Background
Depressive disorders are associated with immune system alterations that can be detected
in the blood. Cytokine concentrations in cerebrospinal fluid (CSF) and their relationship
to aspects of suicidality have previously not been investigated.
Methods
We measured interleukin-1β, interleukin-6 (IL-6), interleukin-8, and tumor necrosis
factor-α (TNF-α) in CSF and plasma of suicide attempters (n = 63) and healthy control subjects (n = 47). Patients were classified according to diagnosis and violent or nonviolent suicide
attempt. We evaluated suicidal ideation and depressive symptoms using the Suicide
Assessment Scale and the Montgomery-Åsberg Depression Rating Scale (MADRS). We also
analyzed the relation between cytokines and monoamine metabolites 5-hydroxyindoleacetic
acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG)
in CSF, as well as the integrity of the blood-brain barrier as reflected by the CSF:serum
albumin ratio.
Results
IL-6 in CSF was significantly higher in suicide attempters than in healthy control
subjects. Patients who performed violent suicide attempts displayed the highest IL-6.
Furthermore, there was a significant positive correlation between MADRS scores and
CSF IL-6 levels in all patients. IL-6 and TNF-α correlated significantly with 5-HIAA
and HVA in CSF, but not with MHPG. Cytokine levels in plasma and CSF were not associated,
and patients with increased blood-brain barrier permeability did not exhibit elevated
cytokine levels.
Conclusions
We propose a role for CSF IL-6 in the symptomatology of suicidal behavior, possibly
through mechanisms involving alterations of dopamine and serotonin metabolism.
Key Words
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References
- The macrophage theory of depression.Med Hypotheses. 1991; 35: 298-306
- Acute phase proteins in major depression.J Psychosom Res. 1997; 43: 529-534
- Increase in interleukin-1beta in late-life depression.Am J Psychiatry. 2005; 162: 175-177
- Raised plasma levels of tumor necrosis factor alpha in patients with depression: Normalization during electroconvulsive therapy.J ECT. 2003; 19: 183-188
- Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis.Eur Neuropsychopharmacol. 2001; 11: 203-208
- Immune activation in non-treated suicidal major depression.Immunol Lett. 1999; 67: 105-108
- Differences in cytokines between non-suicidal patients and suicidal patients in major depression.Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32: 356-361
- Tree pollen peaks are associated with increased nonviolent suicide in women.Mol Psychiatry. 2005; 10: 232-235
- Is seasonality of suicides stronger in victims with hospital-treated atopic disorders?.Psychiatry Res. 2004; 126: 167-175
- The inflammatory response system of brain: Implications for therapy of Alzheimer and other neurodegenerative diseases.Brain Res Brain Res Rev. 1995; 21: 195-218
- Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide.J Psychiatr Res. 2008; 42: 151-157
- Elevated cytokine expression in the orbitofrontal cortex of victims of suicide.Acta Psychiatr Scand. 2008; 117: 198-206
- Cerebrospinal cytokine levels in patients with acute depression.Neuropsychobiology. 1999; 40: 171-176
- Cerebrospinal fluid interleukin (IL)-6 in unipolar major depression.J Affect Disord. 2004; 79: 285-289
- Suicidal impulses in patients with chronic viral hepatitis C during or after therapy with interferon alpha.Gastroenterol Clin Biol. 1998; 22: 353-357
- Depression during therapy with interferon alpha—how long should an antidepressant treatment last?.Pharmacopsychiatry. 2005; 38: 102-104
- The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: Results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine.Mol Psychiatry. 2006; 11: 680-684
- Effects of cytokines and infections on brain neurochemistry.Clin Neurosci Res. 2006; 6: 52-68
- Endotoxin-induced activation of cerebral catecholamine and serotonin metabolism: Comparison with interleukin-1.J Pharmacol Exp Ther. 1992; 261: 964-969
- Mouse interleukin-6 stimulates the HPA axis and increases brain tryptophan and serotonin metabolism.Neurochem Int. 1998; 33: 143-154
- Neurobiology of suicidal behaviour.Nat Rev Neurosci. 2003; 4: 819-828
- Diagnostic and Statistical Manual of Mental Disorders.3rd ed. American Psychiatric Press, Washington, DC1987
- A new depression scale designed to be sensitive to change.Br J Psychiatry. 1979; 134: 382-389
- The suicide assessment scale: A scale evaluating change in suicidal behavior.Psychopharmacol Bull. 1986; 22: 200-205
- Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I).American Psychiatric Press, Washington, DC1997
- Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II).American Psychiatric Press, Washington, DC1997
- HPA-related CSF neuropeptides in suicide attempters.Eur Neuropsychopharmacol. 1992; 2: 99-106
- Simultaneous determination of the three major monoamine metabolites in brain tissue and body fluids by a mass fragmentographic method.Psychopharmacology (Berl). 1976; 48: 147-153
- Reduced cerebrospinal HVA concentrations and HVA/5-HIAA ratios in suicide attempters.Eur Neuropsychopharmacol. 1999; 9: 399-405
- Impairment of the blood-CSF barrier in suicide attempters.Eur Neuropsychopharmacol. 1996; 6: 195-199
- Protein analysis in cerebrospinal fluid.Eur Neurol. 1993; 33: 129-133
- Indicators of immune activation in major depression.Psychiatry Res. 1996; 64: 161-167
- Skeletal myocytes are a source of interleukin-6 mRNA expression and protein release during contraction: Evidence of fiber type specificity.FASEB J. 2004; 18: 992-994
- IL-6 gene expression in human adipose tissue in response to exercise—effect of carbohydrate ingestion.J Physiol. 2003; 550: 927-931
- Evidence for an immune response in major depression: A review and hypothesis.Prog Neuropsychopharmacol Biol Psychiatry. 1995; 19: 11-38
- Passage of cytokines across the blood-brain barrier.Neuroimmunomodulation. 1995; 2: 241-248
- Modulation of hypothalamic-pituitary-adrenal function by transgenic expression of interleukin-6 in the CNS of mice.J Neurosci. 1997; 17: 9473-9480
- IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors.Neurobiol Dis. 2006; 23: 587-594
- Effects of interleukin-1 and endotoxin in the forced swim and tail suspension tests in mice.Pharmacol Biochem Behav. 2005; 81: 688-693
- IL-6 mediated alterations on immobile behavior of rats in the forced swim test via ERK1/2 activation in specific brain regions.Behav Brain Res. 2008; 193: 183-191
- The dopaminergic neurotransmitter system is associated with aggression and agitation in frontotemporal dementia.Neurochem Int. 2008; 52: 1052-1060
- Brain monoamine oxidase A activity predicts trait aggression.J Neurosci. 2008; 28: 5099-5104
- Monoamine metabolites in CSF and suicidal behavior.Arch Gen Psychiatry. 1981; 38: 631-636
- Aggressivity, suicide attempts, and depression: Relationship to cerebrospinal fluid monoamine metabolite levels.Biol Psychiatry. 2001; 50: 783-791
- Prediction of suicidal behavior from biologic tests.J Clin Psychopharmacol. 1992; 12: 21S-26S
- A prospective follow-up study of alcoholic violent offenders and fire setters.Arch Gen Psychiatry. 1996; 53: 523-529
- Cytokines: abnormalities in major depression and implications for pharmacological treatment.Hum Psychopharmacol. 2004; 19: 397-403
- Serotonin, stress and corticoids.J Psychopharmacol. 2000; 14: 139-151
- The stress system in depression and neurodegeneration: Focus on the human hypothalamus.Brain Res Rev. 2008; 57: 531-553
- Salivary cortisol and suicidal behavior—a follow-up study.Psychoneuroendocrinology. 2008; 33: 1061-1068
Article info
Publication history
Published online: March 09, 2009
Accepted:
January 28,
2009
Received in revised form:
January 11,
2009
Received:
October 13,
2008
Identification
Copyright
© 2009 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
