McEwen-Induced Modulation of Endocrine History: A Partial Review

In endless facets of physiology, there are points of homeostatic balance, such that too much or too litttle of something can both be deleterious (i.e., an "inverse U" pattern). This is particularly true when considering glucocorticoids (GCs), the adrenals steroid secreted during stress. In the first part of this paper, I review a number of realms in which a paucity and an excess of GCs are both damaging. Some findings are classical (for example, concerning GC effects upon body weight), while some are quite recent and have considerable implications for both physiology and pathophysiology (for example, inverse U's of GC actions in the realm of immunity and neuronal survival). The second part of the review considers the far thornier issue of how such inverse U's of GC actions are generated on a cellular and molecular level. One solution that has evolved, primarily in the hippocampus within the nervous system, involves the presence of two different types of receptors for GCs within the same cells; so long as the two receptors have very different affinities and mediate opposing effects on some cellular endpoint, an inverse U will emerge. The second solution, found in a number of peripheral tissues, involves GCs having opposing effects on the amount of some signal being generated (e.g., an immune cytokine) and the sensitivity of target tissues to that signal; under conditions that appear to be physiologically relevant, inverse U's emerge from this pattern as well. The final section of this review considers the enormous role played by Bruce McEwen in the emergence of this literature. I suggest that while much of this obviously has to do with the facts that have come from his group, another substantial contribution is from his steadying and supportive personality, the veritable embodiment of homeostatic balance.     

Factors Related to the Long-Term Course of PTSD in Older Ex–Prisoners of War

This study examined relationships between socioenvironmental factors occurring in later-life and current and changing PTSD symptom levels in a sample of 177 community-dwelling World War II and Korean era ex–prisoners of war. Factors examined included negative life events, negative health events, social support, and death acceptance. PTSD was assessed at Time 1. PTSD and the later-life factors were then assessed 4 years later (Time 2). Cross-sectional analysis examined the relationship of the later-life factors to current PTSD symptomatology. Longitudinal analysis examined their relationship to changing PTSD symptomatology over the 4-year interval. Negative health changes, social support, and death acceptance were significantly related to current and changing PTSD symptomatology, but negative life events were not. The authors conclude that health and psychosocial factors that may occur in later-life can be related to PTSD symptom levels even many decades after a traumatic experience.     

Developmental and sex-related differences in preschoolers' affective decision making

This study investigated developmental and sex-related differences in affective decision making, using a two-deck version of Children's Gambling Task administered to 3- and 4-year-old children. The main findings were that 4-year-old children displayed better decision-making performance than 3-year-olds. This effect was independent of developmental changes in inductive reasoning, language, and working memory. There were also sex differences in decision-making performance, which were apparent only in 3-year-old children and favored girls. Moreover, age predicted awareness of task and the correlation between the latter and decision-making performance was significant, but only in 4-year-old children. This study thus indicates that there is a remarkable developmental leap in affective decision making, whose effects are apparent around the age of 4, which according to our results, also marks the age when the correlation of declarative knowledge and decision-making performance becomes significant.     

Stress, Glucocorticoids, and Damage to the Nervous System: The Current State of Confusion

An extensive literature demonstrates that glucocorticoids (GCs), the adrenal steroids secreted during stress, can have a broad range of deleterious effects in the brain. The actions occur predominately, but not exclusively, in the hippocampus, a structure rich in corticosteroid receptors and particularly sensitive to GCs. The first half of this review considers three types of GC effects: a) GC-induced atrophy, in which a few weeks' exposure to high GC concentrations or to stress causes reversible atrophy of dendritic processes in the hippocampus; b) GC neurotoxicity where, over the course of months, GC exposure kills hippocampal neurons; c) GC neuroendangerment, in which elevated GC concentrations at the time of a neurological insult such as a stroke or seizure impairs the ability of neurons to survive the insult. The second half considers the rather confusing literature as to the possible mechanisms underlying these deleterious GC actions. Five broad themes are discerned: a) that GCs induce a metabolic vulnerability in neurons due to inhibition of glucose uptake; b) that GCs exacerbate various steps in a damaging cascade of glutamate excess, calcium mobilization and oxygen radical generation. In a review a number of years ago, I concluded that these two components accounted for the deleterious GC effects. Specifically, the energetic vulnerability induced by GCs left neurons metabolically compromised, and less able to carry out the costly task of containing glutamate, calcium and oxygen radicals. More recent work has shown this conclusion to be simplistic, and GC actions are shown to probably involve at least three additional components: c) that GCs impair a variety of neuronal defenses against neurologic insults; d) that GCs disrupt the mobilization of neurotrophins; e) that GCs have a variety of electrophysiological effects which can damage neurons. The relevance of each of those mechanisms to GC-induced atrophy, neurotoxicity and neuroendangerment is considered, as are the likely interactions among them.     

Coping Functions of Prayer and Posttraumatic Growth

Research on prayer and posttraumatic growth (PTG) indicates that those who pray report more PTG. Research is beginning to identify which types of prayer may be operating in this relationship. We sought to identify specific prayer functions related to PTG while considering differences due to the types of trauma experienced. Participants were trauma survivors from diverse, Midwestern Christian churches (N = 327). Participants completed questionnaires assessing trauma history, prayer coping functions, and PTG. Multiple linear regression analyses found that praying for calm and focus was independently related to higher levels of PTG. When considering all variables in the model, the relationship between prayer for calm and focus and PTG was not significant for those whose most significant trauma was interpersonal in nature, but significant for those with noninterpersonal trauma.     

Comparing posttraumatic stress disorder's symptom structure between deployed and nondeployed veterans

We tested two empirically validated 4-factor models of posttraumatic stress disorder (PTSD) symptoms using the PTSD Checklist: King, Leskin, King, and Weathers' (1998) model including reexperiencing, avoidance, emotional numbing, and hyperarousal factors, and Simms, Watson, and Doebbeling's (2002) model including reexperiencing, avoidance, dysphoria, and hyperarousal. Our aim was to determine which fit better in two groups of military veterans: peacekeepers previously deployed to a war zone (deployed group) and those trained for peacekeeping operations who were not deployed (nondeployed group). We compared the groups using multigroup confirmatory factor analysis. Adequate model fit was demonstrated among the nondeployed group, with no significant difference between King et al.'s (1998) model (separating avoidance and numbing) and Simms et al.'s (2002) similar model involving a dysphoria factor. A better fitting factor structure consistent with Simms et al.'s (2002) model was found in the deployed group. Comprehensive measurement invariance testing demonstrated significant differences between the deployed and nondeployed groups on all structural parameters, except observed variable intercepts (thus indicating similarities only in PTSD item severity). These findings add to researchers' understanding of PTSD's factor structure, given the revision of PTSD that will appear in the forthcoming 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2010)--namely, that the factor structure may be quite different between groups with and without exposure to major traumatic events.