Adaptive learning from outcome contingencies in eating-disorder risk groups.

Eating disorders are characterised by altered eating patterns alongside overvaluation of body weight or shape, and have relatively low rates of successful treatment and recovery. Notably, cognitive inflexibility has been implicated in both the development and maintenance of eating disorders, and understanding the reasons for this inflexibility might indicate avenues for treatment development. We therefore investigate one potential cause of this inflexibility: an inability to adjust learning when outcome contingencies change.

Neurochemical abnormalities in chronic fatigue syndrome: a pilot magnetic resonance spectroscopy study at 7 Tesla.

Rationale: Chronic fatigue syndrome (CFS) is a common and burdensome illness with a poorly understood pathophysiology, though many of the characteristic symptoms are likely to be of brain origin. The use of high-field proton magnetic resonance spectroscopy (MRS) enables the detection of a range of brain neurochemicals relevant to aetiological processes that have been linked to CFS, for example, oxidative stress and mitochondrial dysfunction.

Methods: We studied 22 CFS patients and 13 healthy controls who underwent MRS scanning at 7 T with a voxel placed in the anterior cingulate cortex.

Pharmacotherapies for sleep disturbances in dementia.

Background: Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia, and are associated with significant carer distress, increased healthcare costs, and institutionalisation. Although non-drug interventions are recommended as the first-line approach to managing these problems, drug treatment is often sought and used. However, there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this clinically vulnerable population.

A phase 2a randomised, double-blind, placebo-controlled, parallel-group, add-on clinical trial of ebselen (SPI-1005) as a novel treatment for mania or hypomania.

Rationale: Lithium is an effective prophylactic and anti-manic treatment in bipolar disorder; however, its use is declining through perceived poor tolerance and toxicity. Lithium inhibits inositol monophosphatase (IMPase), a probable key therapeutic mechanism. The anti-inflammatory drug, ebselen, also inhibits IMPase and appears well-tolerated and safe.

Melatonin In Acute Mania Investigation (MIAMI-UK). A randomized controlled trial of add-on melatonin in bipolar disorder.

Objectives: Current options for treating emergent episodes of hypomania and mania in bipolar disorder are limited. Our objective was to compare the effectiveness and safety of add-on melatonin in hypomania or mania over 3 weeks as a well-tolerated therapy.

Methods: A randomized, double-blind, parallel-group, 3-week comparison of modified release melatonin (n = 21) vs placebo (n = 20) in adult bipolar patients aged 18-65 years.

British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders: An update.

This British Association for Psychopharmacology guideline replaces the original version published in 2010, and contains updated information and recommendations. A consensus meeting was held in London in October 2017 attended by recognised experts and advocates in the field. They were asked to provide a review of the literature and identification of the standard of evidence in their area, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice.

Salivary glutathione in bipolar disorder: A pilot study.

Background: Glutathione (GSH) is an important cellular antioxidant and its levels are decreased in some studies of bipolar patients. Saliva provides a simple and feasible means of measuring GSH but has not yet been applied to the study of bipolar disorder. The purpose of the study was to compare salivary levels of GSH and oxidized glutathione (GSSG) in bipolar patients and healthy controls.

Brain glutamate in medication-free depressed patients: a proton MRS study at 7 Tesla.

Background: The possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.

Actigraphic features of bipolar disorder: A systematic review and meta-analysis.

Sleep disruptions represent a core feature of bipolar disorders and have been widely studied through the use of actigraphy, which is an objective measure of motor activity and sleep. Finding objective outcomes, which reliably measure sleep in bipolar disorders, is essential in developing better therapies and improving follow-up monitoring strategies. Our aim is to understand the role of actigraphy as an objective measure of sleep in bipolar disorder.

Brain glutamate in anorexia nervosa: a magnetic resonance spectroscopy case control study at 7 Tesla.

Rationale: Anorexia nervosa (AN) is a serious psychiatric disorder with high morbidity and mortality. There are no established pharmacological treatments and the neurobiology of the condition is poorly understood. Previous studies using magnetic resonance spectroscopy (MRS) have shown that AN may be associated with reductions in indices of brain glutamate; however, at conventional field strengths (≤3 T), it is difficult to separate glutamate from its precursor and metabolite, glutamine.

Pharmacotherapies for sleep disturbances in dementia.

Background: Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia, and are associated with significant caregiver distress, increased healthcare costs, and institutionalisation. Drug treatment is often sought to alleviate these problems, but there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this vulnerable population.

Objectives: To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with dementia, through identification and analysis of all relevant randomised controlled trials (RCTs).

Effects of typhoid vaccine on inflammation and sleep in healthy participants: a double-blind, placebo-controlled, crossover study.

Rationale: An increasing body of evidence links the occurrence of sleep continuity disturbances with increased inflammation and both sleep disturbances and inflammation are associated with clinical depression. Typhoid vaccination results in a mild inflammatory response that significantly increases levels of the proinflammatory cytokine, interleukin (IL)-6.

Objectives: The present exploratory study aimed to enhance our understanding of the link between inflammation, sleep and depression by examining the effects of typhoid vaccine on the sleep polysomnogram.

Effects of the potential lithium-mimetic, ebselen, on brain neurochemistry: a magnetic resonance spectroscopy study at 7 tesla.

Rationale: Lithium is an effective treatment for bipolar disorder, but safety issues complicate its clinical use. The antioxidant drug, ebselen, may be a possible lithium-mimetic based on its ability to inhibit inositol monophosphatase (IMPase), an action which it shares with lithium.

Objectives: Our primary aim was to determine whether ebselen lowered levels of inositol in the human brain.

Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans.

Lithium remains the gold standard in treating bipolar disorder but has unwanted toxicity and side effects. We previously reported that ebselen inhibits inositol monophosphatase (IMPase) and exhibits lithium-like effects in animal models through lowering of inositol. Ebselen has been tested in clinical trials for other disorders, enabling us to determine for the first time the effect of a blood-brain barrier-penetrant IMPase inhibitor on human central nervous system (CNS) function.

Folic acid supplementation for prevention of mood disorders in young people at familial risk: a randomised, double blind, placebo controlled trial.

Background: Clinical mood disorders often become clinically manifest in the later teenage years and early twenties and can be associated with a poor long-term prognosis. The primary prevention of these disorders would therefore have great public health value. Nutritional supplements are a feasible intervention for primary prevention and several epidemiological studies have indicated links between low folate status and depressive symptomatology in the general population.

Pharmacotherapies for sleep disturbances in Alzheimer's disease.

Background: Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering and daytime sleepiness are common clinical problems in dementia due to Alzheimer's disease (AD), and are associated with significant caregiver distress, increased healthcare costs and institutionalisation. Drug treatment is often sought to alleviate these problems, but there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this vulnerable population.

Objectives: To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with Alzheimer's disease through identification and analysis of all relevant randomized controlled trials (RCTs).

An open trial of cognitive therapy for chronic insomnia.

We describe the development of a cognitive therapy intervention for chronic insomnia. The therapy is based on a cognitive model which suggests that the processes that maintain insomnia include: (1) worry and rumination, (2) attentional bias and monitoring for sleep-related threat, (3) unhelpful beliefs about sleep, (4) misperception of sleep and daytime deficits and (5) the use of safety behaviors that maintain unhelpful beliefs. The aim of cognitive therapy for insomnia is to reverse all five maintaining processes during both the night and the day.

Olanzapine increases slow wave sleep and sleep continuity in SSRI-resistant depressed patients.

Objective: The atypical antipsychotic drug olanzapine has been employed as an augmentation treatment in depressed patients unresponsive to treatment with selective serotonin reuptake inhibitors (SSRIs). In healthy subjects, acute olanzapine administration increases sleep continuity and enhances slow wave sleep (SWS). The aim of the present study was to determine if the addition of olanzapine to SSRI treatment in depressed patients produced similar effects on sleep.

Risperidone augmentation decreases rapid eye movement sleep and decreases wake in treatment-resistant depressed patients.

Background: The atypical antipsychotic agent risperidone has beneficial effects on mood in patients with schizophrenia. This study aimed to assess whether risperidone produced typical antidepressant-like effects in the polysomnogram of healthy subjects and in depressed patients unresponsive to antidepressant medication.

Method: We measured the effect of a single dose of risperidone (1 mg) on the polysomnogram of 8 healthy volunteers in a placebo-controlled, double-blind, crossover design.