Cocaine addiction is a chronic disease marked by relapses, co-morbidities and the importance of psychosocial consequences. The etiology of cocaine addiction is complex and involves three types of ...factors: environmental factors, factors linked to the specific effects of cocaine and genetic factors. The latter could explain 40-60% of the risk for developing an addiction. Several studies have looked for a link between cocaine addiction and the genes of the dopaminergic system: the genes DRD2, COMT, SLC6A3 (coding for the dopamine transporter DAT) and DBH (coding for the dopamine beta hydroxylase) but unfortunately very few well established results. Pharmacogenetic approach could be an interesting opportunity for the future. The gene DBH has particularly been linked with the psychotic effects caused by cocaine. This so-called cocaine-induced psychosis (CIP) or cocaine-induced paranoia may influence the development of cocaine addiction. Indeed, these psychotic symptoms during cocaine exposure could cause an aversive effect limiting the development of an addiction. Several functional alterations caused by different mutations of the genes involved in dopaminergic transmission (principally-1021C>T of the gene DBH, but also Val158Met of the gene COMT, TaqI A of the gene DRD2 and VNTR 9 repeat of the DAT) could result in a cocaine-induced psychosis prone phenotype. We are hypothesising that the appearance of CIP during the first contact with cocaine is associated with a lower risk of developing cocaine addiction. This protective effect could be associated with the presence of one or more polymorphisms associated with CIP. A pharmacogenetic approach studying combination of polymorphism could isolate a sub-group of patients at risk for CIPs but more favorably protected from developing an addiction. This theory could enable a better understanding of the protective factors against cocaine addiction and offer new therapeutic or preventive targets in vulnerable sub-groups exposed to cocaine.
Scope
Resistant starches (RSs) are classically considered to elicit health benefits through fermentation. However, it is recently shown that RSs can also support health by direct immune interactions. ...Therefore, it has been hypothesized that the structural traits of RSs might impact the health benefits associated with their consumption.
Methods and results
Effects of crystallinity, molecular weight, and chain length distribution of RSs are determined on immune Toll‐like receptors (TLRs), dendritic cells (DCs), and T‐cell cytokines production. To this end, four type‐3 RSs (RS3) are compared, namely Paselli WFR, JD150, debranched Etenia, and Amylose fraction V, which are extracted from potatoes and enzymatically modified. Dextrose equivalent seems to be the most important feature influencing immune signaling via activation of TLRs. TLR2 and TLR4 are most strongly stimulated. Especially Paselli WFR is a potent activator of multiple receptors. Moreover, the presence of amylose, even to residual levels, enhances DC and T‐cell cytokine responses. Paselli WFR and Amylose fraction V influence T‐cell polarization.
Conclusions
It has been shown here that chain length and particularly dextrose equivalent are critical features for immune activation. This knowledge might lead to tailoring and design of immune‐active RS formulations.
Dietary fibers are crucial components of a healthy diet, and their effects on the immune system depend on their chemical structures. The effects of differences in resistant starch (RS) properties on Toll‐like receptors and on dendritic cells with and without secretory factors from intestinal epithelial cells are tested, and possible effects on T‐cell polarization are evaluated.
Although there is robust evidence linking childhood adversities (CAs) and an increased risk for psychotic experiences (PEs), little is known about whether these associations vary across the ...life-course and whether mental disorders that emerge prior to PEs explain these associations.
We assessed CAs, PEs and DSM-IV mental disorders in 23 998 adults in the WHO World Mental Health Surveys. Discrete-time survival analysis was used to investigate the associations between CAs and PEs, and the influence of mental disorders on these associations using multivariate logistic models.
Exposure to CAs was common, and those who experienced any CAs had increased odds of later PEs odds ratio (OR) 2.3, 95% confidence interval (CI) 1.9-2.6. CAs reflecting maladaptive family functioning (MFF), including abuse, neglect, and parent maladjustment, exhibited the strongest associations with PE onset in all life-course stages. Sexual abuse exhibited a strong association with PE onset during childhood (OR 8.5, 95% CI 3.6-20.2), whereas Other CA types were associated with PE onset in adolescence. Associations of other CAs with PEs disappeared in adolescence after adjustment for prior-onset mental disorders. The population attributable risk proportion (PARP) for PEs associated with all CAs was 31% (24% for MFF).
Exposure to CAs is associated with PE onset throughout the life-course, although sexual abuse is most strongly associated with childhood-onset PEs. The presence of mental disorders prior to the onset of PEs does not fully explain these associations. The large PARPs suggest that preventing CAs could lead to a meaningful reduction in PEs in the population.
The purpose of this study was to determine and compare the test-retest reliability of quadriceps isokinetic endurance testing at two knee angular velocities in patients with chronic obstructive ...pulmonary disease (COPD).
After one familiarization session, 14 patients with moderate to severe COPD (mean age 65±4 years; forced expiratory volume in 1 second (FEV1) 55%±18% predicted) performed two quadriceps isokinetic endurance tests on two separate occasions within a 5-7-day interval. Quadriceps isokinetic endurance tests consisted of 30 maximal knee extensions at angular velocities of 90° and 180° per second, performed in random order. Test-retest reliability was assessed for peak torque, muscle endurance, work slope, work fatigue index, and changes in FEV1 for dyspnea and leg fatigue from rest to the end of the test. The intraclass correlation coefficient, minimal detectable change, and limits of agreement were calculated.
High test-retest reliability was identified for peak torque and muscle total work at both velocities. Work fatigue index was considered reliable at 90° per second but not at 180° per second. A lower reliability was identified for dyspnea and leg fatigue scores at both angular velocities.
Despite a limited sample size, our findings support the use of a 30-maximal repetition isokinetic muscle testing procedure at angular velocities of 90° and 180° per second in patients with moderate to severe COPD. Endurance measurement (total isokinetic work) at 90° per second was highly reliable, with a minimal detectable change at the 95% confidence level of 10%. Peak torque and fatigue index could also be assessed reliably at 90° per second. Evaluation of dyspnea and leg fatigue using the modified Borg scale of perceived exertion was poorly reliable and its clinical usefulness is questionable. These results should be useful in the design and interpretation of future interventions aimed at improving muscle endurance in COPD.
This paper investigates the prevalence of symptoms and various diagnostic criteria of DSM-IV social phobia in a French national representative population of 12,873 subjects, aged 15 or more. ...Respondents filled out a mailed questionnaire based on the social phobia section of the Munich-Composite International Diagnostic Interview (M-CIDI) in the year 1996. Response rate was 80.5%.
Sixty-seven point one percent of the sample acknowledge having at least once in their lifetime a strong fear of one or more of the six prototypical social fear situations that are used as the CIDI social phobia stem items. However, only a few fulfilled all DSM-IV diagnostic criteria for social phobia. Depending on the type of diagnostic algorithms used and the stringency in which these criteria are applied, the resulting prevalence varied between 1.9 and 7.3%. These findings provide some further evidence about the considerable effects of varying diagnostic criteria and thresholds on prevalence rates for social phobia, explaining why most recent surveys have reported considerably higher rates of social phobia than those in the early 1980s.
Abstract Staff members of psychiatric facilities are at high risk of secondhand smoking. Smoking exposure was assessed in 41 nonsmoking employees of a psychiatry department before and after a ban. ...Subjective exposure measures decreased in 76% of the subjects. Salivary cotinine decreased in the subsample of seven subjects with high pre-ban levels (32 ±8 vs 40 ± 17 ng/ml, p = .045).
We explored the psychometric features of the French Temperament and Character Inventory (TCI) in a 602-subject community sample (263 men and 339 women), representative of the French population. The ...factor structures of the temperament and character dimensions, explored separately, were in agreement with the hypothesized constructs, except for the scales Novelty Seeking NS1 (exploratory excitability), Persistence, and Self-Directedness SD4 (self-acceptance). The internal consistency of the main dimensions was good (Cronbach alpha coefficients between 0.68 and 0.82), but weak for Persistence (0.49). The mean scores of the temperament dimensions were notably different from those published in other normative data — especially lower for Novelty Seeking (16.4±5.6) and higher for Harm Avoidance (16.1±7.2) when compared with US data — suggesting cross-cultural differences in personality assessment, and the necessity to use specific normative values with each translated instrument.
This study compared the efficacy and safety of the selective serotonin reuptake inhibitor sertraline with that of the tricyclic antidepressant clomipramine in patients with severe depression, as ...defined by a baseline 17-item Hamilton Depression Rating Scale (HAM-D) of at least 25. The study included 166 outpatients, randomized to double-blind treatment with sertraline (50-200 mg) or clomipramine (50-150 mg) for 8 weeks. The efficacy of both treatments was similar, 74% of patients in the sertraline group and 71% of clomipramine patients being classified as responders at the end-point, as defined by a Clinical Global Impression-Improvement (CGI-I) score of 1 or 2. Mean HAM-D scores fell from 29.8 at baseline to 12.3 at endpoint in the sertraline group, and from 29.6-12.7 in the clomipramine group. There were more withdrawals due to adverse events in the clomipramine group than in the sertraline group (17% versus 12%). Dry mouth, tremor, dizziness and constipation were all substantially more common in the clomipramine group, whereas diarrhoea/loose stools was more common in the sertraline group. Overall, sertraline was as effective as clomipramine in this group of severely depressed outpatients, and showed better tolerability.
On September 18, 2007, a collaborative session between the International Society for CNS Clinical Trials and Methodology and the International Society for CNS Drug Development was held in Brussels, ...Belgium. Both groups, with membership from industry, academia, and governmental and nongovernmental agencies, have been formed to address scientific, clinical, regulatory, and methodological challenges in the development of central nervous system therapeutic agents. The focus of this joint session was the apparent diminution of drug-placebo differences in recent multicenter trials of antipsychotic medications for schizophrenia. To characterize the nature of the problem, some presenters reported data from several recent trials that indicated higher rates of placebo response and lower rates of drug response (even to previously established, comparator drugs), when compared with earlier trials. As a means to identify the possible causes of the problem, discussions covered a range of methodological factors such as participant characteristics, trial designs, site characteristics, clinical setting (inpatient vs outpatient), inclusion/exclusion criteria, and diagnostic specificity. Finally, possible solutions were discussed, such as improving precision of participant selection criteria, improving assessment instruments and/or assessment methodology to increase reliability of outcome measures, innovative methods to encourage greater subject adherence and investigator involvement, improved rater training and accountability metrics at clinical sites to increase quality assurance, and advanced methods of pharmacokinetic/pharmacodynamic modeling to optimize dosing prior to initiating large phase 3 trials. The session closed with a roundtable discussion and recommendations for data sharing to further explore potential causes and viable solutions to be applied in future trials.
Studies of the prevalence of depression and anxiety disorders have shown that there is a high prevalence of comorbidity of these 2 disorders. The resulting disability and burden affect not only the ...individual in terms of decreased productivity, but the level of health care utilization is also increased. The objective of this article is to look at the epidemiology, disability, and global burden of depression and anxiety across the different nations of the world. This article will concentrate on the results from the Cross-National Collaborative Group. The transcultural trends in prevalence and disability presented here must be viewed in the light of the limitations of the study, such as methodology and population sampling, uniformity in the method of clinical assessment, and the collection and processing of data. New studies of depression and anxiety among different cultures are currently in progress in the form of the European Study of Epidemiology on Mental Disorders (ESEMeD), which is closely linked to the World Health Organization (WHO) World Mental Health 2000 initiative. The methodology for ESEMeD is similar to that of the WHO World Mental Health 2000 study, which will facilitate comparisons between the results for Europe and the rest of the world. Results of these studies are awaited with anticipation.
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