Amphetamine as a social drug: effects of d-amphetamine on social processing and behavior.

RATIONALE: Drug users often report using drugs to enhance social situations, and empirical studies support the idea that drugs increase both social behavior and the value of social interactions. One way that drugs may affect social behavior is by altering social processing, for example by decreasing perceptions of negative emotion in others. OBJECTIVES: We examined effects of d-amphetamine on processing of emotional facial expressions and on the social behavior of talking. We predicted amphetamine would enhance attention, identification, and responsivity to positive expressions, and that this in turn would predict increased talkativeness. METHODS: Over three sessions, 36 healthy normal adults received placebo, 10, and 20 mg d-amphetamine under counterbalanced double-blind conditions. At each session, we measured processing of happy, fearful, sad, and angry expressions using an attentional visual probe task, a dynamic emotion identification task, and measures of facial muscle activity. We also measured talking. RESULTS: Amphetamine decreased the threshold for identifying all emotions, increased negative facial responses to sad expressions, and increased talkativeness. Contrary to our hypotheses, amphetamine did not alter attention to, identification of, or facial responses to positive emotions specifically. Interestingly, the drug decreased the threshold to identify all emotions, and this effect was uniquely related to increased talkativeness, even after controlling for overall sensitivity to amphetamine. CONCLUSIONS: The results suggest that amphetamine may encourage sociability by increasing sensitivity to subtle emotional expressions. These findings suggest novel social mechanisms that may contribute to the rewarding effects of amphetamine.

Attentional biases in clinical populations with alcohol use disorders: is co-morbidity ignored?

OBJECTIVE: To identify how psychiatric co-morbidity was identified and assessed, in studies of attentional bias in clinical samples of patients with alcohol use disorders (AUDs). DESIGN: Systematic review methodology was used to identify studies and abstract data on alcohol-related attentional biases and measurement of psychiatric co-morbidity. RESULTS: Seventeen papers were identified that met the criteria for inclusion. All but one study were in patients meeting criteria for alcohol dependence. In 10 of the 17 studies, either no mention or minimal statements were made pertaining to possible co-morbid conditions (including other substance use): five excluded patients with psychiatric diagnoses, (variously defined), and two excluded patients on 'psychotropic medication'. Slow response latencies to all word types were found in studies where co-morbid conditions were not considered. CONCLUSIONS: Despite the high prevalence of psychiatric pathology in patients with AUDs (particularly depression), and the acknowledged impact that this has on aetiology, presentation and outcome, psychiatric co-morbidity has not been consistently measured or described in experimental studies on alcohol-related attentional biases in clinical samples. In order to have an accurate appreciation of the role of attentional biases in patients with AUDs, there needs to be a consistent approach to measuring the co-occurrence of other psychopathology. Further research is needed to assess the impact of co-morbidities on attentional biases in AUDs, to enable the development of more targeted psychological and pharmacological treatments.

Rejection sensitivity and disruption of attention by social threat cues.

Two studies tested the hypothesis that Rejection Sensitivity (RS) increases vulnerability to disruption of attention by social threat cues, as would be consistent with prior evidence that it motivates individuals to prioritize detecting and managing potential rejection at a cost to other personal and interpersonal goals. In Study 1, RS predicted disruption of ongoing goal-directed attention by social threat but not negative words in an Emotional Stroop task. In Study 2, RS predicted attentional avoidance of threatening but not pleasant faces in a Visual Probe task. Threat-avoidant attention was also associated with features of borderline personality disorder. This research extends understanding of processes by which RS contributes to a self-perpetuating cycle of interpersonal problems and distress.

Cholesterol binding by the bacterial type III translocon is essential for virulence effector delivery into mammalian cells.

A ubiquitous early step in infection of man and animals by enteric bacterial pathogens like Salmonella, Shigella and enteropathogenic Escherichia coli (EPEC) is the translocation of virulence effector proteins into mammalian cells via specialized type III secretion systems (TTSSs). Translocated effectors subvert the host cytoskeleton and stimulate signalling to promote bacterial internalization or survival. Target cell plasma membrane cholesterol is central to pathogen-host cross-talk, but the precise nature of its critical contribution remains unknown. Using in vitro cholesterol-binding assays, we demonstrate that Salmonella (SipB) and Shigella (IpaB) TTSS translocon components bind cholesterol with high affinity. Direct visualization of cell-associated fluorescently labelled SipB and parallel immunogold transmission electron microscopy revealed that cholesterol levels limit both the amount and distribution of plasma membrane-integrated translocon. Correspondingly, cholesterol depletion blocked effector translocation into cultured mammalian cells by not only the related Salmonella and Shigella TTSSs, but also the more divergent EPEC system. The data reveal that cholesterol-dependent association of the bacterial TTSS translocon with the target cell plasma membrane is essential for translocon activation and effector delivery into mammalian cells.

The Salmonella pathogenicity island 1 secretion system directs cellular cholesterol redistribution during mammalian cell entry and intracellular trafficking.

The bacterial pathogen Salmonella triggers its own uptake into non-phagocytic mammalian cells. Entry is induced by the delivery of bacterial effector pro-teins that subvert signalling and promote cytoskeletal rearrangement, although the molecular mechanisms that co-ordinate initial pathogen-host cell recognition remain poorly characterized. Here we show that cholesterol is essential for Salmonella uptake. Depletion and chelation of plasma membrane cholesterol specifically inhibited bacterial internalization but not adherence. Cholesterol accumulated at bacterial entry sites in cultured cells, and was retained by Salmonella-containing vacuoles following pathogen internalization. Cellular cholesterol redistribution required bacterial effector protein delivery mediated by the Salmonella pathogenicity island (SPI) 1 type III secretion system, but was independent of the SPI2-encoded system.