Role of Endocrine-Disrupting Chemicals in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: A Comprehensive Review

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required.     

High-Fat Diet Aggravates Cerebral Infarct,Hemorrhagic Transformation and Neuroinflammation in a Mouse Stroke Model

Background: Stroke in context of type 2 diabetes (T2D) is associated with a poorer outcome than in non-diabetic conditions. We aimed at creating a new reproducible mouse model of stroke in impaired glucose tolerance conditions induced by high-fat diet. Methods: Adult C57BL6 mice were fed for 2 months with either normal diet (ND) or high-fat diet (HFD). We used a model of Middle Cerebral Artery Occlusion (MCAO) for 90 min. Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT) were used to assess pre-diabetic status. Brain infarct volume, hemorrhagic transformation (HT) as well as systemic and cerebral inflammatory markers were evaluated. Results: HFD was associated with an increased body weight and glycemia following OGTT. The HFD group presented a significant increase in brain infarct volume (38.7 (IQR 30–46.7%) vs. 28.45 (IQR 21–30%); p = 0.016) and HT (HFD: 2 (IQR 1–5) vs. ND: 0 (IQR 0–1); p = 0.012) and higher levels of IL-6 and MCP-1 in infarcted hemisphere compared to the ND group. Conclusion: Two months of HFD in adult mice were sufficient to alter the lipid profile and the control of hyperglycemia. These metabolic perturbations were significantly associated with increased infarct volume and hemorrhagic complications.     

Functional Dysregulations in CA1 Hippocampal Networks of a 3-Hit Mouse Model of Schizophrenia

For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABA_A receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis.     

Context-Processing Deficits in Schizotypal Personality Disorder.

Research suggests that schizotypal personality disorder (SPD) is a part of the spectrum of schizophrenia-related illnesses. This article hypothesizes that a deficit in the representation and maintenance of context is a core cognitive disturbance in schizophrenia and that SPD individuals should demonstrate context-processing deficits. To test this hypothesis, the authors administered 3 versions of their AX-CPT task, designed to assess context processing, to 35 healthy controls and 26 individuals with DSM-IV SPD. They also administered working memory and selective attention tasks. SPD individuals displayed context representation deficits similar to those found in schizophrenia but did not show the same additional deficits in context maintenance. Context processing was strongly associated with working memory and selective attention performance in the SPD individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exceptions that prove the rule--Using a theory of motivated social cognition to account for ideological incongruities and political anomalies: Reply to Greenberg and Jonas (2003).

A meta-analysis by J. T. Jost, J. Glaser, A. W. Kruglanski, and F. J. Sulloway (2003) concluded that political conservatism is partially motivated by the management of uncertainty and threat. In this reply to J. Greenberg and E. Jonas (2003), conceptual issues are clarified, numerous political anomalies are explained, and alleged counterexamples are incorporated with a dynamic model that takes into account differences between "young" and "old" movements. Studies directly pitting the rigidity-of-the-right hypothesis against the ideological extremity hypothesis demonstrate strong support for the former. Medium to large effect sizes describe relations between political conservatism and dogmatism and intolerance of ambiguity; lack of openness to experience; uncertainty avoidance; personal needs for order, structure, and closure; fear of death; and system threat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Understanding the role of impulsivity and externalizing psychopathology in alcohol abuse: Application of the UPPS Impulsive Behavior Scale.

The present study explores the relation among 4 personality traits associated with impulsive behavior and alcohol abuse. Personality traits were measured using the 4 subscales of the UPPS Impulsive Behavior Scale (UPPS: S. P. Whiteside & D. R. Lynam. 2001). The UPPS and measures of psychopathology were administered to clinical samples of alcohol abusers high in antisocial personality traits (AAPD), alcohol abusers low in antisocial personality traits (AA), and a control group (total N = 60). Separate analyses of variance indicated that AAPDs had significant elevations on all 4 UPPS scales, whereas the AAs and controls differed only on the Urgency subscale. However, when controlling for psychopathology, group differences on the UPPS scales disappeared. The results suggest that personality traits related to impulsive behavior are not directly related to alcohol abuse but rather are associated with the elevated levels of psychopathology found in a subtype of alcohol abusers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contracting, prompting, and reinforcing substance use disorder continuing care: A randomized clinical trial.

Although continuing care is strongly related to positive treatment outcomes for substance use disorder (SUD), participation rates are low and few effective interventions are available. In a randomized clinical trial with 150 participants (97% men), 75 graduates of a residential Veterans Affairs Medical Center SUD program who received an aftercare contract, attendance prompts, and reinforcers (CPR) were compared to 75 graduates who received standard treatment (STX). Among CPR participants, 55% completed at least 3 months of aftercare, compared to 36% in STX. Similarly, CPR participants remained in treatment longer than those in STX (5.5 vs. 4.4 months). Additionally, CPR participants were more likely to be abstinent compared to STX (57% vs. 37%) after 1 year. The CPR intervention offers a practical means to improve adherence among individuals in SUD treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Grand theories of personality cannot be integrated.

Comments on the original article "A New Big Five: Fundamental Principles for an Integrative Science of Personality," by Dan P. McAdams and Jennifer L. Pals (see record 2006-03947-002). McAdams and Pals (April 2006) presented a new model to integrate the field of personality psychology. Cultural and evolutionary factors interact with an individual's basic traits, characteristic adaptations, and life narratives, which in turn are linked to roles, demands, and behaviors. The current authors welcome McAdams and Pals's (2006) model for providing a way to integrate much of the previously disparate empirical findings in personality psychology. However, the current authors also think that McAdams and Pals (2006) overstated the inclusiveness of the model, and more generally, the current authors dispute their assertion that the grand theories of personality can be integrated within a single model. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttraumatic stress in children and adolescents exposed to family violence: I. Overview and issues.

Exposure to child physical abuse and parents' domestic violence can subject youth to pervasive traumatic stress and can lead to posttraumatic stress disorder (PTSD). This article presents evolving conceptualizations in the burgeoning field of trauma related to family violence exposure and describes how the often repeating and ongoing nature of family violence exposure can complicate a PTSD diagnosis. In addition, recent literature indicates that children exposed to family violence may experience problems in multiple domains of functioning and may meet criteria for multiple disorders in addition to PTSD. Considerations salient to the recognition of traumatic stress in this population and that inform assessment and treatment planning are presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Personality and the predisposition to engage in risky or problem behaviors during adolescence.

Longitudinal data from a representative sample of 1,978 Black and White adolescents were used to examine the role of personality in multiple risk or problem behaviors. Results indicate that covariation among diverse behaviors (educational underachievement, delinquent behavior, substance use, sexual behavior) can be adequately modeled by a single higher order factor, and that impulsivity and avoidance coping serve as generalized risk factors for involvement in these behaviors. Whereas none of the personality variables examined explained change in problem behaviors once established, avoidance coping prospectively predicted involvement among a subgroup of adolescents with little or no prior involvement. Results suggest that dysfunctional styles of regulating emotions and emotionally driven behaviors are core features of risky or problem behaviors during adolescence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)