Increased Belief Instability in Psychotic Disorders Predicts Treatment Response to Metacognitive Training.

BACKGROUND AND HYPOTHESIS: In a complex world, gathering information and adjusting our beliefs about the world is of paramount importance. The literature suggests that patients with psychotic disorders display a tendency to draw early conclusions based on limited evidence, referred to as the jumping-to-conclusions bias, but few studies have examined the computational mechanisms underlying this and related belief-updating biases. Here, we employ a computational approach to understand the relationship between jumping-to-conclusions, psychotic disorders, and delusions. STUDY DESIGN: We modeled probabilistic reasoning of 261 patients with psychotic disorders and 56 healthy controls during an information sampling task-the fish task-with the Hierarchical Gaussian Filter. Subsequently, we examined the clinical utility of this computational approach by testing whether computational parameters, obtained from fitting the model to each individual's behavior, could predict treatment response to Metacognitive Training using machine learning. STUDY RESULTS: We observed differences in probabilistic reasoning between patients with psychotic disorders and healthy controls, participants with and without jumping-to-conclusions bias, but not between patients with low and high current delusions. The computational analysis suggested that belief instability was increased in patients with psychotic disorders. Jumping-to-conclusions was associated with both increased belief instability and greater prior uncertainty. Lastly, belief instability predicted treatment response to Metacognitive Training at the individual level. CONCLUSIONS: Our results point towards increased belief instability as a key computational mechanism underlying probabilistic reasoning in psychotic disorders. We provide a proof-of-concept that this computational approach may be useful to help identify suitable treatments for individual patients with psychotic disorders.

The role of relatives in decisions concerning life-prolonging treatment in patients with end-stage malignant disorders: informants, advocates or surrogate decision-makers?

BACKGROUND: This study examines the extent to which relatives of severely ill cancer patients are involved in the decision to limit treatment (DLT), their role in communicating patient wishes and the incidence of and reasons for disagreement with relatives. PATIENTS AND METHODS: This cohort study followed 70 patients with terminal cancer, for whom a limitation of life-prolonging treatment was being considered. 'Embedded researchers' recorded patients' wishes and the relatives' roles and disagreements with DLT. RESULTS: Although 63 out of 70 patients had relatives present during their care, only 32% of relatives were involved in DLT. Physicians were more likely to know the end-of-life (EOL) preferences for those patients who had visiting relatives than those without them (78% versus 29%, P = 0.014). Most relatives supported patients in voicing their preferences (68%), but one-third acted against the known or presumed wishes of patients (32%). Disagreements with patients' relatives occurred in 21% of cases, and predominantly when relatives held views that contradicted known patient preferences (71% versus 7%, P = 0.001). CONCLUSION: If relatives are to play an important part in EOL decision making, we must devise strategies to recognise their potential as patients' advocates as well as their own needs.

Myocardial bradykinin B2-receptor expression at different time points after induction of myocardial infarction.

OBJECTIVE: To characterize the regulation of the myocardial bradykinin B2 receptor after induction of myocardial infarction (MI), we studied its expression at different time points in the left ventricle (LV), right ventricle (RV) and interventricular septum (S) of the heart. DESIGN: Male Sprague-Dawley rats were submitted to permanent occlusion of the left descending coronary artery. Six hours, 24 h or 6 days after MI induction or a sham operation, a Millar-tip catheter was placed in the LV. Left ventricular pressure (LVP) and contractility [(dP/dt)max] were measured. The LV, RV and S of all animals were isolated, and total RNA was extracted. B2-receptor expression was analysed by an RNase-protection assay. In addition, Western blot analysis was used to determine protein levels of the B2 receptor in the infarcted area of the LV. RESULTS: We observed a decrease in LVP and contractility at all time points after MI in comparison with sham-operated animals. Basal B2-receptor expression was detected in the LV and RV, but not in the S of sham-operated rats. In the LV of infarcted hearts, we found a time-dependent up-regulation of the B2-receptor expression, which was increased twofold and fivefold, respectively, 6 h and 24 h after induction of MI compared with controls. This increase was maintained for at least 6 days. Similarly, we also found an up-regulation of the B2-receptor expression in the RV and S. Both reached a peak 24 h after induction of MI. The protein level of the receptor gradually increased up to day 6. CONCLUSION: We conclude that myocardial ischaemia triggers B2-receptor up-regulation in both the infarcted and non-infarcted areas of the heart.