...a nocebo response can occur with an inert or noninert substance as a worsening of the diagnosed condition or as treatment-emergent adverse effects. ...when indication-appropriate active treatment ...is administered, the therapeutic effect may be a combination of the pharmacologic activity of the treating agent and a placebo effect, as demonstrated in an experiment of open and hidden analgesic administration using an infusion pump where pain relief was significantly reduced when the patients were unaware that an analgesic was being administered.2 It is also common usage to refer to all improvement in a placebo arm of a randomized clinical trial (RCT) as a placebo response and all worsening and adverse events as a nocebo response, even though fluctuation of symptoms occurs with the natural progression of many illnesses. ...the terms placebo and nocebo are used differently by different authors or even by the same authors when reporting different studies. References 1 F.G. Miller, T.J. Kaptchuk, The power of context: reconceptualizing the placebo effect, J R Soc Med, Vol. 101, 2008, 222-225 2 L. Colloca, L. Lopiano, M. Lanotte, F. Benedetti, Overt versus covert treatment for pain, anxiety, and Parkinson’s disease, Lancet Neurol, Vol. 3, 2004, 679-684 3 K. Weimer, B. Horing,...
•Post-operative cognitive dysfunction (POCD) is an established risk of surgery.•The proposed feed-forward inflammatory process of POCD is well supported.•Perioperative use of COX-II inhibitors and ...dexmedetomidine preserves cognition.•Evidence for other agents is thin and heterogeneous.
Post-Operative Cognitive Dysfunction (POCD) is a highly prevalent condition with significant clinical, social and financial impacts for patients and their communities. The underlying pathophysiology is becoming increasingly understood, with the role of neuroinflammation and oxidative stress secondary to surgery and anaesthesia strongly implicated. This review aims to describe the putative mechanisms by which surgery-induced inflammation produces cognitive sequelae, with a focus on identifying potential novel therapies based upon their ability to modify these pathways.
Schizophrenia risk has often been conceptualized using a model which requires two hits in order to generate the clinical phenotype-the first as an early priming in a genetically predisposed ...individual and the second a likely environmental insult. The aim of this paper was to review the literature and reformulate this binary risk-vulnerability model. We sourced the data for this narrative review from the electronic database PUBMED. Our search terms were not limited by language or date of publication. The development of schizophrenia may be driven by genetic vulnerability interacting with multiple vulnerability factors including lowered prenatal vitamin D exposure, viral infections, smoking intelligence quotient, social cognition cannabis use, social defeat, nutrition and childhood trauma. It is likely that these genetic risks, environmental risks and vulnerability factors are cumulative and interactive with each other and with critical periods of neurodevelopmental vulnerability. The development of schizophrenia is likely to be more complex and nuanced than the binary two hit model originally proposed nearly thirty years ago. Risk appears influenced by a more complex process involving genetic risk interfacing with multiple potentially interacting hits and vulnerability factors occurring at key periods of neurodevelopmental activity, which culminate in the expression of disease state. These risks are common across a number of neuropsychiatric and medical disorders, which might inform common preventive and intervention strategies across non-communicable disorders.
Abstract Purpose Placebos are commonly used in experimental and patient populations and are known to influence treatment outcomes. The mechanism of action of placebos has been investigated by several ...researchers. This review investigates the current knowledge regarding the theoretical and biological underpinning of the nocebo and placebo phenomena. Method Literature was searched using PubMed using the following keywords: nocebo, placebo, μ-opioid, dopamine, conditioning, and expectancy . Relevant papers were selected for review by the authors. Findings The roles of conditioning and expectancy, and characteristics associated with nocebo and placebo responses, are discussed. These factors affect nocebo and placebo responses, although their effect sizes vary greatly, depending on inter-individual differences and different experimental paradigms. The neurobiology of the nocebo and placebo phenomena is also reviewed, emphasizing the involvement of reward pathways, such as the μ-opioid and dopamine pathways. Neurobiological pathways have been investigated in a limited range of experimental paradigms, with the greatest efforts on experimental models of placebo analgesia. The interconnectedness of psychological and physiological drivers of nocebo and placebo responses is a core feature of these phenomena. Implications Further research is needed to fully understand the underpinnings of the nocebo and placebo phenomena. Neurobiology pathways need to be investigated in experimental paradigms that model the placebo response to a broader range of pathologies. Similarly, although many psychological factors and inter-individual characteristics have been identified as significant mediators and moderators of nocebo and placebo responses, the factors identified to date are unlikely to be exhaustive.
Mitochondria are cellular organelles involved in several biological processes, especially in energy production. Several studies have found a relationship between mitochondrial dysfunction and mood ...disorders, such as major depressive disorder and bipolar disorder. Impairments in energy production are found in these disorders together with higher levels of oxidative stress. Recently, many agents capable of enhancing antioxidant defenses or mitochondrial functioning have been studied for the treatment of mood disorders as adjuvant therapy to current pharmacological treatments. A better knowledge of mitochondrial physiology and pathophysiology might allow the identification of new therapeutic targets and the development and study of novel effective therapies to treat these specific mitochondrial impairments. This could be especially beneficial for treatment-resistant patients. In this article, we provide a focused narrative review of the currently available evidence supporting the involvement of mitochondrial dysfunction in mood disorders, the effects of current therapies on mitochondrial functions, and novel targeted therapies acting on mitochondrial pathways that might be useful for the treatment of mood disorders.
A phasic dysregulation of mitochondrial bioenergetics may operate in bipolar disorder, increased in mania and decreased in depression. We aimed to examine efficacy of two add-on treatments in bipolar ...depression: N-acetylcysteine (NAC) and NAC with a combination of nutraceutical agents that may increase mitochondrial biogenesis.
A three-arm 16-week, double-blind, randomised, placebo-controlled trial, adjunctive to usual treatment, was conducted. Participants (n = 181) with bipolar disorder and current depressive symptoms were randomised to 2000 mg/day NAC (n = 59), 2000 mg/day NAC with the combination nutraceutical treatment (CT, n = 61), or placebo (n = 61). The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 16. Young Mania Rating Scale, Clinical Global Impression (CGI)-Improvement and CGI-Severity scales, Patient Global Impression scale, Social and Occupational Functioning Assessment Scale (SOFAS), Longitudinal Interval Follow-Up Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT), and Quality of Life Enjoyment, and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) were secondary outcomes.
One hundred forty-eight participants had post-randomisation data and were analysed (NAC = 52, CT = 47, Placebo = 49). No between-group differences were found for the rate of change between baseline and 16 weeks on any of the clinical and functioning variables. Improvements in MADRS, BDRS, SOFAS, and LIFE-RIFT scores from baseline to the week 20 post-discontinuation visit were significantly greater in the CT group compared to those in the placebo. At week 20, the CGI-I was significantly lower in the CT group versus placebo. Gastrointestinal symptoms were significantly greater in the NAC than in the placebo group.
These overall negative results, with no significant differences between groups detected at the primary outcome but some positive secondary signals, suggest either delayed benefit of the combination or an improvement of symptoms on withdrawal which warrants further exploration regarding the composition, mechanisms, and application of mitochondrial agents in illnesses characterised by mitochondrial dysfunction.
ANZCTR ( ACTRN12612000830897 ).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Atheoretical large-scale data mining techniques using machine learning algorithms have promise in the analysis of large epidemiological datasets. This study illustrates the use of a hybrid ...methodology for variable selection that took account of missing data and complex survey design to identify key biomarkers associated with depression from a large epidemiological study.
The study used a three-step methodology amalgamating multiple imputation, a machine learning boosted regression algorithm and logistic regression, to identify key biomarkers associated with depression in the National Health and Nutrition Examination Study (2009-2010). Depression was measured using the Patient Health Questionnaire-9 and 67 biomarkers were analysed. Covariates in this study included gender, age, race, smoking, food security, Poverty Income Ratio, Body Mass Index, physical activity, alcohol use, medical conditions and medications. The final imputed weighted multiple logistic regression model included possible confounders and moderators.
After the creation of 20 imputation data sets from multiple chained regression sequences, machine learning boosted regression initially identified 21 biomarkers associated with depression. Using traditional logistic regression methods, including controlling for possible confounders and moderators, a final set of three biomarkers were selected. The final three biomarkers from the novel hybrid variable selection methodology were red cell distribution width (OR 1.15; 95% CI 1.01, 1.30), serum glucose (OR 1.01; 95% CI 1.00, 1.01) and total bilirubin (OR 0.12; 95% CI 0.05, 0.28). Significant interactions were found between total bilirubin with Mexican American/Hispanic group (p = 0.016), and current smokers (p<0.001).
The systematic use of a hybrid methodology for variable selection, fusing data mining techniques using a machine learning algorithm with traditional statistical modelling, accounted for missing data and complex survey sampling methodology and was demonstrated to be a useful tool for detecting three biomarkers associated with depression for future hypothesis generation: red cell distribution width, serum glucose and total bilirubin.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epidemiological evidence supports a relationship between vitamin D and mental well-being, although evidence from large-scale placebo-controlled intervention trials is lacking.
To examine if vitamin D ...supplementation has a beneficial effect on mood in community-dwelling older women; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms; and if there is an association between serum 25-hydroxyvitamin D levels and mental health.
A double-blind, randomised, placebo-controlled trial of women aged 70 or older (the Vital D Study: ISRCTN83409867 and ACTR12605000658617). Participants were randomly assigned to receive 500 000 IU vitamin D(3) (cholecalciferol) orally or placebo every autumn/winter for 3-5 consecutive years. The tools utilised at various time points were the General Health Questionnaire, the 12-item Short Form Health Survey, the Patient Global Impression-Improvement scale and the WHO Well-Being Index. Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants.
In this non-clinical population, no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health. Serum 25-hydroxyvitamin D levels in the vitamin D group were 41% higher than the placebo group 12 months following their annual dose. Despite this difference, scores from the questionnaires did not differ. Furthermore, there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups.
The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3) is a practical intervention to prevent depressive symptoms in older community-dwelling women.
Background: Glutathione is an endogenous antioxidant and has a ubiquitous role in many of the body's defences. Treatment with N-acetylcysteine (NAC) has been shown to increase levels of glutathione. ...NAC has been proposed as a treatment for several illnesses. Objectives: The efficacy and tolerability of NAC was examined across a range of conditions to evaluate the evidence supporting the use of NAC for each indication. Methods: A literature search was conducted using PubMed. Information was also collected from other online sources including the websites of the Therapeutic Goods Administration of Australia and the FDA. Results: Reports ranged from case studies to clinical trials. There is strong evidence to support the use of NAC for the treatment of paracetamol overdose and emerging evidence suggesting it has utility in psychiatric disorders, particularly schizophrenia and bipolar disorder. NAC is safe and well tolerated when administered orally but has documented risks with intravenous administration.
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