Isabelle Plante

The Stress Model of Chronic Pain: Evidence from Basal Cortisol and Hippocampal Structure and Function in Humans.

Recent theories have suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor. The present study examined the associations between basal levels of cortisol collected over seven consecutive days, the hippocampal volumes and brain activation to thermal stimulations administered in 16 patients with chronic back pain and 18 healthy control subjects. Results showed that patients with chronic back pain have higher levels of cortisol than control subjects. In these patients, higher cortisol was associated with smaller hippocampal volume and stronger pain-evoked activity in the anterior parahippocampal gyrus, a region involved in anticipatory anxiety and associative learning. Importantly, path modelling-a statistical approach used to examine the empirical validity of propositions grounded on previous literature-revealed that the cortisol levels and phasic pain responses in the parahippocampal gyrus mediated a negative association between the hippocampal volume and the chronic pain intensity. These findings support a stress model of chronic pain suggesting that the sustained endocrine stress response observed in individuals with a smaller hippocampii induces changes in the function of the hippocampal complex that may contribute to the persistent pain states.

Acute Stress Contributes to Individual Differences in Pain and Pain-Related Brain Activity in Healthy and Chronic Pain Patients

Individual differences in pain sensitivity and reactivity are well recognized but the underlying mechanisms are likely to be diverse. The phenomenon of stress-induced analgesia is well documented in animal research and individual variability in the stress response in humans may produce corresponding changes in pain. We assessed the magnitude of the acute stress response of 16 chronic back pain (CBP) patients and 18 healthy individuals exposed to noxious thermal stimulations administered in a functional magnetic resonance imaging experiment and tested its possible contribution to individual differences in pain perception. The temperature of the noxious stimulations was determined individually to control for differences in pain sensitivity. The two groups showed similar significant increases in reactive cortisol across the scanning session when compared with their basal levels collected over 7 consecutive days, suggesting normal hypothalamic–pituitary–adrenal axis reactivity to painful stressors in CBP patients. Critically, after controlling for any effect of group and stimulus temperature, individuals with stronger cortisol responses reported less pain unpleasantness and showed reduced blood oxygenation level-dependent activation in nucleus accumbens at the stimulus onset and in the anterior mid-cingulate cortex (aMCC), the primary somatosensory cortex, and the posterior insula. Mediation analyses indicated that pain-related activity in the aMCC mediated the relationship between the reactive cortisol response and the pain unpleasantness. Psychophysiological interaction analysis further revealed that higher stress reactivity was associated with reduced functional connectivity between the aMCC and the brainstem. These findings suggest that acute stress modulates pain in humans and contributes to individual variability in pain affect and pain-related brain activity.

Student gender stereotypes: contrasting the perceived maleness and femaleness of mathematics and language

The purpose of this study was to evaluate the gender stereotypes endorsed by elementary and high school students regarding mathematics and language. We developed a questionnaire allowing students to rate mathematics and language as either male or female domains and administered it to a sample of 984 elementary and high school French‐speaking Canadian students (Grades 6, 8, and 10). Results showed that, with the exception of Grade 6 boys, students did not believe that mathematics was a male domain, or even conceived of mathematics as a predominantly female domain, suggesting that the traditional stereotype favouring boys in mathematics might have changed over the past few years. Moreover, language was clearly viewed as a female domain. Overall, our findings suggest that boys seem to be in need of encouragement in school, especially regarding language, where the advantage given to girls is particularly salient.

Impact of glucose concentration on cardiac ventricular repolarization under IKr/IKs blocking agents

Drug-induced QT interval prolongation is a condition likely to be aggravated by diabetes. The objective of this study was to evaluate how glucose concentration may modulate drug effects on ventricular repolarization and on cardiac repolarizing potassium currents. Guinea pig hearts were Langendorff-retroperfused and monophasic action potential duration (MAPD) was measured. Glucose (1, 5 or 20 mmol/L) was tested with either dofetilide (a specific I(Kr) blocker), chromanol 293B (a specific I(Ks) blocker) or both. Effects of glucose (1, 5 or 20 mmol/L) on I(Kr) blockade mediated by dofetilide were also measured in HERG-transfected HEK293 cells in the absence vs presence of the P-glycoprotein drug transporter, using the whole cell patch-clamp technique. Our results suggest that both hypo- and hyperglycemia potentiate the MAPD-prolonging and I(Kr)-blocking properties of dofetilide. P-glycoprotein drug extrusion efficacy appears as a key determinant of dofetilides I(Kr)-blocking effect. This efficacy appears to be affected by glucose concentration, particularly hyperglycemia.

Lengthening of Cardiac Repolarization in Isolated Guinea Pigs Hearts by Sequential or Concomitant Administration of Two IKr Blockers

Block of I(Kr) is of major concern in drug safety. The objective of this study was to assess prolongation of cardiac repolarization during the combined use of two I(Kr) blockers when administered concomitantly or sequentially. (1) When isolated hearts from male guinea pigs were perfused concomitantly with two I(Kr) blockers, prolongation of monophasic action potential duration measured at 90% (MAPD(90)) was less than the summation of effects observed for each drug perfused alone. (2) In sequential administration, when ketoconazole or erythromycin was perfused first, they antagonized MAPD(90)-prolonging effects of domperidone. This effect was absent when domperidone or dofetilide was perfused first. Patch-clamp experiments confirmed that the order of sequential perfusion impacts the decrease in HERG tail amplitude. In conclusion, this study does not support the concept that potentiation of drug effects is observed during the combined administration of two I(Kr) blockers. Furthermore, order of administration of two I(Kr) blockers together may be an important factor in drug-induced long QT syndrome.

Rosuvastatin Blocks hERG Current and Prolongs Cardiac Repolarization

Blocking of the potassium current I(Kr) [human ether-a-go-go related gene (hERG)] is generally associated with an increased risk of long QT syndrome (LQTS). The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor, rosuvastatin, is a methanesulfonamide derivative, which shows structural similarities with several I(Kr) blockers. Hence, we assessed the effects of rosuvastatin on cardiac repolarization by using in vitro, ex vivo, and in vivo models. Patch clamp experiments on hERG-transfected human embryonic kidney (HEK) 293 cells established the potency of rosuvastatin to block hERG [half maximal inhibitory concentration (IC(50) ) = 195 nM]. We showed in isolated guinea pig hearts that 195 nM rosuvastatin prolonged (basic cycle length of 250 ms; p < 0.05) the monophasic action potential duration at 90% repolarization (MAPD(90) ) by 11 ± 1 ms. Finally, rosuvastatin (10 mg/kg, intraperitoneal) prolonged corrected QT interval (QTc) in conscious and unrestrained guinea pigs from 201 ± 1 to 210 ± 2 ms (p < 0.05). Thus, rosuvastatin blocks I(Kr) and prolongs cardiac repolarization. In additional experiments, we also show that hERG blockade in HEK 293 cells was modulated by coexpression of efflux [breast cancer resistance protein (BCRP), multidrug resistance gene (MDR1)] and influx [organic anion transporting polypeptide (OATP) 2B1] transporters involved in the disposition and cardiac distribution of the drug. Genetic polymorphisms observed for BCRP, MDR1, and OATP2B1, and IC(50) determined for hERG blocking lead us to propose that some patients may be at risk of rosuvastatin-induced LQTS.

The Multifaceted Role of Interest in Motivation and Engagement

In this chapter, we review research demonstrating the role of interest in motivation and engagement. First, we discuss the psychological experience of interest, examining how attention and affect shift during a state of interest. Here, studies suggest that, on the one hand, interest is often associated with narrowed attention, eliciting focused engagement, such as when one experiences a state of flow. On the other hand, interest is also linked to broadened attention, eliciting exploratory engagement. We then discuss the implicit theories people hold about interests—whether interests are believed to be inherent and fixed versus able to develop and grow. Recent research suggests that believing interests are developed (vs. fixed) increases interest in new areas and enables people to respond adaptively to motivational challenges by buffering them against a loss of interest when a new activity becomes difficult. Next we review research on how interest affects task performance and persistence, and consider the roles of focused and exploratory modes of engagement. Finally, we examine interest as an outcome of engagement, discussing processes ranging from cognitive dissonance to social interactions. Together, the research reviewed in this chapter converges to highlight the multiple means by which interest is powerfully linked to human motivation and engagement.

Immunohistochemistry and Female Reproductive Toxicology: The Ovary and Mammary Glands

Exposure of women to toxicants represents potentially important consequences for their fertility and on the passage of genetic materials to their offspring. Women are born with a limited number of oocytes, and as they age, the risk for toxicants to accumulate or exert effects on the oocyte increases. Environmental toxicants and endocrine-disrupting chemicals are known to cause toxic effects on developing oocytes that are highly regulated by hormones such as steroids, thyroid, and gonadotropins. Many endocrine diseases, such as diabetes and thyroid dysfunction, are known to affect ovarian function. Hormonal imbalances have been associated with exposure to environmental toxicants, and therefore, these may either directly or indirectly exert effects on the ovary and ovarian function. Studies have also suggested a link between endocrine-disrupting chemicals, particularly estrogenic chemicals, and precocious mammary gland development in young women. Given the increase in the rates of breast cancer in women, it is imperative that we fully understand how toxicants can affect mammary gland development and function. Intercellular communication and cell–cell interaction in tissues are critical for development and function. “This is particularly true in most reproductive tissues where coordinated development and function are tightly regulated. Given the complexity of these interactions and the need to examine how cell-specific interactions may be altered by toxicants, the need for microscopy-based analyses and immunolocalization of the proteins implicated in cell–cell interactions in reproductive tissues is highlighted.

Girls’ internalization of their female teacher’s anxiety: A “real-world” stereotype threat effect?

The deleterious effects that stereotypes can have on girls’ school performance in mathematics are best exemplified by the stereotype threat paradigm (1) showing that when women are reminded of stereotypes alleging male superiority in math, their math performance suffers (2). However, evidence is mixed on how much these threat effects apply to girls’ math performance in “real-world” settings (3), and how girls develop their vulnerability in the first place.

Strategies included in cognitive behavioral therapy programs to treat internalized disorders: a systematic review

Abstract This review aimed to identify the strategies used in programs based on cognitive behavioral therapy (CBT) to prevent and treat symptoms of anxiety, depression, and internalized behaviors of children and adolescents. Based on an online search (ERIC, PsycInfo, Virtuose UQAM, and Google Scholar), 61 studies describing different cognitive behavioral programs were selected. Results showed that 40 strategies were implemented in at least one program. However, none of the strategies were systematically present in all programs, and only few were reported in more than 50% of the studies. Cognitive restructuring and problem-solving were the most popular strategies to treat depressive symptoms, whereas anxiety programs also generally included relaxation and exposure. Furthermore, six strategies were identified in a single anxiety program, whereas nine strategies were implemented in only one depression program. These results suggest that in anxiety and depression programs designed for children and adolescents, the label “CBT” encompasses a wide variety of programs with only few similar strategies. Such findings highlight the need to define a common basis for CBT programs, in order to better reflect CBT theory and to identify the effectiveness of the strategies included in these programs.