Charles A. Morgan

Psychosocial buffers of traumatic stress, depressive symptoms, and psychosocial difficulties in veterans of Operations Enduring Freedom and Iraqi Freedom: The role of resilience, unit support, and postdeployment social support

BACKGROUND Little research has examined the role of protective factors such as psychological resilience, unit support, and postdeployment social support in buffering against PTSD and depressive symptoms, and psychosocial difficulties in veterans of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF). MATERIALS AND METHODS A total of 272 OEF/OIF veterans completed a survey containing PTSD and depression screening measures, and questionnaires assessing resilience, social support, and psychosocial functioning. RESULTS Lower unit support and postdeployment social support were associated with increased PTSD and depressive symptoms, and decreased resilience and psychosocial functioning. Path analyses suggested that resilience fully mediated the association between unit support and PTSD and depressive symptoms, and that postdeployment social support partially mediated the association between PTSD and depressive symptoms and psychosocial functioning. LIMITATIONS Generalizability of results is limited by the relatively low response rate and predominantly older and reserve/National Guard sample. CONCLUSIONS These results suggest that interventions designed to bolster unit support, resilience, and postdeployment support may help protect against traumatic stress and depressive symptoms, and improve psychosocial functioning in veterans.

Severe decrements in cognition function and mood induced by sleep loss, heat, dehydration, and undernutrition during simulated combat

BACKGROUND Military exercises generate high levels of stress to simulate combat, providing a unique opportunity to examine cognitive and physiologic responses of normal humans to acute stress. METHODS Cognitive and physiologic markers of stress were evaluated before, during, and after an intense training exercise conducted for 53 hours in the heat. Cognitive performance, mood, physical activity, sleep, body composition, hydration, and saliva cortisol, testosterone, and melatonin were assessed. Volunteers were 31 male U.S. Army officers from an elite unit, aged 31.6 +/- .4 years. RESULTS Wrist activity monitors documented that soldiers slept only 3.0 +/- .3 hours during the exercise and were active throughout. Volunteers lost 4.1 +/- .2 kg (p < .001) of weight, predominately water (3.1 +/- .3 L) (p < .001). Substantial degradation in cognitive function, assessed with computerized tests, occurred. Vigilance, reaction time, attention, memory, and reasoning were impaired (p < .001). Mood, including vigor (p < .001), fatigue (p < .001), confusion (p < .001), depression (p < .001), and tension (p < .002), assessed by questionnaire, deteriorated. The highest cortisol and testosterone levels were observed before the exercise. CONCLUSIONS This study quantifies the overwhelmingly adverse impact of multiple stressors on cognitive performance, mood, and physiologic parameters, during a continuous but brief military exercise conducted by highly motivated, well-trained officers.

Baseline startle amplitude and prepulse inhibition in Vietnam veterans with posttraumatic stress disorder

Although an exaggerated startle response is a symptom of posttraumatic stress disorder (PTSD), empirical support for elevated baseline startle in PTSD has been weak. The present study investigated the eyeblink component of the acoustic startle reflex and prepulse inhibition (PPI) in 21 unmedicated Vietnam veterans with PTSD and in 17 civilian and 10 combat veteran comparison subjects. Patients with PTSD exhibited normal acoustic startle amplitude, but showed a significant reduction in PPI relative to the civilian subjects. There was only a trend toward a reduction in PPI in the PTSD group compared with the combat control group. The study does not support the hypothesis of exaggerated baseline startle in Vietnam veterans with PTSD but suggests abnormal startle modulation by a prepulse (i.e., PPI). Discrepancies between studies concerning the amplitude of startle in PTSD are discussed.

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.

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.

The neuroendocrinology of posttraumatic stress disorder: new directions.

Studies of the hypothalamic-pituitary-adrenal (HPA) axis in persons with posttraumatic stress disorder (PTSD) have produced variable findings. This review focuses on the factors likely to have affected the outcome of these studies, including population characteristics and experimental design. Also discussed is a possible role for the adrenal neurosteroid dehydroepiandrosterone (DHEA) as a mediator of HPA axis adaptation to extreme stress and the psychiatric symptoms associated with PTSD. The antiglucocorticoid properties of DHEA may contribute to an upregulation of HPA axis responses as well as mitigate possible deleterious effects of high cortisol levels on the brain in some PTSD subpopulations. The neuromodulatory effects of DHEA and its metabolite DHEAS at gamma-aminobutyric acid and N-methyl-D-aspartate receptors in the brain may contribute to psychiatric symptoms associated with PTSD. The possible importance of other neurohormone systems in modulating HPA axis and symptom responses to traumatic stress is also discussed. Understanding the complex interactions of these stress-responsive neurosteroid and peptide systems may help explain the variability in patterns of HPA axis adaptation, brain changes, and psychiatric symptoms observed in PTSD and lead to better targeting of preventive and therapeutic interventions.

Treatment of cocaine abuse with buprenorphine

Intravenous cocaine abuse has become a major public health problem among methadone-maintained patients, as the rate of cocaine-positive urines in these patients has increased severalfold over the last 10 years (Kaul and Davidow 198 1; Chambers et al. 1972; Kosten, Rounsaville, Kleber, 1987). Because these patients tend to use cocaine intravenously and to share needles, they may also spread human immunodeficiency virus (HIV) infection and AIDS (Kosten, Rounsaville, Kleber 1987). Several pharmacological treatments such as desipramine, bromoc~ptine, or amantadine have been added to standard methadone maintenance in order to decrease cocaine craving and use with as yet uncertain efficacy (Dackis and Gold 1985; Kosten, Schumann , Wright, 1988; Kosten, Schumann, Wright, Gamey, Gawin 1987; Morgan et al. 1988; Kosten, in press). An alternative approach is to use a different maintenance agent for treating the primary opioid addiction. A rationale for this approach is that many opioid abusers report a somewhat dysphoric experience when using cocaine by itself. but they find that mixing an opioid agonist such as methadone or heroin with the cocaine-a “speedball”-is quite pleasant and reinforcing (Kosten, Rounsaville, Kleber 1987). An alternative maintenance treatment that

Role of opioid antagonists in treating intravenous cocaine abuse

Intravenous cocaine abuse is a major probel in opioid abusers including those treated in methadone maintenance. Studying 138 opioid addicts, we found that speedballing by combining opioid agonists with cocaine may be blocked by opioid antagonists such as naltrexone and by partial antagonists such as buprenorphine. With both these treatments cocaine abuse was five to eight times less than with methadone treatment.

An Increased Capacity for Adrenal DHEA Release is Associated with Decreased Avoidance and Negative Mood Symptoms in Women with PTSD

We recently found increased adrenal cortisol responses to adrenocorticotropic hormone (ACTH)1–24 and increased pituitary ACTH and adrenal cortisol responses to corticotropin-releasing factor in premenopausal women with chronic post-traumatic stress disorder (PTSD) compared to healthy nontraumatized subjects. This pattern of hypothalamic–pituitary–adrenal axis (HPA) hyper-reactivity has been previously seen in healthy individuals treated with the antiglucocorticoid mifepristone. We therefore investigated whether endogenous plasma levels of antiglucocorticoids such as dehydroepiandrosteroine (DHEA) and progesterone were increased in premenopausal women with PTSD at baseline or in response to adrenal activation by ACTH1−24. The study revealed that DHEA responses to 250 μg ACTH1−24 were increased in 13 PTSD subjects compared to 13 healthy nontraumatized subjects, while DHEA levels were generally increased in the PTSD subjects compared to seven healthy traumatized subjects. Cortisol responses to ACTH1−24 were also higher in the women with PTSD, while progesterone levels and responses were not different among the three groups. In addition, among the PTSD subjects, the peak change in DHEA in response to ACTH1−24 was negatively correlated with the total Clinician Administered PTSD Scale score, while the peak DHEA to cortisol ratio was inversely associated with negative mood symptoms measured by the Profile of Mood States scale. This work suggests that an increased capacity for DHEA release in response to extreme adrenal activation may influence the pattern of HPA axis adaptation to extreme stress, as well as mitigate the severity of PTSD and negative mood symptoms in premenopausal women with PTSD.

Stress-Induced Deficits in Working Memory and Visuo-Constructive Abilities in Special Operations Soldiers

BACKGROUND Pre-clinical and clinical studies have shown acute stress may impair working memory and visuo-spatial ability. This study was designed to clarify the nature of stress-induced cognitive deficits in soldiers and how such deficits may contribute to operational or battlefield errors. METHODS One hundred eighty-four Special Operations warfighters enrolled in Survival School completed pre-stress measures of dissociation and trauma exposure. Subjects were randomized to one of three assessment groups (Pre-stress, Stress, Post-stress) and were administered the Rey Ostereith Complex Figure (ROCF). All subjects completed post-stress measures of dissociation. RESULTS ROCF copy and recall were normal in the Pre- and Post-stress groups. ROCF copy and recall were significantly impaired in the Stress Group. Stress group ROCF copy performance was piecemeal, and ROCF recall was impaired. Symptoms of dissociation were negatively associated with ROCF recall in the Stress group. Baseline dissociation and history of traumatic stress predicted cognitive impairment during stress. CONCLUSIONS Stress exposure impaired visuo-spatial capacity and working memory. In rats, monkeys, and humans, high dopamine and NE turnover in the PFC induce deficits in cognition and spatial working memory. Improved understanding of stress-induced cognitive deficits may assist in identification of soldiers at risk and lead to the development of better countermeasures.