scholarly journals Individual differences in dopamine are associated with reward discounting in clinical groups but not in healthy adults

2018 ◽  
Author(s):  
Jaime J. Castrellon ◽  
Kendra L. Seaman ◽  
Jennifer L. Crawford ◽  
Jacob S. Young ◽  
Christopher T. Smith ◽  
...  
Keyword(s):  
Individual Differences ◽  
Empirical Finding ◽  
Temporal Discounting ◽  
Healthy Adults ◽  
Clinical Samples ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Physical Effort ◽  
Healthy Humans ◽  
Effort Discounting

abstractSome people are more willing to make immediate, risky, or costly reward-focused choices than others, which has been hypothesized to be associated with individual differences in dopamine (DA) function. In two studies using PET imaging, one empirical (Study 1: N=144 males and females across 3 samples) and one meta-analytic (Study 2: N=307 across 12 samples), we sought to characterize associations between individual differences in DA and time, probability, and physical effort discounting in human adults. Study 1 demonstrated that individual differences in DA D2-like receptors were not associated with time or probability discounting of monetary rewards in healthy humans, and associations with physical effort discounting were inconsistent across adults of different ages. Meta-analytic results for temporal discounting corroborated our empirical finding for minimal effect of DA measures on discounting in healthy individuals, but suggested that associations between individual differences in DA and reward discounting depend on clinical features. Addictions were characterized by negative correlations between DA and discounting but other clinical conditions like Parkinson’s Disease, obesity, and ADHD were characterized by positive correlations between DA and discounting. Together the results suggest that trait differences in discounting in healthy adults do not appear to be strongly associated with individual differences in D2-like receptors. The difference in meta-analytic correlation effects between healthy controls and individuals with psychopathology suggests that individual difference findings related to DA and reward discounting in clinical samples may not be reliably generalized to healthy controls, and vice-versa.Significance StatementDecisions to forgo large rewards for smaller ones due to increasing time delays, uncertainty, or physical effort have been linked to differences in dopamine (DA) function, which is disrupted in some forms of psychopathology. It remains unclear whether alterations in DA function associated with psychopathology also extend to explaining associations between DA function and decision making in healthy individuals. We show that individual differences in dopamine D2 receptor availability are not consistently related to monetary discounting of time, probability, or physical effort in healthy individuals across a broad age range. By contrast, we suggest that psychopathology accounts for observed inconsistencies in the relationship between measures of dopamine function and reward discounting behavior.

scholarly journals Distinct striatal subregions and corticostriatal connectivity for effort, action and reward

2020 ◽  
Author(s):  
Shosuke Suzuki ◽  
Victoria M. Lawlor ◽  
Jessica A. Cooper ◽  
Amanda R. Arulpragasam ◽  
Michael T. Treadway
Keyword(s):  
Individual Differences ◽  
Ventral Striatum ◽  
Cost Benefit ◽  
Prior Work ◽  
Physical Effort ◽  
Large Sample ◽  
Subjective Value ◽  
Effort Discounting ◽  
Freely Moving ◽  
The Relationship

AbstractThe ventral striatum is believed to encode the subjective value of cost/benefit options; however, this effect has strikingly been absent during choices that involve physical effort. Prior work in freely-moving animals has revealed opposing striatal signals, with greater response to increasing effort demands and reduced responses to rewards requiring effort. Yet, the relationship between these conflicting signals remains unknown. Using fMRI with a naturalistic, effort-based navigation paradigm, we identified functionally-segregated regions within ventral striatum that separately encoded action, effort, and discounting of rewards by effort. Strikingly, these sub-regions mirrored results from a large-sample connectivity-based parcellation of the striatum. Moreover, individual differences in striatal effort activation and effort discounting signals predicted striatal responses to effort-related choices during an independent fMRI task. Taken together, our results suggest that a dorsomedial region primarily associated with action may instead represent the effort cost of actions, and raises fundamental questions regarding the interpretation of striatal “reward” signals in the context of effort demands.

XMODULATION IN MICEAND MEN: IL-10 PRODUCING CELLS INBLOOD AND LYMPHOID TISSUE

2008 ◽  
Vol 31 (4) ◽  
pp. 3
Author(s):  
L Barrett ◽  
M Grant ◽  
R Liwski ◽  
K West
Keyword(s):  
Immune System ◽  
Peripheral Blood ◽  
Lymphoid Tissue ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
White Blood Cells ◽  
Interleukin 10 ◽  
Healthy Individuals ◽  
Human Immune System ◽  
Healthy Humans

Background: The human immune system provides remarkable protection from a plethora of pathogens, but can cause damage when activated for a prolonged time (as inpersistent infections) or against self (autoimmunity). Therefore, mechanisms of immune system downregulation and control are imperative. There is little data on how the immune system is controlled in healthy individuals. We recently described a novel population of white blood cells that constitutively produce the immunomodulatory cytokine interleukin-10 (IL-10). Our objective was to further delineate the distribution of these cells in human and mouse models, as well as potential triggers for interleukin-10 production in vitro. Methods: Human and animal protocols were reviewed and approved by the institutional ethics board and animal care facilities, and informed consent was obtained from all human donors. The ex vivo percentage of peripheral blood CD36^+IL-10^+ mononuclear cells was assessed by intracellular flow cytometry in 10 healthy individuals. IL-10 production after exposure to twoCD36 ligands, thrombospondin and oxidized low density lipoprotein (oxLDL) was measured at 8 hours. Peripheral blood mononuclear cells and splenocytes from BL/6 (n=5) and Balb/c (n=1) micewere assessed for CD36^+IL-10^+ cells ex vivo as well. Results: The percentage of CD36^+IL-10^+ cells in peripheral blood fromhealthy individuals ranges between 0.1% and 0.9%. The percentage was similar in mouse peripheral blood, with a range of 0.4%-1.1%. These cells were also found in mouse spleen at a higher frequency than peripherally (1.1-1.5%). Human CD36^+IL-10^+ cells have more IL-10 when exposed to thrombospondin, oxLDL. Conclusions: Our novel population of IL-10 producing cells is found not only in healthy humans, but also in lymphoid tissue and blood from pathogen free mice. This highlights the evolutionary conservation of the cell across species, and suggests an important homeostatic function. The physiologic ligands for CD36 are ubiquitous in circulation, and ourin vitro data suggests a link between CD36 ligation and IL-10 production. IL-10 is a known immune system modulator, and its production by these cells may help maintain homeostaticcontrol of the immune system.

scholarly journals BARD1 Autoantibody Blood Test for Early Detection of Ovarian Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 969
Author(s):  
Maxim Pilyugin ◽  
Magda Ratasjka ◽  
Maciej Stukan ◽  
Nicole Concin ◽  
Robert Zeillinger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Blood Test ◽  
Menopausal Status ◽  
Clinical Samples ◽  
Average Risk ◽  
Healthy Controls ◽  
Cancer Antigen 125 ◽  
Cancer Syndrome ◽  
Ovarian Cancer Screening

Background: Ovarian cancer (OC) is the most lethal gynaecological cancer. It is often diagnosed at an advanced stage with poor chances for successful treatment. An accurate blood test for the early detection of OC could reduce the mortality of this disease. Methods: Autoantibody reactivity to 20 epitopes of BARD1 and concentration of cancer antigen 125 (CA125) were assessed in 480 serum samples of OC patients and healthy controls. Autoantibody reactivity and CA125 were also tested for 261 plasma samples of OC with or without mutations in BRCA1/2, BARD1, or other predisposing genes, and healthy controls. Lasso statistic regression was applied to measurements to develop an algorithm for discrimination between OC and controls. Findings and interpretation: Measurement of autoantibody binding to a number of BARD1 epitopes combined with CA125 could distinguish OC from healthy controls with high accuracy. This BARD1-CA125 test was more accurate than measurements of BARD1 autoantibody or CA125 alone for all OC stages and menopausal status. A BARD1-CA125-based test is expected to work equally well for average-risk women and high-risk women with hereditary breast and ovarian cancer syndrome (HBOC). Although these results are promising, further data on well-characterised clinical samples shall be used to confirm the potential of the BARD1-CA125 test for ovarian cancer screening.

scholarly journals Perceptual insensitivity to the modulation of interoceptive signals in depression, anxiety, and substance use disorders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryan Smith ◽  
◽  
Justin S. Feinstein ◽  
Rayus Kuplicki ◽  
Katherine L. Forthman ◽  
...  
Keyword(s):  
Machine Learning ◽  
Substance Use ◽  
Individual Differences ◽  
Substance Use Disorders ◽  
Breath Hold ◽  
Healthy Individuals ◽  
Performance Improvements ◽  
Heartbeat Perception ◽  
Minimal Improvement ◽  
Healthy Participants

AbstractThis study employed a series of heartbeat perception tasks to assess the hypothesis that cardiac interoceptive processing in individuals with depression/anxiety (N = 221), and substance use disorders (N = 136) is less flexible than that of healthy individuals (N = 53) in the context of physiological perturbation. Cardiac interoception was assessed via heartbeat tapping when: (1) guessing was allowed; (2) guessing was not allowed; and (3) experiencing an interoceptive perturbation (inspiratory breath hold) expected to amplify cardiac sensation. Healthy participants showed performance improvements across the three conditions, whereas those with depression/anxiety and/or substance use disorder showed minimal improvement. Machine learning analyses suggested that individual differences in these improvements were negatively related to anxiety sensitivity, but explained relatively little variance in performance. These results reveal a perceptual insensitivity to the modulation of interoceptive signals that was evident across several common psychiatric disorders, suggesting that interoceptive deficits in the realm of psychopathology manifest most prominently during states of homeostatic perturbation.

scholarly journals Dispositional individual differences in cognitive effort investment: establishing the core construct

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Corinna Kührt ◽  
Sebastian Pannasch ◽  
Stefan J. Kiebel ◽  
Alexander Strobel
Keyword(s):  
Individual Differences ◽  
Latent Variables ◽  
Effortful Control ◽  
Factor Model ◽  
Cognitive Effort ◽  
Self Control ◽  
Behavioral Measures ◽  
Effort Discounting ◽  
Cognitive Motivation ◽  
Goal Directed Behavior

Abstract Background Individuals tend to avoid effortful tasks, regardless of whether they are physical or mental in nature. Recent experimental evidence is suggestive of individual differences in the dispositional willingness to invest cognitive effort in goal-directed behavior. The traits need for cognition (NFC) and self-control are related to behavioral measures of cognitive effort discounting and demand avoidance, respectively. Given that these traits are only moderately related, the question arises whether they reflect a common core factor underlying cognitive effort investment. If so, the common core of both traits might be related to behavioral measures of effort discounting in a more systematic fashion. To address this question, we aimed at specifying a core construct of cognitive effort investment that reflects dispositional differences in the willingness and tendency to exert effortful control. Methods We conducted two studies (N = 613 and N = 244) with questionnaires related to cognitive motivation and effort investment including assessment of NFC, intellect, self-control and effortful control. We first calculated Pearson correlations followed by two mediation models regarding intellect and its separate aspects, seek and conquer, as mediators. Next, we performed a confirmatory factor analysis of a hierarchical model of cognitive effort investment as second-order latent variable. First-order latent variables were cognitive motivation reflecting NFC and intellect, and effortful self-control reflecting self-control and effortful control. Finally, we calculated Pearson correlations between factor scores of the latent variables and general self-efficacy as well as traits of the Five Factor Model of Personality for validation purposes. Results Our findings support the hypothesized correlations between the assessed traits, where the relationship of NFC and self-control is specifically mediated via goal-directedness. We established and replicated a hierarchical factor model of cognitive motivation and effortful self-control that explains the shared variance of the first-order factors by a second-order factor of cognitive effort investment. Conclusions Taken together, our results integrate disparate literatures on cognitive motivation and self-control and provide a basis for further experimental research on the role of dispositional individual differences in goal-directed behavior and cost–benefit-models.

scholarly journals Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease

2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Kawaljit Kaur ◽  
Shahram Vaziri ◽  
Marcela Romero-Reyes ◽  
Avina Paranjpe ◽  
Anahid Jewett
Keyword(s):  
Periodontal Disease ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Oral Disease ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Ifn Γ ◽  
And Function

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls. Increased activation induced cell death of peripheral blood mononuclear cells (PBMCs) but not OBMCs from patients with periodontal disease was observed when compared to those from healthy individuals. Unlike those from healthy individuals, OBMC-derived supernatants from periodontitis patients exhibited decreased ability to induce secretion of IFN-γ by allogeneic healthy PBMCs treated with IL-2, while they triggered significant levels of TNF-α, IL-1β and IL-6 by untreated PBMCs. Interaction of PBMCs, or NK cells with intact or NFκB knock down oral epithelial cells in the presence of a periodontal pathogen, F. nucleatum, significantly induced a number of pro-inflammatory cytokines including IFN-γ. These studies indicated that the relative numbers of immune subsets obtained from peripheral blood may not represent the composition of the immune cells in the oral environment, and that orally-derived immune effectors may differ in survival and function from those of peripheral blood.

scholarly journals Peripheral BDNF: a candidate biomarker of healthy neural activity during learning is disrupted in schizophrenia

2014 ◽  
Vol 45 (4) ◽  
pp. 841-854 ◽  
Author(s):  
A. J. Skilleter ◽  
C. S. Weickert ◽  
A. Vercammen ◽  
R. Lenroot ◽  
T. W. Weickert
Keyword(s):  
Functional Neuroimaging ◽  
Brain Activity ◽  
Healthy Adults ◽  
Enzyme Linked Immunosorbent Assay ◽  
Association Learning ◽  
Healthy Humans ◽  
Important Regulator ◽  
Learning Test ◽  
Parietal Cortices ◽  
And Task

Background.Brain-derived neurotrophic factor (BDNF) is an important regulator of synaptogenesis and synaptic plasticity underlying learning. However, a relationship between circulating BDNF levels and brain activity during learning has not been demonstrated in humans. Reduced brain BDNF levels are found in schizophrenia and functional neuroimaging studies of probabilistic association learning in schizophrenia have demonstrated reduced activity in a neural network that includes the prefrontal and parietal cortices and the caudate nucleus. We predicted that brain activity would correlate positively with peripheral BDNF levels during probabilistic association learning in healthy adults and that this relationship would be altered in schizophrenia.Method.Twenty-five healthy adults and 17 people with schizophrenia or schizo-affective disorder performed a probabilistic association learning test during functional magnetic resonance imaging (fMRI). Plasma BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA).Results.We found a positive correlation between circulating plasma BDNF levels and brain activity in the parietal cortex in healthy adults. There was no relationship between plasma BDNF levels and task-related activity in the prefrontal, parietal or caudate regions in schizophrenia. A direct comparison of these relationships between groups revealed a significant diagnostic difference.Conclusions.This is the first study to show a relationship between peripheral BDNF levels and cortical activity during learning, suggesting that plasma BDNF levels may reflect learning-related brain activity in healthy humans. The lack of relationship between plasma BDNF and task-related brain activity in patients suggests that circulating blood BDNF may not be indicative of learning-dependent brain activity in schizophrenia.

scholarly journals A Circulating Exosome RNA Signature Is a Potential Diagnostic Marker for Pancreatic Cancer, a Systematic Study

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2565
Author(s):  
Yixing Wu ◽  
Hongmei Zeng ◽  
Qing Yu ◽  
Huatian Huang ◽  
Beatrice Fervers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Early Detection ◽  
Validation Dataset ◽  
Healthy Controls ◽  
Rna Seq ◽  
Healthy Individuals ◽  
Kras Mutations ◽  
Significant Difference ◽  
Rna Signature

Several exosome proteins, miRNAs and KRAS mutations have been investigated in the hope of carrying out the early detection of pancreatic cancer with high sensitivity and specificity, but they have proven to be insufficient. Exosome RNAs, however, have not been extensively evaluated in the diagnosis of pancreatic cancer. The purpose of this study was to investigate the potential of circulating exosome RNAs in pancreatic cancer detection. By retrieving RNA-seq data from publicly accessed databases, differential expression and random-effects meta-analyses were performed. The results showed that pancreatic cancer had a distinct circulating exosome RNA signature in healthy individuals, and that the top 10 candidate exosome RNAs could distinguish patients from healthy individuals with an area under the curve (AUC) of 1.0. Three (HIST2H2AA3, LUZP6 and HLA-DRA) of the 10 genes in exosomes had similar differential patterns to those in tumor tissues based on RNA-seq data. In the validation dataset, the levels of these three genes in exosomes displayed good performance in distinguishing cancer from both chronic pancreatitis (AUC = 0.815) and healthy controls (AUC = 0.8558), whereas a slight difference existed between chronic pancreatitis and healthy controls (AUC = 0.586). Of the three genes, the level of HIST2H2AA3 was positively associated with KRAS status. However, there was no significant difference in the levels of the three genes across the disease stages (stages I–IV). These findings indicate that circulating exosome RNAs have a potential early detection value in pancreatic cancer, and that a distinct exosome RNA signature exists in distinguishing pancreatic cancer from healthy individuals.

scholarly journals Irritable bowel syndrome and psychological stress

1999 ◽  
Vol 4 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Barbara S Bayne ◽  
Anita D Stuart ◽  
H Gertie Pretorius
Keyword(s):  
Occupational Stress ◽  
Psychological Stress ◽  
The Other ◽  
Theory Building ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Daily Stress ◽  
Stress Inventory ◽  
Irritable Bowel ◽  
The Relationship

The purpose of this study was twofold. The first aim was to clarify the relationship between psychological stress and lrritable Bowel Syndrome (IBS) by establishing whether individuals suffering from IBS experience minor stress differently from healthy individuals in terms of its frequency or intensity. The second aim was more general and concerns theory building in a field filled with ambiguity and confusion. Two groups, one comprising IBS sufferers and the other healthy controls, completed the Daily Stress lnventory and the Occupational Stress lnventory - questionnaires designed to measure minor daily and occupational stress respectively. The findings indicate that IBS sufferers do not experience more stress than healthy individuals, but they experience the stressors with greater intensity.OpsommingDie doel van die studie was tweeledig. Eerstens is daar gepoog om duidelikheid te kry oor die verband tussen sielkundige stres en Prikkelbare Dermsindroom (PDS), deur te bepaal of individue wat aan PDS ly geringe stres anders ervaar as gesonde individue in terme van gereeldheid of intensiteit. Die tweede doelwit was meer algemeen en spreek die kwessie van teorie ontwikkeling aan in 'n veld gevul met dubbelsinningheid en verwarring. Twee groepe, een bestaande uit PDS lyers en die ander 'n gesonde kontrolegroep, het die "Daily Stress Inventory'' en die "Occupational Stress Inventory" voltooi. Die vraelyste is ontwerp om onderskeidelik daaglikse stres en werkstres te meet. Die resultate dui daarop dat PDS lyers nie meer stres ervaar as die gesonde individue nie, maar dat hulle wel die stressors ervaar met groter intensiteit.

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