Examining memory reconsolidation as a mechanism of nitrous oxide's antidepressant action.

There is an ongoing need to identify novel pharmacological agents for the effective treatment of depression. One emerging candidate, which has demonstrated rapid-acting antidepressant effects in treatment-resistant groups, is nitrous oxide (NO)-a gas commonly used for sedation and pain management in clinical settings and with a range of pharmacological effects, including antagonism of NMDA glutamate receptors. A growing body of evidence suggests that subanaesthetic doses of NO (50%) can interfere with the reconsolidation of maladaptive memories in healthy participants and across a range of disorders.

12-month neurological and psychiatric outcomes of semaglutide use for type 2 diabetes: a propensity-score matched cohort study.

Background: While semaglutide, approved for type-2 diabetes mellitus (T2DM), is being investigated as a treatment for brain disorders, concerns over adverse neuropsychiatric events have emerged. More data are therefore needed to assess the effects of semaglutide on brain health. This study provides robust estimates of the risk of neurological and psychiatric outcomes following semaglutide use compared to three other antidiabetic medications.

Direct serotonin release in humans shapes aversive learning and inhibition.

The role of serotonin in human behaviour is informed by approaches which allow in vivo modification of synaptic serotonin. However, characterising the effects of increased serotonin signalling in human models of behaviour is challenging given the limitations of available experimental probes, notably selective serotonin reuptake inhibitors. Here we use a now-accessible approach to directly increase synaptic serotonin in humans (a selective serotonin releasing agent) and examine its influence on domains of behaviour historically considered core functions of serotonin.

Inhibition moderates the effect of attentional bias modification for reducing residual depressive symptoms: A randomized sham-controlled clinical trial.

Objectives: Residual symptoms represent risk factor for relapse. Attention bias modification (ABM) may reduce clinical and sub-clinical depressive symptoms, indicating that is may be of relevance when preventing relapse. Current evidence suggests that executive functions may moderate the outcome of interventions targeting depressive symptoms.

Association between a selective 5-HT receptor agonist and incidence of major depressive disorder: emulated target trial.

Background: The serotonin 4 receptor (5-HTR) is a promising target for the treatment of depression. Highly selective 5-HTR agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established.

Aims: To determine whether prucalopride (a 5-HTR agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system.

Beta and theta oscillations track effort and previous reward in the human basal ganglia and prefrontal cortex during decision making.

Choosing whether to exert effort to obtain rewards is fundamental to human motivated behavior. However, the neural dynamics underlying the evaluation of reward and effort in humans is poorly understood. Here, we report an exploratory investigation into this with chronic intracranial recordings from the prefrontal cortex (PFC) and basal ganglia (BG; subthalamic nuclei and globus pallidus) in people with Parkinson's disease performing a decision-making task with offers that varied in levels of reward and physical effort required.

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo.

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( = 1,384) of medication-free individuals with first-episode and recurrent MDD ( = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( = 699).

Acute neural effects of the mood stabiliser lamotrigine on emotional processing in healthy volunteers: a randomised control trial.

Lamotrigine is an effective mood stabiliser, largely used for the management and prevention of depression in bipolar disorder. The neuropsychological mechanisms by which lamotrigine acts to relieve symptoms as well as its neural effects on emotional processing remain unclear. The primary objective of this current study was to investigate the impact of an acute dose of lamotrigine on the neural response to a well-characterised fMRI task probing implicit emotional processing relevant to negative bias.

Mortality and adverse events associated with statin use in primary care patients with depression: a real-world, population-based cohort study.

Background: New National Institute for Health and Care Excellence (NICE) guidance endorses the prescription of statins in larger population groups for the prevention of cardiovascular and cerebrovascular morbidity and mortality, especially in people with severe mental illness. However, the evidence base for their safety and risk/benefit balance in depression is not established.

Objectives: This study aims to assess the real-world mortality and adverse events of statins in depressive disorders.

Distribution and expression of the aac(6')-Im (aacA16) aminoglycoside resistance gene.

Background: The aac(6')-Im (aacA16) amikacin, netilmicin and tobramycin resistance gene cassette had been circulating globally undetected for many years in a sublineage of Acinetobacter baumannii global clone 2.

Objectives: To identify sources for the aac(6')-Im fragment found in A. baumannii.

Effects of ebselen addition on emotional processing and brain neurochemistry in depressed patients unresponsive to antidepressant medication.

Lithium is an effective augmenting agent for depressed patients with inadequate response to standard antidepressant therapy, but numerous adverse effects limit its use. We previously reported that a lithium-mimetic agent, ebselen, promoted a positive emotional bias-an indicator of potential antidepressant activity in healthy participants. We therefore aimed to investigate the effects of short-term ebselen treatment on emotional processing and brain neurochemistry in depressed patients with inadequate response to standard antidepressants.

Aminoglycoside resistance genes in early members of the Acinetobacter baumannii ST78A (SMAL, Italian clone) reside in an IS26-bounded island in the chromosome.

Background: The Acinetobacter baumannii isolate called SMAL, previously used to determine the structures of capsular polysaccharide and lipooligosaccharide, was recovered in Pavia, Italy in 2002 among the collection of aminoglycoside-resistant isolates designated as SMAL type. This type was later called the Italian clone, then ST78. ST78 isolates are now widely distributed.

IS and the IS family: versatile resistance gene movers and genome reorganizers.

In Gram-negative bacteria, the insertion sequence IS is highly active in disseminating antibiotic resistance genes. IS can recruit a gene or group of genes into the mobile gene pool and support their continued dissemination to new locations by creating pseudo-compound transposons (PCTs) that can be further mobilized by the insertion sequence (IS). IS can also enhance expression of adjacent potential resistance genes.

Beta and theta oscillations track effort and previous reward in human basal ganglia and prefrontal cortex during decision making.

Choosing whether to exert effort to obtain rewards is fundamental to human motivated behavior. However, the neural dynamics underlying the evaluation of reward and effort in humans is poorly understood. Here, we investigate this with chronic intracranial recordings from prefrontal cortex (PFC) and basal ganglia (BG; subthalamic nuclei and globus pallidus) in people with Parkinson's disease performing a decision-making task with offers that varied in levels of reward and physical effort required.

Cognitive Remediation in Bipolar (CRiB2): study protocol for a randomised controlled trial assessing efficacy and mechanisms of cognitive remediation therapy compared to treatment as usual.

Background: A substantial proportion of people with bipolar disorder (BD) experience persistent cognitive difficulties associated with impairments in psychosocial functioning and a poorer disorder course. Emerging evidence suggests that cognitive remediation (CR), a psychological intervention with established efficacy in people with schizophrenia, can also benefit people with BD. Following a proof-of-concept trial showing that CR is feasible and potentially beneficial for people with BD, we are conducting an adequately powered trial in euthymic people with BD to 1) determine whether an individual, therapist-supported, computerised CR can reduce cognitive difficulties and improve functional outcomes; and 2) explore how CR exerts its effects.

Real-world outcomes of concomitant antidepressant and statin use in primary care patients with depression: a population-based cohort study.

Background: Antidepressants are licensed for use in depressive disorders, but non-response and poor adherence to treatment affect a considerable number of patients. Pre-clinical and clinical evidence suggest that statins can augment the effects of antidepressants. However, the acceptability and tolerability of combining statins with antidepressants are unclear, and their add-on efficacy has only been shown in small, short-term clinical trials.

Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial.

Background: Primary adrenal insufficiency (PAI) mortality and morbidity remain unacceptably high, possibly arising as glucocorticoid replacement does not replicate natural physiology. A pulsatile subcutaneous pump can closely replicate cortisol's circadian and ultradian rhythm.

Objectives: To assess the effect of pump therapy on quality of life, mood, functional neuroimaging, behavioural/cognitive responses, sleep and metabolism.

Cognitive predictors of stress-induced mood malleability in depression.

Background & Objectives: Basic attentional control, negative biases in attention and interpretation, and rumination are all cognitive processes associated with depression; however, less is known about their predictive role in depressive mood reactivity and -recovery in response to stress, and their relation to severity of depression.

Design & Methods: We experimentally induced stress based on an autobiographical imagery script in a sample of 92 participants with Major Depressive Disorder with or without comorbid anxiety disorders. We used simple regression analysis for investigating the roles of state- and trait rumination, attentional networks, and attentional and interpretation biases for predicting stress-induced depressive mood reactivity and -recovery, respectively, and whether they in parallel mediated the association between cognitive processes and depression severity.