Responsibility attitude,obsession and compulsion: further support in a non‐clinical sample

Responsibility is one of the most investigated constructs in obsessive‐compulsive disorder (OCD). Although there are an increasing number of studies on this topic, results seem to be questionable. Whereas several authors reported a significant link between OC behaviour and responsibility in nonclinical as well as in clinical samples, the findings of many authors failed to demonstrate the presence of such an association. In the current study, we examined the relationship between obsessive‐compulsive behaviour and responsibility. To this aim, participants filled in five inventories: the Responsibility Attitude Scale (RAS), the Responsibility Questionnaire (RQ), the Padua Inventory Revised (PI‐R), the State‐Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI). Results showed a relationship between obsessive‐compulsive behaviour (PI‐R scores) and responsibility, as measured by both RAS and RQ. A principal component analysis showed that RAS can be interpreted as a four‐factor scale, accounting for 63% of the variance overall. Regression analyses showed that responsibility can be considered a significant predictor of obsession and compulsion behaviour, as measured by PI‐R. Furthermore, showing a connection between specific factors of responsibility and certain kinds of obsessive‐compulsive behaviour, results seem to confirm the hypothesis that responsibility is more salient in checking than in cleaning symptoms. Copyright © 2001 John Wiley & Sons, Ltd.     

Neural mechanisms underlying obesity and drug addiction

Increasing rates of obesity have alarmed health officials and prompted much public dialogue. While the factors leading to obesity are numerous, an inability to control intake of freely available food is central to the problem. In order to understand this, we need to better define the mechanisms by which the brain regulates food intake, and why it is often difficult to control consumption. From this point of view, it seems valuable to consider the commonalities between food intake and drug abuse. While research in the two fields has historically emphasized different neural substrates, recent data have increased interest in better defining elements that may underlie both drug addiction and obesity. Here we discuss some of these shared elements with an emphasis on emerging areas of research that better define common mechanisms leading to overconsumption.     

Serum proteomics of methamphetamine addicts and up-regulation of complement factor H related to methamphetamine addiction

Methamphetamine (METH) is a new type of drug with strong tolerance and addiction. However, the molecular mechanisms underlying the processes of METH addiction are still not fully understood. To determine possible biomarkers and mechanisms that are responsible for METH addiction, a 2-DE based proteomics approach was used to evaluate the changes in protein expression of the serum in Chinese patients addicted to METH, which to the best of our knowledge is the first study of its kind. We identified five proteins that were markedly altered and complement factor H (CFH), the most stably up-expressed protein in each 2-DE experiment, was further studied using the rat conditioned place preference (CPP) model to detect any changes to its expression in the sera and six brain regions of interest. We report, for the first time, that CFH was positive related to METH addiction.     

Assessing clinical trials of Internet addiction treatment: a systematic review and CONSORT evaluation

Although there is ongoing debate concerning the clinical status of Internet addiction, and the quality of the extant literature in this emerging field is not optimal, several clinical trials of both pharmacological and psychological treatments for Internet addiction have been published in recent years. A systematic review investigating the reporting quality of eight treatment studies is presented. Reporting quality was defined according to the 2010 Consolidating Standards of Reporting Trials (CONSORT) statement. An evaluation of the reviewed studies highlighted several key limitations, including (a) inconsistencies in the definition and diagnosis of Internet addiction, (b) a lack of randomization and blinding techniques, (c) a lack of adequate controls or other comparison groups, and (d) insufficient information concerning recruitment dates, sample characteristics, and treatment effect sizes. It is concluded that improvements in future studies' design and reporting would be of significant benefit to both researchers and clinicians, and to the overall positioning of Internet addiction in the behavioral addiction field.     

Drop-out from addiction treatment: A systematic review of risk factors

Completion of addiction treatment is one of the most consistent factors associated with a favorable treatment outcome. Unfortunately, it is more common for a patient to drop-out of addiction treatment than to complete the treatment. To prevent drop-out, risk factors must be identified. This box-score review focuses on studies investigating the risk factors associated with drop-out from addiction treatment published in peer-reviewed journals from 1992 to 2013. A total of 122 studies involving 199,331 participants met the inclusion criteria. Contrary to recommendations from previous reviews, 91% of the included studies focused primarily on enduring patient factors, mainly demographics. The most consistent risk factors across the different study designs, samples, and measurement methods were cognitive deficits, low treatment alliance, personality disorder, and younger age. With the exception of younger age, none of the demographic factors emerged as consistent risk factors. Further research on the relationship between simple demographic factors and drop-out risk is of limited value. However, little is known about the potential risk factors related to treatment programs and to the treatment processes. Based on the review, clinical recommendations include assessing cognitive functioning and personality disorders at baseline and continuous monitoring of treatment alliance.     

Acute alcohol impairs human goal-directed action

There are two forms of motivated behaviour. Goal-directed action is mediated by knowledge of the consequences whereas habitual action is elicited directly by stimuli associated with the action. Alcohol may impair goal-directed control, favouring habit. To evaluate this proposal, participants were administered with 0.4 g/kg of alcohol or placebo before acquiring separate instrumental responses for chocolate and water points. Chocolate was then fed to satiety to devalue this outcome before choice between the two responses was tested in extinction. Any reduction in chocolate choice must be mediated by knowledge of the current incentive value of this outcome, i.e. must be goal-directed. Alcohol attenuated the devaluation effect on choice in extinction, but had no effect on reacquisition performance, the hedonic appraisal of rewards or acquisition of the instrumental contingencies. Acute alcohol impaired goal-directed control of action selection, favouring habit, which may mediate alcohol effects on under-controlled behaviour more broadly.     

Role of orexin/hypocretin in reward-seeking and addiction: Implications for obesity

Orexins (also named hypocretins) are recently discovered neuropeptides made exclusively in the hypothalamus. Recent studies have shown that orexin cells located specifically in lateral hypothalamus (LH) are involved in motivated behavior for drugs of abuse as well as natural rewards. Administration of orexin has been shown to stimulate food consumption, and orexin signaling in VTA has been implicated in intake of high-fat food. In self-administration studies, the orexin 1 receptor antagonist SB-334867 (SB) attenuated operant responding for high-fat pellets, sucrose pellets and ethanol, but not cocaine, demonstrating that signaling at orexin receptors is necessary for reinforcement of specific rewards. The orexin system is also implicated in associations between rewards and relevant stimuli. For example, Fos expression in LH orexin neurons varied in proportion to conditioned place preference (CPP) for food, morphine, or cocaine. This Fos expression was altered accordingly for CPP administered during protracted abstinence from morphine or cocaine, when preference for natural rewards was decreased and drug preference was increased. Additionally, orexin has been shown to be involved in reward-stimulus associations in the self-administration paradigm, where SB attenuated cue-induced reinstatement of extinguished sucrose- or cocaine-seeking. Although the specific circuitry mediating the effects of orexin on food reward remains unknown, VTA seems likely to be a critical target for at least some of these orexin actions. Thus, recent studies have established a role for orexin in reward-based feeding, and further investigation is warranted for determining whether function/dysfunction of the orexin system may contribute to the overeating associated with obesity.The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.     

Neuronal calcium sensor-1 and cocaine addiction: A genetic association study in African-Americans and European Americans

Genes involved in drug reward pathways are plausible candidates for susceptibility to substance use disorders. Given the prominent role of dopamine in drug reward, dopamine receptor-interacting proteins (DRIPs) such as the neuronal calcium sensor-1 (NCS-1) protein have been hypothesized to play a role in the pathophysiology of cocaine addiction (CA). In this study, we investigated whether genetic variants in the NCS-1 gene confer risk to CA. We genotyped 8 SNPs (rs4837479, rs7849345, rs3824544, rs10819611, rs947513, rs2277200, rs7873936 and rs1342043) in our discovery sample (cases n = 796, controls n = 416) of African descent. Confirmation of associated or trending SNPs (rs7849345, rs10819611, rs1342043) was attempted using a replication sample of African American (AA) ethnicity (cases n = 335, controls n = 336) and European-American (EA) ancestry (cases n = 336, controls n = 656). Secondary sex specific analysis was also carried out for each SNP in both AA and EA individuals. Genotyping of the discovery cohort showed significant genotypic (p = 0.0005, corrected q-value) as well as allelic (p = 0.005, corrected q-value) associations of rs1342043 with CA in AAs; however, this marker could not be confirmed in either the AA or EA replication sample. Combined analysis of all AA samples (n = 1883) for rs1342043 showed a significant association with CA (genotypic p = 0.0001, allelic p = 0.002) with a gender specific effect for males (allelic p = 0.005, genotypic p = 0.0003). Our data suggest that genetic variants in the NCS-1 gene contribute to susceptibility of CA in individuals of African descent.     

Intermittent drinking,oxytocin and human health

Looking at a waterhole, it is surprising that so many animals share the same space without visible signs of anxiety or aggression. Although waterholes are the preferred feeding locations of large carnivores, waterholes are shared by all type of herbivores of all sizes and shapes, including elephants. Recent research shows that the homeostatic disturbances leading to the “thirst feeling” not only activate specific substances regulating water and mineral household, but also the “trust and love” hormone oxytocin, while decreasing the production of the typical stress hormone cortisol. People using drugs, seem to be in search for oxytocin, as evidenced in studies with individuals on drugs such as ecstasy and gamma-hydroxybyturate. Hot environment, drought and increased sweating also activate specific oxytocin-producing parts of the hypothalamus, just as breastfeeding does in mother and infant. Water homeostasis is the only allostatic system activating trust neuro-anatomy and we suggest that this is due to the fact that all animals depend on water, whereas food type is species specific. Our hypothesis; regulating drinking behaviour through intermittent bulk drinking could increase oxytocin signalling, recover human trust and increase health by down-regulation of stress axis activity and inflammatory activity of the immune system. Intermittent bulk drinking should be defined as water (including tea and coffee) drinking up to a feeling of satiety and regulated by a mild feeling of thirst. This would mean that people would not drink less quantity but less frequently and that’s how all animals, but also human newborns behave. It is the latter group, which is probably the only group of humans with a normal fluid homeostasis.     

Norovirus immunology: Of mice and mechanisms

Noroviruses (NoVs) are the most common cause of sporadic and epidemic gastroenteritis in the United States and Europe and are responsible for 20% of acute gastroenteritis worldwide. Over the past decade, the understanding of NoV immunology has grown immensely. Studies of the natural immune response to NoV in humans and animal models have laid the foundation for innovations in cell culture systems for NoV and development of new therapeutics. Evidence from animal models, NoV surrogates, observational human research, and human challenge studies suggest that the innate immune response is critical for limiting NoV infection but is insufficient for viral clearance. NoV may antagonize the innate immune response to establish or prolong infection. However, once a robust adaptive immune response is initiated, the immune system clears the infection through the action of T and B cells, simultaneously generating highly specific protective immunologic memory. We review here both the current knowledge on NoV immunity and exciting new developments, with a focus on ongoing vaccine development work, novel cell culture systems, and advances in understanding the role of the gut microbiome. These changes reinforce the need for a better understanding of the human immune response to NoV and suggest novel hypotheses.     

吗啡成瘾戒断对大鼠海马CA1区P-CREB表达的影响

目的探讨吗啡成瘾戒断后大鼠海马CA1区P-CREB的表达变化。方法48只健康雄性成年SD大鼠,随机分为实验组和对照组:实验组腹腔注射吗啡起始剂量5mg/kg,1d2次,逐日递增,连续10d;对照组:以生理盐水代替吗啡。停药后7d、14d和21d处死。用免疫组织化学方法(ABC法)检测海马CA1区P-CREB的表达,图像分析系统测定阳性反应产物的平均灰度值。结果P-CREB表达在7d、14d实验组与对照组相比表达上调(P<0.05),21d与对照组比较无显著差异(P>0.05)。结论海马CA1区CREB磷酸化在吗啡依赖的形成中发挥作用。     

Chronic food restriction: enhancing effects on drug reward and striatal cell signaling

Chronic food restriction (FR) increases behavioral sensitivity to drugs of abuse in animal models and is associated with binge eating, which shares comorbidity with drug abuse, in clinical populations. Behavioral, biochemical and molecular studies conducted in this laboratory to elucidate the functional and mechanistic bases of these phenomena are briefly reviewed. Results obtained to date indicate that FR increases the reward magnitude and locomotor-activating effects of abused drugs, and direct dopamine (DA) receptor agonists, as a result of neuroadaptations rather than changes in drug disposition. Changes in striatal DA dynamics, and postsynaptic cell signaling and gene expression in response to D-1 DA receptor stimulation have been observed. Of particular interest is an upregulation of NMDA receptor-dependent MAP kinase and CaM Kinase II signaling, CREB phosphorylation, and immediate-early and neuropeptide gene expression in nucleus accumbens (NAc) which may facilitate reward-related learning, but also play a role in the genesis of maladaptive goal-directed behaviors. Covariation of altered drug reward sensitivity with body weight loss and recovery suggests a triggering role for one of the endocrine adiposity hormones. However, neither acute nor chronic central infusions of leptin or the melanocortin 3/4 receptor agonist, MTII, have attenuated d-amphetamine reward or locomotor activation in FR rats. Interestingly, chronic intracerebroventricular leptin infusion in ad libitum fed (AL) rats produced a sustained decrease in food intake and body weight that was accompanied by a reversible potentiation of rewarding and locomotor-activating effects of d-amphetamine. This raises the interesting possibility that rapid progressive weight loss is sufficient to increase behavioral sensitivity to drugs of abuse. Whether weight loss produced by leptin infusion produces the same neuroadaptations as experimenter-imposed FR, and whether any of the observed neuroadaptations are necessary for expression of increased behavioral responsiveness to acute drug challenge remain to be investigated.     

Reflex insulin response associated to food intake in human subjects

The occurrence of a reflex insulin discharge at the beginning of a meal, and its possible influence on intake were studied in 7 normal weight humans. Each subject was tested twice under three standard meal conditions. The evolutions of insulinemia and glycemia were recorded over an 84 min observation period, starting 2 min before food presentation. Blood was drawn continuously from an antecubital vein, and collected in 1-min samples for the first 30 min, and then in 3-min samples. The average glycemia curve was stable until some 18-20 min after meal onset. By contrast, a significant rise in plasma insulin appeared as early as the 4th min after meal onset and it is hypothesized to be preabsorptive, of cephalic and/or gastric origin. However, inter-test variations were large even in the same person. Schematically, three types of early insulin responses were observed: high and/or sustained rise, moderate and/or short increase, moderate decrease in plasma insulin. The shape of the early insulin response was not related to any meal characteristic. The potential biological and behavioral significance of the early insulin release is discussed.     

Prevalence of human papillomavirus,human immunodeficiency virus and other sexually transmitted infections among female sex workers in Togo: a national cross-sectional survey

ObjectivesSub-Saharan Africa is a region with high incidence of both human immunodeficiency virus (HIV) and cervical cancer. We conducted the first national study in Togo to assess prevalence of human papillomavirus (HPV), HIV and other sexually transmitted infections (STIs) among female sex workers (FSW).MethodsA multicentric cross-sectional study was conducted among FSW recruited in hot spots (clubs, streets) in four Togolese cities. HPV and STIs were tested from cervical and anal swabs. HIV and syphilis were screened with rapid tests.ResultsIn all, 310 FSW were recruited; HIV and cervical high-risk HPV (hrHPV) prevalence were 10.6% (33/310) and 32.9% (102/310), respectively. The most frequent hrHPV types were HPV58 (13.6%, 19/140), HPV35 (12.9%, 18/140), HPV31 (12.1%, 17/140) and HPV16 (10.7%, 15/140). Prevalence of hrHPV and multiple hrHPV infections showed higher rates in HIV-positive than in HIV-negative FSW (48.5% versus 31.0%, p 0.04 and 21.2% versus 9.0%, p 0.03; respectively). Prevalence of hrHPV was higher in cervical than anal swabs (34.1% versus 20.7%, p 0.0004). High-risk HPV anal infections were more frequent among HIV-positive than HIV-negative FSW (51.9% versus 17.3%, p 2 × 10⁻⁵). Concomitant anal and cervical hrHPV infections were present in 43.2% (41/95) of hrHPV-positive FSW. Overall prevalence in the cervix of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium and Trichomonas vaginalis were 4.2%, 6.1%, 5.5% and 6.5%, respectively.ConclusionsThis first African study on paired cervical and anal samples showed a high prevalence of genital HPV infections with a rather high rate of concomitant HPV infections but low type concordance. We report an unusual distribution of hrHPV types. These findings highlight the critical need for implementation of a national HPV vaccination strategy.