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Transcript of Elucidating Inflammatory Markers of Suicidal Behavior in ...€¦ · Microsoft PowerPoint - SPTG -...
Elucidating Inflammatory Markers of Suicidal Behavior in Depression and Bipolar Disorder
William Coryell, MDUniversity of Iowa
Simon Evans, MDUniversity of Michigan
Holly WilcoxJohns Hopkins University
Funding from American Foundation for Suicide Prevention (AFSP)
Toxoplasmosic gondii form ova only in felines but can exist in any mammal where
cysts locate preferentially in the amygdala and forebrain
in mice the inflammatory process resulting from these cysts result in decreases in fear of open spaces and in aversion to cat urine
Are there analogous effects in humans?
Case‐Control Studies of Toxoplasmosis Titers in Suicide Attempters
Suicide Attempters Controls p
Arling et al. 2009
n 81 158
diagnosis mood disorder mood disorder &
healthy
geometric mean (CI) IgG 0.48 (0.40, 0.57) 0.33 (0.28, 0.39)
# (%) positive titer 11 (13.6) 17 (10.8) 0.004
Yagmur et al. 2010
n 200 200
diagnosis mixed healthy
# (%) seropositive 82 (41.0) 56 (28.0) 0.004
Okusaga et al. 2011
n 351 599
diagnosis schizophrenia schizophrenia
# (%) seropositive 146 (41.6) 226 (37.7) 0.006
Case‐Control Studies of Toxoplasmosis Titers in Suicide Attempters
Suicide Attempters Controls p
Zhang et al. 2012
n 54 30
diagnosis mixed healthy
# (%) seropositive 22 (40.7) 6 (20.0) 0.008
Alvarado‐Esquivel et al. 2013
n 156 127
diagnosis mixed mixed
# (%) positive titer 7 (4.5) 10 (7.9) 0.04
Coryell et al. 2013
n 17 91
diagnosis
mean log (SD) IgG ‐0.78 (0.67) ‐1.14 (0.48) 0.009
# (%) seropositive 2 (11.8) 2 (2.1) 0.09
Inclusion Criteria
• 18 years old or older
• Is in a current episode of DSM IV major depressive disorder or bipolar disorder, depressive phase.
Exclusion Criteria
• Acute or chronic infection in previous month
• Active autoimmune disease
• Current moderate or severe alcohol use disorder
• Daily use of anti-inflammatory agent ever preceding 2 weeks.
Suicide Attempt Group
No Suicide Attempt Group
Lifetime history of at least 2 attempts one of which occurred in previous year.
No lifetime history of suicide attempt.
Hypotheses
#1: The proportions of depressed patients with histories of suicide attempts will increase significantly across quartiles of toxoplasmosis titers.
#2: Time to suicide attempt in the year following intake will be progressively shorter across increasing lgG toxoplasma antibody titre quartiles.
#3: The relationship between lgG toxoplasma antibody titres and time to suicide attempt will be mediated by inflammatory activity as quantified by IL-2, IL-6 and TNF-alpha.
Demographics and Diagnosis by
Absent Present p
n 124 99
Age, mean (SD) 38.4 (15.4) 32.6 (13.3) 0.003
# (%) female 88 (71.0) 64 (64.6)
# (%) living Alone 37 (28.8) 34 (34.3)
highest level of education, mean (50)
5.6 (1.2) 4.9 (1.3) <.0001
Suicide Attempt History
Toxoplasmosis Titers and Suicide Attempt HistoryAbsent Present p
n 124 99
Mean (D) log toxoplasmosis titer
IgG -.76 (.32) -.79 (.28)
IgM -.51 (.34) -.38 (.35) .010
# (%) positive titer
IgG 10 (8.1) 5 (5.1)
IgM 8 (6.5) 15 (15.2)
IgG quartile Proportion with SA
1
2
3
4
33
43
47
58
Proportions with History of Suicide Attempts by Toxoplasmosis IgG Quartile
Toxoplasmosis IgG
MAOS aggression score
SA history
.18** .17**
.15*
.17*
(without aggression in model)
Demographics and Diagnosis
Absent Present p
n 124 99
Mean (D) log toxoplasmosis titer
IgG -.76 (.32) -.79 (.28)
IgM -.51 (.34) -.38 (.35) .010
# (%) positive titer
IgG 10 (8.1) 5 (5.1)
IgM 8 (6.5) 15 (15.2)
Suicide Attempt History