Self-reported exercise frequency and PTSD: results from the National Health and Resilience in Veterans Study.

OBJECTIVE: Physical exercise may serve as a protective factor for posttraumatic stress disorder (PTSD), but little is known about whether physical exercise is associated with PTSD in population-based samples of military veterans. METHODS: We analyzed cross-sectional data on the relation between self-reported physical exercise frequency and the prevalence of probable PTSD in a nationally representative sample of 2832 U.S. military veterans who participated in the National Health and Resilience in Veterans Study. RESULTS: A "U-shaped" association best explained the relation between self-reported exercise frequency and the prevalence of probable PTSD. Compared to veterans without probable PTSD, those with probable PTSD were nearly twice as likely to report no weekly exercise (52.3% vs. 29.3%) or daily (7 days/week) exercise (15.2% vs. 8.5%) and were nearly half as likely to report exercising a median of 3.5 days/week (32.6% vs. 62.1%). No exercise was associated with greater severity of emotional numbing and lower severity of anxious arousal symptoms, while daily exercise was associated with greater severity of re-experiencing symptoms. CONCLUSIONS: Results of this study suggest a "U-shaped" association between self-reported exercise frequency and the prevalence of probable PTSD among U.S. veterans. Veterans with probable PTSD were more likely than those without probable PTSD to report not exercising at all or exercising every day and were less likely to report exercising 1-6 days per week. Clinical implications of these findings are discussed.

Post-traumatic growth among veterans in the USA: results from the National Health and Resilience in Veterans Study.

BACKGROUND: There is increasing recognition that, in addition to negative psychological consequences of trauma such as post-traumatic stress disorder (PTSD), some individuals may develop post-traumatic growth (PTG) following such experiences. To date, however, data regarding the prevalence, correlates and functional significance of PTG in population-based samples are lacking. METHOD: Data were analysed from the National Health and Resilience in Veterans Study, a contemporary, nationally representative survey of 3157 US veterans. Veterans completed a survey containing measures of sociodemographic, military, health and psychosocial characteristics, and the Posttraumatic Growth Inventory-Short Form. RESULTS: We found that 50.1% of all veterans and 72.0% of veterans who screened positive for PTSD reported at least 'moderate' PTG in relation to their worst traumatic event. An inverted U-shaped relationship was found to best explain the relationship between PTSD symptoms and PTG. Among veterans with PTSD, those with PTSD reported better mental functioning and general health than those without PTG. Experiencing a life-threatening illness or injury and re-experiencing symptoms were most strongly associated with PTG. In multivariable analysis, greater social connectedness, intrinsic religiosity and purpose in life were independently associated with greater PTG. CONCLUSIONS: PTG is prevalent among US veterans, particularly among those who screen positive for PTSD. These results suggest that there may be a 'positive legacy' of trauma that has functional significance for veterans. They further suggest that interventions geared toward helping trauma-exposed US veterans process their re-experiencing symptoms, and to develop greater social connections, sense of purpose and intrinsic religiosity may help promote PTG in this population.

Trajectories of PTSD risk and resilience in World Trade Center responders: an 8-year prospective cohort study.

BACKGROUND: Longitudinal symptoms of post-traumatic stress disorder (PTSD) are often characterized by heterogeneous trajectories, which may have unique pre-, peri- and post-trauma risk and protective factors. To date, however, no study has evaluated the nature and determinants of predominant trajectories of PTSD symptoms in World Trade Center (WTC) responders. METHOD: A total of 10835 WTC responders, including 4035 professional police responders and 6800 non-traditional responders (e.g. construction workers) who participated in the WTC Health Program (WTC-HP), were evaluated an average of 3, 6 and 8 years after the WTC attacks. RESULTS: Among police responders, longitudinal PTSD symptoms were best characterized by four classes, with the majority (77.8%) in a resistant/resilient trajectory and the remainder exhibiting chronic (5.3%), recovering (8.4%) or delayed-onset (8.5%) symptom trajectories. Among non-traditional responders, a six-class solution was optimal, with fewer responders in a resistant/resilient trajectory (58.0%) and the remainder exhibiting recovering (12.3%), severe chronic (9.5%), subsyndromal increasing (7.3%), delayed-onset (6.7%) and moderate chronic (6.2%) trajectories. Prior psychiatric history, Hispanic ethnicity, severity of WTC exposure and WTC-related medical conditions were most strongly associated with symptomatic trajectories of PTSD symptoms in both groups of responders, whereas greater education and family and work support while working at the WTC site were protective against several of these trajectories. CONCLUSIONS: Trajectories of PTSD symptoms in WTC responders are heterogeneous and associated uniquely with pre-, peri- and post-trauma risk and protective factors. Police responders were more likely than non-traditional responders to exhibit a resistant/resilient trajectory. These results underscore the importance of prevention, screening and treatment efforts that target high-risk disaster responders, particularly those with prior psychiatric history, high levels of trauma exposure and work-related medical morbidities.

Dimensional structure and course of post-traumatic stress symptomatology in World Trade Center responders.

BACKGROUND: Post-traumatic stress disorder (PTSD) in response to the World Trade Center (WTC) disaster of 11 September 2001 (9/11) is one of the most prevalent and persistent health conditions among both professional (e.g. police) and non-traditional (e.g. construction worker) WTC responders, even several years after 9/11. However, little is known about the dimensionality and natural course of WTC-related PTSD symptomatology in these populations. METHOD: Data were analysed from 10 835 WTC responders, including 4035 police and 6800 non-traditional responders who were evaluated as part of the WTC Health Program, a clinic network in the New York area established by the National Institute for Occupational Safety and Health. Confirmatory factor analyses (CFAs) were used to evaluate structural models of PTSD symptom dimensionality; and autoregressive cross-lagged (ARCL) panel regressions were used to examine the prospective interrelationships among PTSD symptom clusters at 3, 6 and 8 years after 9/11. RESULTS: CFAs suggested that five stable symptom clusters best represent PTSD symptom dimensionality in both police and non-traditional WTC responders. This five-factor model was also invariant over time with respect to factor loadings and structural parameters, thereby demonstrating its longitudinal stability. ARCL panel regression analyses revealed that hyperarousal symptoms had a prominent role in predicting other symptom clusters of PTSD, with anxious arousal symptoms primarily driving re-experiencing symptoms, and dysphoric arousal symptoms primarily driving emotional numbing symptoms over time. CONCLUSIONS: Results of this study suggest that disaster-related PTSD symptomatology in WTC responders is best represented by five symptom dimensions. Anxious arousal symptoms, which are characterized by hypervigilance and exaggerated startle, may primarily drive re-experiencing symptoms, while dysphoric arousal symptoms, which are characterized by sleep disturbance, irritability/anger and concentration difficulties, may primarily drive emotional numbing symptoms over time. These results underscore the importance of assessment, monitoring and early intervention of hyperarousal symptoms in WTC and other disaster responders.

Exposure, probable PTSD and lower respiratory illness among World Trade Center rescue, recovery and clean-up workers.

BACKGROUND: Thousands of rescue and recovery workers descended on the World Trade Center (WTC) in the wake of the terrorist attack of September 11, 2001 (9/11). Recent studies show that respiratory illness and post-traumatic stress disorder (PTSD) are the hallmark health problems, but relationships between them are poorly understood. The current study examined this link and evaluated contributions of WTC exposures. METHOD: Participants were 8508 police and 12 333 non-traditional responders examined at the WTC Medical Monitoring and Treatment Program (WTC-MMTP), a clinic network in the New York area established by the National Institute for Occupational Safety and Health (NIOSH). We used structural equation modeling (SEM) to explore patterns of association among exposures, other risk factors, probable WTC-related PTSD [based on the PTSD Checklist (PCL)], physician-assessed respiratory symptoms arising after 9/11 and present at examination, and abnormal pulmonary functioning defined by low forced vital capacity (FVC). RESULTS: Fewer police than non-traditional responders had probable PTSD (5.9% v. 23.0%) and respiratory symptoms (22.5% v. 28.4%), whereas pulmonary function was similar. PTSD and respiratory symptoms were moderately correlated (r=0.28 for police and 0.27 for non-traditional responders). Exposure was more strongly associated with respiratory symptoms than with PTSD or lung function. The SEM model that best fit the data in both groups suggested that PTSD statistically mediated the association of exposure with respiratory symptoms. CONCLUSIONS: Although longitudinal data are needed to confirm the mediation hypothesis, the link between PTSD and respiratory symptoms is noteworthy and calls for further investigation. The findings also support the value of integrated medical and psychiatric treatment for disaster responders.

Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach.

The anterior hippocampus (aHPC) has a central role in the regulation of anxiety-related behavior, stress response, emotional memory and fear. However, little is known about the presence and extent of aHPC abnormalities in posttraumatic stress disorder (PTSD). In this study, we used a multimodal approach, along with graph-based measures of global brain connectivity (GBC) termed functional GBC with global signal regression (f-GBCr) and diffusion GBC (d-GBC), in combat-exposed US Veterans with and without PTSD. Seed-based aHPC anatomical connectivity analyses were also performed. A whole-brain voxel-wise data-driven investigation revealed a significant association between elevated PTSD symptoms and reduced medial temporal f-GBCr, particularly in the aHPC. Similarly, aHPC d-GBC negatively correlated with PTSD severity. Both functional and anatomical aHPC dysconnectivity measures remained significant after controlling for hippocampal volume, age, gender, intelligence, education, combat severity, depression, anxiety, medication status, traumatic brain injury and alcohol/substance comorbidities. Depression-like PTSD dimensions were associated with reduced connectivity in the ventromedial and dorsolateral prefrontal cortex. In contrast, hyperarousal symptoms were positively correlated with ventromedial and dorsolateral prefrontal connectivity. We believe the findings provide first evidence of functional and anatomical dysconnectivity in the aHPC of veterans with high PTSD symptomatology. The data support the putative utility of aHPC connectivity as a measure of overall PTSD severity. Moreover, prefrontal global connectivity may be of clinical value as a brain biomarker to potentially distinguish between PTSD subgroups.

Abnormal noradrenergic function in posttraumatic stress disorder.

To evaluate possible abnormal noradrenergic neuronal regulation in patients with posttraumatic stress disorder (PTSD), the behavioral, biochemical, and cardiovascular effects of intravenous yohimbine hydrochloride (0.4 mg/kg) were determined in 18 healthy male subjects and 20 male patients with PTSD. A subgroup of patients with PTSD were observed to experience yohimbine-induced panic attacks (70% [14/20]) and flashbacks (40% [8/20]), and they had larger yohimbine-induced increases in plasma 3-methoxy-4-hydroxyphenylglycol levels, sitting systolic blood pressure, and heart rate than those in healthy subjects. In addition, in the patients with PTSD, yohimbine induced significant increases in core PTSD symptoms, such as intrusive traumatic thoughts, emotional numbing, and grief. These data were consistent with a large body of preclinical data that indicated that uncontrollable stress produces substantial increases in noradrenergic neuronal function. We discuss the implications of these abnormalities in noradrenergic functional regulation in relation to the long-term neurobiological sequelae of severe uncontrollable stress and the pathophysiological relationship between PTSD and other anxiety disorders, such as panic disorder.

Noradrenergic and serotonergic function in posttraumatic stress disorder.

BACKGROUND: Yohimbine hydrochloride produces marked behavioral and cardiovascular effects in combat veterans with posttraumatic stress disorder (PTSD). In the present study, yohimbine was used as a probe of noradrenergic activity, and meta-chlorophenylpiperazine (m-CPP) as a probe of serotonergic activity. To our knowledge, this is the first study to describe the behavioral and cardiovascular effects of meta-CPP in patients with PTSD, and to compare these effects with those of yohimbine. METHOD: Twenty-six patients with PTSD and 14 healthy subjects each received an intravenous infusion of yohimbine hydrochloride (0.4 mg/kg), m-CPP (1.0 mg/kg), or saline solution on 3 separate test days in a randomized balanced order and in double-blind fashion. Behavioral and cardiovascular measurements were determined at multiple times. RESULTS: Eleven (42%) of the patients with PTSD experienced yohimbine-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, but not in cardiovascular measurements. Eight patients (31%) with PTSD experienced m-CPP-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, and in standing diastolic blood pressure. Yohimbine-induced panic attacks tended to occur in different patients from m-CPP-induced panic attacks. CONCLUSION: These data suggest the presence of 2 neurobiological subgroups of patients with PTSD, one with a sensitized noradrenergic system, and the other with a sensitized serotonergic system.

Positron emission tomography measurement of cerebral metabolic correlates of yohimbine administration in combat-related posttraumatic stress disorder.

BACKGROUND: We have previously reported an increase in symptoms of anxiety in patients with posttraumatic stress disorder (PTSD) following administration of the beta 2-antagonist yohimbine, which stimulates brain norepinephrine release. Preclinical studies show decreased metabolism in the neocortex and the caudate nucleus with high-dose yohimbine-induced norepinephrine release, but low levels of norepinephrine release result in an increase in metabolism in these areas. METHODS: We used positron emission tomography and fludeoxyglucose F 18 to measure brain metabolism in Vietnam combat veterans with PTSD (n = 10) and healthy age-matched control subjects (n = 10), following administration of yohimbine (0.4 mg/kg) or placebo in a randomized, double-blind fashion. RESULTS: Yohimbine resulted in a significant increase in anxiety in the patients with PTSD, but not in healthy subjects. There was a significant difference in brain metabolic response to yohimbine in patients with PTSD compared with healthy subjects in prefrontal, temporal, parietal, and orbitofrontal cortexes. Metabolism tended to decrease in patients with PTSD and increase in healthy subjects following administration of yohimbine. CONCLUSION: These findings are consistent with our previous hypothesis of enhanced norepinephrine release in the brain with yohimbine in patients with PTSD.

Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorder.

BACKGROUND: The hypothesis that exaggerated startle in Vietnam veterans with posttraumatic stress disorder (PTSD) reflects an anxiogenic response to stressful contexts was tested. METHODS: Thirty-four nonmedicated Vietnam veterans with PTSD, and 17 combat and 14 civilian non-PTSD controls participated in two testing sessions over separate days. Acoustic startle stimuli were delivered alone or in a test of prepulse inhibition. In the first session, startle was assessed without experimental stress. In the second session, startle was investigated during a stressful "threat of shock" experiment, when subjects anticipated the administration of shocks during threat periods and during safe periods when no shocks were anticipated. RESULTS: The magnitude of startle did not differ significantly among the three groups in the first session, but was increased throughout the threat of shock experiment in the PTSD veterans in the second session. The actual increase in startle in the threat compared to the safe condition did not significantly differ among the three groups. Prepulse inhibition was reduced in the PTSD veterans, compared to the non-PTSD civilians, but not compared to the non-PTSD veterans. CONCLUSION: Exaggerated startle in Vietnam veterans with PTSD reflects an anxiogenic response to an environment that is experienced as stressful.

Yohimbine use in a natural setting: effects on posttraumatic stress disorder.

BACKGROUND: Numerous laboratory-based studies have shown that chronic posttraumatic stress disorder (PTSD) is associated with alterations in catecholamines. In a recent neuroendocrine challenge study, IV yohimbine caused exaggerated subjective, behavioral, cardiovascular and catecholamine responses among combat veterans with PTSD compared to healthy controls. Yohimbine is an alpha-2-adrenergic receptor antagonist that activates noradrenergic neurons. METHODS: This report describes the experience of 4 individuals with PTSD who took over-the-counter oral yohimbine that they had purchased from a health food store or pharmacy. RESULTS: All 4 subjects experienced a marked exacerbation of anxiety/panic and PTSD-specific symptoms immediately after ingesting yohimbine in a natural setting. CONCLUSIONS: The response in these individuals closely resembled the response observed after IV yohimbine in combat veterans with PTSD. The present cases occurred in a natural setting and thus complement laboratory-based findings. The authors caution against the recreational or medical use of yohimbine in individuals who have PTSD.

Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder.

This review focuses on the role of norepinephrine (NE) in traumatic stress. The review is divided into three sections. The first section, "Norepinephrine and Arousal," describes preclinical studies related to norepinephrine's role in arousal, orienting to novel stimuli, selective attention and vigilance. It also contains a brief discussion of NE and its relationship to fear-provoking stimuli followed by preclinical and clinical studies that demonstrate heightened noradrenergic neuronal reactivity, increased alpha 2 receptor sensitivity and exaggerated arousal in organisms that have been exposed to chronic uncontrollable stress. The second section, "Norepinephrine and Memory," describes preclinical and clinical studies related to norepinephrine's role in enhanced encoding of memory for arousing and aversive events and in subsequent re-experiencing symptoms such as, intrusive memories and nightmares. The third section, "Norepinephrine and Pharmacologic Treatment," briefly discusses the use of adrenergic blockers, clonidine and propranol, as well as tricyclic and MAO inhibitors, for the treatment of PTSD. Finally, we attempt to synthesize trauma-related preclinical and clinical studies of norepinephrine. We do this, in part, by focusing on a series of yohimbine studies in subjects with PTSD because data from these studies allow for a discussion that brings together preclinical and clinical findings relevant to trauma-related alterations in arousal and memory.

Hypothalamic-pituitary-adrenal dysfunction in posttraumatic stress disorder.

Neuroendocrine studies examining the hypothalamic-pituitary-adrenal (HPA) axis under baseline conditions and in response to neuroendocrine challenges have supported the hypothesis of altered HPA functioning in posttraumatic stress disorder (PTSD). However, to date, there is much debate concerning the nature of HPA changes in PTSD. Furthermore, in studies showing parallel findings in PTSD and major depressive disorder there is controversy regarding whether the HPA alterations suggest a specific pathophysiology of PTSD, or, rather, reflect comorbid major depressive disorder. This review summarizes findings of HPA axis dysfunction in both PTSD and major depressive disorder, and shows distinct patterns of HPA changes, which are probably due to different mechanisms of action for cortisol and its regulatory factors.

Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) show a reliable increase in PTSD symptoms and physiological reactivity following exposure to traumatic pictures and sounds. In this study neural correlates of exposure to traumatic pictures and sounds were measured in PTSD. METHODS: Positron emission tomography and H2[15O] were used to measure cerebral blood flow during exposure to combat-related and neutral pictures and sounds in Vietnam combat veterans with and without PTSD. RESULTS: Exposure to traumatic material in PTSD (but not non-PTSD) subjects resulted in a decrease in blood flow in medial prefrontal cortex (area 25), an area postulated to play a role in emotion through inhibition of amygdala responsiveness. Non-PTSD subjects activated anterior cingulate (area 24) to a greater degree than PTSD patients. There were also differences in cerebral blood flow response in areas involved in memory and visuospatial processing (and by extension response to threat), including posterior cingulate (area 23), precentral (motor) and inferior parietal cortex, and lingual gyrus. There was a pattern of increases in PTSD and decreases in non-PTSD subjects in these areas. CONCLUSIONS: The findings suggest that functional alternations in specific cortical and subcortical brain areas involved in memory, visuospatial processing, and emotion underlie the symptoms of patients with PTSD.

Fear-potentiated startle in posttraumatic stress disorder.

Exaggerated startle is reputed to be one of the cardinal symptoms of posttraumatic stress disorder (PTSD); however, objective studies have given conflicting results as to whether or not startle is increased in PTSD. The present study investigated startle in PTSD during the threat of shock (fear-potentiated startle). The eyeblink component of the startle reflex was measured at various times preceding and following the anticipation of unpleasant electric shocks in 9 PTSD subjects and 10 age-matched, healthy controls. Startle amplitude was significantly greater during baseline and during shock anticipation in the PTSD subjects, compared to the controls. Habituation of the startle reflex was normal. Because other studies in the literature, as well as in our own laboratory, have failed to find exaggerated startle at baseline (i.e., absence of stress) in PTSD patients, it is unlikely that the present results reflect a chronic elevation of startle in this group. Instead, the higher levels of startle in the PTSD group probably resulted from a greater conditioned emotional response in this group, triggered by anticipation of electric shocks that generalized to the unfamiliar experimental context in which testing occurred. Hence, emotionally charged test procedures may be especially informative in distinguishing PTSD patients from other psychiatric diagnostic groups.

Increased pituitary and adrenal reactivity in premenopausal women with posttraumatic stress disorder.

BACKGROUND: Limited studies of hypothalamic-pituitary-adrenal axis regulation in posttraumatic stress disorder have been performed in premenopausal women. We therefore undertook a study of hypothalamic-pituitary-adrenal axis regulation in this population. METHODS: Outpatient posttraumatic stress disorder subjects were compared with healthy, age- and weight-matched nontraumatized subjects. Subjects were free from psychotropic medications, alcohol and other illicit substances for at least 4 weeks before study. Menstrual cycle phase was determined by monitoring the LH surge and plasma progesterone levels. Corticotropin releasing factor and adrenocorticotropin stimulation tests, as well as 24-hour urinary-free cortisol measurements were performed. RESULTS: Corticotropin releasing factor test: Baseline adrenocorticotropic hormone and cortisol levels did not differ between the 12 PTSD and 11 comparison subjects, but the posttraumatic stress disorder group had greater adrenocorticotropic hormone and cortisol responses to corticotropin releasing factor, as well as a later cortisol peak. Adrenocorticotropic hormone test: Baseline cortisol levels did not differ between the 10 posttraumatic stress disorder subjects and seven controls, but the posttraumatic stress disorder group showed greater cortisol responses to adrenocorticotropic hormone. Peak cortisol responses to corticotropin releasing factor and adrenocorticotropic hormone were correlated with each other and with 24-hour urinary-free cortisol excretion. CONCLUSIONS: Pituitary and adrenal hyperreactivity to exogenous corticotropin releasing factor and adrenocorticotropic hormone is demonstrated in premenopausal women with chronic posttraumatic stress disorder. Cortisol hyperreactivity thus may play a role in the pathophysiology of posttraumatic stress disorder in women.

Hormone profiles in humans experiencing military survival training.

BACKGROUND: Clinical models of the human response to intense, acute stress have been limited to laboratory settings or cross sectional characterizations. As a result, data about the sensitivity of the human neuroendocrine activation to realistic stressors of varying magnitudes are limited. The U.S. Army survival course offers a unique opportunity to examine, in a controlled manner, the human response to acute, realistic, military stress. METHODS: Salivary data were collected in 109 subjects at baseline during four stress exposure time points and at recovery. Serum data was collected at baseline and recovery in 72 subjects and at baseline and during stress exposure in a subgroup of subjects (n = 21). RESULTS: Cortisol significantly increased during the captivity experience and was greatest after subjects' exposure to interrogations. Cortisol remained significantly elevated at recovery. Testosterone was significantly reduced within 12 hours of captivity. Reductions of both total and free T4 and of total and free T3 were observed, as were increases in thyrotropin. CONCLUSIONS: The stress of military survival training produced dramatic alterations in cortisol, percent free cortisol, testosterone, and thyroid indices. Different types of stressors had varying effects on the neuroendocrine indices. The degree of neuroendocrine changes observed may have significant implications for subsequent responses to stress.

Plasma neuropeptide-Y concentrations in humans exposed to military survival training.

BACKGROUND: Neuropeptide-Y (NPY) is present in extensive neuronal systems of the brain and is present in high concentrations in cell bodies and terminals in the amygdala. Preclinical studies have shown that injections of NPY into the central nucleus of the amygdala function as a central anxiolytic and buffer against the effects of stress. The objective of this study was to assess plasma NPY immunoreactivity in healthy soldiers participating in high intensity military training at the U.S. Army survival school. The Army survival school provides a means of observing individuals under high levels of physical, environmental, and psychological stress, and consequently is considered a reasonable analogue to stress incurred as a result of war or other catastrophic experiences. METHODS: Plasma levels of NPY were assessed at baseline (prior to initiation of training), and 24 hours after the conclusion of survival training in 49 subjects, and at baseline and during the Prisoner of War (P.O.W.) experience (immediately after exposure to a military interrogation) in 21 additional subjects. RESULTS: Plasma NPY levels were significantly increased compared to baseline following interrogations and were significantly higher in Special Forces soldiers, compared to non-Special Forces soldiers. NPY elicited by interrogation stress was significantly correlated to the subjects' behavior during interrogations and tended to be negatively correlated to symptoms of reported dissociation. Twenty-four hours after the conclusion of survival training, NPY had returned to baseline in Special Forces soldiers, but remained significantly lower than baseline values in non-Special Forces soldiers. NPY was positively correlated with both cortisol and behavioral performance under stress. NPY was negatively related to psychological symptoms of dissociation. CONCLUSIONS: These results provide evidence that uncontrollable stress significantly increases plasma NPY in humans, and when extended, produces a significant depletion of plasma NPY. Stress-induced alterations of plasma NPY were significantly different in Special Forces soldiers compared to non-Special Forces soldiers. These data support the idea that NPY may be involved in the enhanced stress resilience seen in humans.

Low baseline and yohimbine-stimulated plasma neuropeptide Y (NPY) levels in combat-related PTSD.

BACKGROUND: Consistent with many studies demonstrating enhanced reactivity of the sympathetic nervous system in posttraumatic stress disorder (PTSD), the administration of yohimbine, a noradrenergic alpha(2)-antagonist, has been shown to increase core symptoms of PTSD and to induce greater increases in plasma 3-methyl-4-hydroxy-phenyl-glycol (MHPG) in subjects with PTSD compared with healthy control subjects. In turn, neuropeptide Y (NPY) has been shown to inhibit the release of norepinephrine from sympathetic noradrenergic neurons. METHODS: In the following study, plasma NPY responses to yohimbine and placebo were measured in a subgroup of 18 subjects with PTSD and 8 healthy control subjects who participated in the previous study of the effect of yohimbine on plasma MHPG. RESULTS: The PTSD subjects had lower baseline plasma NPY and blunted yohimbine-stimulated increases in plasma NPY compared with the healthy control subjects. Within the PTSD group, baseline plasma NPY levels correlated negatively with combat exposure scale scores, baseline PTSD and panic symptoms, and yohimbine-stimulated increases in MHPG and systolic blood pressure. CONCLUSIONS: This study suggests that combat stress-induced decreases in plasma NPY may mediate, in part, the noradrenergic system hyperreactivity observed in combat-related PTSD. The persistence of this decrease in plasma NPY may contribute to symptoms of hyperarousal and the expression of exaggerated alarm reactions, anxiety reactions, or both in combat veterans with PTSD long after war.