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)

Psychoactive Properties of Parasites

myrmeconema neotropicum: the nematode

and

cephalotes atratus: the ant

Toxoplasmosis gondii

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)

myrmeconema neotropicum: the nematode

and

cephalotes atratus: the ant

plesiometa argyra: the spider

and

hymenoepimecis argyraphaga: the wasp

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

plesiometa argyra: the spider

and

hymenoepimecis argyraphaga: the wasp

Webs of Infected Spiders

• Create cocoon webs on the night that they are to be killed

• Central portion is full• Frame lines shorter and closer to hub

• Smaller diameter with shorter and fewer anchor lines