottesman, I., Jollant, F. & Gould, T. D. The neuroscience of suicidal behaviors: what can we expect from endophenotype strategies? Transl. Psychiatry 1, e7 (2011).
Mann, J. J. et al. Candidate endophenotypes for genetic studies of suicidal behavior. Biol. Psychiatry 65, 556–563 (2009).
Brezo, J. et al. Childhood trajectories of anxiousness and disruptiveness as predictors of suicide attempts. Arch. Pediatr. Adolesc. Med. 162, 1015–1021 (2008).
Brent, D. A. et al. Familial transmission of mood disorders: convergence and divergence with transmission of suicidal behavior. J. Am. Acad. Child Adolesc. Psychiatry 43, 1259–1266 (2004).
Gureje, O. et al. Parental psychopathology and the risk of suicidal behavior in their offspring: results from the World Mental Health surveys. Mol. Psychiatry 16, 1221–1233 (2010).
Brezo, J., Paris, J. & Turecki, G. Personality traits as correlates of suicidal ideation, suicide attempts, and suicide completions: a systematic review. Acta Psychiatr. Scand. 113, 180–206 (2006).
Brezo, J. et al. Broad and narrow personality traits as markers of one-time and repeated suicide attempts: a population-based study. BMC Psychiatry 8, 15 (2008).
Fergusson, D. M., Beautrais, A. L. & Horwood, L. J. Vulnerability and resiliency to suicidal behaviours in young people. Psychol. Med. 33, 61–73 (2003).
Herba, C. M., Ferdinand, R. F., van der Ende, J. & Verhulst, F. C. Long-term associations of childhood suicide ideation. J. Am. Acad. Child Adolesc. Psychiatry 46, 1473–1481 (2007).
Sourander, A. et al. Childhood predictors of completed and severe suicide attempts: findings from the Finnish 1981 Birth Cohort Study. Arch. Gen. Psychiatry 66, 398–406 (2009).
Sareen, J. et al. Anxiety disorders and risk for suicidal ideation and suicide attempts: a population-based longitudinal study of adults. Arch. Gen. Psychiatry 62, 1249–1257 (2005).
Suomi, S. J. Early stress and adult emotional reactivity in rhesus monkeys. Ciba Found. Symposium 156, 171–183 (1991).
Caldji, C. et al. Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proc. Natl Acad. Sci. USA 95, 5335–5340 (1998).
van der Vegt, E. J., van der Ende, J., Ferdinand, R. F., Verhulst, F. C. & Tiemeier, H. Early childhood adversities and trajectories of psychiatric problems in adoptees: evidence for long lasting effects. J. Abnorm Child Psychol. 37, 239–249 (2009).
Johnson, J. G. et al. Childhood adversities, interpersonal difficulties, and risk for suicide attempts during late adolescence and early adulthood. Arch. Gen. Psychiatry 59, 741–749 (2002).
Kim, C. et al. Patterns of co-morbidity in male suicide completers. Psychol. Med. 33, 1299–1309 (2003).
Seguin, M. et al. Life trajectories and burden of adversity: mapping the developmental profiles of suicide mortality. Psychol. Med. 37, 1575–1383 (2007).
Chachamovich, E., Ding, Y. & Turecki, G. Levels of aggressiveness are higher among alcohol-related suicides: results from a psychological autopsy study. Alcohol 46, 529–536 (2012).
Coccaro, E. F. et al. Serotonergic studies in patients with affective and personality disorders. Correlates with suicidal and impulsive aggressive behavior. Arch. Gen. Psychiatry 46, 587–599 (1989).
Freemantle, E., Chen, G. G., Cruceanu, C., Mechawar, N. & Turecki, G. Analysis of oxysterols and cholesterol in prefrontal cortex of suicides. Int. J. Neuropsychopharmacol. 16, 1241–1249 (2013).
Lalovic, A. et al. Cholesterol metabolism and suicidality in Smith-Lemli-Opitz syndrome carriers. Am. J. Psychiatry 161, 2123–2126 (2004).
Lalovic, A. et al. Cholesterol content in brains of suicide completers. Int. J. Neuropsychopharmacol. 10, 159–166 (2007).
Heikkinen, M., Aro, H. & Lonnqvist, J. Recent life events and their role in suicide as seen by the spouses. Acta Psychiatr. Scand. 86, 489–494 (1992).
Qin, P., Agerbo, E. & Bo Mortensen, P. Suicide risk in relation to family history of completed suicide and psychiatric disorders: a nested case-control study based on longitudinal registers. Lancet 360, 1126–1130 (2002).
Angst, F., Stassen, H. H., Clayton, P. J. & Angst, J. Mortality of patients with mood disorders: follow-up over 34–38 years. J. Affect. Disord. 68, 167–181 (2002).
Asberg, M., Thoren, P., Traskman, L., Bertilsson, L. & Ringberger, V. Serotonin depression — a biochemical subgroup within the affective disorders. Science 191, 478–480 (1976). This is the first study to suggest that there is a link between alterations in the serotonergic system and suicidal behaviour.
Stanley, M., Virgilio, J. & Gershon, S. Tritiated imipramine binding sites are decreased in the frontal cortex of suicides. Science 216, 1337–1339 (1982).
Stanley, M. & Mann, J. J. Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet 1, 214–216 (1983).
Arango, V. et al. Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology 25, 892–903 (2001).
Miller, J. M. et al. Positron emission tomography quantification of serotonin transporter in suicide attempters with major depressive disorder. Biol. Psychiatry 74, 287–295 (2013).
Yanowitch, R. & Coccaro, E. F. The neurochemistry of human aggression. Adv. Genet. 75, 151–169 (2011).
Brezo, J. et al. Differences and similarities in the serotonergic diathesis for suicide attempts and mood disorders: a 22-year longitudinal gene–environment study. Mol. Psychiatry 15, 831–843 (2010).
Smith, K. A., Fairburn, C. G. & Cowen, P. J. Relapse of depression after rapid depletion of tryptophan. Lancet 349, 915–919 (1997).
Benkelfat, C., Ellenbogen, M. A., Dean, P., Palmour, R. M. & Young, S. N. Mood-lowering effect of tryptophan depletion. Enhanced susceptibility in young men at genetic risk for major affective disorders. Arch. Gen. Psychiatry 51, 687–697 (1994).
Sequeira, A. et al. Implication of SSAT by gene expression and genetic variation in suicide and major depression. Arch. Gen. Psychiatry 63, 35–48 (2006).
Fiori, L. M. et al. Global gene expression profiling of the polyamine system in suicide completers. Int. J. Neuropsychopharmacol. 14, 595–605 (2011).
Klempan, T. A. et al. Profiling brain expression of the spermidine/spermine N1-acetyltransferase 1 (SAT1) gene in suicide. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 934–943 (2009).
Chen, G. G. et al. Evidence of altered polyamine concentrations in cerebral cortex of suicide completers. Neuropsychopharmacology 35, 1477–1484 (2010).
Guipponi, M. et al. Genetic and epigenetic analysis of SSAT gene dysregulation in suicidal behavior. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 799–807 (2009).
Le-Niculescu, H. et al. Discovery and validation of blood biomarkers for suicidality. Mol. Psychiatry 18, 1249–1264 (2013).
Dahel, K.-d., Al-Saffar, N. & Flayeh, K. Polyamine oxidase activity in sera of depressed and schizophrenic patients after ECT treatment. Neurochem. Res. 26, 415–418 (2001).
Karssen, A. M. et al. Stress-induced changes in primate prefrontal profiles of gene expression. Mol. Psychiatry 12, 1089–1102 (2007).
Fiori, L. M., Gross, J. A. & Turecki, G. Effects of histone modifications on increased expression of polyamine biosynthetic genes in suicide. Int. J. Neuropsychopharmacol. 15, 1161–1166 (2012).
Fiori, L. M. & Turecki, G. Epigenetic regulation of spermidine/spermine N1-acetyltransferase (SAT1) in suicide. J. Psychiatr. Res. 45, 1229–1235 (2011).
Gross, J. A., Fiori, L. M., Labonte, B., Lopez, J. P. & Turecki, G. Effects of promoter methylation on increased expression of polyamine biosynthetic genes in suicide. J. Psychiatr. Res. 47, 513–519 (2013).
Lopez, J. P. et al. Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers. Int. J. Neuropsychopharmacol. 17, 23–32 (2014).
Sequeira, A. et al. Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression. PLoS ONE 4, e6585 (2009).
Choudary, P. V. et al. Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc. Natl Acad. Sci. USA 102, 15653–15658 (2005).
Duman, R. S. Neurobiology of stress, depression, and rapid acting antidepressants: remodeling synaptic connections. Depress. Anxiety 31, 291–296 (2014).
Larkin, G. L. & Beautrais, A. L. A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department. Int. J. Neuropsychopharmacol. 14, 1127–1131 (2011).
Price, R. B. et al. Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. Depress. Anxiety 31, 335–343 (2014).
Raison, C. L., Capuron, L. & Miller, A. H. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 27, 24–31 (2006).
Howren, M. B., Lamkin, D. M. & Suls, J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom. Med. 71, 171–186 (2009).
Dowlati, Y. et al. A meta-analysis of cytokines in major depression. Biol. Psychiatry 67, 446–457 (2010).
Liu, Y., Ho, R. C. & Mak, A. Interleukin (IL)-6, tumour necrosis factor-α (TNFα) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J. Affect Disord. 139, 230–239 (2012).
Shelton, R. C. et al. Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression. Mol. Psychiatry 16, 751–762 (2011).
Capuron, L. & Miller, A. H. Cytokines and psychopathology: lessons from interferon-α. Biol. Psychiatry 56, 819–824 (2004).
Musselman, D. L. et al. Paroxetine for the prevention of depression induced by high-dose interferon-α. N. Engl. J. Med. 344, 961–966 (2001).
Raison, C. L. et al. Depression during pegylated interferon-α plus ribavirin therapy: prevalence and prediction. J. Clin. Psychiatry 66, 41–48 (2005).
Constant, A. et al. Mood alterations during interferon-α therapy in patients with chronic hepatitis C: evidence for an overlap between manic/hypomanic and depressive symptoms. J. Clin. Psychiatry 66, 1050–1057 (2005).
Serafini, G. et al. The role of inflammatory cytokines in suicidal behavior: a systematic review. Eur. Neuropsychopharmacol. 23, 1672–1686 (2013).
Isung, J. et al. Low vascular endothelial growth factor and interleukin-8 in cerebrospinal fluid of suicide attempters. Transl. Psychiatry 2, e196 (2012).
Erhardt, S. et al. Connecting inflammation with glutamate agonism in suicidality. Neuropsychopharmacology 38, 743–752 (2013).
Sublette, M. E. et al. Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder. Brain Behav. Immun. 25, 1272–1278 (2011).
Carlborg, A., Jokinen, J., Jonsson, E. G., Erhardt, S. & Nordstrom, P. CSF kynurenic acid and suicide risk in schizophrenia spectrum psychosis. Psychiatry Res. 205, 165–167 (2013).
Bay-Richter, C. et al. A role for inflammatory metabolites as modulators of the glutamate N-methyl-D-aspartate receptor in depression and suicidality. Brain Behav. Immun. http://dx.doi.org/10.1016/j.bbi.2014.07.012 (2014).
Pandey, G. N. et al. Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims. J. Psychiatr. Res. 46, 57–63 (2012).
Tonelli, L. H. et al. Elevated cytokine expression in the orbitofrontal cortex of victims of suicide. Acta Psychiatr. Scand. 117, 198–206 (2008).
Torres-Platas, S. G., Cruceanu, C., Chen, G. G., Turecki, G. & Mechawar, N. Evidence for increased microglial priming and macrophage recruitment in the dorsal anterior cingulate white matter of depressed suicides. Brain Behav. Immun. http://dx.doi.org/10.1016/j.bbi.2014.05.007 (2014).
Steiner, J. et al. Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J. Psychiatr. Res. 42, 151–157 (2008).
Bellavance, M. A. & Rivest, S. The, H. P. A. - Immune axis and the immunomodulatory actions of glucocorticoids in the brain. Front. Immunol. 5, 136 (2014).
Ehlert, U. Enduring psychobiological effects of childhood adversity. Psychoneuroendocrinology 38, 1850–1857 (2013).
Danese, A. et al. Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Arch. Gen. Psychiatry 65, 409–415 (2008).
Czeh, B., Fuchs, E. & Flugge, G. Altered glial plasticity in animal models for mood disorders. Curr. Drug Targets 14, 1249–1261 (2013).
Banasr, M. et al. Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Mol. Psychiatry 15, 501–511 (2010).
Rajkowska, G. Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol. Psychiatry 48, 766–777 (2000).
Torres-Platas, S. G. et al. Astrocytic hypertrophy in anterior cingulate white matter of depressed suicides. Neuropsychopharmacology 36, 2650–2658 (2011).
Ernst, C. et al. Dysfunction of astrocyte connexins 30 and 43 in dorsal lateral prefrontal cortex of suicide completers. Biol. Psychiatry 70, 312–319 (2011).
Bernard, R. et al. Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression. Mol. Psychiatry 16, 634–646 (2011).
Dere, E. et al. Connexin30-deficient mice show increased emotionality and decreased rearing activity in the open-field along with neurochemical changes. Eur. J. Neurosci. 18, 629–638 (2003).
Frisch, C. et al. Mice with astrocyte-directed inactivation of connexin43 exhibit increased exploratory behaviour, impaired motor capacities, and changes in brain acetylcholine levels. Eur. J. Neurosci. 18, 2313–2318 (2003).
Rose, C. R. et al. Truncated TRKB-T1 mediates neurotrophin-evoked calcium signalling in glia cells. Nature 426, 74–78 (2003).
Razzoli, M. et al. A role for BDNF/TRKB signaling in behavioral and physiological consequences of social defeat stress. Genes Brain Behav. 10, 424–433 (2011).
Roy, A. Hypothalamic–pituitary–adrenal axis function and suicidal behavior in depression. Biol. Psychiatry 32, 812–816 (1992).
Coryell, W. & Schlesser, M. The dexamethasone suppression test and suicide prediction. Am. J. Psychiatry 158, 748–753 (2001).
Pfeffer, C. R., Stokes, P. & Shindledecker, R. Suicidal behavior and hypothalamic–pituitary–adrenocortical axis indices in child psychiatric inpatients. Biol. Psychiatry 29, 909–917 (1991).
Raadsheer, F. C. et al. Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression. Am. J. Psychiatry 152, 1372–1376 (1995).
Raadsheer, F. C., Hoogendijk, W. J., Stam, F. C., Tilders, F. J. & Swaab, D. F. Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 60, 436–444 (1994).
Wang, S. S., Kamphuis, W., Huitinga, I., Zhou, J. N. & Swaab, D. F. Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances. Mol. Psychiatry 13, 786–799 (2008).
Nemeroff, C. B. et al. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 226, 1342–1344 (1984).
Nemeroff, C. B., Owens, M. J., Bissette, G., Andorn, A. C. & Stanley, M. Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Arch. Gen. Psychiatry 45, 577–579 (1988).
Lopez, J. F. et al. Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims. Neuroendocrinology 56, 491–501 (1992).
Dumser, T., Barocka, A. & Schubert, E. Weight of adrenal glands may be increased in persons who commit suicide. Am. J. Forens. Med. Pathol. 19, 72–76 (1998).
Szigethy, E., Conwell, Y., Forbes, N. T., Cox, C. & Caine, E. D. Adrenal weight and morphology in victims of completed suicide. Biol. Psychiatry 36, 374–380 (1994).
McGirr, A. et al. Dysregulation of the sympathetic nervous system, hypothalamic-pituitary-adrenal axis and executive function in individuals at risk for suicide. J. Psychiatry Neurosci. 35, 399–408 (2010).
Malhi, G. S., Tanious, M., Das, P., Coulston, C. M. & Berk, M. Potential mechanisms of action of lithium in bipolar disorder. Current understanding. CNS Drugs 27, 135–153 (2013).
Goodwin, F. K. et al. Suicide risk in bipolar disorder during treatment with lithium and divalproex. JAMA 290, 1467–1473 (2003).
Cipriani, A., Hawton, K., Stockton, S. & Geddes, J. R. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ 346, f3646 (2013).
Ripke, S. et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genet. 45, 1150–1159 (2013).
Fromer, M. et al. De novo mutations in schizophrenia implicate synaptic networks. Nature 506, 179–184 (2014).
Purcell, S. M. et al. A polygenic burden of rare disruptive mutations in schizophrenia. Nature 506, 185–190 (2014).
Lesch, M. & Nyhan, W. L. A. Familial disorder of uric acid metabolism and central nervous system function. Am. J. Med. 36, 561–570 (1964).
Meissner, A. et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454, 766–770 (2008).
Mikkelsen, T. S. et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448, 553–560 (2007).
Lister, R. et al. Global epigenomic reconfiguration during mammalian brain development. Science 341, 1237905 (2013). This is an important study showing that during prenatal and postnatal brain development, neurons and non-neuronal cells undergo different patterns of dynamic methylation at CpG and non-CpG sequences, as well as in 5-hydroxymethylcytosine. This work shows that there is a clear link between these methylation changes and important brain plastic changes, such as synaptogenesis.
Liang, P. et al. Genome-wide survey reveals dynamic widespread tissue-specific changes in DNA methylation during development. BMC Genomics 12, 231 (2011).
Xin, Y. et al. Genome-wide divergence of DNA methylation marks in cerebral and cerebellar cortices. PLoS ONE 5, e11357 (2010).
Xin, Y. et al. Role of CpG context and content in evolutionary signatures of brain DNA methylation. Epigenetics 6, 1308–1318 (2011).
Nakamura, N. et al. Laser capture microdissection for analysis of single cells. Methods Mol. Med. 132, 11–18 (2007).
Jiang, Y., Matevossian, A., Huang, H. S., Straubhaar, J. & Akbarian, S. Isolation of neuronal chromatin from brain tissue. BMC Neurosci. 9, 42 (2008).
Guintivano, J., Aryee, M. J. & Kaminsky, Z. A. A cell epigenotype specific model for the correction of brain cellular heterogeneity bias and its application to age, brain region and major depression. Epigenetics 8, 290–302 (2013).
Liu, D. et al. Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 277, 1659–1662 (1997). This landmark study establishes a link between maternal grooming of pups and regulation of the HPA axis in offspring.
Murgatroyd, C. et al. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nature Neurosci. 12, 1559–1566 (2009). This important study in mice shows that ELA regulates DNA methylation of an intergenic region that regulates the activity of AVP and results in enduring hypersecretion of corticosterone and alterations in passive stress coping and memory.
Weaver, I. C. et al. Epigenetic programming by maternal behavior. Nature Neurosci. 7, 847–854 (2004). This ground-breaking study shows that maternal behaviour regulates the expression of the glucocorticoid receptor by inducing promoter methylation changes.
Klose, R. J. & Bird, A. P. Genomic DNA methylation: the mark and its mediators. Trends Biochem. Sci. 31, 89–97 (2006).
Maunakea, A. K. et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature 466, 253–257 (2010).
Ziller, M. J. et al. Charting a dynamic DNA methylation landscape of the human genome. Nature 500, 477–481 (2013). This study shows that only a minority of CpG nucleotides have variable levels of methylation and that they are mostly located in regulatory gene elements, such as enhancers and transcription factor-binding sites.
Turner, J. D. & Muller, C. P. Structure of the glucocorticoid receptor (NR3C1) gene 5′ untranslated region: identification, and tissue distribution of multiple new human exon 1. J. Mol. Endocrinol. 35, 283–292 (2005).
McCormick, J. A. et al. 5′-heterogeneity of glucocorticoid receptor messenger RNA is tissue specific: differential regulation of variant transcripts by early-life events. Mol. Endocrinol. 14, 506–517 (2000).
Wu, Y., Patchev, A. V., Daniel, G., Almeida, O. F. & Spengler, D. Early-life stress reduces DNA methylation of the Pomc gene in male mice. Endocrinology 155, 1751–1762 (2014).
Bowen, M. T. et al. Active coping towards predatory stress is associated with lower corticosterone and progesterone plasma levels and decreased methylation in the medial amygdala vasopressin system. Horm. Behav. 66, 561–566 (2014).
Bester-Meredith, J. K., Young, L. J. & Marler, C. A. Species differences in paternal behavior and aggression in peromyscus and their associations with vasopressin immunoreactivity and receptors. Horm. Behav. 36, 25–38 (1999).
Wersinger, S. R., Caldwell, H. K., Christiansen, M. & Young, W. S. 3rd. Disruption of the vasopressin 1b receptor gene impairs the attack component of aggressive behavior in mice. Genes Brain Behav. 6, 653–660 (2007).
Wersinger, S. R., Ginns, E. I., O'Carroll, A. M., Lolait, S. J. & Young, W. S. 3rd. Vasopressin V1b receptor knockout reduces aggressive behavior in male mice. Mol. Psychiatry 7, 975–984 (2002).
Barkat, T. R., Polley, D. B. & Hensch, T. K. A critical period for auditory thalamocortical connectivity. Nature Neurosci. 14, 1189–1194 (2011).
Fisher, H. L. et al. The varying impact of type, timing and frequency of exposure to childhood adversity on its association with adult psychotic disorder. Psychol. Med. 40, 1967–1978 (2010).
Jun, H. J. et al. Child abuse and smoking among young women: the importance of severity, accumulation, and timing. J. Adolesc. Health 43, 55–63 (2008).
Blaauw, E., Arensman, E., Kraaij, V., Winkel, F. W. & Bout, R. Traumatic life events and suicide risk among jail inmates: the influence of types of events, time period and significant others. J. Trauma Stress 15, 9–16 (2002).
Talens, R. P. et al. Variation, patterns, and temporal stability of DNA methylation: considerations for epigenetic epidemiology. FASEB J. 24, 3135–3144 (2010).
Ouellet-Morin, I. et al. Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins. Psychol. Med. 43, 1813–1823 (2013).
Kim, J. M. et al. A longitudinal study of SLC6A4 DNA promoter methylation and poststroke depression. J. Psychiatr. Res. 47, 1222–1227 (2013).
Kim, J. M. et al. A longitudinal study of BDNF promoter methylation and genotype with poststroke depression. J. Affect. Disord. 149, 93–99 (2013).
Fiori, L. M. & Turecki, G. Implication of the polyamine system in mental disorders. J. Psychiatry Neurosci. 33, 102–110 (2008).
Pegg, A. E. & Casero, R. A. Jr. Current status of the polyamine research field. Methods Mol. Biol. 720, 3–35 (2011).
Bastida, C. M. et al. Sexual dimorphism of ornithine decarboxylase in the mouse adrenal: influence of polyamine deprivation on catecholamine and corticoid levels. Am. J. Physiol. Endocrinol. Metab. 292, E1010–E1017 (2007).
Williams, K. Modulation and block of ion channels: a new biology of polyamines. Cell. Signal. 9, 1–13 (1997).
Brackley, P. et al. Spermine and philanthotoxin potentiate excitatory amino acid responses of Xenopus oocytes injected with rat and chick brain RNA. Neurosci. Lett. 114, 51–56 (1990).
Galea, E., Regunathan, S., Eliopoulos, V., Feinstein, D. L. & Reis, D. J. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. Biochem. J. 316, 247–249 (1996).
Reis, D. J. & Regunathan, S. Is agmatine a novel neurotransmitter in brain? Trends Pharmacol. Sci. 21, 187–193 (2000).
Doyle, K. M., Kirby, B. P., Murphy, D. & Shaw, G. G. Effect of L-type calcium channel antagonists on spermine-induced CNS excitation in vivo. Neurosci. Lett. 380, 247–251 (2005).
Gilad, G. M. & Gilad, V. H. Overview of the brain polyamine-stress-response: regulation, development, and modulation by lithium and role in cell survival. Cell. Mol. Neurobiol. 23, 637–649 (2003).
Hayashi, Y., Tanaka, J., Morizumi, Y., Kitamura, Y. & Hattori, Y. Polyamine levels in brain and plasma after acute restraint or water-immersion restraint stress in mice. Neurosci. Lett. 355, 57–60 (2004).
Lee, M., Wynder, C., Schmidt, D., McCafferty, D. & Shiekhattar, R. Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chem. Biol. 13, 563–570 (2006).
Piletz, J. E. et al. Agmatine: clinical applications after 100 years in translation. Drug Discov. Today 18, 880–893 (2013).
Gupta, N., Zhang, H. & Liu, P. Behavioral and neurochemical effects of acute putrescine depletion by difluoromethylornithine in rats. Neuroscience 161, 691–706 (2009).
Shopsin, B. The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study. Acta Neuropsychiatr. 25, 113–118 (2013).
Preparation of this Review was supported by grants from the Canadian Institute of Health Research (CIHR), MOP119429 and MOP119430, and by the Fonds de Recherche du Québec – Santé (FRQS), through a Chercheur National salary award to the author and through support to the Réseau québécois sur le suicide, les troubles de l'humeur et les troubles associés (RQSHA). The author is indebted to S. Daniels for expert and essential help in the preparation of this Review.
The author declares no competing financial interests.
This broad term encompasses all forms of suicidal behaviour and suicidal ideation.
- Suicidal ideation
This term describes the wish to die, including thoughts of actively ending one's life.
- Suicidal behaviour
This term describes behaviours that result in self-injury and is generally used to refer to suicide attempts and suicide completion.
This broad term includes suicidal behaviour and non-suicidal self-injurious behaviours.
- Non-suicidal self-injurious behaviours
Deliberate self-injury, often in the form of superficial skin cuts that are made with the intent to decrease emotional pain rather than to die.
- Suicidal behaviour disorder
This disorder has recently been proposed as a condition for further study in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and is defined by the occurrence of at least one suicide attempt with some intent to die within the last 24 months. Conditions for further study in the DSM are disorders that should be investigated and considered for its future versions.
- Suicidal crisis
Period when suicidal ideation becomes acute, which is often associated with emotional instability.
- Distal risk factors
Predisposing factors that occur or are expressed temporally distant from the onset of the phenotype.
- Early-life adversity
(ELA). Acts by a parent or caregiver that result in physical, sexual and/or psychological abuse of a child or that lead to neglect of essential physical or psychological needs of childhood.
- Treatment-emergent suicidal events
This term describes suicidal ideation or suicidal behaviour that occurs in association with treatment and is a common term used in clinical trials of antidepressants.
- Childhood sexual abuse
Any completed or attempted sexual act, or exposure to sexual interactions, with or without physical contact, with a child by a caregiver.
- Childhood physical abuse
The intentional use of physical force against a child that results in, or has the potential to result in, physical injury.
- Parental neglect
Failure to meet a child's basic physical, emotional, medical or dental, or educational needs, or a failure to ensure a child's safety.
- Attachment styles
Stereotypical interpersonal styles that are rooted in early-life interactions with caregivers.
- Biological embedding
The effects of early-life experiences on the differential regulation of biological systems and development.
Variables that can fully or partially explain the relationship between a predictor and a dependent variable.
Traits that associate with an illness in the population, are heritable, state independent, and co-segregate with the condition investigated and are present in non-affected family members of affected individuals at a higher rate than in the general population.
- Impulsive aggressive behaviours
The tendency to react with animosity or overt hostility without consideration of the possible consequences when piqued or under stress.
- Proximal risk factors
Precipitating factors that occur or are expressed temporally close to the onset of the phenotype.
- State markers
Biological, psychological, behavioural or clinical markers associated with a given phenotype.
- Trait markers
Biological, psychological, behavioural or clinical markers that indicate a predisposition to or risk of a given phenotype.
About this article
Psychiatry Investigation (2021)
Suicide in DSM-5: Current Evidence for the Proposed Suicide Behavior Disorder and Other Possible Improvements
Frontiers in Psychiatry (2021)
Early Trauma and Relationships among Recent Stress, Depressive Symptoms, Anxiety Symptoms, and Suicidal Ideation in Korean Women
Journal of Korean Medical Science (2021)
Prediction of suicide attempts in a prospective cohort study with a nationally representative sample of the US population
Psychological Medicine (2021)
Dissecting the Association Between Inflammation, Metabolic Dysregulation, and Specific Depressive Symptoms
JAMA Psychiatry (2021)