Faculty Bibliography

We provide an overview of previous research conducted by our group on risk and resilience factors for PTSD symptoms in police and other first responders. Based on our work, the findings of other investigators on individual differences in risk for PTSD, and drawing on preclinical studies fear conditioning and extinction, we propose a conceptual model for the development of PTSD symptoms emphasizing the role of vulnerability and resilience to peritraumatic panic reactions. We tested this conceptual model in a cross-sectional sample of police officers (n = 715). Utilizing an hierarchical linear regression model we were able to explain 39.7% of the variance in PTSD symptoms. Five variables remained significant in the final model; greater peritraumatic distress (beta = 0.240, P < .001), greater peritraumatic dissociation (beta = 0.174, P < .001), greater problem-solving coping (beta = 0.103, P < .01), greater routine work environment stress (beta = 0.182, P < .001), and lower levels of social support (beta = -0.246, P < .001). These results were largely consistent with the proposed conceptual model. Next steps in this line of research will be to test this model prospectively in a sample of 400 police academy recruits assessed during training and currently being followed for the first 2 years of police service

Studies that have conducted quantitative analysis of the sleep electroencephalogram (EEG) have demonstrated decreased delta sleep in PTSD. Elevations in both hypothalamic (neurohormonal) and extrahypothalamic (neurotransmitter) corticotropin releasing factor (CRF) release is associated with decreased delta sleep activity. We present data from several studies examining the effect of metyrapone administration on the sleep EEG in PTSD and control subjects. Plasma ACTH, cortisol, and 11-deoxycorticol were obtained the morning following polysomnographic sleep recordings before and after metyrapone administration. Delta sleep was measured by period amplitude analysis. The results demonstrate: a) decreased delta sleep in male subjects with PTSD; b) metyrapone administration resulted in an activation of the sleep EEG and a robust decrease in quantitative delta sleep; c) the sleep and endocrine (increase in ACTH) responses to metyrapone were significantly decreased in PTSD in two different study samples; and d) the metyrapone-related disruption to sleep in both samples was predicted by the increase in ACTH measured the following morning. These findings strongly suggest that the delta sleep response to metyrapone is a measure of the brain response to a hypothalamic CRF challenge. The attenuated delta sleep and endocrine response to metyrapone challenge in PTSD is consistent with a model of enhanced negative feedback regulation or downregulation of CRF receptors in an environment of chronically increased CRF activity

Alexithymia has been associated with both posttraumatic stress disorder and neuroendocrine responses to stress. This study examined the relationship of alexithymia to salivary cortisol and 3-methoxy-4-hydroxy-phenylglycol (MHPG) in a sample of police academy recruits exposed to a video stress challenge. Alexithymia scores were negatively associated with catecholamine response to the video challenge but no association was found between alexithymia scores and cortisol reactivity

Intimate partner violence (IPV) is a chronic and recurrent traumatic stressor associated with PTSD; however, its biological correlates are not well understood. This study examined diurnal salivary cortisol and platelet catecholamines in women with lifetime IPV-related PTSD and in women exposed to IPV who did not develop PTSD. Cortisol was elevated in women with lifetime PTSD compared to controls. No differences were found for platelet catecholamines

OBJECTIVE: The authors report an 8-week, double-blind, randomized controlled trial of guanfacine versus placebo for posttraumatic stress disorder (PTSD). METHOD: Veterans with chronic PTSD who were medication-free or receiving stable pharmacotherapy were randomly assigned to guanfacine (N=29) versus placebo (N=34). RESULTS: Guanfacine had no effect on PTSD symptoms, subjective sleep quality, or general mood disturbances. Guanfacine was associated with a number of side effects. CONCLUSIONS: These results do not support the use of alpha 2 agonists in veterans with chronic PTSD

OBJECTIVE: The efficacy of pharmacological relapse prevention in alcoholism with acamprosate and naltrexone has been supported by several controlled trials. It remains uncertain whether any differential indication for treatment exists. METHODS: We evaluated outcome data of a controlled trial on acamprosate and naltrexone in patients with low vs. high baseline somatic distress, depression and anxiety (Symptom Checklist-90, SCL-90), low vs. high baseline craving, and according to typological differentiation as proposed by Cloninger and Lesch. These variables have previously been suggested to be predictors of outcome. RESULTS: Comparing the course of abstinence rates, acamprosate was mainly efficacious in patients with low baseline somatic distress, whereas naltrexone was effective especially in patients with high baseline depression. Baseline craving showed no predictive value. Pharmacological treatment was efficacious in type II alcoholics according to Cloninger. Applying Lesch's typological differentiation, acamprosate was shown to be mainly effective in type I, whereas naltrexone revealed best treatment effects in type III and IV. CONCLUSION: The study supports the hypothesis that different subgroups of alcohol dependent subjects might benefit from a differential treatment with either naltrexone or acamprosate. Baseline psychopathology and especially typological differentiation might be useful in matching patients to distinct pharmacotherapeutic interventions.

OBJECTIVE: Depressive symptoms are associated with an increased risk of cardiac events in patients with heart disease. Elevated catecholamine levels may contribute to this association, but whether depressive symptoms are associated with catecholamine levels in patients with heart disease is unknown. METHOD: The authors examined the association between depressive symptoms (defined by a Patient Health Questionnaire score > or =10) and 24-hour urinary norepinephrine, epinephrine, and dopamine excretion levels in 598 subjects with coronary disease. RESULTS: A total of 106 participants (18%) had depressive symptoms. Participants with depressive symptoms had greater mean norepinephrine excretion levels than those without depressive symptoms (65 microg/day versus 59 mug/day, with adjustment for age, sex, body mass index, smoking, urinary creatinine levels, comorbid illnesses, medication use, and cardiac function). In logistic regression analyses, participants with depressive symptoms were more likely than those without depressive symptoms to have norepinephrine excretion levels in the highest quartile and above the normal range. Depressive symptoms were not associated with dopamine or epinephrine excretion levels. CONCLUSIONS: In patients with coronary disease, depressive symptoms are associated with elevated norepinephrine excretion levels. Future longitudinal studies are needed to determine whether elevations in norepinephrine contribute to adverse cardiac outcomes in patients with depressive symptoms

The appetite regulating peptide leptin has recently been associated with craving for alcohol and lifetime ethanol intake. However, effects of anti-craving drugs on leptin have not been studied until now. The objective of our study was to test the hypothesis whether leptin plasma concentration in abstinent alcohol addicts during treatment with naltrexone vs. acamprosate is associated with abstinence duration and craving for alcohol. Leptin plasma concentration was measured in 160 recently detoxified alcohol addicts during a double-blind, placebo-controlled relapse prevention trial with naltrexone vs. acamprosate vs. naltrexone plus acamprosate. During placebo treatment, increasing leptin plasma concentration was observed, whereas during combined treatment with naltrexone and acamprosate, leptin decreased significantly. The change from baseline of leptin plasma levels after weeks 4, 8 and 12 was inversely correlated with duration of abstinence and, after 4 weeks, positively correlated with self-rated craving. In summary, the study presents first evidence for an association of increasing leptin plasma concentrations with relapse to renewed alcohol intake in detoxified alcoholics. Moreover, there are hints for an interaction between pharmacological anti-craving treatment, plasma concentration of leptin, and abstinence duration

The purpose of this meta-analysis is to examine the association between depression and cortisol responses to psychological stressors. A total of seven studies comparing plasma or cortisol responses to psychological stressors in clinically depressed (MDD) and non-depressed (ND) individuals (N = 196: 98 MDD, 98 ND; 83 men, 113 women; mean age = 40 years) were included. Sample size-adjusted effect sizes (Cohen's d statistic) were calculated and averaged across baseline (before stressor onset), stress (stressor onset up to 25 min after stressor offset), and recovery (more than 25 min after stressor offset) periods. Overall, MDD and ND individuals exhibited similar baseline and stress cortisol levels, but MDD patients had much higher cortisol levels during the recovery period than their ND counterparts. There was also a significant time of day effect in which afternoon studies were more likely to reveal higher baseline cortisol levels, blunted stress reactivity, and impaired recovery in MDD patients. This blunted reactivity-impaired recovery pattern observed among the afternoon studies was most pronounced in studies with older and more severely depressed patients

It is not known whether the metabolic syndrome is associated with poor exercise capacity among patients who have established coronary heart disease. We evaluated the association of the metabolic syndrome with treadmill exercise capacity and heart rate recovery among patients who had coronary heart disease. We measured treadmill exercise capacity (METs) and heart rate recovery (beats per minute) in 943 subjects who had known coronary heart disease. Of these, 377 (40%) had the metabolic syndrome as defined by criteria of the National Cholesterol Education Program. Participants who had the metabolic syndrome were more likely to have poor exercise capacity (METs <5, 33% vs 18%, p <0.0001) and poor heart rate recovery (<or=16 beats/min, 34% vs 21%, p <0.0001) than those who did not have the metabolic syndrome. In ordinal logistic regression analyses, the metabolic syndrome was associated with decreased exercise capacity (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.7 to 2.8, p <0.0001) and decreased heart rate recovery (OR 1.8, 95% CI 1.4 to 2.3, p <0.0001). These associations remained strong after adjusting for potential confounding variables (OR 1.6, 95% CI 1.2 to 2.1, p = 0.003 for decreased exercise capacity; OR 1.4, 95% CI 1.1 to 1.9, p = 0.02 for decreased heart rate recovery). The metabolic syndrome is independently associated with poor exercise capacity and poor heart rate recovery in patients who have established coronary heart disease. Decreased exercise capacity may contribute to the adverse outcomes associated with the metabolic syndrome