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      자살의 생물학적 기전 = Biological Mechanism of Suicide

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      다국어 초록 (Multilingual Abstract)

      Suicide is a behavior that is intended to cause death by itself and requires medical treatment, resulting in suicidal attempt or completion. Suicide causes loss of life, damages the body, costs a lot of medical expenses, and causes families to fall into sorrow and suffering therefore this suicide is a huge loss to family and society. There have been attempts to reduce and prevent suicide by understanding the mechanism of suicide. The mechanism of suicide can be thought of as psychological mechanism and biological mechanism. In the past, if we considered the psychological and biological mechanisms separately, the development of neuroscience now connects and integrates these two. Psychological factors affect biological factors and biological temperaments also affect perception or thinking about the situation and increase psychological vulnerability. Distant factors in suicidal behavior-such as childhood adversity and family and genetic predisposition-increase the lifetime risk of suicide. They alter the response to stress and other processes through changes in gene expression and regulation of emotional and behavioral characteristics. Distant factors affect the biological system and consequently changes in these systems can increase the risk of suicide. In other words, the distal factor does not directly induce suicidal behavior but rather acts indirectly through developmental or mediating factors. These mediating factors are impulsive aggressive and anxious trait, and chronic use of substances. The mechanism of this disorder is the abnormality of the serotonin system and the abnormality of the lipid level. Proximal factors are associated with the onset of suicide events and include changes in the major neurotransmitter systems, inflammatory changes, and dysfunction of glial cells in the brain. A series of studies, including a variety of research methods and postmortem and in-vivo imaging studies, show the impairment of the serotonergic neurotransmitter system and hypothalamic-pituitary-adrenal axis stress response system for suicidal behavior. These disorders lead to suicidal behavior due to difficulty in cognitive control of mood, pessimism, reactive aggression, abnormality in problem solving abilities, excessive response to negative social signals, severe emotional distress, and cognitive dysregulation of suicidal ideation.
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      Suicide is a behavior that is intended to cause death by itself and requires medical treatment, resulting in suicidal attempt or completion. Suicide causes loss of life, damages the body, costs a lot of medical expenses, and causes families to fall in...

      Suicide is a behavior that is intended to cause death by itself and requires medical treatment, resulting in suicidal attempt or completion. Suicide causes loss of life, damages the body, costs a lot of medical expenses, and causes families to fall into sorrow and suffering therefore this suicide is a huge loss to family and society. There have been attempts to reduce and prevent suicide by understanding the mechanism of suicide. The mechanism of suicide can be thought of as psychological mechanism and biological mechanism. In the past, if we considered the psychological and biological mechanisms separately, the development of neuroscience now connects and integrates these two. Psychological factors affect biological factors and biological temperaments also affect perception or thinking about the situation and increase psychological vulnerability. Distant factors in suicidal behavior-such as childhood adversity and family and genetic predisposition-increase the lifetime risk of suicide. They alter the response to stress and other processes through changes in gene expression and regulation of emotional and behavioral characteristics. Distant factors affect the biological system and consequently changes in these systems can increase the risk of suicide. In other words, the distal factor does not directly induce suicidal behavior but rather acts indirectly through developmental or mediating factors. These mediating factors are impulsive aggressive and anxious trait, and chronic use of substances. The mechanism of this disorder is the abnormality of the serotonin system and the abnormality of the lipid level. Proximal factors are associated with the onset of suicide events and include changes in the major neurotransmitter systems, inflammatory changes, and dysfunction of glial cells in the brain. A series of studies, including a variety of research methods and postmortem and in-vivo imaging studies, show the impairment of the serotonergic neurotransmitter system and hypothalamic-pituitary-adrenal axis stress response system for suicidal behavior. These disorders lead to suicidal behavior due to difficulty in cognitive control of mood, pessimism, reactive aggression, abnormality in problem solving abilities, excessive response to negative social signals, severe emotional distress, and cognitive dysregulation of suicidal ideation.

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      목차 (Table of Contents)

      • 서론
      • 원위부(소인) 위험 요인
      • 발달(매개) 위험 요인
      • 근위부(촉발) 요인
      • 자살 행동에 영향을 미치는 뇌 영역
      • 서론
      • 원위부(소인) 위험 요인
      • 발달(매개) 위험 요인
      • 근위부(촉발) 요인
      • 자살 행동에 영향을 미치는 뇌 영역
      • 결론
      • 참고문헌
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      참고문헌 (Reference)

      1 Leyton M, "alpha-[11C]Methyl-L-tryptophan trapping in the orbital and ventral medial prefrontal cortex of suicide attempters" 16 : 220-223, 2006

      2 Dumser T, "Weight of adrenal glands may be increased in persons who commit suicide" 19 : 72-76, 1998

      3 Rose CR, "Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells" 426 : 74-78, 2003

      4 Stanley M, "Tritiated imipramine binding sites are decreased in the frontal cortex of suicides" 216 : 1337-1339, 1982

      5 Mann JJ, "The serotonergic system in mood disorders and suicidal behaviour" 368 : 20120537-, 2013

      6 Serafini G, "The role of inflammatory cytokines in suicidal behavior: a systematic review" 23 : 1672-1686, 2013

      7 O’Connor RC, "The psychology of suicidal behaviour" 1 : 73-85, 2014

      8 Fanous AH, "The prediction of thoughts of death or self-harm in a population-based sample of female twins" 34 : 301-312, 2004

      9 Courtet P, "The neuroscience of suicidal behaviors: what can we expect from endophenotype strategies?" 1 : 2011

      10 Yanowitch R, "The neurochemistry of human aggression" 75 : 151-169, 2011

      1 Leyton M, "alpha-[11C]Methyl-L-tryptophan trapping in the orbital and ventral medial prefrontal cortex of suicide attempters" 16 : 220-223, 2006

      2 Dumser T, "Weight of adrenal glands may be increased in persons who commit suicide" 19 : 72-76, 1998

      3 Rose CR, "Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells" 426 : 74-78, 2003

      4 Stanley M, "Tritiated imipramine binding sites are decreased in the frontal cortex of suicides" 216 : 1337-1339, 1982

      5 Mann JJ, "The serotonergic system in mood disorders and suicidal behaviour" 368 : 20120537-, 2013

      6 Serafini G, "The role of inflammatory cytokines in suicidal behavior: a systematic review" 23 : 1672-1686, 2013

      7 O’Connor RC, "The psychology of suicidal behaviour" 1 : 73-85, 2014

      8 Fanous AH, "The prediction of thoughts of death or self-harm in a population-based sample of female twins" 34 : 301-312, 2004

      9 Courtet P, "The neuroscience of suicidal behaviors: what can we expect from endophenotype strategies?" 1 : 2011

      10 Yanowitch R, "The neurochemistry of human aggression" 75 : 151-169, 2011

      11 van Heeringen K, "The neurobiology of suicide" 1 : 63-72, 2014

      12 Turecki G, "The molecular bases of the suicidal brain" 15 : 802-816, 2014

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      33 Nemeroff CB, "Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims" 45 : 577-579, 1988

      34 Hertzman C, "Putting the concept of biological embedding in historical perspective" 2 : 17160-17167, 2012

      35 Arsenault-Lapierre G, "Psychiatric diagnoses in 3275 suicides: a meta-analysis" 4 : 37-, 2004

      36 Pandey GN, "Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims" 46 : 57-63, 2012

      37 Klempan TA, "Profiling brain expression of the spermidine/spermine N1-acetyltransferase 1(SAT1)gene in suicide" 150B : 934-943, 2009

      38 Turecki G, "Preventing suicide: where are we?" 3 : 597-598, 2016

      39 Pan L, "Preserved hippocampal function during learning in the context of risk in adolescent suicide attempt" 211 : 112-118, 2013

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      43 Miller JM, "Positron emission tomography quantification of serotonin transporter in suicide attempters with major depressive disorder" 74 : 287-295, 2013

      44 Oquendo MA, "Positron emission tomography of regional brain metabolic responses to a serotonergic challenge and lethality of suicide attempts in major depression" 60 : 14-22, 2003

      45 Oquendo MA, "Positron Emission Tomographic Imaging of the Serotonergic System and Prediction of Risk and Lethality of Future Suicidal Behavior" 73 : 1048-1055, 2016

      46 Dahel KA, "Polyamine oxidase activity in sera of depressed and schizophrenic patients after ECT treatment" 26 : 415-418, 2001

      47 Hayashi Y, "Polyamine levels in brain and plasma after acute restraint or water-immersion restraint stress in mice" 355 : 57-60, 2004

      48 Sublette ME, "Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder" 25 : 1272-1278, 2011

      49 Kim C, "Patterns of co-morbidity in male suicide completers" 33 : 1299-1309, 2003

      50 Gilad GM, "Overview of the brain polyaminestress-response: regulation, development, and modulation by lithium and role in cell survival" 23 : 637-649, 2003

      51 Jollant F, "Orbitofrontal cortex response to angry faces in men with histories of suicide attempts" 165 : 740-748, 2008

      52 Mann JJ, "Neurobiology of suicidal behaviour" 4 : 819-828, 2003

      53 Heim C, "Neurobiological and psychiatric consequences of child abuse and neglect" 52 : 671-690, 2010

      54 Brezo J, "Natural history of suicidal behaviors in a population-based sample of young adults" 37 : 1563-1574, 2007

      55 Benkelfat C, "Mood-lowering effect of tryptophan depletion. Enhanced susceptibility in young men at genetic risk for major affective disorders" 51 : 687-697, 1994

      56 Galfalvy H, "Lower CSF MHPG predicts short-term risk for suicide attempt" 12 : 1327-1335, 2009

      57 Isung J, "Low vascular endothelial growth factor and interleukin-8 in cerebrospinal fluid of suicide attempters" 2 : e196-, 2012

      58 Engelberg H, "Low serum cholesterol and suicide" 339 : 727-729, 1992

      59 Lopez JF, "Localization and quantification of proopiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims" 56 : 491-501, 1992

      60 Seguin M, "Life trajectories and burden of adversity: mapping the developmental profiles of suicide mortality" 37 : 1575-1583, 2007

      61 Chachamovich E, "Levels of aggressiveness are higher among alcohol-related suicides: results from a psychological autopsy study" 46 : 529-536, 2012

      62 Roth TL, "Lasting epigenetic influence of early-life adversity on the BDNF gene" 65 : 760-769, 2009

      63 Stanley M, "Increased serotonin-2 binding sites in frontal cortex of suicide victims" 1 : 214-216, 1983

      64 Raadsheer FC, "Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients" 60 : 436-444, 1994

      65 Keller S, "Increased BDNF promoter methylation in the Wernicke area of suicide subjects" 67 : 258-267, 2010

      66 Sequeira A, "Implication of SSAT by gene expression and genetic variation in suicide and major depression" 63 : 35-48, 2006

      67 Steiner J, "Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide" 42 : 151-157, 2008

      68 Roy A, "Hypothalamic-pituitary-adrenal axis function and suicidal behavior in depression" 32 : 812-816, 1992

      69 Fiori LM, "Global gene expression profiling of the polyamine system in suicide completers" 14 : 595-605, 2011

      70 Sequeira A, "Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression" 4 : e6585-, 2009

      71 Labonte B, "Genome-wide methylation changes in the brains of suicide completers" 170 : 511-520, 2013

      72 Zhang X, "Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis" 126 : 1189-1201, 2006

      73 Perlis RH, "Genome-wide association study of suicide attempts in mood disorder patients" 167 : 1499-1507, 2010

      74 Perroud N, "Genome-wide association study of increasing suicidal ideation during antidepressant treatment in the GENDEP project" 12 : 68-77, 2012

      75 Menke A, "Genome-wide association study of antidepressant treatment-emergent suicidal ideation" 37 : 797-807, 2012

      76 Rucker JJ, "Genome-wide association analysis of copy number variation in recurrent depressive disorder" 18 : 183-189, 2013

      77 Guipponi M, "Genetic and epigenetic analysis of SSAT gene dysregulation in suicidal behavior" 150 : 799-807, 2009

      78 Wang SS, "Gene expression analysis in the human hypothalamus in depression by laser microdissection and realtime PCR: the presence of multiple receptor imbalances" 13 : 786-799, 2008

      79 Moscicki EK, "Gender differences in completed and attempted suicides" 4 : 152-158, 1994

      80 Arango V, "Fewer pigmented locus coeruleus neurons in suicide victims: preliminary results" 39 : 112-120, 1996

      81 von Borczyskowski A, "Familial factors and suicide: an adoption study in a Swedish National Cohort" 41 : 749-758, 2011

      82 Tidemalm D, "Familial clustering of suicide risk: a total population study of 11.4 million individuals" 41 : 2527-2534, 2011

      83 McGirr A, "Familial aggregation of suicide explained by cluster B traits: a three-group family study of suicide controlling for major depressive disorder" 166 : 1124-1134, 2009

      84 Kim CD, "Familial aggregation of suicidal behavior:a family study of male suicide completers from the general population" 162 : 1017-1019, 2005

      85 Chen GG, "Evidence of altered polyamine concentrations in cerebral cortex of suicide completers" 35 : 1477-1484, 2010

      86 Torres-Platas SG, "Evidence for increased microglial priming and macrophage recruitment in the dorsal anterior cingulate white matter of depressed suicides" 42 : 50-59, 2014

      87 McGowan PO, "Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse" 12 : 342-348, 2009

      88 Roth TL, "Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder" 45 : 919-926, 2011

      89 Ehlert U, "Enduring psychobiological effects of childhood adversity" 38 : 1850-1857, 2013

      90 Danese A, "Elevated inflammation levels in depressed adults with a history of childhood maltreatment" 65 : 409-415, 2008

      91 Tonelli LH, "Elevated cytokine expression in the orbitofrontal cortex of victims of suicide" 117 : 198-206, 2008

      92 Nemeroff CB, "Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients" 226 : 1342-1344, 1984

      93 Price RB, "Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression" 31 : 335-343, 2014

      94 Doyle KM, "Effect of Ltype calcium channel antagonists on spermine-induced CNS excitation in vivo" 380 : 247-251, 2005

      95 Turecki G, "Early life adversity, genomic plasticity, and psychopathology" 1 : 461-466, 2014

      96 Lopez-Castroman J, "Early childhood sexual abuse increases suicidal intent" 12 : 149-154, 2013

      97 McGirr A, "Dysregulation of the sympathetic nervous system, hypothalamic-pituitary-adrenal axis and executive function in individuals at risk for suicide" 35 : 399-408, 2010

      98 Ernst C, "Dysfunction of astrocyte connexins 30 and 43 in dorsal lateral prefrontal cortex of suicide completers" 70 : 312-319, 2011

      99 Pan LA, "Dissociable patterns of neural activity during response inhibition in depressed adolescents with and without suicidal behavior" 50 : 602-611, 2011

      100 Le-Niculescu H, "Discovery and validation of blood biomarkers for suicidality" 18 : 1249-1264, 2013

      101 Brezo J, "Differences and similarities in the serotonergic diathesis for suicide attempts and mood disorders:a 22-year longitudinal gene-environment study" 15 : 831-843, 2010

      102 Banerjee R, "Decreased mRNA and Protein Expression of BDNF, NGF, and their Receptors in the Hippocampus from Suicide: An Analysis in Human Postmortem Brain" 6 : 1-11, 2013

      103 Willeumier K, "Decreased cerebral blood flow in the limbic and prefrontal cortex using SPECT imaging in a cohort of completed suicides" 1 : e28-, 2011

      104 Jollant F, "Decreased activation of lateral orbitofrontal cortex during risky choices under uncertainty is associated with disadvantageous decision-making and suicidal behavior" 51 : 1275-1281, 2010

      105 Fuchikami M, "DNA methylation profiles of the brain-derived neurotrophic factor(BDNF) gene as a potent diagnostic biomarker in major depression" 6 : e23881-, 2011

      106 Raadsheer FC, "Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression" 152 : 1372-1376, 1995

      107 Perlis RH, "Copy number variation in subjects with major depressive disorder who attempted suicide" 7 : e46315-, 2012

      108 Erhardt S, "Connecting inflammation with glutamate agonism in suicidality" 38 : 743-752, 2013

      109 Lalovic A, "Cholesterol content in brains of suicide completers" 10 : 159-166, 2007

      110 Brezo J, "Childhood trajectories of anxiousness and disruptiveness as predictors of suicide attempts" 162 : 1015-1021, 2008

      111 Weder N, "Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry" 53 : 417.e5-424.e5, 2014

      112 Ziller MJ, "Charting a dynamic DNA methylation landscape of the human genome" 500 : 477-481, 2013

      113 Carlborg A, "CSF kynurenic acid and suicide risk in schizophrenia spectrum psychosis" 205 : 165-167, 2013

      114 Gilbert R, "Burden and consequences of child maltreatment in high-income countries" 373 : 68-81, 2009

      115 Pandey GN, "Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims" 11 : 1047-1061, 2008

      116 Torres-Platas SG, "Astrocytic hypertrophy in anterior cingulate white matter of depressed suicides" 36 : 2650-2658, 2011

      117 Binder EB, "Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults" 299 : 1291-1305, 2008

      118 Supriyanto I, "Association of FKBP5 gene haplotypes with completed suicide in the Japanese population" 35 : 252-256, 2011

      119 Kim JM, "Association of BDNF promoter methylation and genotype with suicidal ideation in elderly Koreans" 22 : 989-996, 2014

      120 Freemantle E, "Analysis of oxysterols and cholesterol in prefrontal cortex of suicides" 16 : 1241-1249, 2013

      121 Ernst C, "Alternative splicing, methylation state, and expression profile of tropomyosin-related kinase B in the frontal cortex of suicide completers" 66 : 22-32, 2009

      122 Parsey RV, "Altered serotonin 1A binding in major depression: a [carbonyl-C-11]WAY100635 positron emission tomography study" 59 : 106-113, 2006

      123 Dwivedi Y, "Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects" 60 : 804-815, 2003

      124 Bernard R, "Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression" 16 : 634-646, 2011

      125 Choudary PV, "Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression" 102 : 15653-15658, 2005

      126 Szigethy E, "Adrenal weight and morphology in victims of completed suicide" 36 : 374-380, 1994

      127 Bay-Richter C, "A role for inflammatory metabolites as modulators of the glutamate N-methyl-D-aspartate receptor in depression and suicidality" 43 : 110-117, 2015

      128 Razzoli M, "A role for BDNF/TrkB signaling in behavioral and physiological consequences of social defeat stress" 10 : 424-433, 2011

      129 Larkin GL, "A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department" 14 : 1127-1131, 2011

      130 Galfalvy H, "A pilot genome wide association and gene expression array study of suicide with and without major depression" 14 : 574-582, 2013

      131 Richard-Devantoy S, "A metaanalysis of neuropsychological markers of vulnerability to suicidal behavior in mood disorders" 44 : 1663-1673, 2014

      132 Willour VL, "A genome-wide association study of attempted suicide" 17 : 433-444, 2012

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