Author's Accepted Manuscript

Posttraumatic and depressive symptoms in β-

endorphin dynamics
Danka Savic, Goran Knezevic, Gordana Matic,
Svetozar Damjanovic, Zeljko Spiric

www.elsevier.com/locate/jad

PII: S0165-0327(15)00211-6
DOI: http://dx.doi.org/10.1016/j.jad.2015.03.063
Reference: JAD7376

To appear in: Journal of Affective Disorders

Received date: 15 July 2014

Revised date: 31 March 2015
Accepted date: 31 March 2015

Cite this article as: Danka Savic, Goran Knezevic, Gordana Matic, Svetozar
Damjanovic, Zeljko Spiric, Posttraumatic and depressive symptoms in β-
endorphin dynamics, Journal of Affective Disorders, http://dx.doi.org/10.1016/j.
jad.2015.03.063

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 Posttraumatic and depressive symptoms in β-endorphin dynamics

Danka Savic ∗, PhD.1, Goran Knezevic, PhD.2, Gordana Matic, PhD.3, Svetozar

Damjanovic, MD, PhD.4, and Zeljko Spiric, MD, PhD.5

1
University of Belgrade, Vinca Institute, Belgrade, Serbia
2
University of Belgrade, School of Psychology, Belgrade, Serbia
3
University of Belgrade, Institute for Biological Research “Sinisa Stankovic”, Belgrade,

Serbia
4
Institute of Endocrinology, Diabetes and Metabolic Disease, University of Belgrade,

Belgrade, Serbia
5
Clinic for Psychiatry, Faculty of Medicine of the Military Medical Academy, University of

Defense, Belgrade, Serbia

∗
Corresponding author: Danka Savic, Vinca Institute, PO Box 522, Belgrade, Serbia, danka.s@sbb.rs
 Beta-endorphin, posttraumatic and depressive symptoms
2

Abstract

A disturbed beta-endorphin system can be a part of the post-traumatic stress disorder

(PTSD) and depression allostasis. Study subjects (N=392) included those with PTSD

and/or (stress-induced) depression, and healthy controls with and without traumas. The

aim of the study was to examine the network of relations centered around plasma beta-

endorphin. The network included anxiety (as a personality trait), traumatic events, pain,

aggressiveness, depressive symptoms, and three clusters of PTSD symptoms: intrusions,

avoidance, and hyperarousal. Beta-endorphin was represented by individual mean from 13

time points (BEmean), reflecting the total amount of the peripherally secreted hormone,

and the coefficient of variation (BEvar), calculated as the ratio of standard deviation to the

mean, reflecting the hormone's dynamics. BEvar correlated with all other variables,

BEmean had no correlations. Structural equation modeling (SEM) was used to examine all

interrelations (including their directions) of BEvar and the state/trait variables in the context

of their entirety. The model revealed that hyperarousal and anxiety were the only direct

agents of peripheral beta-endorphin fluctuations, mediating the effects of other variables.

Traumatic events and intrusions act on BEvar via hyperarousal, while depressive

symptoms, avoidance, and pain act via anxiety. Hyperarousal should be emphasized as

the main agent not only because its effect on BEvar is larger than that of anxiety, but also

because it increases anxiety itself (via avoidance and pain). All influences on BEvar are

positive and they indicate long-term (sensitizing) effects (as opposed to direct stimulation,

for example, by acute pain, anger, etc.). Relations apart from beta-endorphin are also

discussed.

Key words: Beta-endorphin, Hyperarousal, Anxiety, PTSD, Depression, Pain, Aggression,

Structural equation modeling

 Beta-endorphin, posttraumatic and depressive symptoms
3

Introduction

Beta-endorphin belongs to the opioid peptide family. It is produced by cleavage of pro-

opiomelanocortin, along with ACTH and other derivatives, mostly in the pituitary, but also

in the brain (mainly in the hypothalamic arcuate nucleus). It is best known for its analgesic,

euphoric, and sedative effects, achieving them via µ-opioid (predominantly) and δ-opioid

receptors. This hormone is involved in affect, memory, cognition, reward, immunity,

respiration, to name just a few systems in which the role of β-endorphin is still being

investigated. Its "multitasking" relates β-endorphin to many forms of behavior/symptoms,

such as anxiety (Colasanti et al., 2011), anger control (Bruehl, 2009) and aggression

(Roubertoux et al., 2005), depression (Hegadoren et al., 2009), addictions (Barry, 2012),

etc.

Beta-endorphin achieves its actions via the two hormonal systems (central and

peripheral) that do not necessarily work in parallel. Although β-endorphin poorly crosses

the blood-brain barrier, there is indirect evidence of its hypothalamic actions, found in

human (Inder et al., 1996; Catlin et al., 1980) and animal studies (Hargreaves et al., 1990;

Selmanoff & Gregerson, 1986). Van der Kolk et al. (1985) cite evidence that there is a rise

in pituitary β-endorphin during stress that is inversely proportional to subsequent morphine

requirements in surgical patients and which parallels rise of other CNS opioids. De Kloet et

al. (1981) report severe behavioral deficit in mice following the removal of the pituitary.

The same authors, as well as Meisenberg and Simmons (1983), Veening et al. (2012), and

Amir et al. (1980), suggest mechanisms of communication between the central and

peripheral opioid systems.

 Beta-endorphin, posttraumatic and depressive symptoms
4

Beta-endorphin is overly secreted during stress, to suppress the pain and help the

organism react. It also has a role in HPA axis regulation (Amir et al., 1980). For these

reasons, the relations of beta-endorphin with traumas and related disorders are also

examined, post-traumatic stress disorder (PTSD) among them (Merenlender-Wagner et al.,

2009). Hoffman et al. (1989) propose plasma β-endorphin as a marker for PTSD after

finding the hormone diurnal levels to be significantly lower than in controls. Although

traumas are not explicitly included in the diagnosis of any type of depression as they are in

PTSD, trauma history is a factor in etiology of depression. In patients with trauma history, it

is often difficult to disentangle between these two disorders having extremely high

comorbidity rate (for example, Brown et al. (2001) report 80% with respect to PTSD) as

their symptomatologies largely overlap. Kotov et al. (2011) suggest that unipolar

depression would fit better with anxiety disorders than with bipolar disorders. The common

symptoms encompass sleep and dream abnormalities, pain, aggression (in the context of

defensive behavior and pain), disturbed memory, heightened anxiety, low mood and

anhedonia, loss of interests, social malfunctioning, etc. The listed phenomena are

accompanied by endogenous opioid system dysregulation (Hamner and Hitri, 1992; Lutz,

2013). This is confirmed in research with opioid receptor antagonists (Pitman et al., 1990;

Glover, 1993). Besides, Risch (1982) and Goodwin et al. (1993) found hightened plasma

β-endorphin levels in depression, Kubryak et al. (2012) suggested plasma β-endorphin as

an indicator of response to depression treatment, while Darko et al. (1992) obtained

correlations of plasma β-endorphin levels with anxiety and phobia in a mixed sample of

control and depressed subjects, as well as correlations with obsessions/compulsions in

depressed patients only.

According to DSM-IV, both PTSD and depression belong to Axis I disorders, for which

it was shown to be connected to personality traits (Malouff et al., 2005). Traits are basic
 Beta-endorphin, posttraumatic and depressive symptoms
5

behavioral dispositions, relatively stable over time, underlain by biological mechanisms

(Zuckerman, 2005). Beside psychiatric aspect of anxiety as a syndrome forming the base

of a disorder spectrum, a degree of anxiety is present in each individual as an intrinsic part

of personality. The difference between the two aspects is only quantitative (Iwata et al.,

2000). In the Big Five model (Costa & McCrae, 1992), it is operationalized as a

subdimension of the trait (dimension) Neuroticism which is a general tendency toward

negative emotions. More specifically, anxiety is a disposition to be nervous, tense, upset,

and fearful, and in its core lies anticipation of negative events. As beta-endorphin is a

natural anxiolytic, it is reasonable to suppose that it might be related to anxiety.

When excessive, anxiety leads to illness (Hensley & Varela, 2008; Weems et al.,

2007). We thus supposed that the connections between beta-endorphin and this trait

would be more pronounced in subjects exhibiting posttraumatic and depressive

symptomatology. On the other hand, there is a finding (Savic et al., 2012a; de Kloet et al.,

2007) that the sole number of traumatic events (without taking into account the intensity of

stressors and the accompanying subjective experience) adds to dysregulation of the

hypothalamo-pituitary-adrenocortical (HPA) axis independently of biological mechanisms

manifested as personality traits. This finding led us to suppose that traumatic events might

have an additional, independent contribution to beta-endorphin levels (being a product of

pituitary) as well.

The main task of this study was to examine the network of connections between

plasma beta-endorphin, anxiety, traumas, posttraumatic and depressive symptoms, pain

and aggressiveness, which frequently accompany PTSD and depression. Assessment of

all measures on the same individuals and application of Structural equation modeling

(SEM) enabled us to investigate each relation (whose existence is known from the

literature) within the context of all mutual influences among the variables of interest and to
 Beta-endorphin, posttraumatic and depressive symptoms
6

perceive the entirety of this network. The starting hypothesis was that anxiety (as a

personality disposition) and traumatic events lie in the root of the relations of beta-

endorphin with posttraumatic/depressive symptoms. The work was done within a larger

project “Psychobiology of post-traumatic stress disorder” aimed at correlating the

psychology and biology of PTSD (only the data relevant to the title are presented here).

Although PTSD itself is not in the main focus of this article, we used the advantage of the

project's comprehensiveness to achieve the stated goal.

Methods

More detailed description of inclusion/exclusion and diagnostic criteria, classification of

subjects, recruitment procedure and sources, hospital protocol, and the instruments NEO-

PI-R and WSAQ–R are given in Savic et al. (2012a).

Subjects

For the original project, four hundred male subjects (mean age 43.0±9.1) were recruited

and classified into four groups: current PTSD (N=133), lifetime PTSD (N=66), trauma

controls (N=102) and healthy controls (N=99), matched by age and education level. Eight

of them did not have beta-endorphin measures and were excluded from this study, leaving

392 subjects. Ethical approval was obtained from the Ethical Review Board of the

University Medical School, Belgrade, Serbia. All participants signed written consent,

after having detailed oral explanations at their disposal.

Procedure

The participants were hospitalized for 2.5 days for the purpose of this study, following a

standardized protocol, within which they filled out self-report questionnaires and underwent
 Beta-endorphin, posttraumatic and depressive symptoms
7

hourly blood sampling (via an iv line) during the first night, from 2200h to 0900h (plus at

0730h to follow the morning rise of HPA axis activity).

Variables and assessment instruments

The analyses for this report were done on the whole sample using continuous variables.

The levels of intrusion, avoidance, and hyperarousal (posttraumatic symptoms) were

estimated by scores on The Clinician Administered PTSD Scale CAPS-DX (Blake et al.,

1996), clusters B, C, and D, respectively. The range of scores was 0-8 per item, obtained

by summing the intensity and frequency levels. When administering the CAPS-DX to

healthy subjects, the instruction was to relate the questions to the most distressing event

in their life. All other used instruments are self-reporting questionnaires with 5-point Likert-

type scale response format. Depression symptoms were assessed by Beck Depression

Inventory BDI II (Beck et al.,1996) consisting of 21 items.

Pain was estimated as a sum of scores on four items (1,12, 27, 42) from The Symptom

Checklist 90 - Revised (SCL-90-R): Headaches, Pains in heart or chest, Pains in lower

back, and Soreness of muscles. SCL-90-R (Derogatis, 1983) is an instrument with 90 items

for assessing the current complex of psychological symptoms, acute stress and global

psychopathological status, according to the axis I DSM IV for mental disorder classification.

Anxiety was evaluated as a sum of scores on eight items intended to measure this

component of the personality trait Neuroticism in the self-reporting NEO Personality

Inventory Revised, NEO-PI-R (Costa, McCrae, 1992).

Aggression was assessed by the Aggression Questionnaire, AQ (Buss & Perry, 1992),

an instrument with 29 items encompassing physical and verbal aggression, anger and

hostility.

Traumatic events were calculated by summing the experienced war and civilian (life)
 Beta-endorphin, posttraumatic and depressive symptoms
8

stressors. War stressors were assessed by War Stressors Assessment Questionnaire,

WSAQ–R (Jovic et al., 2002) with 67 items, and civilian stressors were assessed by self-

reporting instrument Life Event Check List LS-17 (Wolfe & Kimerling, 1997). It is a list of 16

possible traumatic life events plus an open item offering a possibility to add a distressing

life experience not listed. The response format of LS-17 is yes/no.

Beta-endorphin was determined from plasma of 13 samples by competitive RIA

method (Euro Diagnostica, Malmo, Sweden) after extraction using sep-pak C18 cartridges.

In this assay, antibodies against synthetic human beta endorphin were used. Intra-assay

and inter-assay variations were less than 8%. The lowest detection limit of the assay was

3 pmol/L (10 pg/mL).

Two beta-endorphin variables were calculated: BEmean, an individual mean value of

beta-endorphin obtained from 13 night/morning time measurements, and BEvar, the

coefficient of variation of beta-endorphin, which is a standard deviation to mean ratio. We

chose nocturnal measurements of all hormones in the original study as a better

representation of the resting state (reduced external stimuli) than the day values. For beta-

endorphin particularly, we wanted to see whether its rise would accompany nightmares,

but no subject reported having them during the hospital stay.

Statistical analysis

Data were analyzed using SPSS version 11.5 (SPSS Inc., USA) and LISREL 8.53

(Joreskog and Sorbom, 2002). Continuous variables are presented as means±standard

deviation. Groups were compared by ANOVA and post hoc Tukey HSD (honest significant

difference) and Bonferroni tests. To detect possible relations between beta-endorphin

measures and other chosen variables, Pearson's correlations were calculated (after

normalization), with Bonferroni correction for statistical significance. Structural equation

 Beta-endorphin, posttraumatic and depressive symptoms
9

modeling (SEM) - path analysis - was used to test the directions of these relations

(causality) in the context of the entirety of all postulated interrelations. In other words, a

"path" suggests a direct cause-consequence relation between two variables (technically, it

is beta weight from multiple regressions, predicting a variable from all other variables

having a direct effect on it). Path analysis also enables decomposing the total effect of a

group of predictors into direct and indirect (through mediators) influences. For an adequate

fit, Hu and Bentler’s (1999) combinational rule was followed. Root Mean Square Error of

Approximation (RMSEA) should be less than .06, Comparative Fit Index (CFI) above .95,

and Standardized Root Mean Square Residual (SRMR) less than .08. Models’χ2 statistics

and associated df, confidence intervals for RMSEA are also presented. The model is fit

using maximum-likelihood estimation in LISREL 8.53.

Results

To illustrate the structure of the sample, the means and standard deviations of the studied

variables are shown by groups in Table 1.

Table 1 about here

There are no group differences on BEmean, while BEvar differs between current

PTSD and both controls, lifetime PTSD differs only from the healthy, trauma controls only

from the current PTSD group, and healthy from both PTSD groups. All groups, except

lifetime PTSD and trauma controls that are statistically the same, differ in the number of

traumatic events, and all groups, except both controls (statistically the same), differ in

aggression. All groups differ in Anxety, intrusions, avoidance, hyperarousal, depression,

and pain (all differences are significant at the 0.05 level).

 Beta-endorphin, posttraumatic and depressive symptoms
10

All further analyses were performed on the whole sample as it provides broad ranges

of variable variances that enable to establish proper relations among them.

The first step was to examine whether beta-endorphin was related to the chosen

state/trait variables. After normalization of variables, we calculated Pearson’s correlations.

BEmean had no correlations (the range of sigma (2-tailed): 0.333-0.972), while BEvar was

significantly correlated with all other variables (the range of sigma (2-tailed): 0.000-0.001),

satisfying the Bonferroni correction at the .003125 level (Table 2). Therefore, only BEvar

entered SEM.

Table 2 about here

The structural model

The suggested model of the directions, context (direct and indirect effects), and the

strengths of influences on beta-endorphin fluctuations (Figure 1) were found to fit the data

adequately χ2=26.35, df=18, p=0.09, RMSEA (90% CI) =0.034 (0.000; 0.061), CFI=1.00,

SRMR=0.026. All variables (except Aggressiveness) had total effects on BEvar, but most

of them only indirect (except Hyperarousal and Anxiety that had the direct effect). All paths

shown are significant. None of the paths going from BEvar had a satisfactory fit.

Figure 1 about here

Discussion

Although we have supposed that Anxiety (capital A signifies the NEO-PI R measure) and

traumatic events would influence both measures of plasma beta-endorphin, BEmean did

not have correlations with any of the observed variables (Table 2). This is in line with

studies that found no significant differences in resting plasma beta-endorphin levels

 Beta-endorphin, posttraumatic and depressive symptoms
11

between healthy controls and groups with PTSD (Baker et al. 1997; Hamner and Hitri,

1992) or depression (studies cited in the review of Hegadoren et al., 2009). In the same

vein, no significant correlations of resting beta-endorphin levels with BDI scores (Darko et

al., 1992) or with severity of pain perception (Bernstein et al., 1995) were reported.

. Contrary to BEmean, BEvar correlates with all the symptom variables (Table 2).

BEvar represents night fluctuations of the hormone which can be interpreted in part as

responses to internal stressors. We had expected that intrusions (distressing dreams)

would act as internal stressors and directly induce beta-endorphin fluctuations. However,

none of the subjects reported having nightmares which we ascribed to their perception of

hospital as a safe setting.

Structural Equation Modeling (SEM) inserted further accuracy into our understanding

of the relations by taking into account all of them, together with the postulated directions

(paths). An important fact for interpretation of the results is that beta-endorphin was

measured overnight directly, while all other variables were assessed by psychiatric

interview (CAPS) or self-questionnaires, not as direct stimuli (e. g., not during a state of

acute pain, aggressive outburst, or in the midst of a depressive episode). Therefore, the

contributions of the variables to BEvar could be understood as long-term influences on the

peripheral beta-endorphin system. Seeing that all paths to BEvar are positive (Figure 1),

these contributions would mean sensitization of the system. It is very likely that for the

same reason (no direct stimuli), none of the paths goes from β-endorphin.

Figure 1 shows that hyperarousal and Anxiety have notable mediating effect, i.e. other

variables actually achieve their long-term effects on beta-endorphin by increasing

hyperarousal (traumatic events, intrusions) or Anxiety (depression, avoidance, pain).

However, comparison of these two shows that hyperarousal is the key agent of peripheral

beta-endorphin fluctuations because it influences Anxiety itself via avoidance or pain.

 Beta-endorphin, posttraumatic and depressive symptoms
12

The hyperarousal symptoms, as measured by CAPS, encompass irritability,

hypervigilance, exaggerated startle response, difficulties with concentration, and difficulties

with falling and staying asleep (this last component is probably most directly responsible

for increase in BEvar). Although these symptoms are strongly related to traumatic events,

the traumas are not a necessary condition for their appearance, as shown by the part (one

third) of variance not explained by the events. However, all the measured variables are

interrelated via stress response mechanism, thus some degree of stress (chronic or past)

was involved. Physiological arousal (immediately activated in a stressful situation) is the

result of the locus coeruleus-norepinephrine (LC/NE) system and it has reciprocal relations

with the opioid system (Van der Kolk et al., 1985). The regulatory role of beta-endorhin in

the LC would correspond to a negative path from BEvar to hyperarousal, but the

introduction of such a path resulted in an unsatisfactory model fit. As said above, the

differences in assessment between the hormone and all other variables should be borne in

mind.

Along with its other functions (Aston-Jones & Cohen, 2005), LC/NE system is a part of

the complex fear/anxiety network. When overly persistent, the LC tonic activity becomes

maladaptive and leads to anxiety disorders, together with impairments of gabaergic and

serotonergic systems. Finan and Smith (2013) argue that the mesolimbic dopamine

system is involved in the "comorbidity triad" insomnia, pain, and depression, emphasizing

the connection between opioids and arousal. This triad is included in the network of

connections in Figure 1, with paths going from hyperarousal (which encompasses

insomnia).

It is well known that anxiety and trauma-induced disorders have reciprocal links (for

example, Marshall et al., 2010). Anxious individuals are more prone to develop a disorder

that, once developed, further increases the level of anxiety. In our data, it seems that
 Beta-endorphin, posttraumatic and depressive symptoms
13

Anxiety (assessed as a current self-report) is more a reflection of the disorders than of the

risk factor, because the paths from depressive and PTSD symptoms to Anxiety render a

better fit than the ones with opposite direction that were also examined.

Bruehl et al. (2009) started their review on anger expression and endogenous opioids

with the sentence: "For more than 60 years, the experience of pain has been reported to

be associated with various negative emotional states, including depression, anxiety, fear,

and anger". Our result that Anxiety, depression, and pain influence aggression fits well

with these reports which include acute and chronic pain, as well as diverse assessments

of anger/aggression. Aggression does not always stem from anger, but these notions

sufficiently overlap, behaviorally as well as neurofunctionally, that Bruehl et al. included

studies on both phenomena in their review. Actually, the type of aggression linked to anger

and fear/anxiety is termed affective, as opposed to predatory aggression (McEllistrem,

2004). In our model, the former type enters the mentioned circuits (with Anxiety,

depression, and pain), while the latter (encompassed by the Buss and Perry's AQ used

here) is probably responsible for the part of variance not explained by the model. Buss and

Perry (1992) found that the AQ components Anger and Hostility correlate with a

personality trait Emotionality.

Opioids seem to relieve chronic (assessed here) and dull pain more than acute one

(Ribeiro 2005). There was a suggestion that they act only on affective component of pain

that increases as a function of time, but newer evidence speaks in favor of opioid actions

at multiple levels, including perception. Pain threshold is found to be lower in PTSD

(Schwartz et al, 2006), as well as in depression and insomnia (Finan & Smith, 2013). Chiu

(2005) found that poor sleep and depression independently contribute to the reduction of

pain threshold. Our model shows the same: paths from hyperarousal (sleep problems) and

depressive symptoms lead to pain.

 Beta-endorphin, posttraumatic and depressive symptoms
14

The path from traumatic events to depression symptoms confirms our earlier

conclusion that the depression in our subjects is trauma-induced (Savic et al, 2012b), as

its influence on dexamethasone suppression test is the same as that of PTSD (increased

suppression). The path from PTSD to depressive symptoms probably means that the

comorbid depression diagnosed in a number of subjects with PTSD is developed later than

PTSD which is in line with Kessler et al. (1996) and Regier et al. (1998).

An interesting path leads from avoidance to Anxiety. Avoidance could be understood

as a defense mechanism and it is to a great extent the result of hyperarousal and intrusion

(only 23% of its variance is not explained by the model).

The strenghts of some paths (effect sizes) are small. However, Møller and Jennions (2002,

p.497) state that "even a minute effect size may be biologically important” because

organisms "are affected by innumerable biotic and abiotic factors”. The path from Anxiety

to BEvar is 0.13, but taking into account that personality trait is a distant aspect of the

underlying biology, any significant relation is worth acknowledging.

Only a few subjects were positive on the CAPS measures of dissociation, so it could

not have been included. Knowing that this phenomenon is tightly related to opioids, its

detailed assessment would enable enriching the model. The study would have also

benefitted from more comprehensive measures of anxiety.

Conclusion

To resume, the fact that BEmean is not affected by the same variables that do affect

BEvar seems to tell that peripheral beta-endorphin dynamics is susceptible to changes by

the examined variables while the overall quantity of the secreted hormone is not.

Traumatic events, intrusion, avoidance, depression, pain, and in the first place,

hyperarousal and Anxiety sensitize the peripheral beta-endorphin system, i.e., stimulate its
 Beta-endorphin, posttraumatic and depressive symptoms
15

readiness to react. All these variables, together with aggression, form a network of

relations with underlying interweaved neurophysiological and neurobiochemical systems.

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Figure caption

Figure 1 Structural model of Anxiety, traumatic events, PTSD symptoms (intrusion,

avoidance, hyperarousal), depressive symptoms, aggression, pain, and beta endorphin

fluctuations. The arrowed lines between boxes denote significant paths; the arrows show
 Beta-endorphin, posttraumatic and depressive symptoms
23

the directions of influences; the associated numbers denote path coefficients; small arrows

stand for residuals.

Beta-endorphin, posttraumatic and depressive symptoms
24

Table 1. Mean values of the examined variables in the whole sample and by groups. The
meanings of variables given in the text.

BEmea BEva Anxiet Trauma Intrusio Avodanc Depressio Aggressio

Hyper-
n Pain
GROUP arous
(pmol/L r y s n e n n
al
)
Total Mea 8299.20 .17 16.40 43.77 14.83 15.16 11.49 16.39 6.85 79.02
n
N 392 392 392 392 392 392 392 392 392 392
Std. 2542.60 .14 6.06 36.57 9.76 7.90 7.61 12.93 4.59 19.02
Dev.
PTSD Mea 8311.16 .21 20.81 69.34 23.80 20.22 18.41 26.36 10.3 90.94
current n 5
N 129 129 129 129 129 129 129 129 129 129
Std. 2579.41 .17 4.64 32.93 4.84 4.90 3.67 12.35 3.48 17.70
Dev.
PTSD Mea 8267.24 .20 17.67 49.52 16.17 16.87 12.94 18.00 7.78 81.93
lifetime n
N 63 63 63 63 63 63 63 63 63 63
Std. 2812.57 .16 5.05 29.05 7.88 6.20 5.64 11.19 4.20 16.29
Dev.
Traum Mea 8481.66 .16 14.74 47.50 10.61 13.40 8.57 11.46 5.28 72.73
a n
control N 101 101 101 101 101 101 101 101 101 101
s Std. 3038.78 .09 4.58 28.05 8.69 8.00 6.68 9.38 4.07 15.96
Dev.
Health Mea 8117.82 .12 11.53 2.98 6.61 9.27 4.52 7.41 3.31 68.06
y n
control N 99 99 99 99 99 99 99 99 99 99
s Std. 1614.78 .06 5.25 2.36 6.30 7.38 5.07 7.74 2.89 15.87
Dev.

Table 2. Pearson correlations between beta-endorphin and state/trait variables. N=392.

Beta-endorphin, posttraumatic and depressive symptoms
25

ANXIET TRAUMA INTRUSIO AVODANC HYPERAROUS DEPRESSIO PAI AGGRESSIO

Y S N E AL N N N

-
BEmea -.041 -.033 -.005 -.025 -.003 .002 -.049
.027
n
.419 .516 .929 .617 .955 .972 .601 .333

.219
** ** ** ** ** ** **
.252 .205 .218 .273 .275 .171 .218
**
BEvar

.000 .000 .000 .000 .000 .001 .000 .000

 Beta-endorphin, posttraumatic and depressive symptoms
26

Role of the funding sources

This work was financed by European Commission, via Sixth Framework Programme

research project INCO-CT-2004-509213 and in part by the Ministry of Science, Serbia,

Projects Nos 179018 and 41009. The funders had no role in: the study design; collection,

analyses and interpretation of the data; writing of the report; submitting of the paper.

Contributors

All authors designed and wrote the protocol of the study whose part is this manuscript.
Also, all authors have participated in the interpretation of results and approved the final
manuscript. Danka Savic wrote the manuscript and together with Goran Knezevic
performed statistical analyses.

Conflicts of interest statement

The authors declare no conflict of interest.

Role of the funding sources

This work was financed by European Commission, via Sixth Framework Programme

research project INCO-CT-2004-509213 and in part by the Ministry of Science, Serbia,

Projects Nos 179018 and 41009. The funders had no role in: the study design; collection,

analyses and interpretation of the data; writing of the report; submitting of the paper.
Figure(s)

AGGRESSION .14 PAIN

.56 .53
.53

.39 0.27
.27
.22
.41
.56 DEPRESSIVE
ANXIETY
SYMPTOMS .32
.47

.35
.18
.13
.25

1.00 TRAUMATIC
EVENTS
β-ENDORPHIN
.26
.56 fluctuations
.91

INTRUSIONS
.69 .18 .20

.39
.71

AVOIDANCE HYPERAROUSAL
.23 .53 .32