Gut microbiota-mediated metabolism of green tea catechins and the biological consequences: An updated review.

Multiple beneficial effects have been attributed to green tea catechins (GTCs). However, the bioavailability of GTCs is generally low, with only a small portion directly absorbed in the small intestine. The majority of ingested GTCs reaches the large intestinal lumen, and are extensively degraded via biotransformation by gut microbiota, forming many low-molecular-weight metabolites such as phenyl-γ-valerolactones, phenolic acids, butyrate, and acetate. This process not only improves the overall bioavailability of GTC-derived metabolites but also enriches the biological activities of GTCs. Therefore, the intra- and inter-individual differences in human gut microbiota as well as the resulting biological contribution of microbial metabolites are crucial for the ultimate health benefits. In this review, the microbial degradation of major GTCs was characterized and an overview of the in vitro models used for GTC metabolism was summarized. The intra- and inter-individual differences of human gut microbiota composition and the resulting divergence in the metabolic patterns of GTCs were highlighted. Moreover, the potential beneficial effects of GTCs and their gut microbial metabolites were also discussed. Overall, the microbial metabolites of GTCs with higher bioavailability and bioactive potency are key factors for the observed beneficial effects of GTCs and green tea consumption.

Individual prediction tendencies do not generalize across modalities.

Predictive processing theories, which model the brain as a "prediction machine", explain a wide range of cognitive functions, including learning, perception and action. Furthermore, it is increasingly accepted that aberrant prediction tendencies play a crucial role in psychiatric disorders. Given this explanatory value for clinical psychiatry, prediction tendencies are often implicitly conceptualized as individual traits or as tendencies that generalize across situations. As this has not yet explicitly been shown, in the current study, we quantify to what extent the individual tendency to anticipate sensory features of high probability generalizes across modalities. Using magnetoencephalography (MEG), we recorded brain activity while participants were presented with a sequence of four different (either visual or auditory) stimuli, which changed according to predefined transitional probabilities of two entropy levels: ordered vs. random. Our results show that, on a group-level, under conditions of low entropy, stimulus features of high probability are preactivated in the auditory but not in the visual modality. Crucially, the magnitude of the individual tendency to predict sensory events seems not to correlate between the two modalities. Furthermore, reliability statistics indicate poor internal consistency, suggesting that the measures from the different modalities are unlikely to reflect a single, common cognitive process. In sum, our findings suggest that quantification and interpretation of individual prediction tendencies cannot be generalized across modalities.

Comparative analysis of gestation in three rhinoceros species (Diceros bicornis; Ceratotherium simum; Rhinoceros unicornis).

This comparative analysis evaluated endocrine profiles and gestation length data of captive pregnant black rhinoceros (Diceros bicornis), white rhinoceros (Ceratotherium simum), and greater one-horned (GOH) rhinoceros (Rhinoceros unicornis). Hormone profiles were collected over three decades as part of pregnancy diagnoses. After the third month of gestation, the luteo-placental shift in progesterone production in pregnant rhinoceroses causes a significant increase in the concentration of faecal progesterone metabolites. We defined a laboratory-specific value of 1000 ng/g faeces as a threshold for incipient feto-placental progesterone production. Using this value allowed a comparison between species and revealed significant individual differences within a species. The mean ± SEM gestation days for reaching the 1000 ng/g faeces threshold were 89.5 ± 2.9 (range 56-138 days; n = 39) in black, 96.0 ± 2.6 (58-138; n = 39) in white, and 117.8 ± 5.3 (74-173; n = 19) in GOH rhinoceroses. For the calculations of gestation length, we complemented our results from three decades of reproductive monitoring with data from the literature, resulting in about 70 values for each species. Gestation length in the black, the white and the GOH rhinoceros was 460.6 ± 1.5 (range: 436 - 486), 503.8 ± 1.3 (range: 480 - 525) and 480.5 ± 1.1 (range: 453 - 505) days, respectively. Daylight length significantly affected gestation length, while the sex of offspring had no effect. On average, pregnancies with parturitions in spring and summer were one week shorter than those in autumn and winter. Although rhinoceroses are non-seasonal breeders, most parturitions in captivity occur in autumn and winter. We also analysed preconception endocrine profiles in the white rhinoceros. Conceptions in this species occurred after oestrous cycles of approximately 35 days (n = 18), 70 days (n = 3), 15 days (n = 1), after periods of ovarian inactivity (n = 5), and during a foal heat within one month after stillbirth parturition (n = 1). In conclusion, this study provides a comprehensive overview of gestational parameters in three rhinoceros species.

How solitude relates to well-being in old age: A review of inter-individual differences.

Older adults are more likely to live alone and engage in solitary activities than young adults, leading to decrement in their well-being. However, researchers have discovered beneficial implications of solitude, and some of them even have established that the negative and positive effects of solitude coexist. The study's purposes are to investigate the relationship between solitude and well-being among older adults and to further examine the inter-individual differences in this relationship. In the database of Google Scholar, the systematic review methods are used and 17 articles meet the inclusion criteria. The study concludes that older adults experience solitude both negatively and positively; the complex relationship between solitude and well-being can be better understood and explained by inter-individual differences based on intrapersonal, interpersonal, and cultural factors. This systematic review adopts a perspective that spans individual and social/cultural levels and helps grasp the link between solitude and well-being in older adults. Based on this review, the researcher can develop appropriate interventions to help older people maximize the benefits of solitude while minimizing the drawbacks to further achieve a higher quality of life.

Inter-individual variation in chlorpyrifos toxicokinetics characterized by physiologically based kinetic (PBK) and Monte Carlo simulation comparing human liver microsome and Supersome™ cytochromes P450 (CYP)-specific kinetic data as model input.

The present study compares two approaches to evaluate the effects of inter-individual differences in the biotransformation of chlorpyrifos (CPF) on the sensitivity towards in vivo red blood cell (RBC) acetylcholinesterase (AChE) inhibition and to calculate a chemical-specific adjustment factor (CSAF) to account for inter-individual differences in kinetics (HKAF). These approaches included use of a Supersome™ cytochromes P450 (CYP)-based and a human liver microsome (HLM)-based physiologically based kinetic (PBK) model, both combined with Monte Carlo simulations. The results revealed that bioactivation of CPF exhibits biphasic kinetics caused by distinct differences in the Km of CYPs involved, which was elucidated by Supersome™ CYP rather than by HLM. Use of Supersome™ CYP-derived kinetic data was influenced by the accuracy of the intersystem extrapolation factors (ISEFs) required to scale CYP isoform activity of Supersome™ to HLMs. The predicted dose-response curves for average, 99th percentile and 1st percentile sensitive individuals were found to be similar in the two approaches when biphasic kinetics was included in the HLM-based approach, resulting in similar benchmark dose lower confidence limits for 10% inhibition (BMDL10) and HKAF values. The variation in metabolism-related kinetic parameters resulted in HKAF values at the 99th percentile that were slightly higher than the default uncertainty factor of 3.16. While HKAF values up to 6.9 were obtained when including also the variability in other influential PBK model parameters. It is concluded that the Supersome™ CYP-based approach appeared most adequate for identifying inter-individual variation in biotransformation of CPF and its resulting RBC AChE inhibition.

In vitro-in silico-based prediction of inter-individual and inter-ethnic variations in the dose-dependent cardiotoxicity of R- and S-methadone in humans.

New approach methodologies predicting human cardiotoxicity are of interest to support or even replace in vivo-based drug safety testing. The present study presents an in vitro-in silico approach to predict the effect of inter-individual and inter-ethnic kinetic variations in the cardiotoxicity of R- and S-methadone in the Caucasian and the Chinese population. In vitro cardiotoxicity data, and metabolic data obtained from two approaches, using either individual human liver microsomes or recombinant cytochrome P450 enzymes (rCYPs), were integrated with physiologically based kinetic (PBK) models and Monte Carlo simulations to predict inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. Chemical specific adjustment factors were defined and used to derive dose-response curves for the sensitive individuals. Our simulations indicated that Chinese are more sensitive towards methadone-induced cardiotoxicity with Margin of Safety values being generally two-fold lower than those for Caucasians for both methadone enantiomers. Individual PBK models using microsomes and PBK models using rCYPs combined with Monte Carlo simulations predicted similar inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. The present study illustrates how inter-individual and inter-ethnic variations in cardiotoxicity can be predicted by combining in vitro toxicity and metabolic data, PBK modelling and Monte Carlo simulations. The novel methodology can be used to enhance cardiac safety evaluations and risk assessment of chemicals.

Implicit and explicit safety evaluation of foods: The importance of food processing.

Identifying beneficial foods in the environment, while avoiding ingesting something toxic, is a crucial task humans face on a daily basis. Here we directly examined adults' implicit and explicit safety evaluations of the same foods presented with different degrees of processing, ranging from unprocessed (raw) to processed (cut or cooked). Moreover, we investigated whether individual characteristics (e.g., Body Mass Index, food neophobia and hunger) modulated their evaluations. We hypothesized that adults would associate the processed form of a food with safety more than its unprocessed form since processing techniques, which are ubiquitously applied in different cultures, often reduce the toxicity of foods, and signal previous human intervention and intended consumption. Adults (N = 109, 43 females) performed an implicit Go/No-Go association task (GNAT) online, assessing the association between safety attributes and food images differing on their degree of processing, both unfamiliar and familiar foods were used. Then each food was explicitly evaluated. Results revealed that individual self-reported characteristics affected both implicit and explicit evaluations. Individuals with excess weight and obesity had a strong and positive implicit association between processed foods and safety attributes, but explicitly rated cooked foods as the least safe overall, this latter result was found in highly neophobic individuals as well. Yet, at the explicit level, when looking at unfamiliar foods only, processed foods were rated safer than unprocessed foods by all participants. Our results are the first evidence that directly highlights the relevance of the degree of processing in food safety evaluation and suggest that thinking of the important tasks humans face regarding food selection enriches our understanding of food behaviors.

Two faces of temporal binding: Action- and effect-binding are not correlated.

Research on the sense of agency has proliferated a range of explicit and implicit measures. However, the relation of different measures is poorly understood with especially mixed findings on the correlation between explicit judgments of agency and the implicit perceptual bias of temporal binding. Here, we add to the conundrum by showing that the two sub-components of temporal binding - action-binding and effect-binding, respectively - are not correlated across participants either, suggesting independent processes for both components. Research on inter-individual differences regarding the sense of agency is thus well-advised to rely on other implicit measures until the phenomenon of temporal binding is better understood.

Single-trial characterization of neural rhythms: Potential and challenges.

The average power of rhythmic neural responses as captured by MEG/EEG/LFP recordings is a prevalent index of human brain function. Increasing evidence questions the utility of trial-/group averaged power estimates however, as seemingly sustained activity patterns may be brought about by time-varying transient signals in each single trial. Hence, it is crucial to accurately describe the duration and power of rhythmic and arrhythmic neural responses on the single trial-level. However, it is less clear how well this can be achieved in empirical MEG/EEG/LFP recordings. Here, we extend an existing rhythm detection algorithm (extended Better OSCillation detection: "eBOSC"; cf. Whitten et al., 2011) to systematically investigate boundary conditions for estimating neural rhythms at the single-trial level. Using simulations as well as resting and task-based EEG recordings from a micro-longitudinal assessment, we show that alpha rhythms can be successfully captured in single trials with high specificity, but that the quality of single-trial estimates varies greatly between subjects. Despite those signal-to-noise-based limitations, we highlight the utility and potential of rhythm detection with multiple proof-of-concept examples, and discuss implications for single-trial analyses of neural rhythms in electrophysiological recordings. Using an applied example of working memory retention, rhythm detection indicated load-related increases in the duration of frontal theta and posterior alpha rhythms, in addition to a frequency decrease of frontal theta rhythms that was observed exclusively through amplification of rhythmic amplitudes.

Impact of anthropogenic factors on affiliative behaviors among bonnet macaques.

OBJECTIVES: In primates, allogrooming and other affiliative behaviors confer many benefits and may be influenced by many socioecological factors. Of these, the impact of anthropogenic factors remain relatively understudied. Here we ask whether interactions with humans decreased macaques' affiliative behaviors by imposing time-constraints, or increased these behaviors on account of more free-/available-time due to macaques' consumption of high-energy human foods. MATERIALS AND METHODS: In Southern India, we collected data on human-macaque and macaque-macaque interactions using focal-animal sampling on two groups of semi-urban bonnet macaques for 11 months. For each macaque within each climatic season, we calculated frequencies of human-macaque interactions, rates of monitoring human activity and foraging on anthropogenic food, dominance ranks, grooming duration, number of unique grooming partners, and frequencies of other affiliative interactions. RESULTS: We found strong evidence for time-constraints on grooming. Macaques that monitored humans more groomed for shorter durations and groomed fewer partners, independent of their group membership, sex, dominance rank, and season. However, monitoring humans had no impact on other affiliative interactions. We found no evidence for the free-time hypothesis: foraging on anthropogenic food was unrelated to grooming and other affiliation. DISCUSSION: Our results are consistent with recent findings on other urban-dwelling species/populations. Macaques in such environments may be especially reliant on other forms of affiliation that are of short duration (e.g., coalitionary support, lip-smacking) and unaffected by time-constraints. We stress on the importance of evaluating human impact on inter-individual differences in primate/wildlife behavior for conservation efforts.

Issues in the determination of 'responders' and 'non-responders' in physiological research.

NEW FINDINGS: What is the topic for this review? We discuss the dichotomization of continuous-level physiological measurements into 'responders' and 'non-responders' when interventions/treatments are examined in robust parallel-group studies. What advances does it highlight? Sample responder counts are biased by pre-to-post within-subject variability. Sample differences in counts may be explained wholly by differences in mean response, even without individual response heterogeneity and even if test-retest measurement error informs the choice of response threshold. A less biased and more informative approach uses the SD of individual responses to estimate the chance a new person from the population of interest will be a responder. ABSTRACT: As a follow-up to our 2015 review, we cover more issues on the topic of 'response heterogeneity', which we define as clinically important individual differences in the physiological responses to the same treatment/intervention that cannot be attributed to random within-subject variability. We highlight various pitfalls with the common practice of counting the number of 'responders', 'non-responders' and 'adverse responders' in samples that have been given certain treatments or interventions for research purposes. We focus on the classical parallel-group randomized controlled trial and assume typical good practice in trial design. We show that sample responder counts are biased because individuals differ in terms of pre-to-post within-subject random variability in the study outcome(s) and not necessarily treatment response. Ironically, sample differences in responder counts may be explained wholly by sample differences in mean response, even if there is no response heterogeneity at all. Sample comparisons of responder counts also have relatively low statistical precision. These problems do not depend on how the response threshold has been selected, e.g. on the basis of a measurement error statistic, and are not rectified fully by the use of confidence intervals for individual responses in the sample. The dichotomization of individual responses in a research sample is fraught with pitfalls. Less biased approaches for estimating the proportion of responders in a population of interest are now available. Importantly, these approaches are based on the SD for true individual responses, directly incorporating information from the control group.

Trait-like characteristics of sleep EEG power spectra in adolescents across sleep opportunity manipulations.

The electroencephalographic power spectra of non-rapid eye movement sleep in adults demonstrate trait-like consistency within participants across multiple nights, even when prior sleep deprivation is present. Here, we examined the extent to which this finding applies to adolescents who are habitually sleep restricted on school-days and sleep longer on weekends. We evaluated 78 adolescents across three sleep restriction groups who underwent different permutations of adequate sleep (9 hr time-in-bed), sleep restriction (5 hr time-in-bed), afternoon naps (1 hr afternoon) and recovery sleep (9 hr time-in-bed) that simulate behaviour on school-days and weekends. The control group comprised a further 22 adolescents who had 9 hr of sleep opportunity each night. Intra-class correlation coefficients showed moderate to almost perfect within-subject stability in electroencephalographic power spectra across multiple nights in both sleep restriction and control groups, even when changes to sleep macrostructure were observed. While nocturnal intra-class correlation metrics were lower in the low-frequency and spindle frequency bins in the sleep restriction compared with the control group, hierarchical clustering measures could still identify multi-night electroencephalographic spectra as originating from the same individual. The trait-like characteristics of electroencephalographic spectra from an adolescent remain identifiable despite the disruptive effects of multi-night sleep restriction to sleep architecture.

Individuals in space: personality-dependent space use, movement and microhabitat use facilitate individual spatial niche specialization.

Personality-dependent space use and movement might be crucially influencing ecological interactions, giving way to individual niche specialization. This new approach challenges classical niche theory with potentially great ecological consequences, but so far has only scarce empirical support. Here, we investigated if and how consistent inter-individual differences in behavior predict space use and movement patterns in free-ranging bank voles (Myodes glareolus) and thereby contribute to individual niche specialization. Individuals were captured and marked from three different subpopulations in North-East Germany. Inter-individual differences in boldness and exploration were quantified via repeated standardized tests directly in the field after capture. Subsequently, space use and movement patterns of a representative sample of the behavioral variation (n = 21 individuals) were monitored via automated VHF telemetry for a period of four days, yielding on average 384 locations per individual. Bolder individuals occupied larger home ranges and core areas (estimated via kernel density analyses), moved longer distances, spatially overlapped with fewer conspecifics and preferred different microhabitats based on vegetation cover compared to shyer individuals. We found evidence for personality-dependent space use, movement, and occupation of individual spatial niches in bank voles. Thus, besides dietary niche specialization also spatial dimensions of ecological niches vary among individuals within populations, which may have important consequences for ecological interactions within- and between species.

Contrasting Grammatical and Lexical Determiners.

This paper investigates the difference between the production of grammatical determiners and lexical determiners in the production of adjective-noun phrases (NPs) in Danish. Models of sentence processing (Garrett in Psychology of learning and motivation, Academic press, New York, pp 133-177, 1975; Bock in J Mem Lang 26(2):119-137, 1987) suggest that the phonological encoding stage of grammatical items can only be specified once lexical items have been phonologically encoded. In their usage-based linguistic theory of the grammar-lexicon distinction, Boye and Harder (Lang 88(1):1-44, 2012) propose that this later encoding of grammatical elements is motivated by two specific features of grammatical elements. The first feature, dependence, is that grammatical items (morphemes, words, constructions) cannot be produced in isolation, but are always dependent on a lexical host item. This feature entails a more complex processing which might lead to longer reaction times when comparing the production of NPs with a grammatical determiner to a lexical one. Additionally, a more complex processing might lead to a lower accuracy rate for the grammatical condition relative to the lexical one. The second feature, low prominence, is that grammatical items code background information and therefore cannot convey the main point of a linguistic message. Less focus on grammatical elements might lead to a lower accuracy rate for the production of grammatical elements relative to lexical ones. Those predictions were tested in a task comparing the production of Danish grammatical determiners (indefinite articles) with the production of lexical ones (numerals, which are homonymous with the articles except for a stress difference) in similar contexts. Group-based analyses were performed in order to take inter-individual differences into account. The results show that the two features as proposed by Boye and Harder (2012) are only revealed for the fastest speakers group but not the slower ones.

Data-driven analysis of simultaneous EEG/fMRI reveals neurophysiological phenotypes of impulse control.

Response inhibition is the ability to suppress inadequate but prepotent or ongoing response tendencies. A fronto-striatal network is involved in these processes. Between-subject differences in the intra-individual variability have been suggested to constitute a key to pathological processes underlying impulse control disorders. Single-trial EEG/fMRI analysis allows to increase sensitivity for inter-individual differences by incorporating intra-individual variability. Thirty-eight healthy subjects performed a visual Go/Nogo task during simultaneous EEG/fMRI. Of 38 healthy subjects, 21 subjects reliably showed Nogo-related ICs (Nogo-IC-positive) while 17 subjects (Nogo-IC-negative) did not. Comparing both groups revealed differences on various levels: On trait level, Nogo-IC-negative subjects scored higher on questionnaires regarding attention deficit/hyperactivity disorder; on a behavioral level, they displayed slower response times (RT) and higher intra-individual RT variability while both groups did not differ in their inhibitory performance. On the neurophysiological level, Nogo-IC-negative subjects showed a hyperactivation of left inferior frontal cortex/insula and left putamen as well as significantly reduced P3 amplitudes. Thus, a data-driven approach for IC classification and the resulting presence or absence of early Nogo-specific ICs as criterion for group selection revealed group differences at behavioral and neurophysiological levels. This may indicate electrophysiological phenotypes characterized by inter-individual variations of neural and behavioral correlates of impulse control. We demonstrated that the inter-individual difference in an electrophysiological correlate of response inhibition is correlated with distinct, potentially compensatory neural activity. This may suggest the existence of electrophysiologically dissociable phenotypes of behavioral and neural motor response inhibition with the Nogo-IC-positive phenotype possibly providing protection against impulsivity-related dysfunction. Hum Brain Mapp 37:3114-3136, 2016. © 2016 Wiley Periodicals, Inc.

Consistent inter-individual differences in common marmosets (Callithrix jacchus) in Boldness-Shyness, Stress-Activity, and Exploration-Avoidance.

The study of animal personality, defined as consistent inter-individual differences in correlated behavioral traits stable throughout time and/or contexts, has recently become one of the fastest growing areas in animal biology, with study species ranging from insects to non-human primates. The latter have, however, only occasionally been tested with standardized experiments. Instead their personality has usually been assessed using questionnaires. Therefore, this study aimed to test 21 common marmosets (Callithrix jacchus) living in three family groups, in five different experiments, and their corresponding controls. We found that behavioral differences between our animals were not only consistent over time, but also across different contexts. Moreover, the consistent behaviors formed a construct of four major non-social personality components: Boldness-Shyness in Foraging, Boldness-Shyness in Predation, Stress-Activity, and Exploration-Avoidance. We found no sex or age differences in these components, but our results did reveal differences in Exploration-Avoidance between the three family groups. As social environment can have a large influence on behavior of individuals, our results may suggest group-level similarity in personality (i.e., "group personality") in common marmosets, a species living in highly cohesive social groups. Am. J. Primatol. 78:961-973, 2016. © 2016 Wiley Periodicals, Inc.

Middle-range exploratory activity in adult rats suggests higher resilience to chronic social defeat.

OBJECTIVE: Stressful life events play an important role in the aetiology of human mood disorders and are frequently modelled by chronic social defeat (SD) in rodents. Exploratory phenotype in rats is a stable trait that is likely related to inter-individual differences in reactivity to stress. The aim of the study was to confirm that low levels of exploratory activity (LE) are, in rodents, a risk factor for passive stress coping, and to clarify the role of medium (ME) and high (HE) exploratory disposition in the sensitivity to SD. METHODS: We examined the effect of SD on male Wistar rats with LE, ME, and HE activity levels as measured in the exploration box. After SD, the rats were evaluated in social preference, elevated zero maze, and open-field tests. Brain tissue levels of monoamines were measured by high-performance liquid chromatography. RESULTS: Rats submitted to SD exhibited lower weight gain, higher sucrose consumption, showed larger stress-induced hyperthermia, lower levels of homovanillic acid in the frontal cortex, and higher levels of noradrenaline in the amygdala and hippocampus. Open-field, elevated zero maze, and social preference tests revealed the interaction between stress and phenotype, as only LE-rats were further inhibited by SD. ME-rats exhibited the least reactivity to stress in terms of changes in body weight, stress-induced hyperthermia, and sucrose intake. CONCLUSION: Both low and high novelty-related activity, especially the former, are associated with elevated sensitivity to social stress. This study shows that both tails of a behavioural dimension can produce stress-related vulnerability.

Structural brain correlates of associative memory in older adults.

Associative memory involves binding two or more items into a coherent memory episode. Relative to memory for single items, associative memory declines greatly in aging. However, older individuals vary substantially in their ability to memorize associative information. Although functional studies link associative memory to the medial temporal lobe (MTL) and prefrontal cortex (PFC), little is known about how volumetric differences in MTL and PFC might contribute to individual differences in associative memory. We investigated regional gray-matter volumes related to individual differences in associative memory in a sample of healthy older adults (n=54; age=60years). To differentiate item from associative memory, participants intentionally learned face-scene picture pairs before performing a recognition task that included single faces, scenes, and face-scene pairs. Gray-matter volumes were analyzed using voxel-based morphometry region-of-interest (ROI) analyses. To examine volumetric differences specifically for associative memory, item memory was controlled for in the analyses. Behavioral results revealed large variability in associative memory that mainly originated from differences in false-alarm rates. Moreover, associative memory was independent of individuals' ability to remember single items. Older adults with better associative memory showed larger gray-matter volumes primarily in regions of the left and right lateral PFC. These findings provide evidence for the importance of PFC in intentional learning of associations, likely because of its involvement in organizational and strategic processes that distinguish older adults with good from those with poor associative memory.

TNFα G308A polymorphism is associated with resilience to sleep deprivation-induced psychomotor vigilance performance impairment in healthy young adults.

Cytokines such as TNFα play an integral role in sleep/wake regulation and have recently been hypothesized to be involved in cognitive impairment due to sleep deprivation. We examined the effect of a guanine to adenine substitution at position 308 in the TNFα gene (TNFα G308A) on psychomotor vigilance performance impairment during total sleep deprivation. A total of 88 healthy women and men (ages 22-40) participated in one of five laboratory total sleep deprivation experiments. Performance on a psychomotor vigilance test (PVT) was measured every 2-3h. The TNFα 308A allele, which is less common than the 308G allele, was associated with greater resilience to psychomotor vigilance performance impairment during total sleep deprivation (regardless of time of day), and also provided a small performance benefit at baseline. The effect of genotype on resilience persisted when controlling for between-subjects differences in age, gender, race/ethnicity, and baseline sleep duration. The TNFα G308A polymorphism predicted less than 10% of the overall between-subjects variance in performance impairment during sleep deprivation. Nonetheless, the differential effect of the polymorphism at the peak of performance impairment was more than 50% of median performance impairment at that time, which is sizeable compared to the effects of other genotypes reported in the literature. Our findings provided evidence for a role of TNFα in the effects of sleep deprivation on psychomotor vigilance performance. Furthermore, the TNFα G308A polymorphism may have predictive potential in a biomarker panel for the assessment of resilience to psychomotor vigilance performance impairment due to sleep deprivation.

The day-to-day concurrence of bodily complaints and affect in patients with severe somatoform disorder.

Based on the concept of somatization, psychological distress can be experienced as symptoms of physical illness. This suggests a close-fitting intra-individual association between bodily complaints and mood in patients with somatoform disorder (SFD). The contemporaneous day-to-day complaints-mood association was investigated in patients with severe chronic SFD using an ecological momentary assessment (EMA) design. Eleven patients, who had recently received specialized tertiary care treatment for severe chronic SFD, kept an online electronic diary for four consecutive weeks. They were prompted at intervals throughout the day to complete questions on their momentary primary symptoms (pain and fatigue), and mood state (negative and positive). For each measure, day-mean aggregated values were computed and analyzed using linear multilevel (mixed model) regression analysis. Fixed factor results showed that symptoms were associated with both negative mood state (ß = 0.47) and positive mood state (ß = -0.59). Random results, however, indicated large inter-individual differences, with correlations varying between 0.17 and 0.99 for negative affect, and between -0.88 and 0.14 for positive affect. A substantial day-to-day contemporaneous association between symptoms and affect across subjects, as well as large inter-individual differences in this association, were demonstrated in patients with severe chronic SFD. EMA-data showing the relationship between both negative and (inverse) positive mood and complaints has potential clinical relevance: providing SFD patients with feedback consisting of their personal day-to-day concurrency graph may promote their understanding of their own complaints in a broader context than the somatic area.