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Introduction: Abnormal cortisol suppression in borderline personality disorder has been consistently reported in previous studies, suggesting that a hypersensitivity response of the hypothalamic-pituitary-adrenal (HPA) axis might occur in these patients. In this study, the abnormalities of the cortisol response in borderline personality disorder (BPD) are investigated through the cellular expression of the glucocorticoid receptors (GR) in BPD patients and its relationship with traumatic experiences. Methodology: Sixty-nine male and female patients diagnosed with BPD and 62 healthy controls were studied. Peripheral blood mononuclear cells were obtained to investigate the expression of glucocorticoid receptors. Western blot was used to measure protein expression. Statistical correlations of GR expression with BPD clinical features and intensity of previous traumatic events were investigated. Results: A significant decrease in the nuclear expression of glucocorticoid receptors was found in BPD patients compared to healthy controls in a regression analysis controlling for the eect of medication. GR expression decrease correlated significantly with clinical levels of anxiety and depression, but not with previous traumatic experiences in patients. Conclusions: BPD patients had a lower nuclear expression of glucocorticoid receptors than healthy controls, when it was controlled for the eect of medication. The reduced GR expression in BPD patients was not associated with previous traumatic events and might be associated with other aspects of BPD, such as emotional instability; more studies with larger samples of patients are still needed to understand the relevance and the implications of these findings. [ABSTRACT FROM AUTHOR]

Background The mechanism(s) underlying the effects of l-carnitine (β-hydroxy-γ- N-trimethylammonium-butyrate; LC) in cardiovascular diseases are not well clarified. Previous studies have demonstrated that oxidative stress and inflammation contribute to arterial hypertension, and antioxidant and/or anti-inflammatory therapies have been proposed. We hypothesized that LC might attenuate the hypertensive status through an inhibition of inflammation process. Methods Heart mRNA expression and plasma levels of inflammatory markers, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were measured in rats that were made hypertensive with Nω-nitro-l-arginine methyl ester (l-NAME) and subjected to a simultaneous administration of LC. To clarify the role of the renin-angiotensin system (RAS) in this effect of LC, the activity and expression of angiotensin I-converting enzyme (ACE) as well as the expression of angiotensin II type I receptor (AT1R) in the heart were also determined. Results LC produced a significant, but not complete, reduction of blood pressure in l-NAME-treated rats. Plasma levels and heart expression of IL-1β, IL-6, and TNF-α showed an increase in the L-NAME group, which was reversed by LC treatment. The plasma ACE activity was not modified between normotensive and hypertensive rats although LC treatment produced a reduction of these values in the latter. Finally, protein and mRNA expression of ACE and AT1R was enhanced in the heart of l-NAME-treated animals, and LC reversed these values. Conclusions The chronic administration of LC reduces blood pressure and attenuates the inflammatory process associated with arterial hypertension. LC might produce a partial inactivation in the RAS resulting in a reduction in the production and effects of angiotensin II. [ABSTRACT FROM AUTHOR]

Background: Anxiety disorders are among the most common psychiatric illnesses, with generalized anxiety disorder (GAD) being one of the most common. Sleep disturbances are highly prevalent in GAD patients. While treatment with pregabalin has been found to be associated with significant improvement in GAD-related sleep disturbance across many controlled clinical trials, mediational analysis has suggested that a substantial portion of this effect could be the result of a direct effect of pregabalin. Thus, the objective of this study was to model the longitudinal latent effect of pregabalin or usual care (UC) therapies on changes in sleep in outpatients with GAD under routine clinical practice., Methods: Male and female GAD outpatients, aged 18 years or above, from a 6-month prospective noninterventional trial were analyzed. Direct and indirect effects of either pregabalin or UC changes in anxiety symptoms (assessed with Hamilton Anxiety Scale) and sleep disturbances (assessed with Medical Outcomes Study-Sleep Scale [MOS-S]) were estimated by a conditional latent curve model applying structural equation modeling., Results: A total of 1,546 pregabalin-naïve patients were analyzed, 984 receiving pregabalin and 562 UC. Both symptoms of anxiety and sleep disturbances were significantly improved in both groups, with higher mean (95% confidence interval) score reductions in subjects receiving pregabalin: -15.9 (-15.2; -16.6) vs -14.5 (-13.5; -15.5), P=0.027, in Hamilton Anxiety Scale; and -29.7 (-28.1; -31.3) vs -24.0 (-21.6; -26.4), P<0.001, in MOS-S. The conditional latent curve model showed that the pregabalin effect on sleep disturbances was significant (γ =-3.99, P<0.001), after discounting the effect on reduction in anxiety symptoms. A mediation model showed that 70% of the direct effect of pregabalin on sleep remained after discounting the mediated effect of anxiety improvement., Conclusion: A substantial proportion of the incremental improvements in anxiety-related sleep disturbances with pregabalin vs UC were explained by its direct effect, not mediated by improvements in anxiety symptoms.

Background: Generalized anxiety disorder (GAD) is a prevalent health condition which seriously affects both patient quality of life and the National Health System. The aim of this research was to carry out a post hoc cost-effectiveness analysis of the effect of pregabalin versus selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) in treated benzodiazepine-refractory outpatients with GAD., Methods: This post hoc cost-effectiveness analysis used secondary data extracted from the 6-month cohort, prospective, noninterventional ADAN study, which was conducted to ascertain the cost of illness in GAD subjects diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Benzodiazepine-refractory subjects were those who claimed persistent symptoms of anxiety and showed a suboptimal response (Hamilton Anxiety Rating Scale ≥ 16) to benzodiazepines, alone or in combination, over 6 months. Patients could switch to pregabalin (as monotherapy or addon) or to an SSRI or SNRI, alone or in combination. Effectiveness was expressed as quality-adjusted life years gained, and the perspective was that of the National Health System in the year 2008. A sensitivity analysis was performed using bootstrapping techniques (10,000 resamples were obtained) in order to obtain a cost-effectiveness plane and a corresponding acceptability curve., Results: A total of 282 subjects (mean Hamilton Anxiety Rating Scale score 25.8) were identified, comprising 157 in a pregabalin group and 125 in an SSRI/SNRI group. Compared with SSRI/SNRI, pregabalin (average dose 163 mg/day) was associated with higher quality-adjusted life years gained (0.1086 ± 0.0953 versus 0.0967 ± 0.1003, P = 0.334), but increased health care costs (€1014 ± 762 versus €846 ± 620, P = 0.166) and drug costs (€376 ± 252 versus 220 ± 140, P < 0.001), resulting in an incremental cost-effectiveness ratio of €25,304 (95% confidence interval dominant 149,430) per quality-adjusted life years gained for health care costs and €25,454 (dominant 124,562) when drug costs were considered alone. Eighty-six percent of resamples fell below the threshold of €30,000 per quality-adjusted life years., Conclusion: This evaluation suggests that pregabalin may be cost-effective in comparison with SSRIs/SNRIs in benzodiazepine-refractory outpatients with GAD treated in mental health care settings under usual medical practice in Spain.