Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity.
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-1beta, interleukin-6 (IL-6), interleukin-8, and tumor necrosis factor-alpha (TNF-alpha) 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-Asberg 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-alpha 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.
Lindqvist
Daniel
D
Department of Clinical Sciences, Section of Psychiatry, Lund University Hospital, Lund SE-221 85, Sweden.
Janelidze
Shorena
S
Hagell
Peter
P
Erhardt
Sophie
S
Samuelsson
Martin
M
Minthon
Lennart
L
Hansson
Oskar
O
Björkqvist
Maria
M
Träskman-Bendz
Lil
L
Brundin
Lena
L
D000328:Adult; D000704:Analysis of Variance; D001812:Blood-Brain Barrier / Q000503:physiopathology; D016207:Cytokines / Q000097:blood / Q000134:cerebrospinal fluid; D003863:Depression / Q000134:cerebrospinal fluid* / Q000523:psychology*; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D015850:Interleukin-6 / Q000134:cerebrospinal fluid*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013129:Spinal Puncture / Q000379:methods; D018709:Statistics, Nonparametric; D013406:Suicide, Attempted; D055815:Young Adult
D016207:Cytokines; D015850:Interleukin-6; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid