Aggressivity, suicide attempts, and depression: relationship to cerebrospinal fluid monoamine metabolite levels

BACKGROUND We have proposed a stress-diathesis model for suicidal behavior, in which major depression is a stressor and the diathesis is shared with aggression. Neurotransmitter correlates of the stress or diathesis have not been adequately evaluated by previous studies, because they did not simultaneously examine the relationship of multiple neurotransmitters to all three psychopathologies in the same population. In the present study we investigated the relationship of monoamine metabolites to aggressivity, suicidal behavior, and depression in patients with mood disorders. METHODS Ninety-three drug-free subjects with a major depressive episode underwent lumbar puncture and psychiatric evaluation. Cerebrospinal fluid CSF levels of 5hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA) and methoxy-hydroxy-phenylglycol (MHPG) were assayed. The relationships between monoamine metabolites and clinical variables were statistically evaluated. RESULTS Higher lifetime aggressivity correlated significantly with lower CSF 5-HIAA. Lower CSF 5-HIAA and greater suicidal intent were found in high-lethality suicide attempters compared with low-lethality suicide attempters. Low-lethality attempters did not differ biologically from nonattempters. No correlation between CSF HVA and any of the psychopathological variables was found. Only aggression showed a trend statistically in correlating positively with CSF MHPG levels. CONCLUSIONS Lower CSF 5-HIAA concentration was independently associated with severity of lifetime aggressivity and a history of a higher lethality suicide attempt and may be part of the diathesis for these behaviors. The dopamine and norepinephrine systems do not appear to be as significantly involved in suicidal acts, aggression, or depression. The biological correlates of suicide intent warrant further study.

[1]  D. Rubinow,et al.  CSF 5HIAA and personal and family history of suicide in affectively III patients: A negative study , 1983, Psychiatry Research.

[2]  P. Keck,et al.  Uncoupling of serotonergic and noradrenergic systems in depression: Preliminary evidence from continuous cerebrospinal fluid sampling , 1997, Depression and anxiety.

[3]  H. Ågren.  Symptom patterns in unipolar and bipolar depression correlating with monoamine metabolites in the cerebrospinal fluid: II. Suicide , 1980, Psychiatry Research.

[4]  C. Nemeroff,et al.  CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers. , 1994, Archives of general psychiatry.

[5]  E. Gershon,et al.  Cerebrospinal Fluid Studies of Bipolar Patients with and without a History of Suicide Attempts , 1986, Annals of the New York Academy of Sciences.

[6]  J. Mann,et al.  Association of aggressive behavior with altered serotonergic function in patients who are not suicidal. , 2000, The American journal of psychiatry.

[7]  A. Beck,et al.  Assessment of suicidal intention: the Scale for Suicide Ideation. , 1979, Journal of consulting and clinical psychology.

[8]  J. Sweeney,et al.  Attempted Suicide Characteristics and Cerebrospinal Fluid Amine Metabolites in Depressed Inpatients , 1996, Neuropsychopharmacology.

[9]  M. Åsberg,et al.  5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? , 1976, Archives of general psychiatry.

[10]  C Waternaux,et al.  Toward a clinical model of suicidal behavior in psychiatric patients. , 1999, The American journal of psychiatry.

[11]  M. Åsberg,et al.  Monoamine metabolites in CSF and suicidal behavior. , 1981, Archives of general psychiatry.

[12]  Y. Lecrubier,et al.  CSF 5-HIAA levels are lower in impulsive as compared to nonimpulsive violent suicide attempters and control subjects , 1999, Biological Psychiatry.

[13]  D. Nixon,et al.  Depression among alcoholics. , 1987, The International journal of the addictions.

[14]  F. Goodwin,et al.  Human aggression and suicide: their relationship to neuropsychiatric diagnoses and serotonin metabolism. , 1982, Advances in biochemical psychopharmacology.

[15]  J. Mann,et al.  Cerebrospinal fluid amines and higher-lethality suicide attempts in depressed inpatients , 1997, Biological Psychiatry.

[16]  M. Scheinin,et al.  Simultaneous determination of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, and homovanillic acid in cerebrospinal fluid with high-performance liquid chromatography using electrochemical detection. , 1983, Analytical biochemistry.

[17]  S. Paul,et al.  Reduced CSF concentrations of homovanillic acid and homovanillic acid to 5-hydroxyindoleacetic acid ratios in depressed patients: relationship to suicidal behavior and dexamethasone nonsuppression. , 1986, The American journal of psychiatry.

[18]  M. Linnoila,et al.  Cerebrospinal fluid monoamine metabolites and suicidal behavior in depressed patients. A 5-year follow-up study. , 1989, Archives of general psychiatry.

[19]  C. Horváth,et al.  Catecholamines and related compounds , 1978 .

[20]  C. Nordin.  Relationships between clinical symptoms and monoamine metabolite concentrations in biochemically defined subgroups of depressed patients , 1988, Acta psychiatrica Scandinavica.

[21]  C. Alling,et al.  Prediction of Suicidal Behavior from Biologic Tests , 1992, Journal of clinical psychopharmacology.

[22]  M. Åsberg,et al.  5-HYDROXYINDOLEACETIC ACID LEVELS IN ATTEMPTED SUICIDES WHO HAVE KILLED THEIR CHILDREN , 1984, The Lancet.

[23]  J. Csernansky,et al.  Impulsive Aggression in Personality Disorder Correlates with Platelet 5-HT2A Receptor Binding , 1997, Neuropsychopharmacology.

[24]  Frederick K. Goodwin,et al.  Aggression in humans correlates with cerebrospinal fluid amine metabolites , 1979, Psychiatry Research.

[25]  S. Koslow,et al.  CSF and urinary biogenic amines and metabolites in depression and mania. A controlled, univariate analysis. , 1983, Archives of general psychiatry.

[26]  W. J. Klein,et al.  Aggression, suicide, and serotonin: relationships to CSF amine metabolites. , 1982, The American journal of psychiatry.

[27]  M. Åsberg,et al.  Skin conductance habituation and cerebrospinal fluid 5-hydroxyindoleacetic acid in suicidal patients. , 1986, Archives of general psychiatry.

[28]  S. Montgomery,et al.  Suicide and Antidepressants , 2012, Drugs.

[29]  J. Mann,et al.  CSF 5-HIAA and HVA concentrations in elderly depressed patients who attempted suicide. , 1990, The American journal of psychiatry.

[30]  M Linnoila,et al.  Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. , 1983, Life sciences.

[31]  M. Hamilton.  A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[32]  R. Cowdry,et al.  CSF metabolites in borderline personality disorder compared with normal controls , 1990, Biological Psychiatry.

[33]  M. Linnoila,et al.  Depression among alcoholics. Relationship to clinical and cerebrospinal fluid variables. , 1991, Archives of general psychiatry.

[34]  Pamela D. Butler,et al.  Depression and anxiety: Role of the locus coeruleus and corticotropin-releasing factor , 1994, Brain Research Bulletin.

[35]  C. Bánki,et al.  Biochemical markers in suicidal patients. Investigations with cerebrospinal fluid amine metabolites and neuroendocrine tests. , 1984, Journal of affective disorders.

[36]  D. J. King,et al.  5-hydroxyindoleacetic acid in cerebrospinal fluid and prediction of suicidal behaviour in schizophrenia , 1992, The Lancet.

[37]  H. M. Praag.  Central monoamine metabolism in depressions. II. Catecholamines and related compounds. , 1980 .

[38]  W. Verhoeven,et al.  CSF monoamine metabolites in patients and controls: support for a bimodal distribution in major affective disorders , 1988, Acta psychiatrica Scandinavica.

[39]  S. Koslow,et al.  Depressive mania versus agitated depression: Biogenic amine and hypothalamic-pituitary-adrenocortical function , 1994, Biological Psychiatry.

[40]  A. Beck,et al.  Components of suicidal intent in completed and attempted suicides. , 1976, The Journal of psychology.

[41]  M. Linnoila,et al.  A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids , 1998, Biological Psychiatry.

[42]  M. Linnoila,et al.  A prospective follow-up study of alcoholic violent offenders and fire setters. , 1996, Archives of general psychiatry.

[43]  S. Khanna,et al.  CSF amine metabolites in depression , 1992, Biological Psychiatry.

[44]  M. Åsberg,et al.  CSF monoamine metabolites in melancholia , 1984, Acta psychiatrica Scandinavica.

[45]  M. Åsberg,et al.  CSF 5-HIAA predicts suicide risk after attempted suicide. , 1994, Suicide & life-threatening behavior.

[46]  H. Ågren.  Depressive symptom patterns and urinary MHPG excretion , 1982, Psychiatry Research.

[47]  F. Goodwin,et al.  Cerebrospinal fluid amine metabolites and cyclic nucleotides in human aggression [proceedings]. , 1981, Psychopharmacology bulletin.

[48]  Gerald L. Brown,et al.  Cerebrospinal Fluid Correlates of Suicide Attempts and Aggression , 1986, Annals of the New York Academy of Sciences.

[49]  A. Beck,et al.  Classification of suicidal behaviors: I. Quantifying intent and medical lethality. , 1975, The American journal of psychiatry.

[50]  Gerald L. Brown,et al.  Human aggression and suicide. , 1986, Suicide & life-threatening behavior.

[51]  A. Beck,et al.  An inventory for measuring depression. , 1961, Archives of general psychiatry.