Update on the role of antipsychotics in the treatment of Tourette syndrome

Tourette syndrome (TS) is a neuropsychiatric disorder with typical onset in childhood and characterized by chronic occurrence of motor and vocal tics. The disorder can lead to serious impairments of both quality of life and psychosocial functioning, particularly for those individuals displaying complex tics. In such patients, drug treatment is recommended. The pathophysiology of TS is thought to involve a dysfunction of basal ganglia-related circuits and hyperactive dopaminergic innervations. Congruently, dopamine receptor antagonism of neuroleptics appears to be the most efficacious approach for pharmacological intervention. To assess the efficacy of the different neuroleptics available, a systematic, keyword-related search in PubMed (National Library of Medicine, Washington, DC) was undertaken. Much information on the use of antipsychotics in the treatment of TS is based on older data. Our objective was to give an update and therefore we focused on papers published in the last decade (between 2001 and 2011). Accordingly, the present review aims to summarize the current and evidence-based knowledge on the risk-benefit ratio of both first and second generation neuroleptics in TS

Introducing yesterday's phage therapy in today's medicine

The worldwide emergence of 'superbugs' and a dry antibiotic pipeline threaten modern society with a return to the preantibiotic era. Phages - the viruses of bacteria - could help fight antibiotic-resistant bacteria. Phage therapy was first attempted in 1919 by Felix d'Herelle and was commercially developed in the 1930s before being replaced by antibiotics in most of the western world. The current antibiotic crisis fueled a worldwide renaissance of phage therapy. The inherent potential of phages as natural biological bacterium controllers can only be put to use if the potential of the coevolutionary aspect of the couplet phage-bacterium is fully acknowledged and understood, including potential negative consequences. We must learn from past mistakes and set up credible studies to gather the urgently required data with regard to the efficacy of phage therapy and the evolutionary consequences of its (unlimited) use, Unfortunately, our current pharmaceutical economic model, implying costly and time-consuming medicinal product development and marketing, and requiring strong intellectual property protection, is not compatible with traditional sustainable phage therapy. A specific framework with realistic production and documentation requirements, which allows a timely (rapid) supply of safe, tailor-made, natural bacteriophages to patients, should be developed. Ultimately, economic models should be radically reshaped to cater for more sustainable approaches such as phage therapy. This is one of the biggest challenges faced by modern medicine and society as a whole

Pavlovian-to-Instrumental Transfer in Alcohol Dependence: A Pilot Study

This publication is with permission of the rights owner freely accessible due to an alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. Methods: Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.Peer Reviewe

Model-Based and Model-Free Decisions in Alcohol Dependence

This publication is with permission of the rights owner freely accessible due to an alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Background: Human and animal work suggests a shift from goal-directed to habitual decision-making in addiction. However, the evidence for this in human alcohol dependence is as yet inconclusive. Methods: Twenty-six healthy controls and 26 recently detoxified alcohol-dependent patients underwent behavioral testing with a 2-step task designed to disentangle goal-directed and habitual response patterns. Results: Alcohol-dependent patients showed less evidence of goal-directed choices than healthy controls, particularly after losses. There was no difference in the strength of the habitual component. The group differences did not survive controlling for performance on the Digit Symbol Substitution Task. Conclusion: Chronic alcohol use appears to selectively impair goal-directed function, rather than promoting habitual responding. It appears to do so particularly after nonrewards, and this may be mediated by the effects of alcohol on more general cognitive functions subserved by the prefrontal cortex.Peer Reviewe

Patient Preferences for Multiple Myeloma Treatments : A Multinational Qualitative Study

Background: Investigational and marketed drugs for the treatment of multiple myeloma (MM) are associated with a range of characteristics and uncertainties regarding long term side-effects and efficacy. This raises questions about what matters most to patients living with this disease. This study aimed to understand which characteristics MM patients find most important, and hence should be included as attributes and levels in a subsequent quantitative preference survey among MM patients. Methods: This qualitative study involved: (i) a scoping literature review, (ii) discussions with MM patients (n = 24) in Belgium, Finland, Romania, and Spain using Nominal Group Technique, (iii) a qualitative thematic analysis including multi-stakeholder discussions. Results: MM patients voiced significant expectations and hopes that treatments would extend their lives and reduce their cancer signs and symptoms. Participants however raised concerns about life-threatening side-effects that could cause permanent organ damage. Bone fractures and debilitating neuropathic effects (such as chronic tingling sensations) were highlighted as major issues reducing patients' independence and mobility. Patients discussed the negative impact of the following symptoms and side-effects on their daily activities: thinking problems, increased susceptibility to infections, reduced energy, pain, emotional problems, and vision problems. MM patients were concerned with uncertainties regarding the durability of positive treatment outcomes, and the cause, severity, and duration of their symptoms and side-effects. Patients feared short-term positive treatment responses complicated by permanent, severe side-effects and symptoms. Conclusions: This study gained an in-depth understanding of the treatment and disease-related characteristics and types of attribute levels (severity, duration) that are most important to MM patients. Results from this study argue in favor of MM drug development and individual treatment decision-making that focuses not only on extending patients' lives but also on addressing those symptoms and side-effects that significantly impact MM patients' quality of life. This study underscores a need for transparent communication toward MM patients about MM treatment outcomes and uncertainties regarding their long-term efficacy and safety. Finally, this study may help drug developers and decision-makers understand which treatment outcomes and uncertainties are most important to MM patients and therefore should be incorporated in MM drug development, evaluation, and clinical practice.Peer reviewe

Taking Bacteriophage Therapy Seriously:A Moral Argument

The excessive and improper use of antibiotics has led to an increasing incidence of bacterial resistance. In Europe the yearly number of infections caused by multidrug resistant bacteria is more than 400.000, each year resulting in 25.000 attributable deaths. Few new antibiotics are in the pipeline of the pharmaceutical industry. Early in the 20th century, bacteriophages were described as entities that can control bacterial populations. Although bacteriophage therapy was developed and practiced in Europe and the former Soviet republics, the use of bacteriophages in clinical setting was neglected in Western Europe since the introduction of traditional antibiotics. Given the worldwide antibiotic crisis there is now a growing interest in making bacteriophage therapy available for use in modern western medicine. Despite the growing interest, access to bacteriophage therapy remains highly problematic. In this paper, we argue that the current state of affairs is morally unacceptable and that all stakeholders (pharmaceutical industry, competent authorities, lawmakers, regulators, and politicians) have the moral duty and the shared responsibility towards making bacteriophage therapy urgently available for all patients in need

Processing speed enhances model-based over model-free reinforcement learning in the presence of high working memory functioning

Theories of decision-making and its neural substrates have long assumed the existence of two distinct and competing valuation systems, variously described as goal-directed versus habitual, or, more recently and based on statistical arguments, as model-free versus model-based reinforcement-learning. Though both have been shown to control choices, the cognitive abilities associated with these systems are under ongoing investigation. Here we examine the link to cognitive abilities, and find that individual differences in processing speed covary with a shift from model-free to model-based choice control in the presence of above-average working memory function. This suggests shared cognitive and neural processes; provides a bridge between literatures on intelligence and valuation; and may guide the development of process models of different valuation components. Furthermore, it provides a rationale for individual differences in the tendency to deploy valuation systems, which may be important for understanding the manifold neuropsychiatric diseases associated with malfunctions of valuation

Illusions of control without delusions of grandeur

We frequently experience feelings of agency over events we do not objectively influence – so-called ‘illusions of control’. These illusions have prompted widespread claims that we can be insensitive to objective relationships between actions and outcomes, and instead rely on grandiose beliefs about our abilities. However, these illusory biases could instead arise if we are highly sensitive to action-outcome correlations, but attribute agency when such correlations emerge simply by chance. We motion-tracked participants while they made agency judgements about a cursor that could be yoked to their actions or follow an independent trajectory. A combination of signal detection analysis, reverse correlation methods and computational modelling indeed demonstrated that ‘illusions’ of control could emerge solely from sensitivity to spurious action-outcome correlations. Counterintuitively, this suggests that illusions of control could arise because agents have excellent insight into the relationships between actions and outcomes in a world where causal relationships are not perfectly deterministic