자살의 신경생물학적 요인 = Neurobiological Factors of Suicide

다국어 초록 (Multilingual Abstract)

Suicide is a complex behavior associated with various neurobiological and psychosocial factors. It is considered that genetic polymorphism combined with environmental stress such as child-adolescent trauma make differences in neurobiological systems, which cause psychiatric disorders or pessimistic personality, impulse-aggressive behaviors, lack of judgment, and finally result in suicidal behavior. Much progress in the neurobiology of suicide has been made over the several decades. There seems to be a hereditary disposition to suicide independent of psychiatric disorder. The changes in neurotransmitters, neurohormones, neurotrophic factors, cytokines, lipid metabolisms related with their genetic polymorphism can contribute to disturbance of signal transductions and neuronal circuits vulnerable to suicide. It is likely that the main factors are dysfunctions of serotonin (5-HT) and hypothalamus-pituitary-adrenal (HPA) axis. Our understanding about the neurobiology of suicide is still limited. However, clinical practice could be assisted by neurobiological findings capable of making the detection of risk populations with higher sensitivity and the development of new treatment interventions. The settlement of biological markers in suicidal behaviors and their relationships is required.

참고문헌 (Reference)

1 Pandey GN, "What can post-mortem studies tell us about the pathoetiology of suicide?" 5 : 701-720, 2010

2 Rao ML, "Upregulation of the platelet Serotonin2A receptor and low blood serotonin in suicidal psychiatric patients" 38 : 84-89, 1998

3 New AS, "Tryptophan hydroxylase genotype is associated with impulsive- aggression measures: a preliminary study" 81 : 13-17, 1998

4 Mann JJ, "Toward a clinical model of suicidal behavior in psychiatric patients" 156 : 181-189, 1999

5 Sinai C, "Thyroid hormones and personality traits in attempted suicide" 34 : 1526-1532, 2009

6 Duval F, "Thyroid axis activity and suicidal behavior in depressed patients" 35 : 1045-1054, 2010

7 Heim C, "The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies" 49 : 1023-1039, 2001

8 Jollant F, "The influence of four serotonin-related genes on decision-making in suicide attempters" 144 : 615-624, 2007

9 Coryell W, "The dexamethasone suppression test and suicide prediction" 158 : 748-753, 2001

10 Pregelj P, "The association between brain-derived neurotrophic factor polymorphism (BDNF Val66Met) and suicide" 128 : 287-290, 2011

11 Fawcett J, "Suicide: a four-pathway clinical-biochemical model" 836 : 288-301, 1997

12 Ernst C, "Suicide neurobiology" 89 : 315-333, 2009

13 Sunnqvist C, "Suicide attempters: biological stressmarkers and adverse life events" 258 : 456-462, 2008

14 Currier D, "Stress, Genes and the Biology of Suicidal Behavior" 31 : 247-269, 2008

15 Perroud N, "Simultaneous analysis of serotonin transporter, tryptophan hydroxylase 1 and 2 gene expression in the ventral prefrontal cortex of suicide victims" 153 : 909-918, 2010

16 Loosen PT, "Serum thyrotropin response to thyrotropinreleasing hormone in psychiatric patients: a review" 139 : 405-416, 1982

17 Arango V, "Serotonin brain circuits involved in major depression and suicide" 136 : 443-453, 2002

18 Zill P, "SNP- and haplotype analysis of the tryptophan hydroxylase 2 gene in alcohol-dependent patients and alcohol-related suicide" 32 : 1687-1694, 2007

19 Dwivedi Y, "Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects" 77 : 916-928, 2001

20 Cook EH Jr, "Primary structure of the human platelet serotonin 5-HT2A receptor: identify with frontal cortex serotonin 5-HT2A receptor" 63 : 465-469, 1994

21 Beautrais AL, "Prevalence and comorbidity of mental disorders in persons making serious suicide attempts: a case-control study" 153 : 1009-1014, 1996

22 van Heeringen C, "Prefrontal 5-HT2a receptor binding index, hopelessness and personality characteristics in attempted suicide" 74 : 149-158, 2003

23 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

24 Pandey GN, "Platelet serotonin-2A receptors: a potential biological marker for suicidal behavior" 152 : 850-855, 1995

25 Montgomery SA, "Pharmacological prevention of suicidal behaviour" 4 : 291-298, 1982

26 Bredt DS, "Nitric oxide: a physiologic messenger molecule" 63 : 175-195, 1994

27 Martinowich K, "New insights into BDNF function in depression and anxiety" 10 : 1089-1093, 2007

28 Karege F, "Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs" 136 : 29-37, 2005

29 Brown SM, "Neuroimaging studies of serotonin gene polymorphisms: exploring the interplay of genes, brain, and behavior" 6 : 44-52, 2006

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

31 Butterfield MI, "Neuroactive steroids and suicidality in posttraumatic stress disorder" 162 : 380-382, 2005

32 Rujescu D, "NOS-I and -III gene variants are differentially associated with facets of suicidal behavior and aggression-related traits" 147 : 42-48, 2008

33 Boldrini M, "More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides" 1041 : 19-28, 2005

34 Passamonti L, "Monoamine oxidase-a genetic variations influence brain activity associated with inhibitory control: new insight into the neural correlates of impulsivity" 59 : 334-340, 2006

35 Olié E, "Measurement of total serum cholesterol in the evaluation of suicidal risk" 133 : 234-238, 2011

36 Zetterström TS, "Manipulations of brain 5-HT levels affect gene expression for BDNF in rat brain" 39 : 1063-1073, 1999

37 Oquendo MA, "Lower cortisol levels in depressed patients with comorbid post-traumatic stress disorder" 28 : 591-598, 2003

38 Sher L, "Lower cerebrospinal fluid homovanillic acid levels in depressed suicide attempters" 90 : 83-89, 2006

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

40 Mann JJ, "Lower 3H-paroxetine binding in cerebral cortex of suicide victims is partly due to fewer high affinity, non-transporter sites" 103 : 1337-1350, 1996

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

42 Kim YK, "Low plasma BDNF is associated with suicidal behavior in major depression" 31 : 78-85, 2007

43 Muldoon MF, "Low or lowered cholesterol and risk of death from suicide and trauma" 42 : 45-56, 1993

44 Troisi A, "Low cholesterol is a risk factor for attentional impulsivity in patients with mood symptoms" 188 : 83-87, 2011

45 Austin MC, "Localized decrease in serotonin transporter-immunoreactive axons in the prefrontal cortex of depressed subjects committing suicide" 114 : 807-815, 2002

46 Arango V, "Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims" 688 : 121-133, 1995

47 Agren H, "Life at risk: markers of suicidality in depression" 1 : 89-103, 1983

48 Duval F, "Lack of effect of HPA axis hyperactivity on hormonal responses to d-fenfluramine in major depressed patients: implications for pathogenesis of suicidal behaviour" 26 : 521-537, 2001

49 Perez-Rodriguez MM, "Lack of association between testosterone and suicide attempts" 63 : 125-130, 2011

50 Słuzewska A, "Interleukin-6 serum levels in depressed patients before and after treatment with fluoxetine" 762 : 474-476, 1995

51 Reif A, "Influence of Functional Variant of Neuronal Nitric Oxide Synthase on Impulsive Behaviors in Humans" 66 : 41-50, 2009

52 Sluzewska A, "Indicators of immune activation in major depression" 64 : 161-167, 1996

53 Kim YK, "Increased plasma nitric oxide level associated with suicide attempt in depressive patients" 30 : 1091-1096, 2006

54 Jokinen J, "HPT axis, CSF monoamine metabolites, suicide intent and depression severity in male suicide attempters" 111 : 119-124, 2008

55 Tripodianakis J, "Gonadal axis hormones in psychiatric male patients after a suicide attempt" 257 : 135-139, 2007

56 Noga JT, "Glutamate receptors in the postmortem striatum of schizophrenic, suicide, and control brains" 27 : 168-176, 1997

57 Roy A, "Gene-environment interaction and suicidal behavior" 15 : 282-288, 2009

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

59 Turecki G, "Dissecting the suicide phenotype: the role of impulsiveaggressive behaviours" 30 : 398-408, 2005

60 Connor TJ, "Depression, stress and immunological activation: the role of cytokines in depressive disorders" 62 : 583-606, 1998

61 Weiss JM, "Depression and anxiety: role of the locus coeruleus and corticotropin- releasing factor" 35 : 561-572, 1994

62 Xing G, "Decreased calcium- dependent constitutive nitric oxide synthase (cNOS) activity in prefrontal cortex in schizophrenia and depression" 58 : 21-30, 2002

63 Seidel A, "Cytokine production and serum proteins in depression" 41 : 534-538, 1995

64 Janelidze S, "Cytokine levels in the blood may distinguish suicide attempters from depressed patients" 25 : 335-339, 2011

65 Pandey GN, "Cyclic AMP response element-binding protein in post-mortem brain of teenage suicide victims: specific decrease in the prefrontal cortex but not the hippocampus" 10 : 621-629, 2007

66 Yehuda R, "Cortisol regulation in posttraumatic stress disorder and major depression: a chronobiological analysis" 40 : 79-88, 1996

67 Sheard MH, "Clinical pharmacology of aggressive behavior" 11 : 483-492, 1988

68 Yehuda R, "Clinical correlates of DHEA associated with post-traumatic stress disorder" 114 : 187-193, 2006

69 Kalkman HO, "Circumstantial evidence for a role of glutamine-synthetase in suicide" 76 : 905-907, 2011

70 Markianos M, "Christopoulos M, Papageorgopoulos P, et al. Suicide attempt by jumping: a study of gonadal axis hormones in male suicide attempters versus men who fell by accident" 170 : 82-85, 2009

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

72 Golomb BA, "Cholesterol and violence: is there a connection?" 128 : 478-487, 1998

73 Mann JJ, "Cerebrospinal fluid amines and higher-lethality suicide attempts in depressed inpatients" 41 : 162-171, 1997

74 Coccaro EF, "Cerebrospinal fluid 5-hydroxyindolacetic acid and homovanillic acid: reciprocal relationships with impulsive aggression in human subjects" 117 : 241-248, 2010

75 Mann JJ, "Can biological tests assist prediction of suicide in mood disorders?" 9 : 465-474, 2006

76 Nordström P, "CSF 5-HIAA predicts suicide risk after attempted suicide" 24 : 1-9, 1994

77 Dwivedi Y, "Brain-derived neurotrophic factor: role in depression and suicide" 5 : 433-449, 2009

78 Sher L, "Brain-derived neurotrophic factor and suicidal behavior" 104 : 455-458, 2011

79 Cheetham SC, "Brain GABAA/benzodiazepine binding sites and glutamic acid decarboxylase activity in depressed suicide victims" 460 : 114-123, 1988

80 Mann JJ, "Blunted serotonergic responsivity in depressed inpatients" 13 : 53-64, 1995

81 Rujescu D, "Association of anger-related traits with SNPs in the TPH gene" 7 : 1023-1029, 2002

82 Thiblin I, "Anabolic androgenic steroids and suicide" 11 : 223-231, 1999

83 Pandey GN, "Altered serotonin function in suicide. Evidence from platelet and neuroendocrine studies" 836 : 182-200, 1997

84 Lalovic A, "Altered expression of lipid metabolism and immune response genes in the frontal cortex of suicide completers" 120 : 24-31, 2010

85 Nowak G, "Alterations in the N-methyl-D-aspartate(NMDA) receptor complex in the frontal cortex of suicidevictims" 675 : 157-164, 1995

86 Ordway GA, "Agonist binding to alpha 2-adrenoceptors is elevated in the locus coeruleus from victims of suicide" 63 : 617-624, 1994

87 Anguelova M, "A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: II. Suicidal behavior" 8 : 646-653, 2003

88 Manuck SB, "A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity" 95 : 9-23, 2000

89 McKinnon MC, "A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder" 34 : 41-54, 2009

90 Mann JJ, "A current perspective of suicide and attempted suicide" 136 : 302-311, 2002

91 Cooper SJ, "5-Hydroxyindoleacetic acid in cerebrospinal fluid and prediction of suicidal behaviour in schizophrenia" 340 : 940-941, 1992