Psychiatry Research 260 (2018) 193–198

Contents lists available at ScienceDirect

Psychiatry Research
journal homepage: www.elsevier.com/locate/psychres

Correlation between interferon γ and interleukin 6 with PTSD and resilience T

a,c b a a c
Dagmar Bruenig , Divya Mehta , Charles P. Morris , Bruce Lawford , Wendy Harvey ,
⁎
Ross McD Youngb, Joanne Voiseya,
a
Institute of Health and Biomedical Innovation (IHBI) and School of Biomedical Sciences, 60 Musk Avenue, Queensland University of Technology, Kelvin Grove,
Queensland 4059, Australia
b
Institute of Health and Biomedical Innovation (IHBI) and School of Psychological and Counselling, 60 Musk Avenue, Queensland University of Technology, Kelvin Grove,
Queensland 4059, Australia
c
Gallipoli Medical Research Institute, Greenslopes Private Hospital, Newdegate Street, Greenslopes, Queensland 4120, Australia

A R T I C L E I N F O A B S T R A C T

Keywords: Posttraumatic Stress Disorder (PTSD) is a debilitating psychiatric disorder with decreased general health
Cytokines prognosis and increased mortality. Inflammation has been hypothesised to be a link between PTSD and the most
PTSD common co-morbid medical disorders. However, the relationship between inflammation and PTSD is not clear.
Mood Individual inflammatory markers have shown variable associations with PTSD. This study investigates the
Resilience
correlations between serum cytokines, PTSD and resilience in a cohort of Caucasian Vietnam combat veterans (n
Veterans
Inflammation
= 299). After correction for multiple testing, PTSD severity was correlated with small but significant decreases
in interleukin 6 and interferon γ (p = 0.004, p = 0.013, respectively) whereas resilience was correlated with
increased levels of interleukin 6 and interferon γ (p = 0.023; p = 0.007, respectively). Analyses of sub-symp-
toms of PTSD revealed that mood and arousal symptoms showed the most significant effect on interleukin 6 and
interferon γ. More research is needed to further elucidate the mechanisms underlying the relationship between
cytokine levels, PTSD sub-symptoms and trauma outcomes to improve the knowledge base of differences in
trauma response and the biological system.

1. Introduction
Posttraumatic Stress Disorder (PTSD) is a debilitating psychiatric
disorder (American Psychiatric Association, 2013). Cohorts with high
risks of trauma exposure are at particular risk of developing PTSD. For
military personnel it is estimated that between 20% and 30% of ve-
terans will develop PTSD (Australian Government, D.o.V.A, 2014;
Dohrenwend et al., 2006; Hoge et al., 2004). In addition to the severe
negative psychological sequelae, PTSD has also been linked to poorer
general health and higher mortality (Boscarino, 2008), especially an
increased risk for cardiovascular problems and autoimmune disorders
such as rheumatoid arthritis (Edmondson et al., 2013; Lee et al., 2016;
Stein et al., 2016; Wolf et al., 2016). The molecular mechanisms un-
derlying the psychological sequelae and medical disorders remain un-
clear. However, inflammatory pathways have been hypothesised as a
potential link (Leonard and Maes, 2012). For example, interferon γ is a
cytokine that has been shown to affect serotonin through the trypto-
phan-kynurenine pathway and is implicated in age-related medical and
psychiatric processes (Oxenkrug, 2011). Interleukin 6 is a cytokine that
can also cross the blood-brain barrier impacting on the hypothalamus to
regulate body temperature but also influencing sleep and stress reac-
tions (Rohleder et al., 2012).
Studies investigating inflammatory markers have consistently
shown increased inflammation in PTSD patients (Groer et al., 2015;
Lindqvist et al., 2016, 2014; O'Donovan et al., 2015), and two recent
genome-wide association studies found associations with genes that are
relevant in the context of inflammation (Powers et al., 2016; Stein et al.,
2016). Case/control studies investigating individual inflammatory
markers and PTSD have shown mixed results (Guo et al., 2012;
O'Donovan et al., 2015; von Kanel et al., 2007), and the evidence is
even less clear with depression, one of the most frequent co-morbidities
of PTSD (Dahl et al., 2014; Schmidt et al., 2016). A recent meta-analysis
found increased levels of interleukin 6 (IL6), interleukin 1β (IL1β),
tumour necrosis factor α (TNFα) and interferon γ (IFN γ) in a PTSD
cohort as opposed to healthy controls. However, heterogeneity of data
was high, mostly due to factors such as medication and major depres-
sive disorder (Passos et al., 2015). Only a small number of studies with
limited participant numbers for IFNγ analysis were recorded (n = 79)
and a potential publication bias for IL 1β was noted (Passos et al.,
2015). A replication of the meta-analysis showed that the potential

⁎
Corresponding author.
E-mail address: j.voisey@qut.edu.au (J. Voisey).

https://doi.org/10.1016/j.psychres.2017.11.069
Received 23 February 2017; Received in revised form 4 September 2017; Accepted 25 November 2017
Available online 28 November 2017
0165-1781/ Crown Copyright © 2017 Published by Elsevier Ireland Ltd. All rights reserved.
D. Bruenig et al. Psychiatry Research 260 (2018) 193–198

effect size of IL 6 was probably overestimated (Nilsonne et al., 2016). Table 1

Two replication studies investigating inflammatory markers in large Demographics and clinical summary.
military cohorts found increased overall levels of inflammation but
PTSD No PTSD p-value
varying evidence for increased cytokine levels on an individual marker (159) (140)
basis (Lindqvist et al., 2016, 2014). The authors consistently found
elevated IL 6 levels based on PTSD diagnosis but not in relation to PTSD Age M (SD) 68.47 (4.16) 69.23 (4.13) 0.113
Marital Status (current) 0.494
severity. They did not find a significant association between IFNγ and
Married (current) 116 108
PTSD. Increased levels of IFNγ in PTSD were found in an Asian cohort Divorced/Separated (current) 9 8
(Guo et al., 2012) and a very small study cohort of combat veterans Psychotropic Medication Yes: 94 Yes: 15 5.498E-19
(Hammad et al., 2012), but a study in a much larger military cohort No: 51 No: 112
could not replicate these findings (Lindqvist et al., 2016). Education level 0.005
Less than year 10 26 8
A recent study using a cohort of trauma exposed Nepali child sol-
Year 10 29 23
diers identified decreased inflammatory gene expression profiles to be Vocational 32 20
associated with increased resilience r (Kohrt et al., 2016). These gene Year 11 or 12 34 33
expression profiles were similar to PTSD free civilian children. A study University 37 56
Comorbiditiesa
with a female cohort found that women in recovery from PTSD have the
Major depression 21 2 4.190E-04
same levels of inflammation as healthy controls, suggesting that im- Suicide risk 31 2 2.000E-06
proved psychological states and associated health perceptions con- Agoraphobia 33 6 8.000E-05
tributed to reduced levels of inflammation (Gill et al., 2013). Another Social phobia 8 0 0.017
study found that coping factors such as pride and contentment are as- Alcohol dependence 22 6 0.019
Alcohol abuse 4 1 0.029
sociated with decreased levels of IL 6 (Stellar et al., 2015). These
Generalised anxiety disorder 12 3 0.092
findings suggest that positive beliefs and emotions are associated with Auto-Immune Disorders 0.806
reduced inflammation. Resilience is typically associated with generally Rheumatoid Arthritis 3 5
positive attitudes and emotions (Bonanno, 2004) and is worthy of closer Psoriasis 2 0
Other 7 5
investigation regarding the association with inflammatory markers.
Given the mixed research findings the correlation between serum
Note. M = mean; SD = standard deviation.
cytokine levels and PTSD, symptom severity and resilience in a large a
all comorbidity counts as per Mini International Neuropsychiatric Interview (MINI)
Vietnam veteran cohort was investigated. PTSD diagnosis was hy- for DSM IV (Sheehan et al., 1998). Only a subset of all comorbidities is shown. Rare
pothesised to be associated with increased levels of cytokines. It was comorbidities with no current information or both groups = 0 were excluded from the
further hypothesised that increased symptom severity would positively table. Only autoimmune disorders are shown for physical conditions.
correlate with the inflammatory marker and resilience negatively cor-
relate with cytokine levels. then spun at 1500 g for 10 min at 20 °C. The serum was aliquoted into
micro-tubes with a minimum 0.5 ml each. The tubes were stored frozen
2. Method at −80 °C. A commercial laboratory, Sullivan Nicolaides Pathology,
Brisbane, tested a range of cytokines in standard multiplex assay (in-
2.1. Participants terleukin-1 α, interleukin-1β, interleukin-6, interleukin-10, tumour
necrosis factor α, and interferon γ) in duplicate using Luminex 100
A total of 299 male and age-matched participants were recruited Milliplex cytokine multiplex bead assay (HCYTOMAG-60K; assay sen-
through Greenslopes Private Hospital and the Returned and Services sitivity: 0.8 pg/ml; intra-assay CV% = 1.6; inter-assay CV% = 12.0).
League of Australia by the Gallipoli Medical Research Foundation. Of Findings relating to Tumour Necrosis Factor Alpha in connection with
these, 159 participants met criteria for PTSD diagnosis and the re- genetics hypotheses have previously been published by us (Bruenig
maining 140 participants were assigned to the control group. PTSD et al., 2017) The remaining cytokines were further analysed for serum
diagnosis was obtained through structured interviews by psychiatrists level association of PTSD severity and resilience. Samples (n = 37) that
with substantial clinical expertise in the assessment and differential were approaching detectable limit for at least one of the cytokines as-
diagnosis of PTSD. Inclusion criteria included deployment to Vietnam sayed on the multiplex were reanalysed. Taken together, 299 data
during the Vietnam War in the Australian and New Zealand Defence points remained for subsequent analyses across all cytokines based on
Force. The mean age of the cohort was 68.82 years (SD = 4.2). Clinical averages from the first run or, if detectable values were observed, from
psychologists performed further assessments using validated psycholo- the second run. Data was recoded to 0 if a reading was below lower
gical measures. Medical Officers conducted semi-structured interviews detection limit (LDT) yielding the following percentage of data below
to collect a medical history for each participant. Table 1 shows an lower detection limit (IL1 α = 53.85%, IL 1β = 91.64%, IL 6 =
overview of the characteristics of the cohort by diagnostic status. 85.00%, IL 10 = 66.90%, IFNγ = 43.81%).

2.2. Ethics 2.4. Scales

Each participant gave written informed consent before commence-
ment of data collection. Ethics approval for the project was obtained
from the Human Research Ethics Committees of the Queensland
University of Technology and Greenslopes Private Hospital. This study
was carried out in accordance with The Code of Ethics of the World
Medical Association (Declaration of Helsinki).
2.3. Biomarker analysis
A fasting sample of peripheral blood was taken from participants.
Whole blood was collected in an 8.5 ml serum separator tube (SST). The
tubes were left standing upright for 30 min for clotting to occur and
Clinician-Administered PTSD Scale for DSM 5 (CAPS-5): Clinical
psychologists assessed severity of PTSD with the Clinician Administered
PTSD Scale for DSM 5 (CAPS-5) (Weathers et al., 2014). Higher scores
reflect increased PTSD severity.
The Connor-Davidson Resilience Scale (CD RISC) measures resi-
lience via a range of self-reported behaviours and beliefs thought to be
successful in dealing with adverse situations (Connor and Davidson,
2003). The scale has sound psychometric properties (Bezdjian et al.,
2016). Higher scores indicate higher resilience. Cronbach's Alpha was
high: α = 0.92.
The Mini International Neuropsychiatric Interview DSM IV (MINI),
an instrument designed to assess Axis 1 disorders with high validity and

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D. Bruenig et al. Psychiatry Research 260 (2018) 193–198

reliability (Sheehan et al., 1998), was used to assess common psycho-
logical comorbidities.
2.5. Co-variates
Based on previous literature (Lindqvist et al., 2016), we assessed the
following co-variates for the cytokines through a Tweedie Model.
Age: Age was assessed through self-report.
control group (p = 5.498E-19).
Independent sample t-tests revealed that mean scores for PTSD se-
verity were significantly different between the groups, with higher
mean scores in the PTSD group than the controls (p = 2.637E-36; PTSD:
M = 15.64; SD = 9.79; No PTSD: M = 2.52; SD = 3.72) and with the
resilience scale showing opposing results as would be expected (p =
1.332E-11; PTSD: M = 68.28; SD = 15.37; No PTSD: M = 70.12; SD =
11.08).

2.5.1. Body-Mass-Index (BMI) 3.2. Co-variates

BMI was assessed during the medical assessment through a Medical
Officer.
2.5.2. Medication
Medication intake was coded based on the World Health
Organisation's Collaborating Centre for Drug Statistics Methodology
(http://www.whocc.no/atc_ddd_index/) top level coding categories.
The approach of a cumulative score was chosen as all medications from
the prescribed list of drugs were deemed to potentially influence in-
flammation in this cohort. Medication was scored by number of pre-
scribed medication per category. That means that a participant would,
for example, score 2 points in Category A if he was taking two different
medications from the corresponding Anatomical Therapeutic Chemical
(ATC) category. A cumulative score was calculated per participant with
higher scores reflecting higher intake of medication types.
2.5.3. Depression
The Depression Anxiety Stress Scale 21 (DASS-21) is a self-report
scale measuring three different constructs of psychological states:
stress, depression and anxiety (Lovibond and Lovibond, 1995). The
depression subscale was used to control for a potential influence of
depression on cytokine levels in this study. Increased symptoms of
depression are represented by higher subscale scores. Cronbach's Alpha
was high: α = 0.95.
2.5.4. Alcohol
Alcohol history was dichotomised into high-intake vs low-intake
lifetime history. The classification was based on qualitative data pro-
vided by participants and reconciled with AUDIT risk scores (Alcohol
Use Disorder Identification Test; (Bohn et al., 1995)).
Smoking: Number of years smoked as reported by participants in-
formed this potential covariate.
IL 1β had very few values above lower detection limit (n = 25),
hence the variable was dichotomised for analyses. None of the analyses
yielded significant results. All of these analyses were considered for
correction for multiple testing. All other cytokines were tested for a
range of potential covariates per Tweedie Model with Log Link. Less
than 10% of the participants were diagnosed with comorbid MDD. The
data from the depression subscale of the DASS was hence used to
control for depressive symptoms. Depression showed a significant as-
sociation with IFNγ levels and IL 6 levels (p = 0.005, respectively).
Medication showed a significant association with IL 10 (p = 0.015). All
subsequent analyses were performed using the fitted residuals for these
cytokines. There were no influential co-variates for IL 1α and the raw
data was subsequently used.
Table 2 shows the p-values for the co-variates across the different
cytokines.
3.3. Assessment of cytokines with PTSD and resilience
3.3.1. Group differences
To test for differences in serum cytokine levels across the groups,
Mann-Whitney U Tests were applied. IL 1α and IFNγ levels were not
significantly different between the groups (p = 0.704, p = 129, re-
spectively). A marginal group difference was observed for IL 6 (p
=0.045; PTSD: M = 0.720; SD = 16.207; No PTSD: M = −0.855, SD
= 8.009). IL 10 levels showed significant group differences (p =0.018;
PTSD: M = −1.708; SD = 22.495; No PTSD: M = 1.933, SD =
25.052). For both cytokines, mean levels were significantly lower in the
PTSD group than in the control group. After adjusting for multiple
testing, none of these findings remained significant in either the FDR or
the Bonferroni approach.

2.6. Statistical analyses 3.3.2. PTSD symptom severity

All statistics were performed using SPSS 23 (IBM SPSS, 2015).
Tweedie Model with Log Link was used to observe any potential in-
fluence of covariates on cytokine levels and to account for the zero
inflation for each cytokine. All subsequent analyses were performed
non-parametrically to account for the non-normal distribution of the
data. To control for multiple testing, a False Discovery Rate (FDR) and
Bonferroni adjustment was applied using R (https://www.r-project.
org/).
3. Results
Spearman's rho correlation (2-tailed) revealed a trend-line negative
correlation between PTSD severity and IL 6 (r = −0.177; r2 =0.031; p
= 0.004), IL 10 (marginal; r = −0.126; r2 =0.016; p = 0.042) and
IFNγ (r = −0.153; r2 =0.023; p = 0.013) and PTSD severity. IL1α had
no significant correlation with PTSD severity (p = 0.219). After cor-
recting for multiple testing, our findings for IL 6 and IFNγ remained
significant (FDR 5%). When applying Bonferroni adjustment, none of
the findings remained significant.
3.3.3. Sub-scale analyses
Given the trend-line finding for PTSD severity and IL 6, IL 10, and

3.1. Demographics Table 2

Co-variate association between cytokines (p-values).
A total of 299 participants yielded usable cytokine data and were
Depression Age Medication BMI Smoking Alcohol
used for analysis (cases: n = 159; controls: n = 140). Table 1 shows the
demographic descriptors of the participants included in the study. As IL 1α 0.264 0.727 0.787 0.316 0.173 0.098
would be expected, the PTSD group had higher rates of co-morbid IL 6 0.005 0.421 0.407 0.764 0.978 0.251
IL 10 0.169 0.681 0.015 0.696 0.704 0.158
psychological disorders, such as MDD, agoraphobia and suicide risk p
IFNγ 0.005 0.526 0.742 0.504 0.124 0.137
= 4.190E-04, 8.000E-0, 52.000E-06 respectively. The PTSD group had
significantly higher numbers of participants taking psychotropic med- Note: IL1α = interleukin1 α, IL6 = interleukin 6, IL10 = interleukin 10, IFNγ = in-
ications, such as antidepressants and anti-anxiety medications, than the terferon γ; BMI – Body Mass Index.

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D. Bruenig et al.
Table 3
Spearman's rho correlations between sub-symptoms of PTSD and IL 6, IL 10 and IFNγ.
Criterion B Criterion C Criterion D
(intrusions) (avoidance) (mood)
IL 6 −0.121 −0.100 −0.196
p (2-tailed) 0.050 0.105 0.001
IL 10 −0.088 −0.083 −0.145
p (2-tailed) 0.157 0.183 0.019
IFNγ −0.082 −0.138 −0.183
p (2-tailed) 0.183 0.026 0.003
Note: IL6 = interleukin 6, IL10 = interleukin 10, IFNγ = interferon γ.
IFNγ levels, we pursued sub-symptom analyses to elucidate the poten-
tial role of different sub-symptom criteria. Criterion D (negative cog-
nitions and mood) showed small but significant negative correlations
with all three cytokines (p = 0.001 (IL 6)); p = 0.019 (IL 10); p =
0.003 (IFNγ). Criterion C (avoidance) was significantly negatively
correlated with IFNγ (p = 0.026). Criteria B (intrusions; marginally)
and E (arousal; marginally) were significantly negatively correlated
with IL 6 (p = 0.050; p = 0.010; respectively). After correction for
multiple testing, the findings for IL 6 for criterion D (FDR 5%;
Bonferroni) and E (FDR 5% only), and the finding for IFNγ and criterion
D and C (FDR5% only) remained significant. Table 3 shows the corre-
lations of sub-symptoms and p-values per cytokine.
3.3.4. Resilience
The correlation between the cytokines and resilience was tested
through Spearman's rho test. We observed significant but small positive
correlations for IL 6 (r = 0.138; p = 0.023) and IFNγ (r = 0.162; p =
0.007). These findings withstood correction for multiple testing with
FDR 5% but not Bonferroni adjustment. IL 1α and IL 10 did not show a
significant correlation with resilience (p = 0.461; p = 0.114, respec-
tively).
4. Discussion
This study systematically investigated the role of individual cyto-
kines with a large and well controlled group of participants with
comparable trauma exposure across patients and controls. After cor-
recting for multiple testing, group differences between IL 6, IFNγ and
PTSD and controls were observed. A role of IL 6 in PTSD has been
implied before (Lindqvist et al., 2016, 2014; Passos et al., 2015). In-
creased inflammatory markers (Lindqvist et al., 2016, 2014) and gen-
eral ill-health (Edmondson et al., 2013; Lee et al., 2016; Stein et al.,
2016; Wolf et al., 2016) have been observed in PTSD patients, however
in our studies lower levels of cytokines were observed in the PTSD
group than the controls. Studies investigating other inflammatory
markers, such as C-reactive protein and serum amyloid A in PTSD have
reported negative correlations (Sondergaard et al., 2004).
In contrast to Guo et al. (2012) and Hammad et al. (2012) (Guo
et al., 2012; Hammad et al., 2012) we did not observe group differences
for IFNγ. This is in line with two other studies employing larger cohorts
than the previous two studies that also did not find group differences
for IFNγ (Hoge et al., 2009; Lindqvist et al., 2016). However, a recent
meta-analysis with a sample size closer to our present study did find a
significant effect (Passos et al., 2015). Similarly, this study did not find
a significant difference in cytokine levels for IL 6 whereas other studies
have been able to establish such an effect (Passos et al., 2015).
For symptom severity score, the correlations with the cytokines
showed small effects that remained significant after multiple testing for
IL6 and IFNγ, only. Other studies did not find a significant correlation
between a summative inflammatory score and PTSD severity (Lindqvist
et al., 2016). The cohort sizes and average age between this study and
the previously published study were substantially different in that this
study had a much older and larger cohort which may have potentially
Psychiatry Research 260 (2018) 193–198
contributed to the difference in findings. We further pursued sub-
symptom testing for severity scores to uncover potential differential
drivers of cytokine levels. Our analyses revealed the IL 6 was driven by
Criterion E
(arousal) arousal and mood symptoms and IFNγ by mood and intrusion symp-
toms. This is of interest as these findings may indicate differential in-
−0.160 fluences of sub-systems on inflammatory markers. It may be important
0.010
in the future to examine symptom clusters of PTSD with inflammatory
−0.097
0.119 markers to better understand the relationship between psychological
−0.109 distress and inflammation to identify specific therapeutic targets.(Del
0.078 Grande da Silva et al., 2016; Ragen et al., 2015)
Both, IL 6 and IFNγ also showed significant correlations with resi-
lience that withstood multiple testing. A previous study showed positive
affect such as contentment and pride to be associated with lower levels
of Interleukin 6 (Stellar et al., 2015). Another study identified self-ef-
ficacy as a crucial resilience factor for normalised mRNA expression
(Kohrt et al., 2016; Stellar et al., 2015).
Taken together, our findings replicate the association of inflamma-
tion in PTSD, but with lower levels of inflammation found with in-
creased PTSD severity. Our study design included an ageing cohort that
was well enough to participate in a comprehensive research study. This
implies relatively high levels of functioning which might account for
the small effect sizes we observed in all analyses and might also account
for the differences in findings with some of the literature. Increased
resilience may impact negatively on the stress system reflected by the
extra effort that has to be applied to maintain a more normalised level
of functioning (Schoenfeld et al., 2017). Research has shown that there
is a wide range of post-trauma outcomes that can influence a person's
life after a life-shattering experience (Tedeschi and Calhoun, 2004).
These evaluations occur in the face of PTSD symptoms with research
showing that moderate levels of PTSD correlate to personal growth
(Shakespeare-Finch and Lurie-Beck, 2014). While we did not measure
personal growth in our participants, the moderate mean of PTSD
symptom severity in our cohort may hint at mechanisms of survival and
potential reconstruction of meaning in life (growth) that may be at play.
More research is needed to further disentangle the likely complex re-
lationship of PTSD and positive trauma outcomes (Sondergaard et al.,
2004).
There are limitations to our study that should be noted. All effect
sizes in our study are small. While they reached significance the utility
of these findings need to be interpreted with caution. Generally, in-
flammation within PTSD has been associated with low-grade levels.
Statistical overestimation of the relationship with individual in-
flammatory levels and PTSD has previously been suggested (Nilsonne
et al., 2016). Inflammatory markers are highly variable and it is hence
possible that despite all efforts to control for co-variates, the variance
between studies may stem from sources that are difficult to control
(Nilsonne et al., 2016).
A large number of analyses were performed to identify correlations
between individual markers, PTSD and resilience. We accounted for this
by applying methodologies that counter-act Type 1 errors. Other studies
have taken different approaches to avoiding type 1 error rates, however
these approaches come at the cost of granularity on an individual
marker level (Lindqvist et al., 2016). We measured PTSD and resilience
as trauma outcomes, however a wider range of potential outcomes has
been suggested (Shakespeare-Finch and Enders, 2008; Tedeschi and
Calhoun, 2004). The relationship between trauma response and mental
and medical well-being may be more complex than our dichotomous
and cross-sectional approach was able to assess.
Because of the high variability of cytokine elevation in individuals,
it would be preferable in the future to apply longitudinal measures that
include several times points of cytokine measurements for the de-
termination of a relationship between PTSD, resilience and cytokines.
Differences in assay performance and limitations of assay reliabilities
make comparability of results across studies difficult. A more unified
approach with standard protocols would enhance the area of research
significantly. Lastly, comorbidity of PTSD with other disorders such as
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D. Bruenig et al.
MDD is often problematic due to overlaps of phenotypical symptoms
and common molecular pathways. However, we were able to assess a
range of potentially confounding parameters, including depressive
symptoms through a comprehensive data set. Given that our cohort was
an all-male war veteran cohort limits the generalisability of the data.
5. Conclusion
This study systematically investigated the role of individual cyto-
kines in a well-screened and large cohort of Vietnam veterans. A mar-
ginal correlation between IL 6, IFNγ and PTSD was established, likely
driven by sub-symptoms of PTSD. Replication studies in equally large
and well-screened cohorts are recommended with a particular emphasis
on symptom clusters within PTSD and their correlation with in-
flammation. Research into the contribution of more positive trauma
outcomes, such as resilience, adaptive coping and posttraumatic growth
on inflammation may help in improving our understanding of the
complex relationship between trauma, trauma response and well-being.
Acknowledgements
The first author would like to thank the Gallipoli Medical Research
Foundation for their generous provision of a scholarship to DB, and
Miriam Dwyer and Dr Sarah McLeay for their project management
support. The authors would also like to acknowledge Dr Madeline
Romaniuk for psychological input, Dr John Gibson and the team at the
Keith Payne Unit, and the staff and investigators at Greenslopes Private
Hospital for their valuable contribution to the study. All authors would
like to extend their gratitude to the participants of our study for their
generous provision of data and time. The Gallipoli Medical Research
Foundation wishes to thank the RSL QLD for their generous donation,
and Sullivan Nicolaides Pathology and Queensland X-Ray for their in-
kind support.
Conflict of interest
None.
Author contributions
Dagmar Bruenig and Joanne Voisey substantially contributed to the
study design, statistical analyses, writing and critical editing of the
manuscript. Charles P. Morris substantially contributed to the study
design, writing and critical editing of the manuscript. Divya Mehta
substantially contributed to the statistical analyses and critical editing
of the manuscript. Bruce Lawford and Ross McD Young substantially
contributed to the study design and critical editing of the manuscript.
Wendy Harvey substantially contributed to the study design, ethics
submission and data collection. All authors reviewed and approved the
final version of the manuscript for publication.
Role of funding
The PTSD Initiative (or ‘This study’) was funded by the Queensland
Branch of the Returned & Services League of Australia (RSL QLD).
Financial support was also provided by the Institute of Health and
Biomedical Innovation and the School of Biomedical Sciences,
Queensland University of Technology, Australia.
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