Lauren Owen

Dysbiosis of the gut microbiota in disease

There is growing evidence that dysbiosis of the gut microbiota is associated with the pathogenesis of both intestinal and extra-intestinal disorders. Intestinal disorders include inflammatory bowel disease, irritable bowel syndrome (IBS), and coeliac disease, while extra-intestinal disorders include allergy, asthma, metabolic syndrome, cardiovascular disease, and obesity. In many of these conditions, the mechanisms leading to disease development involves the pivotal mutualistic relationship between the colonic microbiota, their metabolic products, and the host immune system. The establishment of a ‘healthy’ relationship early in life appears to be critical to maintaining intestinal homeostasis. Whilst we do not yet have a clear understanding of what constitutes a ‘healthy’ colonic microbiota, a picture is emerging from many recent studies identifying particular bacterial species associated with a healthy microbiota. In particular, the bacterial species residing within the mucus layer of the colon, either through direct contact with host cells, or through indirect communication via bacterial metabolites, may influence whether host cellular homeostasis is maintained or whether inflammatory mechanisms are triggered. In addition to inflammation, there is some evidence that perturbations in the gut microbiota is involved with the development of colorectal cancer. In this case, dysbiosis may not be the most important factor, rather the products of interaction between diet and the microbiome. High-protein diets are thought to result in the production of carcinogenic metabolites from the colonic microbiota that may result in the induction of neoplasia in the colonic epithelium. Ever more sensitive metabolomics methodologies reveal a suite of small molecules produced in the microbiome which mimic or act as neurosignallers or neurotransmitters. Coupled with evidence that probiotic interventions may alter psychological endpoints in both humans and in rodent models, these data suggest that CNS-related co-morbidities frequently associated with GI disease may originate in the intestine as a result of microbial dysbiosis. This review outlines the current evidence showing the extent to which the gut microbiota contributes to the development of disease. Based on evidence to date, we can assess the potential to positively modulate the composition of the colonic microbiota and ameliorate disease activity through bacterial intervention.

Effects of chocolate on cognitive function and mood: a systematic review

A systematic review was conducted to evaluate whether chocolate or its constituents were capable of influencing cognitive function and/or mood. Studies investigating potentially psychoactive fractions of chocolate were also included. Eight studies (in six articles) met the inclusion criteria for assessment of chocolate or its components on mood, of which five showed either an improvement in mood state or an attenuation of negative mood. Regarding cognitive function, eight studies (in six articles) met the criteria for inclusion, of which three revealed clear evidence of cognitive enhancement (following cocoa flavanols and methylxanthine). Two studies failed to demonstrate behavioral benefits but did identify significant alterations in brain activation patterns. It is unclear whether the effects of chocolate on mood are due to the orosensory characteristics of chocolate or to the pharmacological actions of chocolate constituents. Two studies have reported acute cognitive effects of supplementation with cocoa polyphenols. Further exploration of the effect of chocolate on cognitive facilitation is recommended, along with substantiation of functional brain changes associated with the components of cocoa.

Systematic Literature Review Shows That Appetite Rating Does Not Predict Energy Intake

ABSTRACT Ratings of appetite are commonly used to assess appetite modification following an intervention. Subjectively rated appetite is a widely employed proxy measure for energy intake (EI), measurement of which requires greater time and resources. However, the validity of appetite as a reliable predictor of EI has not yet been reviewed systematically. This literature search identified studies that quantified both appetite ratings and EI. Outcomes were predefined as: (1) agreement between self-reported appetite scores and EI; (2) no agreement between self-reported appetitescores and EI. The presence of direct statistical comparison between the endpoints, intervention type and study population were also recorded. 462 papers were included in this review. Appetite scores failed to correspond with EI in 51.3% of the total studies. Only 6% of all studies evaluated here reported a direct statistical comparison between appetite scores and EI. χ2 analysis demonstrated that any relationship between EI and appetite was independent of study type stratification by age, gender or sample size. The very substantive corpus reviewed allows us to conclude that self-reported appetite ratings of appetite do not reliably predict EI. Caution should be exercised when drawing conclusions based from self-reported appetite scores in relation to prospective EI.

A critical analysis of alcohol hangover research methodology for surveys or studies of effects on cognition

RationaleAlcohol hangover may be defined as an adverse effect of heavy alcohol consumption present after sufficient time has elapsed for the alcohol to have been eliminated from the blood. Understanding how hangover may impair performance is important for public safety; yet, there is relatively little hangover research. This paper outlines good practice for future studies.ObjectivesThis paper presents a critical analysis of hangover methodology for surveys or studies of effects on cognition with human subjects and provides suggestions for optimum research practice for laboratory-based and naturalistic alcohol hangover studies.ResultsFour hangover symptom scales have been developed and subjected to psychometric testing. For retrospective assessment, we recommend the Hangover Symptoms Scale (HSS) or the Alcohol Hangover Severity Scale (AHSS). For concurrent assessment of hangover symptoms, we recommend either the Acute Hangover Scale (AHS), the five-item version of the HSS, or the AHSS. In research aiming to assess the cognitive effects of alcohol hangover, we suggest focusing on the cognitive domains of attention, memory and executive function, and we specify a number of tests within these cognitive domains that are likely to be sensitive to any decrements due to hangover. Finally, we argue that naturalistic studies should assess biological markers to improve the accuracy of estimates of alcohol consumption. Specifically, we recommend the assessment of ethyl glucuronide (EtG) for this purpose.ConclusionsRecommendations are made with respect to assessing hangover symptoms, cognitive effects of hangover and biological markers of alcohol consumption.

Response variability to glucose facilitation of cognitive enhancement

Glucose facilitation of cognitive function has been widely reported in previous studies (including our own). However, several studies have also failed to detect glucose facilitation. There is sparsity of research examining the factors that modify the effect of glucose on cognition. The aims of the present study were to (1) demonstrate the previously observed enhancement of cognition through glucose administration and (2) investigate some of the factors that may exert moderating roles on the behavioural response to glucose, including glucose regulation, body composition (BC) and hypothalamic–pituitary–adrenal axis response. A total of twenty-four participants took part in a double-blind, placebo-controlled, randomised, repeated-measures study, which examined the effect of 25 and 60 g glucose compared with placebo on cognitive function. At 1 week before the study commencement, all participants underwent an oral glucose tolerance test. Glucose facilitated performance on tasks of numeric and spatial working memory, verbal declarative memory and speed of recognition. Moderating variables were examined using several indices of glucoregulation and BC. Poorer glucoregulation predicted improved immediate word recall accuracy following the administration of 25 g glucose compared with placebo. Those with better glucoregulation showed performance decrements on word recall accuracy following the administration of 25 g glucose compared with placebo. These findings are in line with accumulating evidence that glucose load may preferentially enhance cognition in those with poorer glucoregulation. Furthermore, the finding that individuals with better glucoregulation may suffer impaired performance following a glucose load is novel and requires further substantiation.

Improved working memory performance following administration of a single dose of American ginseng (Panax quinquefolius L.) to healthy middle-age adults

A ginsenoside‐rich extract of American ginseng (Panax quinquefolius L.), CereboostTM, was previously shown to improve working memory and mood in healthy young individuals. The present study represented a partial replication investigating whether these effects extended to healthy middle‐aged individuals.

Hangover research needs: proceedings of the 5th Alcohol Hangover Research Group meeting.

Hangover is the most commonly reported negative consequence of heavy alcohol consumption. A large variety of symptoms have been reported the day after heavy drinking, which together are called the alcohol hangover. Frequently reported hangover symptoms include thirst, headache, drowsiness, and reduced alertness [1]. Although hangover is a common phenomenon in society and has serious socioeconomic consequences, it has received relatively little research attention. To increase research and international collaboration to examine the alcohol hangover, in 2010 the Alcohol Hangover Research Group (AHRG) was founded. This paper covers the research topics discussed at the 5th Alcohol Hangover Research Group meeting, held August 1–2, 2013 in Keele, UK.

The Effect of Alcohol Hangover on Choice Response Time

The effect of alcohol hangover on cognitive processing has received little attention. We explored the effect of alcohol hangover on choice response time (RT), a dominant dependent variable (DV) in cognitive research. Prior research of the effect of hangover on RT has produced mixed findings; all studies reviewed relied exclusively on estimates of central tendency (e.g. mean RT), which has limited information value. Here we present novel analytical methods by going beyond mean RT analysis. Specifically, we examined performance in hangover conditions (n=31) across the whole RT distribution by fitting ex-Gaussian models to participant data, providing a formal description of the RT distribution. This analysis showed detriments to performance under hangover conditions at the slower end of the RT distribution and increased RT variance under hangover conditions. We also fitted an explicit mathematical process model of choice RT – the diffusion model – which estimates parameters reflecting psychologically-meaningful processes underlying choice RT. This analysis showed that hangover reduced information processing efficiency during response selection, and increased response caution; changes in these parameters reflect hangover affecting core decisional-components of RT performance. The implications of the data as well as the methods used for hangover research are discussed.

Systematic Literature Review Shows That Appetite Rating does Not Predict Energy Intake

Self-report ratings of appetite, particularly visual analogue scales (VAS) are commonly used to measure subjective appetite and to assess modifications thereof following an intervention. Subjective rated appetite is a widely employed proxy measure for Actual Energy Intake (AEI), measurement of which requires greater time and resources. The validity of selfreport measures of appetite as surrogate measures of AEI have not been systematically reviewed elsewhere. To identify the corpus of papers assessing both self -reported appetite and AEI in the same trial and to establish whether selfreport scales reliably predict AEI. A literature search was undertaken spanning 1999 to 2015 identifying studies recording both VAS ratings and AEI, generally in response to a nutrient or food intervention. Outcomes were pre-defined as there being agreement between self-reported appetite and AEI (link) or no agreement between self-reported appetite scores and AEI (no link). The presence of statistical (direct) comparison between the two methods was also recorded, the type of intervention, subject or patient were also noted. Each paper was scored independently by two authors. 462 papers were included in this review. Appetite scores failed to correspond with AEI in 51·3 % of total studies. Only 6 % of studies evaluated directly compared the two measures statistically. A Chi Squared test revealed a significant departure (P < 0·001) from observed and expected frequencies for direct assessment of a link when studies were separated by ‘intervention type’. This effect appears to be, in part, due to the use of pharmaceutical interventions and particularly where satiety regulating hormones were manipulated. The very substantive corpus identified in this review allows us to conclude that self-reported appetite ratings of appetite do not reliably predict AEI. Caution should be exercised when deriving conclusions based from self -report appetite data alone in relation to prospective energy intake.

S14THE HEALTH AND BEHAVIOURAL CONSEQUENCES OF ALCOHOL HANGOVER

# S14.1 BEHAVIOURAL CONSEQUENCES OF THE ALCOHOL HANGOVER - PRELIMINARY FINDINGS {#article-title-2} Attention and memory appear broadly to be affected by alcohol hangover, but research examining these effects in greater detail, together with executive functioning, is required (Ling et al, 2010). We have recently secured an EU Marie Curie Research Fellowship to allow Dr Lauren to conduct research assessing the cognitive consequences of the alcohol hangover. In this on-going randomised, repeated measures, crossover trial, participants are being recruited from Keele University to take part in a study assessing neurocognitive effects of alcohol hangover in a sample of 200 adults. In order to comprehensively assess the cognitive domains most susceptible to the effects of alcohol hangover a battery of Computerised Mental Performance Assessment (COMPASS) tasks are being used. Cognitive domains assessed include; immediate and delayed declarative memory, working memory, attention and executive function and mood. Participants are tested on 2 occasions following both an evening alcohol consumption and abstention. The Bond Lader Visual Analogue scale revealed significantly reduced feelings of alertness, contentment and a trend for reduced feelings of calmness, following a hangover. Alcohol hangover also resulted in impaired performance on the spatial working memory, and numeric working memory as well as significantly slower reaction times on the attention and response inhibition task. Alcohol hangover also leads to greater number of errors during Rapid Visual Information Processing. The present results suggest that tasks, which rely heavily on medial temporal and frontal processing, appear to be most greatly affected. Furthermore overall speed of information processing appears to be impeded. # S14.2 PROSPECTIVE MEMORY DEFICITS ASSOCIATED WITH A STATE OF ALCOHOL HANGOVER {#article-title-3} Background. Alcohol hangover leads to deficits on a range higher order cognitive processes, including executive functions. The current study attempts to extend this focus to observe whether alcohol hangover impedes everyday prospective memory (PM: memory for future events). Methods. An existing groups design was used to compare a group of students who were recovering from alcohol hangover the day after a heavy drinking session, with a group who were hangover-free. A hangover rating scale was used to measure hangover effects; a drug-use questionnaire measured alcohol and other drug use; the Hospital Anxiety and Depression Scale measured mood and the Prospective Remembering Video Procedure (PRVP) measured objective PM. Anyone who reported using an illegal substance or suffering from a psychiatric illness (such as depression) were excluded from the study. Results. After observing no significant between-group differences on age, weekly alcohol use, weekly cigarette use, anxiety or depression scores, the alcohol hangover group recalled significantly fewer items on the PRVP than the hangover-free control group. Conclusion. Impaired Everyday PM should be added to the list of cognitive deficits associated with a state of alcohol hangover. # S14.3 LAPSES OF ATTENTION DURING DRIVING IN THE ALCOHOL HANGOVER STATE {#article-title-4} Background. The morning after a drinking session, i.e. during the alcohol hangover state, people commonly report reduced alertness and ability to concentrate. Thus, it is likely that lapses of attention may occur. These lapses may compromise safety in potentially dangerous activities such as driving a car. The purpose of this study was to examine the presence of lapses of attention during driving in the hangover state. Methods. In N = 47 healthy volunteers, driving performance was tested the morning following an evening of consuming on average 10.2 (4.2) alcoholic drinks (alcohol hangover) and on a control day (no alcohol consumed). Subjects performed a standardized 100-km highway driving test in the STISIM driving simulator when BAC was zero. Lapses of attention were examined, defined as a continuous change of lateral position >100 cm for at least 8 seconds. The number of lapses, maximum lateral deviation, and total time of lapses were computed. Results were compared with subjective assessments of driving quality and driving style. Hangover severity was scored with a visual analog scale ranging from 0 (absent) to 10 (extreme). Δlapses (hangover – control) was related to subjective outcome measures. Results. Data from 4 subjects were excluded as they reported that they had no hangover. Another subject was excluded because he scored positively (6out of 10) on the hangover scale on the control day. Data from N = 42 subjects are presented. During hangover, a significantly increased number of lapses relative to the control day (7.7 versus 5.3 lapses, p = 0.019), and an increased total lapse time (182.7 versus 127.3 seconds, p = 0.040) were observed. The maximum lapse deviation did not differ between hangover and control sessions (p = 0.130). Δlapses was significantly correlated to difference scores on subjective driving quality (p = 0.025) and mental effort to perform the test (p = 0.042). Δlapses was not significantly related to subjective assessments of driving style, sleep quality, or sleepiness scores obtained before or after driving. Driving impairment was significantly related to hangover severity scores. A significant positive relationship was found between difference scores on hangover severity and number of lapses (r = 0.373, p = 0.015) and total lapse time (r = 0.380, p = 0.013). There was no relationship with the number of consumed alcoholic drinks the night before. Conclusions. Driving is significantly impaired during alcohol hangover. Funding: This study was funded by Utrecht University. # S14.4 BIOLOGICAL, PSYCHOLOGICAL, AND BEHAVIORAL CORRELATES OF THE ALCOHOL HANGOVER {#article-title-5} Background. Alcohol intake is a necessary precondition for a hangover. However the amount of alcohol consumed is not proportionally related to the presence and/or severity of the hangover symptoms. Although increased research attention has provided some knowledge regarding its contributory factors, the etiology of the hangover remains merely unknown. Methods. A naturalistic study consisting of an alcohol and a control (alcohol-free) condition was set up, in order to investigate several biological, psychological and behavioral correlates of alcohol hangovers in social drinkers. The day following an evening of alcohol consumption, participants completed a survey and saliva samples were collected. The same procedure was followed after an evening on which no alcohol was consumed. Results. Psychological complaints, smoking, sleeping time, age and sex do not seem to play a decisive role in hangover etiology. Hangover severity and binge drinking were accompanied by a significantly suppressed immune effect compared to the control condition. Hangover severity could be predicted for 36% by blood alcohol concentration estimates, dancing activity, hangover frequency and changes in IFN-γ and TNF-α levels. Conclusions. The day after an evening of alcohol consumption, a suppression of both pro-inflammatory and anti-inflammatory cytokines was observed. More research is needed to investigate how and to what extent changes of cytokine concentrations, psychological and personality characteristics, and other biomarkers are related to the presence and severity of alcohol hangover. Funding: This study was funded by Utrecht University.