Rationale Pharmacological agents used in the treatment of anxiety have been reported to decrease threat relevant processing in patients and healthy controls, suggesting a potentially relevant mechanism of action. However, the effects of the anxiolytic diazepam have typically been examined at sedative doses, which do not allow the direct actions on emotional processing to be fully separated from global effects of the drug on cognition and alertness.Objectives The aim of this study was to investigate the effect of a lower, but still clinically effective, dose of diazepam on emotional processing in healthy volunteers.Materials and methods Twenty-four participants were randomised to receive a single dose of diazepam (5 mg) or placebo. Sixty minutes later, participants completed a battery of psychological tests, including measures of non-emotional cognitive performance (reaction time and sustained attention) and emotional processing (affective modulation of the startle reflex, attentional dot probe, facial expression recognition, and emotional memory). Mood and subjective experience were also measured.Results Diazepam significantly modulated attentional vigilance to masked emotional faces and significantly decreased overall startle reactivity. Diazepam did not significantly affect mood, alertness, response times, facial expression recognition, or sustained attention.Conclusions At non-sedating doses, diazepam produces effects on attentional vigilance and startle responsivity that are consistent with its anxiolytic action. This may be an underlying mechanism through which benzodiazepines exert their therapeutic effects in clinical anxiety.

Objectives. Patients with aortic aneurysms have significant comorbidities which influence outcome. Our practice includes comprehensive assessment to identify comorbidities, allowing subsequent medical optimisation prior to aneurysm repair. The aim of this study was to assess this process and to identify any factors predictive of outcome.Design. Prospective observational study.Materials. Medical case notes of 200 patients referred with aortic pathology.Methods. Data analysed included preoperative, perioperative and postoperative factors. Multiple logistic regression analysis was performed to identify predictors of outcome.Results. Following assessment 17 patients (8.5%) were found to be unfit for intervention and 165 patients (82.5%) proceeded to aneurysm repair. In this group assessment uncovered previously undiagnosed cardiac, respiratory and renal comorbidity in 19%, 57% and 29% of patients respectively. Multiple logistic regression analysis indicated that optimisation by a renal physician reduced post-operative renal impairment (OR 0.12, 95% CI 0.03-0.45, P = 0.002) while optimisation by a cardiologist reduced respiratory complications (OR 0.7, 95% CI 0.05-0.99, P = 0.049). An abnormal echocardiogram was associated with pneumonia (OR 6.9, 95% CI 1.6-29, P = 0.01) and death (OR 7.9, 95% Cl 1.15-54, P = 0.036).Conclusion. Pre-operative assessment identifies previously undiagnosed comorbidity in a significant proportion of patients. Subsequent medical optimisation may reduce post-operative morbidity and mortality.

Increased resting-state functional connectivity (rsFC) between the default mode network (DMN) and subgenual anterior cingulate cortex (sgACC) is consistently reported in adults and youth with psychopathologies related to affect dysregulation (e.g. depression, posttraumatic stress disorder). This pattern of increased rsFC is thought to underlie ruminative thought patterns through integration of negative affect (via sgACC) into self-referential operations supported by the DMN. Neurobiological studies in adults show that behavioral activation system (BAS) sensitivity is a potential protective factor against the development of psychopathology, particularly in the context of stress and trauma exposure. However, whether BAS sensitivity is associated with variation in DMN-sgACC stress-vulnerability circuitry in youth, particularly those at risk for affect dysregulation, has not yet been studied. This association was tested in a sample of ninety-eight children and adolescents (ages 6–17) at high sociodemographic risk for psychopathology (i.e., urban, lower income, high frequency of violence and abuse exposure). Participants underwent a six-minute resting-state functional magnetic resonance imaging scan. Using a targeted, small-volume corrected approach, we found that youth with higher BAS sensitivity demonstrated lower DMN-sgACC rsFC, suggesting a potential link between the purported protective effects of BAS sensitivity and stress-vulnerability circuitry. This work suggests that interventions that augment BAS sensitivity, such as behavioral activation therapy, may protect against the development of stress-related psychopathology by modifying a critical rumination circuitry in the brain. Such interventions may be especially important for bolstering resiliency in at-risk urban youth, who are disproportionately burdened by early stress and associated psychopathology.