An overview of psychological and neurobiological mechanisms by which early negative experiences increase risk of mood disorders

Objective: Early life experiences are associated with severe and long-lasting effects on behavioural and emotional functioning, which in turn are thought to increase the risk for unipolar depression and other disorders of affect regulation. The neurobiological and psychological mechanisms through which adverse early life experiences confer risk are poorly understood. Method: Alterations in brain structure and function in limbic and prefrontal cortical regions have been linked to early negative experiences and to mood disorders. Results: There are a number of psychological domains that may be dysfunctional in people with mood disorders, and which, if the dysfunction occurs prior to onset of mood symptoms, may signify a risk factor for depression. Cognitive dysfunction has been examined in patients with mood disorders, with some suggestion that changes in cognitive function may antedate the onset of mood symptoms, and may be exacerbated in those who experienced early negative trauma. Social cognition, including emotion comprehension, theory of mind and empathy, represent under-studied domains of psychological function that may be negatively influenced by early adverse experience. Temperament and personality factors may also leave people vulnerable to mood instability. Conclusion: This review summarizes the evidence for dysfunction in each of these domains for people with mood disorders.

α-Tocopherol supplementation does not affect monocyte endothelial adhesion or C-reactive protein levels but reduces soluble vascular adhesion molecule-1 in the plasma of healthy subjects

Vascular monocyte retention in the subintima is pivotal to the development of cardiovascular disease and is facilitated by up-regulation of adhesion molecules on monocytes/endothelial cells during oxidative stress. Epidemiological studies have shown that cardiovascular disease risk is inversely proportional to plasma levels of the dietary micronutrients, vitamin C and vitamin E (α-tocopherol). We have tested the hypothesis that α-tocopherol supplementation may alter endothelial/monocyte function and interaction in subjects with normal ascorbate levels (> 50 μM), as ascorbate has been shown to regenerate tocopherol from its oxidised tocopheroxyl radical form in vitro. Healthy male subjects received α-tocopherol supplements (400 IU RRR-α-tocopherol /day for 6 weeks) in a placebo-controlled, double-blind intervention study. There were no significant differences in monocyte CD11b expression, monocyte adhesion to endothelial cells, plasma C-reactive protein or sICAM- 1 concentrations post-supplementation. There was no evidence for nuclear translocation of NF-κB in isolated resting monocytes, nor any effect of α-tocopherol supplementation. However, post-supplementation, sVCAM-1 levels were decreased in all subjects and sE-selectin levels were increased in the vitamin C-replete group only; a weak positive correlation was observed between sE-selectin and α-tocopherol concentration. In conclusion, α-tocopherol supplementation had little effect on cardiovascular disease risk factors in healthy subjects and the effects of tocopherol were not consistently affected by plasma vitamin C concentration. © W. S. Maney & Son Ltd.

The variant rpoS allele of S. enteritidis strain 27655R does not affect virulence in a chick model nor constitutive curliation but does generate a cold-sensitive phenotype

Adherence of pathogenic Escherichia coli and Salmonella spp. to host cells is in part mediated by curli fimbriae which, along with other virulence determinants, are positively regulated by RpoS. Interested in the role and regulation of curli (SEF17) fimbriae of Salmonella enteritidis in poultry infection, we tested the virulence of naturally occurring S. enteritidis PT4 strains 27655R and 27655S which displayed constitutive and null expression of curli (SEF17) fimbriae, respectively, in a chick invasion assay and analysed their rpoS alleles. Both strains were shown to be equally invasive and as invasive as a wild-type phage type 4 strain and an isogenic derivative defective for the elaboration of curli. We showed that the rpoS allele of 27655S was intact even though this strain was non-curliated and we confirmed that a S. enteritidis rpoS::strr null mutant was unable to express curli, as anticipated. Strain 27655R, constitutively curliated, possessed a frameshift mutation at position 697 of the rpoS coding sequence which resulted in a truncated product and remained curliated even when transduced to rpoS::strr. Additionally, rpoS mutants are known to be cold-sensitive, a phenotype confirmed for strain 27655R. Collectively, these data indicated that curliation was not a significant factor for pathogenesis of S. enteritidis in this model and that curliation of strains 27655R and 27655S was independent of RpoS. Significantly, strain 27655R possessed a defective rpoS allele and remained virulent. Here was evidence that supported the concept that different naturally occurring rpoS alleles may generate varying virulence phenotypic traits.

Relational diversity, social integration and individual effectiveness: a social self-regulation perspective

Relational demographers and dissimilarity researchers contend that group members who are dissimilar (vs. similar) to their peers in terms of a given diversity attribute (e.g. demographics, attitudes, values or traits) feel less attached to their work group, experience less satisfying and more conflicted relationships with their colleagues, and consequently are less effective. However, qualitative reviews suggest empirical findings tend to be weak and inconsistent (Chattopadhyay, Tluchowska and George, 2004; Riordan, 2000; Tsui and Gutek, 1999), and that it remains unclear when, how and to what extent such differences (i.e. relational diversity) affect group members social integration (i.e. attachment with their work group, satisfaction and conflicted relationships with their peers) and effectiveness (Riordan, 2000). This absence of meta-analytically derived effect size estimates and the lack of an integrative theoretical framework leave practitioners with inconclusive advice regarding whether the effects elicited by relational diversity are practically relevant, and if so how these should be managed. The current research develops an integrative theoretical framework, which it tests by using meta-analysis techniques and adding two further empirical studies to the literature. The first study reports a meta-analytic integration of the results of 129 tests of the relationship between relational diversity with social integration and individual effectiveness. Using meta-analytic and structural equation modelling techniques, it shows different effects of surface- and deep-level relational diversity on social integration Specifically, low levels of interdependence accentuated the negative effects of surface-level relational diversity on social integration, while high levels of interdependence accentuated the negative effects of deep-level relational diversity on social integration. The second study builds on a social self-regulation framework (Abrams, 1994) and suggests that under high levels of interdependence relational diversity is not one but two things: visibility and separation. Using ethnicity as a prominent example it was proposed that separation has a negative effect on group members effectiveness leading for those high in visibility and low in separation to overall positive additive effects, while to overall negative additive effects for those low in visibility and high in separation. These propositions were sustained in a sample of 621 business students working in 135 ethnically diverse work groups in a business simulation course over a period of 24 weeks. The third study suggests visibility has a positive effect on group members self-monitoring, while separation has a negative effect. The study proposed that high levels of visibility and low levels of separation lead to overall positive additive effects on self-monitoring but overall negative additive effects for those low in visibility and high in separation. Results from four waves of data on 261 business students working in 69 ethnically diverse work groups in a business simulation course held over a period of 24 weeks support these propositions.

Environmental regulation induced foreign direct investment

The last decade has witnessed a renewed interest in the relationship between environmental regulations and international capital flows. However, empirical studies have so far failed to find conclusive evidence for this so-called pollution haven or race to the bottom effect where foreign direct investment (FDI) is assumed to be attracted to low regulation countries, regions or states. In this paper we present a simple theoretical framework to demonstrate that greater stringency in environmental standards can lead to a strategic increase in capital inflows which we refer to as environmental regulation induced FDI. Our result reveals a possible explanation for the mixed results in the empirical literature and provides an illustration of the conditions under which environmental regulations in the host country can affect the location decision of foreign firms.

The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives

Background - The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala-prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action. Method - We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls. Results - Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls. Conclusions - Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity. © 2010 Cambridge University Press.

Credit rating agency regulation after the UK's EU membership referendum

Assesses the implications of the UK's decision to withdraw from the EU for the regulation of its credit rating industry. Discusses the current rules of the Credit Rating Agencies Regulations 2010. Considers how the likelihood that a "post-Brexit" UK will be increasingly dependent on its financial services sector might affect the approach taken towards its regulation.