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.     

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.     

An Indicator of Suicidal Ideation on the Rorschach Test

We examined the impact of patient- and therapist-rated alliance developed during psychological assessment on the subsequent alliance measured early and late in formal psychotherapy. We hypothesized that a working alliance developed during psychological assessment conducted from a collaborative therapeutic model of assessment (TMA; Finn &; Tonsager, 1992, 1997; Fischer, 1994) between the patient and therapist would carry into formal psychotherapy. We also hypothesized that alliance for those patients receiving a TMA would be significantly greater than patients receiving psychological testing as usual. To test this hypothesis, we administered the Combined Alliance Short Form-Patient Version (Hatcher &; Barends, 1996) and the Combined Alliance Short Form-Therapist Version (Hatcher, 1999) to a sample of outpatients and their therapists at the end of the assessment feedback session, early, and late in psychotherapy. The hypotheses were supported as alliance scales rated at the assessment feedback session demonstrated positive and significant relationships with alliance throughout formal psychotherapy and in relation to a control group. The clinical utility and research implications of these findings are discussed.     

Support for religio‐political aggression among teenaged boys in Gaza: Part I: psychological findings

Politically aggressive militant groups usually rely on support from a larger community, although evidence suggests that only some members of that larger community support that aggression. A major subtype of political aggression is that associated with religious differences—or Religio‐Political Aggression (RPA). Little previous research has explored demographic or psychological factors that might distinguish supporters from non‐supporters of RPA. In an exploratory study, we investigated whether factors previously associated with aggression might correlate with support for RPA in the case of the Israeli/Palestinian conflict. During the second intifada, fifty‐two 14‐year‐old Palestinian boys in Gaza completed self‐report measures of life events, emotional status, and political attitudes. Teenaged boys who reported family members having been wounded or killed by the Israeli Defense Forces (IDF) expressed greater support for RPA (t(50)=?2.30, P=.026). In addition, boys who felt their group was treated unjustly reported greater support for RPA compared with those who did not (t(50)=?2.273, P=.027). Implications of these preliminary data are discussed. Aggr. Behav. 36:219–231, 2010. © 2010 Wiley‐Liss, Inc.     

Support for religio-political aggression among teenaged boys in Gaza: part II: neuroendocrinological findings

Hormones seem to play important roles in the regulation of human aggression. Multiple studies have confirmed that testosterone (T) levels exhibit complex relationships with aggression, dominance, and/or risk-taking behavior. Some evidence suggests that cortisol (CORT) interacts with T and may also be associated with aspects of mood and aggression. However, almost no research to date has investigated the possibility that these neuroendocrine factors are associated with variations in political attitudes or with political aggression. During the second intifada, we tested the hypothesis that morning salivary T and/or salivary CORT levels might be associated with self-rated aggression or with support for religio-political aggression (RPA) among 14-year-old Palestinian boys living in Gaza. We obtained and averaged weekly 09:00 hr salivary measures of T and CORT for more than 1 month. Averaged morning T levels did not correlate with self-rated aggression, but were positively associated with agreement with the statement "religious ends justify any means," (r = .355, P = .014) and marginally associated with a composite measure of support for RPA (r = .247, P = .094). Average CORT levels were inversely correlated with self-rated aggression (r = -.328, P = .037) and with anger (r = -.373, P = .016), but CORT levels were not associated with support for RPA or with the statement "religious ends justify any means." Acknowledging that a modest sample size and methodological issues necessarily limit confidence in our conclusions, these results may represent the first findings regarding neurobiological correlates of support for political aggression.     

Rapid stimulatory effects of testosterone upon myotubule metabolism and sugar transport,as assessed by silicon microphysiometry

A considerable number of studies have revealed behavioral circumstances that give rise to small or transient differences in circulating testosterone concentrations; however, careful consideration of androgen physiology leads to the disquieting conclusion that these differences are often unlikely to have much physiologic or behavioral significance. In the present report, we observe that small transients of testosterone secretion could have very rapid anabolic effects on a cultured muscle-derived cell line. Specifically, we have examined the effects of testosterone on metabolism in cultured C2C12 myotubules, using a silicon microphysiometer. The instrument monitors cellular extrusion of protons and acidic metabolites, and such extrusion is directly linked to ATP hydrolysis, thus providing a real-time measure of cellular metabolism. Testosterone caused a small but significant increase in metabolism. The most striking feature of this effect was its rapidity, in that it occurred within 3 hr. This rapid enhancement of metabolism suggested that testosterone might be enhancing substrate uptake even more rapidly. Indeed, we found that testosterone increased 2-deoxyglucose uptake within 1 min. The rapidity of this effect seemed to preclude mediation by classical intracellular steroid receptors. In support of this, we were unable to detect specific intracellular binding of testosterone. These findings show that testosterone can exert rapid anabolic effects on substrate transport and metabolism in myotubules. Should this finding general to muscle in vivo, it suggests that relatively small individual differences in testosterone profiles, in response to various social interactions, may have very real consequence for subsequent muscle physiology. © 1996 Wiley-Liss, Inc.     

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.