The role of dysregulated ghrelin/LEAP-2 balance in anorexia nervosa.

LEAP-2 is a ghrelin antagonist with an anorexigenic drive. This study investigates the evolution of plasma ghrelin and LEAP-2 concentrations in 29 patients with anorexia nervosa (AN) before and after refeeding and compares it to physiological adaptations during fasting in healthy controls or to mouse model of chronic food restriction and refeeding. Acute and chronic food restriction decrease LEAP-2 and increase ghrelin concentrations in both humans and mice, while patients with AN displayed higher ghrelin and LEAP-2 concentrations before than after refeeding (p = 0.043). After 6 months follow-up, patients with unstable weight gain (n = 17) had significantly decreased LEAP-2 concentrations after refeeding (p = 0.044), in contrast to patients with stable weight gain (n = 12). We provide evidence that the ghrelin/LEAP-2 system is not regulated according to the nutritional status in AN, in contrast to what is physiologically expected when coping with food restriction.

Chronic food restriction in mice and increased systemic ghrelin induce preference for running wheel activity.

OBJECTIVES: In eating disorders, particularly anorexia nervosa (AN), patients exhibit intense physical activity which is inappropriate regarding food restriction and chronic undernutrition, and exacerbates weight loss and energy deprivation. Rodent models of food restriction exhibit increased running wheel activity in the food anticipation period, also known as Food Anticipatory Activity (FAA). FAA probably has various physiological and/or neurobiological origins. Plasma concentrations of the orexigenic hormone ghrelin are, for example, increased during FAA. We hypothesize that the drive for physical activity in chronic food restriction is triggered by metabolic factors but also relies on motivational aspects that we aim to decipher in this study. METHODS: Young female C57Bl6/J mice were exposed to a paradigm based on a progressive 50% quantitative food restriction alone (FR) or associated with running wheel activity (Food Restriction Wheel: FRW) in their home-cage during 15 days. We measured preference for running wheel in a three-chamber apparatus in which animals could choose to explore either a known running wheel or a novel object. Testing took place either during resting or during FAA. We calculated the time spent in each compartment and the activity in running wheels. After progressive refeeding over 10 days, mice were tested again when refed. Plasma levels of both ghrelin isoforms were measured with selective immunoassays. RESULTS: When tested during FAA period, food restricted mice displayed increased preference for the running wheel compared to ad libitum fed controls. Both FR and FRW mice exhibited increased running time and distance in the wheel and running distance was correlated with ghrelin levels. Similar preference and behavior were found when testing took place during the resting period. Animals housed without an active wheel also exhibited active running. Progressive refeeding resulted in body weight restoration, a decrease in FAA and completely abolished preference for the running wheel. Refed animals displayed similar behavior as ad libitum fed controls. CONCLUSIONS: These data provide evidence that food restriction-induced physical activity is closely correlated with metabolic adaptations to nutritional status implicating ghrelin in the quantity of physical activity.

Obsessive-Compulsive Symptoms in Schizophrenia: an Up-To-Date Review of Literature.

PURPOSE OF REVIEW: This review will aim to summarize the current body of epidemiological, clinical and therapeutic knowledge concerning specific co-occurrence of obsessive-compulsive symptoms (OCSs) and schizophrenia spectrum disorder. RECENT FINDINGS: Almost 30% of the patients with schizophrenia display OCS, and three main contexts of emergence are identified: prodromal symptoms of schizophrenia, co-occurrence of OCS and schizophrenia and antipsychotics-induced OCS. Recent clinical studies show that patients with SZ and OCS have more severe psychotic and depressive symptoms, higher suicidality and lower social functioning. A recent cognitive investigation found that OCS and delusions share specific metacognitive profiles, particularly through a heightened need to control thoughts. Finally, a recent cross-sectional study of clozapine-induced OCS found a dose-response relationship between clozapine and OCS. OCS appeared reliably as linked to poorer outcomes among patients with schizophrenia. However, the specific clinical value of OCS among other prodromal symptoms of schizophrenia remains unknown.

[Seclusion and mechanical restraints in psychiatric care: Prescriptions procedures, pharmacological management, and monitoring]. / Isolement et contention mécanique dans les soins psychiatriques : modalités de prescription, prise en charge et surveillance.

We will briefly summarize the French recommendations concerning the use of seclusion and mechanical restraint. Acute agitation and aggression or self-injurious activity during psychotic and manic episodes are the main indication of prescription of the coercive measures. Their prescriptions respect specific modalities that will be explained. Although they proved to be efficient, seclusion and restrain need to stay a last resort option, considering the risk of physical complications and psychological consequences. Specific pharmacological prescription will necessarily be associated with coercive measures and we present prescription guidelines. Finally, physical complications need to be prevented and we submit specific protocol concerning constipation and thromboembolic risk management.

The Place of Antipsychotics in the Therapy of Anxiety Disorders and Obsessive-Compulsive Disorders.

PURPOSE OF REVIEW: The purpose of this review was to assess and present the findings up to this date on the efficacy of antipsychotics in the treatment of generalized anxiety disorders (GAD), social anxiety disorders (SAD), panic disorders (PD), and obsessive-compulsive disorders (OCD), mostly based on published randomized controlled trials (RCTs) or on open-label studies when RCT were lacking. RECENT FINDINGS: Quetiapine could be recommended in patients with GAD. The efficacy of aripiprazole in two open-label studies on patients with antidepressant-refractory GAD should be assessed in RCTs. Despite preliminary positive results in open studies, there are currently no strong evidence for the effectiveness of antipsychotics in refractory SAD and in refractory PD. Conversely, risperidone and aripiprazole can be used for the treatment of refractory OCD as augmentation agents to antidepressants. Contrary to SAD and PD, this review found evidence for the use of second-generation antipsychotics in GAD and OCD. Otherwise, first-generation antipsychotics cannot be recommended in anxiety disorders and OCD.