This study yielded two main findings: First, the level of salivary MHPG after 20 minutes of recovery correlated positively with the PCL-S score after 12 months of police service, so that participants who had prolonged elevations in response to a video challenge during police academy training were at a greater risk to develop PTSD symptoms. Second, this relationship was fully mediated by the degree of peritraumatic emotional distress experienced during the critical incident.
The video challenge evoked both subjective distress and a small, but statistically significant increase of the mean salivary MHPG level as expected from other psychological stress challenge tests (Okamura et al., 2010
; Schommer et al., 2003
). The possible source of the salivary MHPG increase is complex, as MHPG is the major metabolite of norepinephrine, which is involved as a neurotransmitter in the central nervous system and in the peripheral sympathetic nervous system, and as a stress hormone in the adreno-medullary system. The interpretation of plasma norepinephrine is very complex, depending on site of collection, balance of release and clearance, or metabolism (Goldstein, 1995
; McFall et al., 1990
). Salivary MHPG might represent an increase in post-ganglionic sympathetic input to the salivary glands reflecting a systemic increase in peripheral sympathetic activity. Salivary MHPG levels are also highly correlated with plasma (Drebing et al., 1989
; Yajima et al., 2001
; Yang et al., 1997
) and with cerebrospinal fluid levels (Reuster et al., 2002
). MHPG as a glycol can easily pass the blood-brain barrier (Goldstein, 1995
). Although the metabolism of peripheral norepinephrine or the clearance of MHPG from saliva may influence measured levels, salivary MHG is seen as an indicator of the central “noradrenergic activity” (Drici et al., 1991
; Hamer et al., 2007
; Reuster et al., 2002
). It also has been shown that salivary MHPG levels do not fluctuate with diurnal rhythms or with salivary flow (Yajima et al., 2001
Salivary MHPG is easy to obtain but it might not be the most sensitive measure for sympathetic activity. Therefore in future studies it might be interesting to compare salivary MHPG with other measures of anxious arousal, e.g., neuropeptide Y, corticotrophin releasing factor, plasma epinephrine or norepinephrine, heart rate, or blood pressure, to investigate which variable responds most robustly to experimental stressors and might be a sensitive marker for discriminating individuals with vulnerability to PTSD symptoms following trauma exposure.
In this analysis the 83 subjects reporting childhood trauma on average showed a continued rise in MHPG levels during the challenge video and the recovery period, whereas those without childhood trauma returned to baseline during the recovery period. The finding in this sample missed the statistical significance level but has the same direction as the previous analysis of a subsample of n=76 including 16 subjects with childhood trauma (Otte et al., 2005
). An increase in heterogeneity of this larger sample and an overestimation of the effect size in the previous subsample are possible explanations for the loss of statistical significance.
Several studies have shown that experience of childhood trauma increases the risk for anxiety disorders in adulthood (Bremner et al., 1993
; Kendler et al., 1992
; Kessler et al., 1997
; Yehuda, 2004
). A putative mechanism for this correlation is longer duration of anxious arousal with elevated catecholamine levels in response to stress in individuals with a history of childhood trauma. Sustained anxiety reactions at the time of trauma exposure and associated increased noradrenergic activity in the brain are thought to increase the risk of PTSD by enhancing memory encoding (Krystal & Neumeister, 2009
; McGaugh, 2000
; O’Donnell et al., 2004
; Orr et al., 2000
; Southwick et al., 2002
) and over-consolidation of traumatic memories (McGaugh, 1989
; Roozendaal et al., 1997
; Southwick et al., 1999
; van Stegeren, 2008
). Elevated levels of norepinephrine in the cerebrospinal fluid of patients with chronic PTSD and their correlation with symptom severity suggests that noradrenergic activity is also involved in the maintenance of PTSD symptoms (Geracioti et al., 2001
We found a trend for the relationship between more childhood trauma and prolonged elevation of MHPG levels in response to the laboratory stressor and a significant relationship between prolonged elevation of MHPG levels and higher PTSD symptoms, supporting the hypothesis described above. However, we did not find a direct correlation between childhood trauma and the development of PTSD symptoms in this study. A probable cause is that the participants in our study are at an early stage of their career and have low levels of PTSD symptoms after one year of service, reducing the power to detect this association. A complementary explanation could be that participants choosing a career in police despite the experience of childhood trauma are especially resilient.
As expected, we found that higher peritraumatic emotional distress as reported by higher scores in the PDI questionnaire, predicted higher levels of PTSD symptoms. In the path analysis, peritraumatic distress was found to fully mediate the effect of prolonged elevation of salivary MHPG on the later development of PTSD symptoms. Interestingly, the delayed off-switch rather than the acute response was predictive. These results suggest that prolonged arousal measured by salivary MHPG in response to a laboratory stressor is an individual vulnerability factor which is associated with greater emotional distress at the time of trauma and the subsequent development of PTSD symptoms. This finding is congruent with earlier findings from this prospective longitudinal cohort study focusing on individual differences in acoustic startle testing during academy training (Pole et al., 2009
). We found that elevated sympathetic nervous system reactivity to acoustic startle in the context of explicit threat and a lack of habituation to repeated startle stimuli are vulnerability factors which predicted greater PTSD symptom severity following critical incident exposure.
This finding also agrees with results from Guthrie and Bryant who found that post-startle eye blink and skin conductance responses during academy training predicted later PTSD symptoms in firefighters (Guthrie & Bryant, 2005
). Similarly, Morgan et al. had concluded that biological differences may exist before the index trauma exposure by showing that under uncontrollable stress Special Forces soldiers demonstrated a greater capacity for norepinephrine and neuropeptide Y release with a rapid return to baseline levels at recovery compared to other soldiers (Morgan et al., 2001
). Together, these findings add to growing evidence that prolonged arousal in response to a stress challenge that does not rapidly return to baseline following cessation of the stressor is a vulnerability factor for PTSD predating the trauma exposure in adulthood.
It has been suggested that the neurotransmitter norepinephrine is mainly involved in the hyperarousal and re-experiencing symptoms of PTSD (O’Donnell et al., 2004
; Southwick et al., 1999
), however we found that avoidance, a typical anxiety behavior, was the most relevant PTSD symptom cluster in the path analysis. This supports the results from a review article which concluded that avoidance and numbing symptoms appear to be the most specific for the identification of PTSD (North et al., 2009
). As MHPG’s parent compound norepinephrine is involved in the neural circuitry of anxiety (Hughes et al., 2004
; Itoi, 2008
; van West et al., 2008
), the tendency to react to stressors, both laboratory challenges and real life critical incidents, with longer duration of anxious arousal may lead to greater fear conditioning and memory consolidation with pathogenic beliefs about danger and therefore avoidant behavior.
Prior studies have utilized video challenges to provoke stress responses and measure the catecholamine response. For example, Takai measured the increase of salivary amylase in healthy participants and found that salivary amylase significantly increased during a challenge video and correlated with the score of the State-Trait Anxiety Inventory (Takai et al., 2004
; Takai et al., 2007
). McFall found that veterans with PTSD had an increased autonomic and plasma epinephrine – but not plasma norepinephrine - response after watching a combat video compared to a video depicting a stressful car accident and also compared to healthy controls (McFall et al., 1990
). Geracioti found an increase of norepinephrine in the cerebrospinal fluid of PTSD patients in response to a trauma related video challenge but no increase in response to a neutral video (Geracioti et al., 2008
). However, to our knowledge the current study is unique in examining MHPG response to a video challenge paradigm prior to critical incident exposure using a prospective longitudinal cohort design.
Several limitations of this study have to be considered: The main limitation of this study is the measurement of MHPG peripherally in saliva, because this collection method is non-invasive and feasible. Salivary MHPG may be an imperfect proxy for norepinephrine neurotransmission in the brain. Second, generalizability may be limited in the highly selected, young, healthy, and well educated population studied. Third, we report PTSD symptoms after one year of active service when the participants are at a very early stage of their police career. At this time most officers have not yet been repeatedly exposed to severe critical incidents and present with relatively low levels of PTSD symptoms. As there is already a pattern recognizable in this early stage, prolonged salivary MHPG increase and peritraumatic distress may prove distinctive later in those participants who develop full PTSD after exposure to repeated severe traumatic stressors. It will be important to model the MHPG response to the video challenge as a predictor of PTSD symptoms as cumulative exposure increases over the years. Another limitation of this study may be that the video challenge, although using real life footage, is a laboratory test and a situation in real life may be far more stressful. Fifth, the peritraumatic distress caused by the worst incident during this time was assessed retrospectively and may be biased by memory fading and symptom recovery. An important limitation is the fact that PTSD is a complex disorder with a multifactorial causality including environmental, genetic and psychological factors, and this model explains only one facet of it (Yehuda, 2002
In conclusion, prolonged elevations of salivary MHPG in response to an experimental stressor prior to duty related critical incident exposure, predicted the later development of PTSD symptoms. This relationship was mediated by peritraumatic distress, capturing perceived life threat and physical reactions during and immediately after critical incident exposure. Our data indicate that longer duration of anxious arousal in response to experimental stress could be useful in identifying individuals at risk for developing PTSD. This merits further investigation and replication in other samples.