Neural effects of cannabinoid CB1 neutral antagonist tetrahydrocannabivarin (THCv) on food reward and aversion in healthy volunteers

Disturbances in the regulation of reward and aversion in the brain may underlie disorders such as obesity and eating disorders. We previously showed that the cannabis receptor subtype (CB1) inverse agonist rimonabant, an antiobesity drug withdrawn due to depressogenic side effects, diminished neural reward responses yet increased aversive responses (Horder et al., 2010). Unlike rimonabant, tetrahydrocannabivarin is a neutral CB1 receptor antagonist (Pertwee, 2005) and may therefore produce different modulations of the neural reward system. We hypothesized that tetrahydrocannabivarin would, unlike rimonabant, leave intact neural reward responses but augment aversive responses. Methods: We used a within-subject, double-blind design. Twenty healthy volunteers received a single dose of tetrahydrocannabivarin (10mg) and placebo in randomized order on 2 separate occasions. We measured the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (picture of moldy strawberries and/or a less pleasant strawberry taste) using functional magnetic resonance imaging. Volunteers rated pleasantness, intensity, and wanting for each stimulus. Results: There were no significant differences between groups in subjective ratings. However, tetrahydrocannabivarin increased responses to chocolate stimuli in the midbrain, anterior cingulate cortex, caudate, and putamen. Tetrahydrocannabivarin also increased responses to aversive stimuli in the amygdala, insula, mid orbitofrontal cortex, caudate, and putamen. Conclusions: Our findings are the first to show that treatment with the CB1 neutral antagonist tetrahydrocannabivarin increases neural responding to rewarding and aversive stimuli. This effect profile suggests therapeutic activity in obesity, perhaps with a lowered risk of depressive side effects. Keywords: reward, THCv, obesity, fMRI, cannabinoid

Effect of cinnamon on gastric emptying, arterial stiffness, postprandial lipemia, glycemia, and appetite responses to high-fat breakfast

Abstract BACKGROUND: Cinnamon has been shown to delay gastric emptying of a high-carbohydrate meal and reduce postprandial glycemia in healthy adults. However, it is dietary fat which is implicated in the etiology and is associated with obesity, type 2 diabetes and cardiovascular disease. We aimed to determine the effect of 3 g cinnamon (Cinnamomum zeylanicum) on GE, postprandial lipemic and glycemic responses, oxidative stress, arterial stiffness, as well as appetite sensations and subsequent food intake following a high-fat meal. METHODS: A single-blind randomized crossover study assessed nine healthy, young subjects. GE rate of a high-fat meal supplemented with 3 g cinnamon or placebo was determined using the 13C octanoic acid breath test. Breath, blood samples and subjective appetite ratings were collected in the fasted and during the 360 min postprandial period, followed by an ad libitum buffet meal. Gastric emptying and 1-day fatty acid intake relationships were also examined. RESULTS: Cinnamon did not change gastric emptying parameters, postprandial triacylglycerol or glucose concentrations, oxidative stress, arterial function or appetite (p < 0.05). Strong relationships were evident (p < 0.05) between GE Thalf and 1-day palmitoleic acid (r = -0.78), eiconsenoic acid (r = -0.84) and total omega-3 intake (r = -0.72). The ingestion of 3 g cinnamon had no effect on GE, arterial stiffness and oxidative stress following a HF meal. CONCLUSIONS: 3 g cinnamon did not alter the postprandial response to a high-fat test meal. We find no evidence to support the use of 3 g cinnamon supplementation for the prevention or treatment of metabolic disease. Dietary fatty acid intake requires consideration in future gastrointestinal studies.

Does domperidone, a D2-antagonist alter gastric emptying rates and appetite sensations in healthy adults with high-fat meal? A block-randomised, single-blind placebo-controlled study

BACKGROUND: Accelerated gastric emptying (GE) may lead to reduced satiation, increased food intake and is associated with obesity and type 2 diabetes. Domperidone is a dopamine 2 (D(2)) receptor antagonist with claims of gastrointestinal tract pro-kinetic activity. In humans, domperidone is used as an anti-emetic and treatment for gastrointestinal bloating and discomfort. AIM: To determine the effect of acute domperidone administration on GE rate and appetite sensations in healthy adults. METHODS: A single-blind block randomised placebo-controlled crossover study assessed 13 healthy adults. Subjects ingested 10 mg domperidone or placebo 30 min before a high-fat (HF) test meal. GE rate was determined using the (13)CO(2) octanoic acid breath test. Breath samples and subjective appetite ratings were collected in the fasted and during the 360 min postprandial period. RESULTS:Gastric emptying half-time was similar following placebo (254 ± 54 min) and 10 mg domperidone (236 ± 65 min). Domperidone did not change appetite sensations during the 360 min postprandial period (P > 0.05). CONCLUSIONS: In healthy adults, acute administration of 10 mg domperidone did not change GE or appetite sensations following a HF test meal.

Stay calm! Regulating emotional responses by implementation intentions: assessing the impact on physiological and subjective arousal

Implementation intention (IMP) has recently been highlighted as an effective emotion regulatory strategy (Schweiger Gallo et al., 2009). Most studies examining the effectiveness of IMPs to regulate emotion have relied on self-report measures of emotional change. In two studies we employed electrodermal activity (EDA) and heart rate (HR) in addition to arousal ratings (AR) to assess the impact of an IMP on emotional responses. In Study 1, 60 participants viewed neutral and two types of negative pictures (weapon vs. non-weapon) under the IMP “If I see a weapon, then I will stay calm and relaxed!” or no self-regulatory instructions (Control). In Study 2, additionally to the Control and IMP conditions, participants completed the picture task either under goal intention (GI) to stay calm and relaxed or warning instructions highlighting that some pictures contain weapons. In both studies, participants showed lower EDA, reduced HR deceleration and lower AR to the weapon pictures compared to the non-weapon pictures. In Study 2, the IMP was associated with lower EDA compared to the GI condition for the weapon pictures, but not compared to the weapon pictures in the Warning condition. AR were lower for IMP compared to GI and Warning conditions for the weapon pictures.

Do online hotel rating schemes influence booking behaviours?

Travelers’ hotel booking behaviors increasingly depend on peers' opinions and online ratings. This study investigates the effects of online hotel ratings on travelers' attitudes toward the hotel and booking intentions, using a 2 × 2 experimental research design. The results suggest that online rating lists are more useful and credible when published by well-known online travel communities (e.g., TripAdvisor). More favorable attitudes toward a hotel and higher booking intentions emerge when the hotel appears in best hotels lists. Finally, for the entries on best hotels lists, better attitudes and higher booking intentions result if the list is published on a well-known online travel community (Tripadvisor), whereas for entries on a worst hotel list, attitudes and booking intentions decrease even further if the list appears on TripAdvisor.

Treatment of child anxiety in the context of maternal anxiety disorder: a randomised controlled trial and economic analysis

Background Cognitive–behavioural therapy (CBT) for childhood anxiety disorders is associated with modest outcomes in the context of parental anxiety disorder. Objectives This study evaluated whether or not the outcome of CBT for children with anxiety disorders in the context of maternal anxiety disorders is improved by the addition of (i) treatment of maternal anxiety disorders, or (ii) treatment focused on maternal responses. The incremental cost-effectiveness of the additional treatments was also evaluated. Design Participants were randomised to receive (i) child cognitive–behavioural therapy (CCBT); (ii) CCBT with CBT to target maternal anxiety disorders [CCBT + maternal cognitive–behavioural therapy (MCBT)]; or (iii) CCBT with an intervention to target mother–child interactions (MCIs) (CCBT + MCI). Setting A NHS university clinic in Berkshire, UK. Participants Two hundred and eleven children with a primary anxiety disorder, whose mothers also had an anxiety disorder. Interventions All families received eight sessions of individual CCBT. Mothers in the CCBT + MCBT arm also received eight sessions of CBT targeting their own anxiety disorders. Mothers in the MCI arm received 10 sessions targeting maternal parenting cognitions and behaviours. Non-specific interventions were delivered to balance groups for therapist contact. Main outcome measures Primary clinical outcomes were the child’s primary anxiety disorder status and degree of improvement at the end of treatment. Follow-up assessments were conducted at 6 and 12 months. Outcomes in the economic analyses were identified and measured using estimated quality-adjusted life-years (QALYs). QALYS were combined with treatment, health and social care costs and presented within an incremental cost–utility analysis framework with associated uncertainty. Results MCBT was associated with significant short-term improvement in maternal anxiety; however, after children had received CCBT, group differences were no longer apparent. CCBT + MCI was associated with a reduction in maternal overinvolvement and more confident expectations of the child. However, neither CCBT + MCBT nor CCBT + MCI conferred a significant post-treatment benefit over CCBT in terms of child anxiety disorder diagnoses [adjusted risk ratio (RR) 1.18, 95% confidence interval (CI) 0.87 to 1.62, p = 0.29; adjusted RR CCBT + MCI vs. control: adjusted RR 1.22, 95% CI 0.90 to 1.67, p = 0.20, respectively] or global improvement ratings (adjusted RR 1.25, 95% CI 1.00 to 1.59, p = 0.05; adjusted RR 1.20, 95% CI 0.95 to 1.53, p = 0.13). CCBT + MCI outperformed CCBT on some secondary outcome measures. Furthermore, primary economic analyses suggested that, at commonly accepted thresholds of cost-effectiveness, the probability that CCBT + MCI will be cost-effective in comparison with CCBT (plus non-specific interventions) is about 75%. Conclusions Good outcomes were achieved for children and their mothers across treatment conditions. There was no evidence of a benefit to child outcome of supplementing CCBT with either intervention focusing on maternal anxiety disorder or maternal cognitions and behaviours. However, supplementing CCBT with treatment that targeted maternal cognitions and behaviours represented a cost-effective use of resources, although the high percentage of missing data on some economic variables is a shortcoming. Future work should consider whether or not effects of the adjunct interventions are enhanced in particular contexts. The economic findings highlight the utility of considering the use of a broad range of services when evaluating interventions with this client group. Trial registration Current Controlled Trials ISRCTN19762288. Funding This trial was funded by the Medical Research Council (MRC) and Berkshire Healthcare Foundation Trust and managed by the National Institute for Health Research (NIHR) on behalf of the MRC–NIHR partnership (09/800/17) and will be published in full in Health Technology Assessment; Vol. 19, No. 38.

The perception of support received from breast care nurses by depressed patients following a diagnosis of breast cancer

INTRODUCTION Due to their specialist training, breast care nurses (BCNs) should be able to detect emotional distress and offer support to breast cancer patients. However, patients who are most distressed after diagnosis generally experience least support from care staff. To test whether BCNs overcome this potential barrier, we compared the support experienced by depressed and non-depressed patients from their BCNs and the other main professionals involved in their care: surgeons and ward nurses. PATIENTS AND METHODS Women with primary breast cancer (n = 355) 2–4 days after mastectomy or wide local excision, self-reported perceived professional support and current depression. Analysis of variance compared support ratings of depressed and non-depressed patients across staff types. RESULTS There was evidence of depression in 31 (9%) patients. Depressed patients recorded less surgeon and ward nurse support than those who were not depressed but the support received by patients from the BCN was high, whether or not patients were depressed. CONCLUSIONS BCNs were able to provide as much support to depressed patients as to non-depressed patients, whereas depressed patients felt less supported by surgeons and ward nurses than did non-depressed patients. Future research should examine the basis of BCNs' ability to overcome barriers to support in depressed patients. Our findings confirm the importance of maintaining the special role of the BCN.

Thirst for knowledge: the effects of curiosity and interest on memory in younger and older adults

Given age-related memory impairments, one’s level of curiosity or interest could enhance memory for certain information. In the current study, younger and older adults read trivia questions, rated how curious they were to learn each answer, provided confidence and interest ratings, and judgments of learning (JOL) after learning the answer. No age-related differences in memory were found. Analyses indicated that curiosity and interest contributed to the formation of JOLs. Additionally, interest had a unique increasing relationship with older, but not younger, adults’ memory performance after a week. The results suggest that subjective interest may serve to enhance older adults’ memory.

Cognitive behaviour therapy (CBT) for depression by computer vs. therapist: patient experiences and therapeutic processes

This case series compares patient experiences and therapeutic processes between two modalities of cognitive behaviour therapy (CBT) for depression: computerized CBT (cCBT) and therapist-delivered CBT (tCBT). In a mixed-methods repeated-measures case series, six participants were offered cCBT and tCBT in sequence, with the order of delivery randomized across participants. Questionnaires about patient experiences were administered after each session and a semi-structured interview was completed with each participant at the end of each therapy modality. Therapy expectations, patient experiences and session impact ratings in this study generally favoured tCBT. Participants typically experienced cCBT sessions as less meaningful, less positive and less helpful compared to tCBT sessions in terms of developing understanding, facilitating problem-solving and building a therapeutic relationship.

The Effect of Mental Health Problems on Children’s Ability to Discriminate Amongst Thoughts, Feelings and Behaviours

Many young children appear to have skills sufficient to engage in basic elements of cognitive behaviour therapy (CBT). Previous research has, however, typically used children from non-clinical populations. It is important to assess children with mental health problems on cognitive skills relevant to CBT and to compare their performance to children who are not identified as having mental health difficulties. In this study 193 6 and 7 year old children were assessed using a thought–feeling–behaviour discrimination task [Quakley et al. Behav. Res. Therapy 42 (2004) 343] and a brief IQ test (the WASI). Children were assigned to groups (at risk, borderline, low risk) according to ratings of their mental health made by their teachers and parents on the Strengths and Difficulties Questionnaire [Goodman, J. Am. Acad. Child Adolescent Psych. 40 (2001) 1337]. After controlling for IQ, children ‘at risk’ of mental health problems performed significantly less well than children with a ‘low risk’ of mental health problems. Before receiving CBT, children’s meta-cognitive development should be assessed and additional help provided to those with meta-cognitive difficulties.

Investigating subtypes of reward processing deficits as trait markers for depression

Background: Anhedonia, the loss of pleasure in usually enjoyable activities, is a central feature of major depressive disorder (MDD). The aim of the present study was to examine whether young people at a familial risk of depression display signs of anticipatory, motivational or consummatory anhedonia, which would indicate that these deficits may be trait markers for MDD. Methods: The study was completed by 22 participants with a family history of depression (FH+) and 21 controls (HC). Anticipatory anhedonia was assessed by asking participants to rate their anticipated liking of pleasant and unpleasant foods which they imagined tasting when cued with images of the foods. Motivational anhedonia was measured by requiring participants to perform key presses to obtain pleasant chocolate taste rewards or to avoid unpleasant apple tastes. Additionally, physical consummatory anhedonia was examined by instructing participants to rate the pleasantness of the acquired tastes. Moreover, social consummatory anhedonia was investigated by asking participants to make preference-based choices between neutral facial expressions, genuine smiles, and polite smiles. Results: It was found that the FH+ group’s anticipated liking of unpleasant foods was significantly lower than that of the control group. By contrast, no group differences in the pleasantness ratings of the actually experienced tastes or in the amount of performed key presses were observed. However, controls preferred genuine smiles over neutral expressions more often than they preferred polite smiles over neutral expressions, while this pattern was not seen in the FH+ group. Conclusion: These findings suggest that FH+ individuals demonstrate an altered anticipatory response to negative stimuli and show signs of social consummatory anhedonia, which may be trait markers for depression.

Do online hotel rating schemes influence booking behaviors?

Travelers’ hotel booking behaviors increasingly depend on peers' opinions and online ratings. This study investigates the effects of online hotel ratings on travelers' attitudes toward the hotel and booking intentions, using a 2 × 2 experimental research design. The results suggest that online rating lists are more useful and credible when published by well-known online travel communities (e.g., TripAdvisor). More favorable attitudes toward a hotel and higher booking intentions emerge when the hotel appears in best hotels lists. Finally, for the entries on best hotels lists, better attitudes and higher booking intentions result if the list is published on a well-known online travel community (Tripadvisor), whereas for entries on a worst hotel list, attitudes and booking intentions decrease even further if the list appears on TripAdvisor.

Determinants of satisfaction amongst tenants of UK Offices

Purpose – Corporate Occupiers require offices and services which meet their business needs, whilst landlords must attract and retain occupiers in order to maximise occupancy and rental income. The purpose of this research is to help landlords and corporate occupiers understand each other better, in order to achieve a mutually beneficial relationship. Design/methodology/approach - This paper analyses interviews with 1334 office tenants in the UK, conducted over an 11-year period, to investigate determinants of occupier satisfaction, loyalty and advocacy. Structural equation modelling and regressions are performed using respondents’ ratings of satisfaction with many aspects of occupancy as explanatory variables. The dependent variables include satisfaction with property management, value for money, overall occupier satisfaction, lease renewal intentions and occupiers’ willingness to recommend their landlord. Findings - The aspects with most impact on occupiers’ satisfaction are the office building itself, its location and amenities, and also communication with their property manager, a belief that their business needs are understood and the property manager’s responsiveness to occupiers’ requests. Occupiers’ loyalty depends mainly upon feeling that their rent and service charges provide value for money, an amicable leasing process, the professionalism of their property manager and the Corporate Social Responsibility of the Landlord. ‘Empathy’ is crucial to occupiers’ willingness to recommend their landlord, and clear documentation and efficient legal process improve occupiers’ perception of receiving ‘Value for Money’. Research Limitations - The sample is skewed towards occupiers of prime office buildings in the UK, owned by landlords who care sufficiently about their tenants to commission studies into occupier satisfaction. Practical implications - This research should help to improve the landlord – tenant relationship, benefitting the businesses that rent property and helping building managers understand where to focus their efforts to achieve maximum effect on occupier satisfaction, loyalty and advocacy. Originality/value - There has been little academic research into the determinants of satisfaction of occupiers of UK commercial property. This large-scale study enables the most influential factors to be identified and prioritised.

Exploring the effects of genotypical and phenotypical variations in bitter taste sensitivity on perception, liking and intake of brassica vegetables in the UK

Brassicaceous vegetables (BV) have chemoprotective effects and yet consumption of BV in the UK is low. Previous studies suggest perception, liking and intake of BV are influenced by bitter taste sensitivity which this study further explores. Phenotypical taste sensitivity of 136 subjects was classified using propythiouracil (PROP) and sodium chloride and fungiform papillae density (FPD) was measured from tongue images. Polymorphisms of TAS2R38 and gustin (CA6) genes were analysed. Liking and bitterness of four raw vegetables (two BV (broccoli and white cabbage) and two non-BV (spinach and courgette)), as well as habitual consumption, were evaluated. There was a significant association between TAS2R38 genotype and PROP taster status (p<0.0001) and between FPD and PROP taster status (p=0.029). Individuals with greater sensitivity for PROP predominantly had TAS2R38 PAV/PAV genotype and greater FPD. BV were perceived as more bitter than non-BV (p<0.0001) with PAV/PAV subjects perceiving significantly stronger bitter intensity. There was a significant difference in liking for the four vegetables (p=0.002), and between consumers of different TAS2R38 genotype (p=0.0024). Individuals with TAS2R38 AVI/AVI genotype liked BV more. Regarding intake, both PAV/PAV and AVI/AVI individuals consumed more total vegetables and BV than PAV/AVI. Although PROP nontasters tended to consume more vegetables and BV than the other two phenotype groups, liking and vegetable intake were not significantly affected by taste phenotype. Although there was not a significant effect of CA6 genotype on bitterness ratings, there was a significant interaction between CA6 and TAS2R38, and in addition CA6 genotype was significantly associated with BV intake. However, these effects require validation as the proportions of the population with the CA6 G/G genotype was extremely small (7%). Our results confirmed that bitter taste perception in vegetables was influenced by both genotype and phenotype of bitter taste sensitivity. Moreover, our findings demonstrated that neither genotype nor phenotype of taste sensitivity alone accurately predict vegetable liking and intake as demographic factors were found to have a substantial influence.

Associations between interpretation bias and depression in adolescents

Interpretation biases have been shown to play a role in adult depression and are a target in cognitive behavioural therapy. Adolescence is a key risk period for the development of depression and a period of rapid cognitive and emotional development but little research has investigated the relationship between interpretation biases and depression in adolescents. This study adapted a measure of interpretation bias, the Ambiguous Scenarios Test for Depression, for adolescents and evaluated its reliability and validity. A community sample of 206 young people aged 12 to 18 years completed a validated measure of depression symptoms (Mood and Feelings Questionnaires) and the adapted Ambiguous Scenarios Test. The Ambiguous Scenarios Test for Depression in Adolescents had good internal consistency and split half reliability. Depression symptoms were associated with participants’ ratings of the valence of ambiguous situations and with interpretation biases. Importantly, symptoms of depression and anxiety were independently associated with interpretation bias. This research suggests that interpretation biases can be measured in this age group, that negative interpretation biases exist in adolescents and that these are associated with depression symptoms.