Neuroactive steroids in depression and anxiety disorders: Clinical studies

Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3 alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3 alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment, we studied the impact of nonpharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation, nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder, changes in neuroactive steroid composition have been observed opposite to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3 alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(A) receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds. Copyright (c) 2006 S. Karger AG, Basel

Prospect and barrier of 3D concrete: a systematic review

This paper aims to explore the current state of the art and potential of 3D concrete printing and its use in large-scale applications. The study analysed 373 academic research, all of which were obtained from the Scopus database. The review conducted on some crucial issues on development of 3D concrete that included materials and their desirable properties, printer nozzle developments, reinforcement in printing, geopolymers as printing materials, and the use of coarse graded aggregates. This study provides researchers and institutions with an in-depth insight into 3D concrete printing and research trends worldwide and assesses the future of 3D concrete printing in large-scale applications. The requirement of more research on the mechanics of 3D printers, standardising a printer nozzle, the automation of reinforcing processes, and use of coarse graded aggregate for large-scale structural application were identified in this review. It also shows how 3D concrete printing has evolved and changed over time and gives an insight into the future of 3D concrete printing—making this scientometric review a framework for future studies

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

A comprehensive approach to reablement in dementia

This is the final version of the article. Available from Elsevier via the DOI in this record.© 2017 The Authors As society grapples with an aging population and increasing prevalence of disability, “reablement” as a means of maximizing functional ability in older people is emerging as a potential strategy to help promote independence. Reablement offers an approach to mitigate the impact of dementia on function and independence. This article presents a comprehensive reablement approach across seven domains for the person living with mild-to-moderate dementia. Domains include assessment and medical management, cognitive disability, physical function, acute injury or illness, assistive technology, supportive care, and caregiver support. In the absence of a cure or ability to significantly modify the course of the disease, the message for policy makers, practitioners, families, and persons with dementia needs to be “living well with dementia”, with a focus on maintaining function for as long as possible, regaining lost function when there is the potential to do so, and adapting to lost function that cannot be regained. Service delivery and care of persons with dementia must be reoriented such that evidence-based reablement approaches are integrated into routine care across all sectors.Authors of this article were supported by the International Federation on Ageing and DaneAge to attend the Global Think Tank on Ageing in Copenhagen, Denmark, in late 2015

Fronto-striatal dysfunction during decision-making in Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder

Background The aim of the current paper was to provide the first comparison of computational mechanisms and neurofunctional substrates in adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) and adolescents with Obsessive-Compulsive Disorder (OCD) during decision-making under ambiguity. Methods Sixteen boys with ADHD, 20 boys with OCD and 20 matched controls (aged 12-18) completed a functional magnetic resonance imaging (fMRI) version of the Iowa gambling task. Brain activation was compared between groups using three-way ANCOVA. Hierarchical Bayesian analysis was used to compare computational modelling parameters between groups. Results Patient groups shared reduced choice consistency and relied less on reinforcement learning during decision-making relative to controls, while adolescents with ADHD alone demonstrated increased reward sensitivity. During advantageous choices, both disorders shared underactivation in ventral striatum, while OCD patients showed disorder-specific underactivation in ventromedial orbitofrontal cortex (vmOFC). During outcome evaluation, shared underactivation to losses in patients relative to controls was found in medial prefrontal cortex (MPFC) and shared underactivation to wins was found in left putamen/caudate. ADHD boys showed disorder-specific dysfunction in right putamen/caudate, which was activated more to losses in patients with ADHD, but activated more to wins in controls. Conclusions The findings suggest shared deficits in using learned reward expectancies to guide decision-making, as well as shared dysfunction in medial-fronto-striato-limbic brain regions. However, findings of unique dysfunction in vmOFC in OCD and in right putamen in ADHD indicate additional, disorder-specific abnormalities, and extend similar findings from inhibitory control tasks in the disorders to the domain of decision-making under ambiguity

Ten research priorities related to youth sport, physical activity and health

Background: Sport has been identified as one of the 7 best investments for increasing physical activity levels across the life span. Several questions remain on how to effectively utilize youth sport as a strategy for increasing physical activity and improving health in youth. The purpose of this paper is to identify the main research priorities in the areas of youth sport and physical activity for health. Methods: An international expert panel was convened, selected to cover a wide spectrum of topics related to youth sport. The group developed a draft set of potential research priorities, and relevant research was scoped. Through an iterative process, the group reached consensus on the top 10 research priorities. Results: The 10 research priorities were identified related to sport participation rates, physical activity from sport, the contribution of sport to health, and the overall return on investment from youth sport. For each research priority, the current evidence is summarized, key research gaps are noted, and immediate research needs are suggested. Conclusion: The identified research priorities are intended to guide researchers, policymakers, and practitioners to increase the evidence base on which to base the design, delivery, and policies of youth sport programs to deliver health benefits

Adolescents, Adults and Rewards: Comparing Motivational Neurocircuitry Recruitment Using fMRI

Background: Adolescent risk-taking, including behaviors resulting in injury or death, has been attributed in part to maturational differences in mesolimbic incentive-motivational neurocircuitry, including ostensible oversensitivity of the nucleus accumbens (NAcc) to rewards. Methodology/Principal Findings: To test whether adolescents showed increased NAcc activation by cues for rewards, or by delivery of rewards, we scanned 24 adolescents (age 12–17) and 24 adults age (22–42) with functional magnetic resonance imaging while they performed a monetary incentive delay (MID) task. The MID task was configured to temporally disentangle potential reward or potential loss anticipation-related brain signal from reward or loss notification-related signal. Subjects saw cues signaling opportunities to win or avoid losing $0,$.50, or $5 for responding quickly to a subsequent target. Subjects then viewed feedback of their trial success after a variable interval from cue presentation of between 6 to17 s. Adolescents showed reduced NAcc recruitment by reward-predictive cues compared to adult controls in a linear contrast with non-incentive cues, and in a volume-of-interest analysis of signal change in the NAcc. In contrast, adolescents showed little difference in striatal and frontocortical responsiveness to reward deliveries compared to adults. Conclusions/Significance: In light of divergent developmental difference findings between neuroimaging incentive paradigms (as well as at different stages within the same task), these data suggest that maturational differences i

Severity of Depression, Anxious Distress and the Risk of Cardiovascular Disease in a Swedish Population-Based Cohort.

Background: Depression is known to be associated with cardiovascular diseases (CVD). This population-based cohort study aimed to determine the association between depression of varying severity and risk for CVD and to study the effect of concomitant anxious distress on this association. Methods: We utilized data from a longitudinal cohort study of mental health, work and relations among adults (20–64 years), with a total of 10,443 individuals. Depression and anxious distress were assessed using psychiatric rating scales and defined according to DSM-5. Outcomes were register-based and self-reported cardiovascular diseases. Findings: Overall increased odds ratios of 1.5 to 2.6 were seen for the different severity levels of depression, with the highest adjusted OR for moderate depression (OR 2.1 (95% CI 1.3, 3.5). Similar odds ratios were seen for sub-groups of CVD: ischemic/hypertensive heart disease and stroke, 2.4 (95% CI 1.4, 3.9) and OR 2.1 (95%CI 1.2, 3.8) respectively. Depression with anxious distress as a specifier of severity showed OR of 2.1 (95% CI 1.5, 2.9) for CVD. Conclusion: This study found that severity level of depression seems to be of significance for increased risk of CVD among depressed persons, although not in a dose-response manner which might be obscured due to treatment of depression. Further, we found a higher risk of CVD among depressed individuals with symptoms of anxious distress

Chronic Activation of Corticotropin-Releasing Factor Type 2 Receptors Reveals a Key Role for 5-HT1A Receptor Responsiveness in Mediating Behavioral and Serotonergic Responses to Stressful Challenge

BackgroundThe corticotropin-releasing factor type 2 receptor (CRFR2) is suggested to play an important role in aiding recovery from acute stress, but any chronic effects of CRFR2 activation are unknown. CRFR2 in the midbrain raphé nuclei modulate serotonergic activity of this key source of serotonin (5-HT) forebrain innervation.MethodsTransgenic mice overexpressing the highly specific CRFR2 ligand urocortin 3 (UCN3OE) were analyzed for stress-related behaviors and hypothalamic-pituitary-adrenal axis responses. Responses to 5-HT receptor agonist challenge were assessed by local cerebral glucose utilization, while 5-HT and 5-hydroxyindoleacetic acid content were quantified in limbic brain regions.ResultsMice overexpressing urocortin 3 exhibited increased stress-related behaviors under basal conditions and impaired retention of spatial memory compared with control mice. Following acute stress, unlike control mice, they exhibited no further increase in these stress-related behaviors and showed an attenuated adrenocorticotropic hormone response. 5-HT and 5-hydroxyindoleacetic acid content of limbic nuclei were differentially regulated by stress in UCN3OE mice as compared with control mice. Responses to 5-HT type 1A receptor challenge were significantly and specifically reduced in UCN3OE mice. The distribution pattern of local cerebral glucose utilization and 5-HT type 1A receptor messenger RNA expression levels suggested this effect was mediated in the raphé nuclei.ConclusionsChronic activation of CRFR2 promotes an anxiety-like state, yet with attenuated behavioral and hypothalamic-pituitary-adrenal axis responses to stress. This is reminiscent of stress-related atypical psychiatric syndromes such as posttraumatic stress disorder, chronic fatigue, and chronic pain states. This new understanding indicates CRFR2 antagonism as a potential novel therapeutic target for such disorders