Interindividual Differences In Sensitivity Research Articles

Modeling Individual Differences in Food Metabolism through Alternating Least Squares.

Understanding how macronutrients (e.g., carbohydrates, protein, fat) affect blood glucose is of broad interest in health and dietary research. The general effects are well known, e.g., adding protein and fat to a carbohydrate-based meal tend to reduce blood glucose. However, there are large individual differences in food metabolism, to where the same meal can lead to different glucose responses across individuals. To address this problem, we present a technique that can be used to simultaneously (1) model macronutrients' effects on glucose levels over time and (2) capture inter-individual differences in sensitivity to macronutrients. The model assumes that each macronutrient adds a basis function to the differences in macronutrient metabolism. The technique performs a linear decomposition of glucose responses, alternating between estimating the macronutrients' effect over time and capturing an individual's sensitivity to macronutrients. On an experimental dataset containing glucose responses to a variety of mixed meals, the technique is able to extract basis functions for the macronutrients that are consistent with their hypothesized effects on PPGRs, and also characterize how macronutrients affect individuals differently.

Load-dependent alpha suppression is related to working memory capacity for numbers

Alpha suppression is proposed to reflect a surge in cortical excitability to enhance stimulus processing in working memory. The attenuated state of alpha might reflect the prioritisation of behaviourally relevant information, making it a proxy for working memory functioning. Despite the growing interest in utilising the advancement of brain-based measures to evaluate individuals’ cognitive processes, there was a lack of consistent evidence on the relationship between alpha suppression and working memory performance. To investigate whether interindividual differences in alpha suppression might be related to variability in working memory capacity, we recorded participants’ electroencephalography (EEG) while they performed an arithmetic task of either low or high working memory load. Participants were required to calculate either the product of digits (i.e., low-load condition) or the difference between the product of digits (i.e., high-load condition). We found alpha suppression at parietal regions, which became more prominent as working memory load increased. The pattern was present in approximately 80% of the participants. Importantly, the more the alpha suppressed as working memory load increased, the larger the drops in behavioural performance and the lower the Digit Span score. That is, alpha suppression was more prominent in participants of poor working memory capacity. Our findings suggest that alpha activity, subject to interindividual differences in sensitivity, could serve as a brain-based measure of an individual’s working memory functioning.

Experiences of Adults High in the Personality Trait Sensory Processing Sensitivity: A Qualitative Study.

Sensory processing sensitivity (SPS) is a personality trait reflecting inter-individual differences in sensitivity to negative and positive environmental information. Being high in SPS is associated with increased stress-related problems if environments are unfavourable but also appears to enhance one’s ability to benefit from health-promoting environments. In understanding SPS, therefore, lies the potential for innovating the ways we use to promote mental health. However, as a young research field, the core characteristics of SPS are yet debated. Qualitative research interviewing highly sensitive adults is important to conduct ecologically valid research connected with the complex realities of people. This study was the first to systematically report the perceptions and experiences of SPS characteristics in adults high in this trait. Semi-structured interviews (n = 26) were analysed thematically and described following consolidated criteria for reporting qualitative research. Six themes emerged: (1) emotional responding; (2) relatedness to others; (3) thinking; (4) overstimulation; (5) perceiving details; and (6) global SPS characteristics. With regards to coping with negative consequences of high SPS, the main themes were: (1) reducing sensory input and (2) psychological strategies. We gained fine-grained information on experiences of adults high in SPS and derived new hypotheses regarding the fostering of well-being related to high SPS.

Are Sensitivity to Punishment, Sensitivity to Reward and Effortful Control Transdiagnostic Mechanisms Underlying the Eating Disorder/Obesity Spectrum?

Although it has been postulated that eating disorders (EDs) and obesity form part of a broad spectrum of eating- and weight-related disorders, this has not yet been tested empirically. In the present study, we investigated interindividual differences in sensitivity to punishment, sensitivity to reward, and effortful control along the ED/obesity spectrum in women. We used data on 286 patients with eating disorders (44.6% AN-R, 24.12% AN-BP, and 31.82% BN), 126 healthy controls, and 640 Class II/III obese bariatric patients (32.81% Class II and 67.19% Class III) with and without binge eating. Participants completed the behavioral inhibition and behavioral activation scales, as well as the effortful control scale, to assess sensitivity to punishment and reward and effortful control. Results showed that patients with EDs scored significantly higher on punishment sensitivity (anxiety) compared to healthy controls and Class II/III obese patients; the different groups did not differ significantly on reward sensitivity. Patients with binge eating or compensatory behaviors scored significantly lower on effortful control than patients without binge eating. Differences in temperamental profiles along the ED/obesity spectrum appear continuous and gradual rather than categorical. This implies that it may be meaningful to include emotion regulation and impulse regulation training in the treatment of both EDs and obesity.

Expected value and sensitivity to punishment modulate insular cortex activity during risky decision making

The exact contribution of the insula to risky decision making remains unclear, as are the specific outcome parameters and inter-individual characteristics that modulate insular activity prior to a risky choice. This fMRI study examines the contributions of outcome valence, magnitude, probability, and expected value (EV) to insular activity during risky decision making, and explores the influence of sensitivity to reward and to punishment, and anxiety, to insular activity. Participants (N = 31) performed a gambling task requiring choice between two roulettes with different outcome magnitude, probability and EV, under gain and loss conditions separately, and filled questionnaires assessing sensitivity to punishment/reward, and state/trait anxiety. Parametric analyses were conducted to examine the modulation of brain activity during decision making in relation to each task parameter. Correlations were examined between insular activity and psychometric questionnaires. EV of the selected roulette was associated with right posterior insula activation during decision making. Higher sensitivity to punishment was associated with lower bilateral insular activation. These findings suggest that the right posterior insula is involved in tracking the EV of a risky option during decision making. The involvement of the insula when making risky decisions also appears to be influenced by inter-individual differences in sensitivity to punishment.

Neonatal hippocampal volume moderates the effects of early postnatal enrichment on cognitive development

Environmental enrichment, particularly during the early life phases of enhanced neuroplasticity, can stimulate cognitive development. However, individuals exhibit considerable variation in their response to environmental enrichment. Recent evidence suggests that certain neurophenotypes such as hippocampal size may index inter-individual differences in sensitivity to environmental conditions. We conducted a prospective, longitudinal investigation in a cohort of 75 mother-child dyads to investigate whether neonatal hippocampal volume moderates the effects of the postnatal environment on cognitive development. Newborn hippocampal volume was quantified shortly after birth (26.2 ± 12.5 days) by structural MRI. Measures of infant environmental enrichment (assessed by the IT-HOME) and cognitive state (assessed by the Bayley-III) were obtained at 6 months of age (6.09 ± 1.43 months). The interaction between neonatal hippocampal volume and enrichment predicted infant cognitive development (b = 0.01, 95 % CI [0.00, 0.02], t = 2.08, p = .04), suggesting that exposure to a stimulating environment had a larger beneficial effect on cognitive outcomes among infants with a larger hippocampus as neonates. Our findings suggest that the effects of the postnatal environment on infant cognitive development are conditioned, in part, upon characteristics of the newborn brain, and that newborn hippocampal volume is a candidate neurophenotype in this context.

Sussing out sensitivity to light: How evening light impacts individuals’ circadian systems

Interindividual differences in sensitivity to evening light may present a new component of circadian disruption.

High sensitivity and interindividual variability in the response of the human circadian system to evening light

Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (<30 lux) environmental light-stimuli at extreme ends of the circadian system's dose-response curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30-300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose-response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18-30) were exposed to a dim control (<1 lux) and a range of experimental light levels (10-2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock's role in human health and disease.

Molecular determinism of specific anosmia to 2‐bromo‐4‐methylphenol

AbstractSeveral studies have revealed considerable variations in human chemosensory capacities. Considerable interindividual differences in sensitivity to various odorants and specific hyposmias are well known. Many chemical studies have focused on elucidating structure‐odour relationships on the basis of detection threshold measurements. The basic idea of quantitative structure‐activity relationship studies is that a molecule's structure provides information about its biological activity. In a recent sensory assay of 2‐bromo‐4‐methylphenol, Barbe et al. (2014) highlighted a noticeable bimodal distribution of individual sensitivity with large interindividual differences. The aim of the present study was to investigate the link between the chemical structure of 2‐bromo‐4‐methylphenol and this bimodal distribution. The olfactory phenotypes for a selection of six structurally related halogenated compounds were compared using detection thresholds determination. This study revealed that specific anosmia for 2‐bromo‐4‐methylphenol was apparently linked to the halogenated substitution position. Copyright © 2016 John Wiley &amp; Sons, Ltd.

The Structural Correlates of Statistical Information Processing during Speech Perception.

The processing of continuous and complex auditory signals such as speech relies on the ability to use statistical cues (e.g. transitional probabilities). In this study, participants heard short auditory sequences composed either of Italian syllables or bird songs and completed a regularity-rating task. Behaviorally, participants were better at differentiating between levels of regularity in the syllable sequences than in the bird song sequences. Inter-individual differences in sensitivity to regularity for speech stimuli were correlated with variations in surface-based cortical thickness (CT). These correlations were found in several cortical areas including regions previously associated with statistical structure processing (e.g. bilateral superior temporal sulcus, left precentral sulcus and inferior frontal gyrus), as well other regions (e.g. left insula, bilateral superior frontal gyrus/sulcus and supramarginal gyrus). In all regions, this correlation was positive suggesting that thicker cortex is related to higher sensitivity to variations in the statistical structure of auditory sequences. Overall, these results suggest that inter-individual differences in CT within a distributed network of cortical regions involved in statistical structure processing, attention and memory is predictive of the ability to detect structural structure in auditory speech sequences.

Effective method of continuous rocuronium administration based on effect-site concentrations using a pharmacokinetic/pharmacodynamic model during propofol-remifentanil anesthesia.

Rocuronium bromide (Rb) is a rapid onset, intermediate-acting neuromuscular blocking agent that is suitable for continuous administration. The appropriate rate of rocuronium administration is, however, difficult to determine due to large interindividual differences in sensitivity to rocuronium. The aim of this study was to clarify whether the simulated rocuronium concentration at the time of recovery to %T1 > 0 % after the initial administration of rocuronium is a good indicator of optimal effect-site concentrations during continuous rocuronium administration. Twenty-one patients were anesthetized with propofol. After induction, Rb 0.6 mg/kg was administered intravenously, and nerve stimulation using the single stimulation mode was conducted every 15 s. When %T1 recovered to >0 % after the initial administration of Rb, the effect-site concentration of rocuronium, calculated by pharmacokinetic simulation with Wierda's set of parameters, was recorded and defined as the recovery concentration (Rb r.c.). The administration rate of rocuronium was adjusted to maintain the Rb r.c. during surgery. Rb administration was discontinued just before the end of surgery, and the recovery time until %T1 > 25 % was recorded. Plasma Rb concentrations were measured at 1 and 3 h after the initiation of continuous Rb administration. The mean Rb r.c. was 1.56 ± 0.35 μg/ml, with minimum and maximum values of 1.09 and 2.08 μg/ml, respectively. The %T1 did not increase above 10 % in any of the patients during continuous administration of Rb, and the recovery period to %T1 > 25 % ranged from 9 to 29 min. The effect-site concentrations of Rb calculated with Wierda's parameters significantly correlated with plasma concentrations (P < 0.01) at both 1 and 3 h after the initial administration of Rb. The results suggest that our method may be one of the most reliable protocols for the continuous administration of Rb described to date for maintaining suitable muscle relaxation during surgery without excessively prolonged effects.

Metabolism of aflatoxins: key enzymes and interindividual as well as interspecies differences.

Aflatoxins are potent hepatocarcinogen in animal models and suspected carcinogen in humans. The most important aflatoxin in terms of toxic potency and occurrence is aflatoxin B1 (AFB1). In this review, we mainly summarized the key metabolizing enzymes of AFB1 in animals and humans. Moreover, the interindividual and the interspecies differences in AFB1 metabolism are highly concerned. In human liver, CYP3A4 plays an important role in biotransforming AFB1 to the toxic product AFB1-8,9-epoxide. In human lung, CYP2A13 has a significant activity in metabolizing AFB1 to AFB1-8,9-epoxide and AFM1-8,9-epoxide. The epoxide of AFB1-8,9-epoxide could conjugate with glutathione to reduce the toxicity by glutathione-S-transferase (GST). In poultry species, CYP2A6, CYP3A37, CYP1A5, and CYP1A1 are responsible for bioactivation of AFB1. There are interindividual variations in the rate of activation of aflatoxins in various species, and there are also differences between children and adults. The age and living regions are important factors affecting resistance of species to AFB1. The rate of AFB1-8,9-epoxide formation and its conjugation with glutathione are key parameters in interspecies and interindividual differences in sensitivity to the toxic effect of AFB1. This review provides an important information for key metabolizing enzymes and the global metabolism of aflatoxins in different species.

Cytochrome P450 CYP1B1 Interacts with 8-Methoxypsoralen (8-MOP) and Influences Psoralen-Ultraviolet A (PUVA) Sensitivity

BackgroundThere are unpredictable inter-individual differences in sensitivity to psoralen-UVA (PUVA) photochemotherapy, used to treat skin diseases including psoriasis. Psoralens are metabolised by cytochrome P450 enzymes (P450), and we hypothesised that variability in cutaneous P450 expression may influence PUVA sensitivity. We previously showed that P450 CYP1B1 was abundantly expressed in human skin and regulated by PUVA, and described marked inter-individual differences in cutaneous CYP1B1 expression.ObjectivesWe investigated whether CYP1B1 made a significant contribution to 8-methoxypsoralen (8-MOP) metabolism, and whether individuality in CYP1B1 activity influenced PUVA sensitivity.MethodsWe used E. coli membranes co-expressing various P450s and cytochrome P450 reductase (CPR) to study 8-MOP metabolism and cytotoxicity assays in CYP1B1-expressing mammalian cells to assess PUVA sensitivity.ResultsWe showed that P450s CYP1A1, CYP1A2, CYP1B1, CYP2A6 and CYP2E1 influence 8-MOP metabolism. As CYP1B1 is the most abundant P450 in human skin, we further demonstrated that: (i) CYP1B1 interacts with 8-MOP (ii) metabolism of the CYP1B1 substrates 7-ethoxyresorufin and 17-β-estradiol showed concentration-dependent inhibition by 8-MOP and (iii) inhibition of 7-ethoxyresorufin metabolism by 8-MOP was influenced by CYP1B1 genotype. The influence of CYP1B1 on PUVA cytotoxicity was further investigated in a Chinese hamster ovary cell line, stably expressing CYP1B1 and CPR, which was more sensitive to PUVA than control cells, suggesting that CYP1B1 metabolises 8-MOP to a more phototoxic metabolite(s).ConclusionOur data therefore suggest that CYP1B1 significantly contributes to cutaneous 8-MOP metabolism, and that individuality in CYP1B1 expression may influence PUVA sensitivity.

Amygdala volume predicts inter-individual differences in fearful face recognition.

The present study investigates the relationship between inter-individual differences in fearful face recognition and amygdala volume. Thirty normal adults were recruited and each completed two identical facial expression recognition tests offline and two magnetic resonance imaging (MRI) scans. Linear regression indicated that the left amygdala volume negatively correlated with the accuracy of recognizing fearful facial expressions and positively correlated with the probability of misrecognizing fear as surprise. Further exploratory analyses revealed that this relationship did not exist for any other subcortical or cortical regions. Nor did such a relationship exist between the left amygdala volume and performance recognizing the other five facial expressions. These mind-brain associations highlight the importance of the amygdala in recognizing fearful faces and provide insights regarding inter-individual differences in sensitivity toward fear-relevant stimuli.

Association Between Polymorphisms in Serotonin and Dopamine-Related Genes and Endogenous Pain Modulation

Genetic studies have become indispensable in understanding pain mechanisms, shedding light on the role of monoamine pathways in pain modulation. The present study was aimed to explore the relationship between functional polymorphisms in serotonin and dopamine-related genes and pain modulation. Two paradigms of pain modulation were administered to 191 healthy participants in a random order: Conditioned Pain Modulation in response to painful stimuli (CPM painful) tested by the coadministration of repeated short painful heat stimuli and a conditioning tonic cold pain stimulation; and Conditioned Pain Modulation in response to nonpainful stimuli (CPM nonpainful) tested similarly, except for using a painless conditioning stimulation. Using the Transmission Disequilibrium Test (TDT), functional variable number of tandem repeat (VNTR) polymorphisms of the following candidate genes were studied: 1) serotonin transporter (5-HTTLPR); 2) dopamine transporter (DAT1); 3) dopamine receptor 4 (DRD4); and 4) monoamine oxidase A (MAOA). DNA samples from both participants and their parents were analyzed. A significant association was found between CPM nonpainful and the 5-HTTLPR polymorphism ( P = .001). More specifically, carriers of the long allele exhibited a significantly higher magnitude of CPM nonpainful than carriers of the short allele. No associations were found between the dopamine-related genes and both types of pain modulation. These results highlight the importance of serotonin in endogenous analgesia. Perspective This article presents an association between the serotonin transporter gene polymorphism (5-HTTLPR) and pain modulation derived by nonpainful conditioned pain modulation (CPM nonpainful), rather than painful conditioned pain modulation (CPM painful). These findings emphasize the complex role of serotonin in pain modulation, and highlight the importance of genetic studies in the understanding of interindividual differences in sensitivity to pain.

Variation in umami taste perception in the German and Norwegian population

In this study, we investigated inter-individual differences in sensitivity to mono-sodium glutamate (MSG) and elucidated the familiarity to umami taste in two European populations. The study consisted of two parts: (1) a survey based on questionnaire and (2) psychophysical screening for inter-individual variation of MSG sensitivity. The psychophysical tests revealed that 3.2% of the German participants and 4.6% of the Norwegian participants were potential non-tasters of MSG. In conclusion, our study confirms inter-individual differences in sensitivity to MSG in humans.

O-Methylation of Catechol Estrogens by Human Placental Catechol-O-Methyltransferase: Interindividual Differences in Sensitivity to Heat Inactivation and to Inhibition by Dietary Polyphenols

The human catechol-O-methyltransferase (COMT) is a polymorphic enzyme that catalyzes the O-methylation of catechol estrogens. Recent animal studies showed that placental COMT is involved in the development of placentas and embryos, probably via the formation of 2-methoxyestradiol. In this study, we analyzed a total of 36 human term placentas to determine their cytosolic COMT activity for the O-methylation of catechol estrogens as well as their sensitivity to inhibition by heat and dietary compounds. Large variations (up to 4-fold) in the COMT activity for the formation of methoxyestrogens were noted with different human placental samples. The cytosolic COMTs in different human placentas also displayed considerable differences in their sensitivity to heat inactivation. This differential sensitivity was not associated with the overall catalytic activity for the O-methylation of catechol estrogen substrates. It was observed that there was a positive correlation (r = 0.760) between the sensitivity of the human placental COMT to heat inactivation and its sensitivity to inhibition by (-)-epigallocatechin-3-gallate (a well known tea polyphenol with COMT-inhibiting activity) but an inverse correlation (r = 0.544) between heat inactivation and inhibition by quercetin (another dietary COMT inhibitor). The differences in inhibition by these two dietary compounds are due to different mechanisms of COMT inhibition involved.

Rapamycin shows anticancer activity in primary chronic lymphocytic leukemia cells in vitro, as single agent and in drug combination

The mammalian target of rapamycin inhibitor rapamycin and its analogues show promising anticancer activity in various experimental tumor models and are presently evaluated in clinical trials. We, here, evaluated the in vitro activity of rapamycin with regard to tumor-type specificity and possible mechanisms of drug resistance in 97 tumor cell samples from patients and in a resistance-based cell line panel, using the fluorometric microculture cytotoxicity assay. Rapamycin was dose-dependently cytotoxic in patient tumor cells and in cell lines. In primary cells, rapamycin was more active in hematological than in solid tumor samples, with chronic lymphocytic leukemia (CLL) and acute lymphocytic leukemia being the most sensitive tumor types. Considerable inter-individual differences in sensitivity were apparent among CLL samples, but no difference was observed between IGHV mutated and unmutated CLL samples, whereas a tendency to lower rapamycin sensitivity was indicated for samples displaying poor-prognostic genomic markers. Combination experiments in CLL cells indicated that rapamycin acted synergistically with vincristine, cisplatin, chlorambucil and taxotere. These results and the clinically-experienced good tolerance to rapamycin analogues encourage clinical studies of rapamycin in CLL treatment as single agent but also in combination with, e.g., vincristine and chlorambucil.

Effect of low gravitational stimulation on the perception of target elevation: Role of spatial expertise

To examine the interindividual differences in the judgment of the visually perceived eye level (VPEL-upright position) and of the visually perceived apparent zenith (VPAZ-supine position) when the subject is subjected to low gravitational-inertial force (GIF), we independently altered GIF in two different populations: control subjects and spatial experts. Subjects were instructed to set a luminous target to the eye level while they were in total darkness and motionless or undergoing low radial acceleration with respect to the threshold of the otolithic system (0.015-1.67 m/sec2 for the VPEL and 0.55-2.19 m/sec2 for the VPAZ, respectively). Results showed that (1) low GIFs, close to those met during daily life, induced an eye level lowering in the upright and supine positions for the control group, and (2) the spatial expertise modified the influence of low GIF. Whereas an oculogravic illusion was found for the control group, this phenomenon was absent (VPAZ) or weaker (VPEL) for the spatial experts. Thus, the relations that the subjects maintain with their spatial environment and the knowledge acquired through experience modify the processing of sensory information and the perceptive construction resulting from it. The interindividual differences in sensitivity to the oculogravic illusion are discussed in terms of sensory dominance and of a better efficiency in the use of the available sensory information.

Homozygous Null Genotype at Glutathione S-transferase M1 Locus as a Risk Factor for Oral Squamous Cell Carcinoma in Indian Tobacco Users

KEYWORDS Indian population; tobacco smoking/chewing; oral SCC; GSTM1; GSTT1; CYP1A1; CYP2E1; genetic polymorphism ABSTRACT Inter-individual differences in sensitivity to chemical carcinogens may contribute to differences in susceptibility to human cancer subsequent to environmental exposures. It has been reported that polymorphisms in glutathione S-transferase (GST) and cytochrome P-450 oxidase (CYP) genes are associated with increased risk of tobacco-related cancers in different ethnic populations. In this study, we investigated polymorphisms in GSTM1, GSTT1, CYP1A1 and CYP2E1 genes in 80 oral squamous cell carcinoma (SCC) patients and 67 controls from one Indian population. Prevalence of the GSTM1 homozygous null genotype was 39 in 80 patients (49%) compared to 18 in 67 controls (27%) (age and sex adjusted OR=1.8, 95% CI=1.0-3.6). Analyses of data on polymorphisms in GSTT1, CYP1A1 and CYP2E1 did not reveal significant differences in distribution of genotypes between patient and control groups. Our results confirm that GSTM1 homozygous null genotype adds to the risk of oral cancer development among tobacco users. But low sample size limited the power to estimate tobacco dose-genotype interactions.