Effects of LY354740, a novel glutamatergic metabotropic agonist, on nonhuman primate hypothalamic-pituitary-adrenal axis and noradrenergic function

The search for novel anxiolytics and antidepressants has focused on compounds with the potential to reduce excessive hypothalamic-pituitary-adrenal (HPA) axis activity. L-glutamate, an excitatory neurotransmitter ubiquitously present within the central nervous system, conceivably plays an important role in activating the neural sites involved in stress modulation. Deactivation of the HPA axis by glutamatergic neurotransmission modulation may represent a novel therapeutic approach. Accordingly, the acute intravenous effects of the novel metabotropic (mGlu2/3) agonist LY354740 were tested on bonnet macaques (Macaca radiata) undergoing acute infusions of yohimbine, a noradrenergic stimulant. Dependent measures were the magnitude of the increase of plasma cortisol and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) customarily elicited by yohimbine. Next, the effects of 6 weeks of chronic oral administration of LY354740 on baseline (postcapture) plasma cortisol and MHPG levels in comparison to the identical measure in untreated controls were assessed. Subjects chronically treated with LY354740 received yohimbine infusions which were compared to yohimbine infusions and saline infusions in non-LY354740-treated subjects. Preliminary evidence supports the view that acute LY354740 infusion resulted in a marked diminution of yohimbine-induced stress response, as manifest by a substantial attenuation of cortisol and MHPG response observed in comparison to the saline-treated yohimbine condition. Chronic oral administration of LY354740 led to postcapture baseline cortisol levels which were markedly reduced (approximately 50 percent) in comparison to untreated control subjects; however, there were no significant parallel differences in MHPG levels. Yohimbine infusions elicited an increase in cortisol and MHPG levels in both LY354740-treated and non-LY354740-treated subjects, in comparison to declines in cortisol values observed following vehicle infusions (group X time interaction; P<.0001). Chronic LY354740-treated subjects failed to achieve cortisol levels comparable in range to those of untreated subjects primarily because of their low baseline cortisol levels. In contrast, despite equivalent baselines, yohimbine-induced MHPG values were increased overall in the chronically treated group compared to the saline and yohimbine-alone groups. Thus, LY354740 markedly reduced the acute corticoid and noradrenergic response elicited by yohimbine infusion. Chronic administration of LY354740 appears to present a safe and effective mechanism to markedly down-modulate the HPA axis while retaining noradrenergic responsivity.     

A longitudinal study of psychosocial distress in breast cancer: prevalence and risk factors

This longitudinal study was conducted among 102 women with non-metastasic breast cancer to identify the time evolution and prevalence of distress at specific times through diagnosis and treatment of disease: preliminary diagnosis, surgery, definitive diagnosis and chemotherapy. Additionally, the study aimed to examine the role of demographic, medical and psychosocial factors on distress. The results indicated that prevalence of distress was higher at initial diagnosis (25%) than the following time points (approximately 17%). The differences inter-individuals in the levels of distress were observed over the four assessments. No relation between distress and demographic and medical factors was found. However, psychosocial aspects were significant risk factors. Patterns of emotional suppression and specific coping responses like helplessness/hopelessness, anxious preoccupation, cognitive avoidance and fatalism were positively related to distress, whereas fighting spirit and perceived social support showed a protective role. Moreover, helplessness/hopelessness and anxious preoccupation jointly predicted 75% of cases and 98% non-cases of distress. Finally, a mediational model between emotional suppression and distress through helplessness/hopelessness was tested. Results support the necessity of routine distress screening all through the illness. Implications of data for psychosocial interventions with breast cancer patients are highlighted.     

Trait empathy as a predictor of individual differences in perceived loneliness

Loneliness has been shown to be inversely correlated with empathy in younger adults. The present study extends previous research by investigating the association between empathy and loneliness across the adult lifespan and examining the role of relevant demographic and personality factors. 110 community-dwelling adults (18 to 81 years old) completed the UCLA Loneliness Scale and the Empathy Quotient. Empathy scores were inversely associated with rated loneliness and predicted 8.7% of variance in loneliness scores after accounting for sex, age, relationship status, education, and neuroticism. The Social Skills factor of the Empathy Quotient was the strongest predictor of the association between perceived empathy and loneliness. Previous research is extended by the finding that rated loneliness was inversely associated with empathy scores across the adult lifespan. Underlying this relationship may be negative perceptions of personal social proclivity as a function of difficulty in understanding the mental states of others and high trait neuroticism.     

Cerebellum and processing of negative facial emotions: cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness

Some evidence suggests that the cerebellum participates in the complex network processing emotional facial expression. To evaluate the role of the cerebellum in recognising facial expressions we delivered transcranial direct current stimulation (tDCS) over the cerebellum and prefrontal cortex. A facial emotion recognition task was administered to 21 healthy subjects before and after cerebellar tDCS; we also tested subjects with a visual attention task and a visual analogue scale (VAS) for mood. Anodal and cathodal cerebellar tDCS both significantly enhanced sensory processing in response to negative facial expressions (anodal tDCS, p=.0021; cathodal tDCS, p=.018), but left positive emotion and neutral facial expressions unchanged (p>.05). tDCS over the right prefrontal cortex left facial expressions of both negative and positive emotion unchanged. These findings suggest that the cerebellum is specifically involved in processing facial expressions of negative emotion.     

Insights into spared memory capacity in amnestic MCI and Alzheimer's Disease via minimal interference

Impairment on standard tests of delayed recall is often already maximal in the aMCI stage of Alzheimer's Disease. Neuropathological work shows that the neural substrates of memory function continue to deteriorate throughout the progression of the disease, hinting that further changes in memory performance could be tracked by a more sensitive test of delayed recall. Recent work shows that retention in aMCI patients can be raised well above floor when the delay period is devoid of further material - 'Minimal Interference'. This memory enhancement is thought to be the result of improved memory consolidation. Here we used the minimal interference/interference paradigm (word list retention following 10 min of quiet resting vs. picture naming) in a group of 17 AD patients, 25 aMCI patients and 25 controls. We found (1) that retention can be improved significantly by minimal interference in patients with aMCI and patients with mild to moderate AD; (2) that the minimal interference paradigm is sensitive to decline in memory function with disease severity, even when performance on standard tests has reached floor; and (3) that this paradigm can differentiate well (80% sensitivity and 100% specificity) between aMCI patients who progress and do not progress to AD within 2 years. Our findings support the notion that the early memory dysfunction in AD is associated with an increased susceptibility to memory interference and are suggestive of a gradual decline in consolidation capacity with disease progression.     

Grouping by achromatic color and surface segregation

The study explored the achromatic-color determinants of grouping of uniform surfaces. The stimuli were a set of separate uniform achromatic disks on either a uniform or a bipartite achromatic background. The participants rated the salience of grouping of these disks for different combinations of stimulus luminances. The results show that achromatic color similarity alone could not sufficiently explain the pattern of obtained factorial curves but this factor coupled with the factor of surface segregation could. Luminance contrast similarity per se was found to be unimportant for grouping.     

From aesthetics to ethics: Testing the link between an emotional experience of awe and the motive of quixoteism on (un)ethical behavior

Motivation and Emotion - According to the awe-quixoteism hypothesis, one experience of awe may lead to the engagement in challenging actions aimed at increasing the welfare of the world. However,...     

Inference and coherence in causal-based artifact categorization

In four experiments, we tested conditions under which artifact concepts support inference and coherence in causal categorization. In all four experiments, participants categorized scenarios in which we systematically varied information about artifacts’ associated design history, physical structure, user intention, user action and functional outcome, and where each property could be specified as intact, compromised or not observed. Consistently across experiments, when participants received complete information (i.e., when all properties were observed), they categorized based on individual properties and did not show evidence of using coherence to categorize. In contrast, when the state of some property was not observed, participants gave evidence of using available information to infer the state of the unobserved property, which increased the value of the available information for categorization. Our data offers answers to longstanding questions regarding artifact categorization, such as whether there are underlying causal models for artifacts, which properties are part of them, whether design history is an artifact’s causal essence, and whether physical appearance or functional outcome is the most central artifact property.     

Proactive Personality at Work: Seeing More to Do and Doing More?

Purpose

The purpose of this study was to develop and test a model relating proactive personality to job behaviors (task and citizenship behaviors) through the intervening mediator of perceived role breadth.

Design/methodology/approach

Survey data were obtained from 530 faculty members in 69 U. S. research universities.

Findings

Proactive personality was positively related to task behavior and OCB. Perceived role breadth mediated the relationship between proactive personality and OCB, but did not mediate the relationship between proactive personality and task behavior. Despite not viewing their role more broadly, individuals higher in proactive personality engaged more frequently in both task behavior and OCB; and also worked more hours per week.

Implications

Having a better understanding of proactive individuals is important in terms of managing them. Because these individuals tend to do more in their jobs and subsequently work more hours, they may be more susceptible to burnout and may require additional help in determining priorities and balancing their work and lives.

Originality/value

This is the first study to show that proactive personality is positively related to the frequency with which these individuals engage in task and citizenship behavior. Although role breadth is generally an antecedent of such job behaviors, individuals higher in proactive personality engage more frequently in task behaviors regardless of whether or not they perceive them as part of their role. This is one of the first studies to show that working more hours each week is a potential cost of having a proactive personality.