Reward Activity Research Articles

Two-year trajectories of anhedonia in adolescents at transdiagnostic risk for severe mental illness: Association with clinical symptoms and brain-symptom links.

Anhedonia emerges during adolescence and is characteristic of severe mental illness (SMI). To understand how anhedonia emerges, changes with time, and relates with other symptoms, there is a need to understand patterns of this symptom's course reflecting change or stability-and associations with clinical symptoms and neural reward circuitry in adolescents at risk of SMI. In total, 113 adolescents at low or high familial risk of developing SMI completed clinical measures at up to five time points across 2 years and functional magnetic resonance imaging scanning during a guessing reward task at baseline. Growth curve analysis was used to determine the trajectory of anhedonia across 2 years, including different phases (consummatory and anticipatory) and their association with clinical features (risk status, average suicidal ideation, and average depression across time) and neural activation in response to rewards (ventral striatum and dorsal medial prefrontal cortex). The findings revealed anhedonia decreased across 2 years. Furthermore, lower depression severity was associated with decreases in anhedonia across 2 years. There were no interactions between neural reward activation and anhedonia slopes in predicting clinical features. Exploratory analyses examining latent classes revealed three trajectory classes of anhedonia across phases. While preliminary, in the low and decreasing consummatory anhedonia trajectory class, there was a positive association between neural activation of the right ventral striatum in response to rewards and depression. Certain patterns of anhedonia development could confer risk or resilience for specific types of psychopathologies. The results are preliminary but do highlight the complexity and heterogeneity in anhedonia development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

W23 - Effect of Acute THC, Sex, and Lifetime Cannabis Use on Neural Reward Activation

W23 - Effect of Acute THC, Sex, and Lifetime Cannabis Use on Neural Reward Activation

Blunted midbrain reward activation during smoking withdrawal: a preliminary study.

Tobacco smoking is the leading preventable cause of death, causing more than six million deaths annually worldwide, mainly due to cardiovascular disease and cancer. Many habitual smokers try to stop smoking but only about 7% are successful, despite widespread knowledge of the risks. Development of addiction to a range of substances is associated with progressive blunting of brain reward responses and sensitisation of stress responses, as described by the allostasis theory of addiction. There is pre-clinical evidence from rodents for a dramatic decrease in brain reward function during nicotine withdrawal. Here we tested the hypothesis that habitual smokers would also exhibit blunted reward function during nicotine withdrawal using a decision-making task and fMRI. Our findings supported this hypothesis, with midbrain reward-related responses particularly blunted. We also tested the hypothesis that smokers with a longer duration of smoking would have more pronounced abnormalities. Contrary to expectations, we found that a shorter duration of smoking in younger smokers was associated with the most marked abnormalities, with blunted midbrain reward related activation including the dopaminergic ventral tegmental area. Given the substantial mortality associated with smoking, and the small percent of people who manage to achieve sustained abstinence, further translational studies on nicotine addiction mechanisms are indicated.

Significance of Triazole in Medicinal Chemistry: Advancement in Drug Design, Reward and Biological Activity.

One of the triazole tautomers, 1,2,4-triazole derivatives, has a wide range of biological activities that suggest its potential therapeutic utility in medicinal chemistry. These actions include anti-inflammatory, anti-cancer, anti-bacterial, anti-tuberculosis, and anti-diabetic effects. Using computational simulations and models, we investigate the structure-activity relationships of 1,2,4-triazoles, showing how various modifications to the triazole core yield a variety of clinical therapeutic benefits. The review highlights the anti-inflammatory effect of 1,2,4-triazoles in relation to their ability to disrupt significant inflammatory mediators and pathways. We present in-silico data that illuminate the triazoles' capacity to inhibit cell division, encourage apoptosis, and stop metastasis in a range of cancer models. This review looks at the bactericidal and bacteriostatic properties of 1,2,4-triazole derivatives, with a focus on their potential efficacy against multi-drug resistant bacterial infections and their usage in tuberculosis therapy. In order to better understand these substances' potential anti-diabetic benefits, this review also looks at how they affect glucose metabolism regulation and insulin responsiveness. Coordinated efforts are required to translate the efficacy of 1,2,4-triazole compounds in preclinical models into practical therapeutic benefits. Based on the information provided, it can be concluded that 1,2,4-triazole derivatives are a promising class of diverse therapeutic agents with potential utility in a range of disorders. Their development and improvement might herald a new era of medical care that will be immensely advantageous to both patients and the medical community as a whole. This comprehensive research, which is further reinforced by in-silico investigations, highlights the great medicinal potential of 1,2,4-triazoles. Additionally, this study encourages more research into these substances and their enhancement for use in pharmaceutical development.

Neural basis of reward expectancy inducing proactive aggression.

Proactive aggression refers to deliberate and unprovoked behavior, typically motivated by personal gain or expected reward. Reward expectancy is generally recognized as a critical factor that may influence proactive aggression, but its neural mechanisms remain unknown. We conducted a task-based functional magnetic resonance imaging (fMRI) experiment to investigate the relationship between reward expectancy and proactive aggression. 37 participants (20 females, mean age = 20.8 ± 1.42, age range = 18-23 years) completed a reward-harm task. In the experiment, reward valence expectancy and reward possibility expectancy were manipulated respectively by varying amounts (low: 0.5-1.5 yuan; high: 10.5-11.5 yuan) and possibilities (low: 10%-30%; high: 70%-90%) of money that participants could obtain by choosing to aggress. Participants received fMRI scans throughout the experiment. Brain activation regions associated with reward expectancy mainly involve the middle frontal gyrus, lingual gyrus, inferior temporal gyrus, anterior cuneus, caudate nucleus, inferior frontal gyrus, cingulate gyrus, anterior central gyrus, and posterior central gyrus. Associations between brain activation and reward expectancy in the left insula, left middle frontal gyrus, left thalamus, and right middle frontal gyrus were found to be related to proactive aggression. Furthermore, the brain activation regions primarily involved in proactive aggression induced by reward expectancy were the insula, inferior frontal gyrus, inferior temporal gyrus, pallidum, and caudate nucleus. Under conditions of high reward expectancy, participants engage in more proactive aggressive behavior. Reward expectancy involves the activation of reward- and social-cognition-related brain regions, and these associations are instrumental in proactive aggressive decisions.

Transdiagnostic Mood, Anxiety, and Trauma Symptom Factors in Alcohol Use Disorder: Neural Correlates Across 3 Brain Networks

BackgroundAlcohol use disorder (AUD) is associated with high rates of trauma, mood, and anxiety disorders. Across these diagnoses, individual symptoms substantially overlap, highlighting the need for a transdiagnostic approach. Furthermore, there is limited research on how transdiagnostic psychopathology impacts the neural correlates of AUD. Thus, we aimed to identify symptom factors spanning diagnoses and examine how they relate to the neurocircuitry of addiction. MethodsEighty-six veterans with AUD completed self-report measures and reward, incentive salience, and cognitive control functional magnetic resonance imaging tasks. Factor analysis was performed on self-reported trauma, depression, anxiety, and stress symptoms to obtain transdiagnostic symptom compositions. Neural correlates of a priori–defined regions of interest in the 3 networks were assessed. Independent sample t tests were used to compare the same nodes by DSM-5 diagnosis. ResultsFour symptom factors were identified: Trauma distress, Negative affect, Hyperarousal, and Somatic anxiety. Trauma distress score was associated with increased cognitive control activity during response inhibition (dorsal anterior cingulate cortex). Negative affect was related to lower activation in reward regions (right caudate) but higher activation in cognitive control regions during response inhibition (left dorsolateral prefrontal cortex). Hyperarousal was related to lower reward activity during monetary reward anticipation (left caudate, right caudate). Somatic anxiety was not significantly associated with brain activation. No difference in neural activity was found by posttraumatic stress disorder, major depressive disorder, or generalized anxiety disorder diagnosis. ConclusionsThese hypothesis-generating findings offer transdiagnostic symptom factors that are differentially associated with neural function and could guide us toward a brain-based classification of psychiatric dysfunction in AUD. Results warrant further investigation of transdiagnostic approaches in addiction.

The cerebellum directly modulates the substantia nigra dopaminergic activity.

Evidence of direct reciprocal connections between the cerebellum and basal ganglia has challenged the long-held notion that these structures function independently. While anatomical studies have suggested the presence of cerebellar projections to the substantia nigra pars compacta (SNc), the nature and function of these connections (Cb-SNc) is unknown. Here we show, in mice, that Cb-SNc projections form monosynaptic glutamatergic synapses with dopaminergic and non-dopaminergic neurons in the SNc. Optogenetic activation of Cb-SNc axons in the SNc is associated with increased SNc activity, elevated striatal dopamine levels and increased locomotion. During behavior, Cb-SNc projections are bilaterally activated before ambulation and unilateral lever manipulation. Cb-SNc projections show prominent activation for water reward and higher activation for sweet water, suggesting that the pathway also encodes reward value. Thus, the cerebellum directly, rapidly and effectively modulates basal ganglia dopamine levels and conveys information related to movement initiation, vigor and reward processing.

Non-Playable Character (NPC) based on Behaviour Tree for Enhanced Immersive Experience in the Serious Game "Warik's Adventure"

Video games, or digital games, have transcended their traditional role of mere entertainment and are now being leveraged for more serious purposes, such as education and cultural preservation. Serious games offer the advantage of presenting content in an interactive and enjoyable manner. A crucial element in gameplay for creating interactivity and a pleasurable experience is the non-playable character (NPC). In serious games, replayability is pivotal for optimizing the comprehension of learning content, with the gameplay experience being a key factor influencing replayability. While games are known for their entertaining aspects, immersion design in serious games often falls short, resulting in a subpar experience. The NPC design in this study is grounded in appreciative learning, emphasizing positive outcomes such as possibilities, peak successes, exploration, and future optimism. The reward activity is structured across four levels: Discovery, Dream, Design, and Destiny. Behaviour Tree is employed to govern NPC behavior throughout all four stages. To evaluate the effectiveness of the immersive design, the Game Experience Questionnaire (GEQ) is employed, measuring three primary components—sensory, imaginative, and challenge-based immersion. The GEQ result indicates a score of 3.2, showcasing a slight improvement from the previous version's score of 3.07. This research contributes to the enhancement of serious game design by focusing on NPC behavior and immersive experiences, ultimately fostering more effective and engaging learning environments.

Neurocognitive reward processes measured via event-related potentials are associated with binge-eating disorder diagnosis and ecologically-assessed behavior

Altered reward processing has been implicated in the onset and maintenance of binge-eating disorder (BED). However, it is unclear which precise neurocognitive reward processes may contribute to BED. In the present study, 40 individuals with BED and 40 age-, sex-, and BMI-matched controls completed a reward (incentive delay) task while their neural activity was recorded using electroencephalography (EEG). Individuals with BED also completed a 10-day ecological momentary assessment (EMA) protocol assessing binge-eating behavior in the natural environment. Event-related potential (ERP) analysis of the EEG indicated that individuals with BED had stronger anticipatory (CNV) and outcome-related (RewP) neural reward activity to food and monetary rewards, compared to controls. However, within the BED group, greater frequency of binge eating during the EMA protocol was associated with stronger anticipatory (CNV) but weaker outcome-related (RewP) neural reward activity. These associations within the BED group were unique to food, and not monetary, rewards. Although preliminary, these results suggest that both anticipatory (“wanting”) and outcome (“liking”) reward processes may be generally amplified in BED. However, they also suggest that among individuals with BED, disorder severity may be associated with increased anticipatory reward processes (“wanting”), but relatively decreased reward-outcome processing (“liking”), of food rewards specifically.

Ghrelin is related to lower brain reward activation during touch.

The gut hormone ghrelin drives food motivation and increases food intake, but it is also involved in the anticipation of and response to rewards other than food. This pre-registered study investigated how naturally varying ghrelin concentrations affect the processing of touch as a social reward in humans. Sixty-seven volunteers received slow caressing touch (so-called CT-targeted touch) as a social reward and control touch on their shins during 3T functional imaging on two test days. On one occasion, participants were fasted, and on another, they received a meal. On each occasion, plasma ghrelin was measured at three time points. All touch was rated as more pleasant after the meal, but there was no association between ghrelin concentrations and pleasantness. CT-targeted touch was rated as the most pleasant and activated somatosensory and reward networks (whole brain). A region-of-interest in the right medial orbitofrontal cortex (mOFC) showed lower activation during all touches, the higher the ghrelin concentrations were. During CT-targeted touch, a larger satiety response (ghrelin decrease after the meal) was associated with higher mOFC activation, and this mOFC activation was associated with higher experienced pleasantness. Overall, higher ghrelin concentrations appear to be related to a lower reward value for touch. Ghrelin may reduce the value of social stimuli, such as touch, to promote food search and intake in a state of low energy. This suggests that the role of ghrelin goes beyond assigning value to food reward.

Pain catastrophizing is associated with reduced neural response to monetary reward.

Pain catastrophizing, a measure of an individual's negative emotional and cognitive appraisals of pain, has been included as a key treatment target in many psychological interventions for pain. However, the neural correlates of pain catastrophizing have been understudied. Prior neuroimaging evidence suggests that adults with pain show altered reward processing throughout the mesocorticolimbic reward circuitry. In this study, we tested the association between Pain Catastrophizing Scale (PCS) scores and neural activation to the Monetary Incentive Delay (MID) reward neuroimaging task in 94 adults reporting a range of pain, insomnia, and mood symptoms. Results indicated that PCS score but not pain intensity was significantly associated with blunted activation in the caudate and putamen in response to feedback of successful vs. unsuccessful trials on the MID task. Mediation analyses indicated that PCS score fully mediated the relationship between depression symptoms and reward activation. These findings provide evidence that pain catastrophizing is independently associated with altered striatal function apart from depression symptoms and pain intensity. Thus, in individuals experiencing pain and/or co- morbid conditions, reward dysfunction is directly related to pain catastrophizing.

Exploring behavioral systems of the reinforcement sensitivity theory in people with epilepsy: A cross-sectional study

ObjectivesAlthough epilepsy has previously been associated with behavioral changes, no previous study has utilized the behavioral models of the reinforcement sensitivity theory (RST) to investigate the impact of epilepsy on behavior. Therefore, the objective of this cross-sectional study is to examine the potential relationship between epilepsy and the neurobehavioral systems of the RST. MethodsUsing the Reinforcement Sensitivity Theory–Personality Questionnaire (RST-PQ), this cross-sectional study assessed the behavioral systems of the RST in a sample of 27 epilepsy patients and 27 age- and gender-matched healthy individuals. The RST-PQ was designed to assess the different behavioral systems of the RST. The behavioral approach system (BAS) is responsible of the approach behavior, in high values related to risk seeking and addictive behavior and in low values well related to depression. The behavioral inhibition system (BIS) is well related to anxiety in high levels, and the fight flight freeze system (FFFS) is responsible for the avoidance behavior. ResultsAfter adjusting for age, no significant differences were found in demographic information (gender and marital status) between the general population and epilepsy patients. Gender distribution was similar, with 55.6% females in both groups. Marital status also showed no significant difference, with 74% single in the control group and 63% in the epilepsy group. Significant differences were observed in the behavioral systems of the RST. The epilepsy group had higher scores compared with the control group in several areas. BAS reward activity had a median score of 23 in the epilepsy group and 21 in the control group (p = 0.001). BAS goal drive persistence (p = 0.04), BAS impulsivity (p = 0.014), FFFS (p = 0.002), and BIS (median score of 77 in the epilepsy group and 66 in the control group) also showed significant differences, with p = 0.001. These significant differences remained consistent before and after matching the control group, indicating their robustness. The only exception was BAS reward activity, which did not show a significant difference after matching, with p = 0.106 and p = 0.051 before and after matching, respectively. ConclusionsThe study suggests a potential positive association between epilepsy and the BIS, potentially mediated by the hippocampus. The relationship between epilepsy and the BAS, as well as the FFFS, may also be influenced by the BIS. These findings have clinical implications, but further research is needed to confirm these relationships.

Erotic cue exposure increases neural reward responses without modulating temporal discounting

Abstract Humans prefer smaller sooner over larger later rewards, a tendency denoted as temporal discounting. Discounting of future rewards is increased in multiple maladaptive behaviors and clinical conditions. Although temporal discounting is stable over time, it is partly under contextual control. Appetitive (erotic) cues might increase preferences for immediate rewards, although evidence to date remains mixed. Reward circuit activity was hypothesized to drive increases in temporal discounting following cue exposure, yet this was never tested directly. We examined erotic vs. neutral cue exposure effects on subsequent temporal discounting in a preregistered within-subjects study in healthy male participants (n = 38). Functional magnetic resonance imaging assessed neural cue-reactivity, value-computations, and choice-related effects. We replicated previous findings of value-coding in ventromedial prefrontal cortices, striatum, and cingulate cortex. Likewise, as hypothesized, lateral prefrontal cortex activity increased during delayed reward choices, potentially reflecting cognitive control. Erotic cue exposure was associated with increased activity in attention and reward circuits. Contrary to preregistered hypotheses, temporal discounting was unaffected by cue exposure, and cue responses in reward circuits did not reliably predict changes in behavior. Our results raise doubts on the hypothesis that upregulation of (dopaminergic) reward systems following erotic cue exposure is sufficient to drive myopic approach behavior towards immediate rewards.

High-intensity sweet taste as a predictor of subjective alcohol responses to the ascending limb of an intravenous alcohol prime: an fMRI study.

High-intensity sweet-liking has been linked to alcohol use disorder (AUD) risk. However, the neural underpinning of this association is poorly understood. To find a biomarker predictive of AUD, 140 participants (social and heavy drinkers, ages 21-26) underwent functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task and stimulation with high (SucroseHigh)- and low-concentration sucrose, as well as viscosity-matched water. On another day after imaging, and just before free-access intravenous alcohol self-administration, participants experienced a 30 mg% alcohol prime (10 min ascent) using the Computerized Alcohol Infusion System. Principal component analysis (PCA) of subjective responses (SR) to the prime's ascending limb generated enjoyable (SRenjoy) and sedative (SRsed) intoxication components. Another PCA created one component reflective of self-administered alcohol exposure (AE) over 90 min. Component loadings were entered as regressors in a voxel-wise general linear fMRI model, with reward type as a fixed factor. By design, peak prime breath alcohol concentration was similar across participants (29 ± 3.4 mg%). SRenjoy on the prime's ascending limb correlated positively with [SucroseHigh > Water] in the supplementary motor area and right dorsal anterior insula, implicating the salience network. Neither SR component correlated with the brain's response to MID. AE was unrelated to brain reward activation. While these findings do not support a relationship between alcohol self-administration and (1) subjective liking of or (2) regional brain response to an intensely sweet taste, they show that alcohol's enjoyable intoxicating effects on the rising limb correspond with anterior insular and supplementary motor area responses to high-concentration sucrose taste. No such associations were observed with MID despite robust activation in those regions. Insula and supplementary motor area responses to intense sensations relate to a known risk factor for AUD in a way that is not apparent with a secondary (monetary) reward.

Opioid receptor antagonism and neural response to monetary rewards: Pilot studies in light and heavy alcohol users.

Alcohol use disorder (AUD) is a prevalent condition associated with high degree of comorbidity and mortality. Among the few approved pharmacotherapies for AUD, two involve opioid receptor antagonism. Naltrexone and nalmefene are thought to act via opioid receptor blockage to reduce neural response to alcohol and drug-associated cues and consumption, but there have been limited efforts to characterize these effects in humans. In these studies, we sought to test the magnitude of opioid antagonism effects on neural response to monetary rewards in two groups: light drinkers (for the naltrexone study) and heavy drinkers (for the nalmefene study). We conducted double-blind, randomized, crossover pilot studies of reward activation in the brain following acute administration of opioid antagonist and placebo in 11 light and 9 heavy alcohol users. We used a monetary incentive delay task during functional MRI. We found a main effect of cue type on BOLD activation in the nucleus accumbens, demonstrating a neural reward response. The effect of opioid antagonism, relative to placebo, was small and nonsignificant for reward activation in the accumbens for both light and heavy alcohol users. Based on the results of two pilot studies, opioid antagonist medications do not appear to decrease neural activation to monetary rewards in the nucleus accumbens relative to placebo.

Potential biomarker of brain response to opioid antagonism in adolescents with eating disorders: a pilot study.

Eating Disorders (ED) affect up to 5% of youth and are associated with reward system alterations and compulsive behaviors. Naltrexone, an opioid antagonist, is used to treat ED behaviors such as binge eating and/or purging. The presumed mechanism of action is blockade of reward activation; however, not all patients respond, and the optimal dose is unknown. Developing a tool to detect objective drug response in the brain will facilitate drug development and therapeutic optimization. This pilot study evaluated neuroimaging as a pharmacodynamic biomarker of opioid antagonism in adolescents with ED. Youth aged 13-21 with binge/purge ED completed functional magnetic resonance imaging (fMRI) pre- and post-oral naltrexone. fMRI detected blood oxygenation-level dependent (BOLD) signal at rest and during two reward probes (monetary incentive delay, MID, and passive food view, PFV) in predefined regions of interest associated with reward and inhibitory control. Effect sizes for Δ%BOLD (post-naltrexone vs. baseline) were estimated using linear mixed effects modeling. In 12 youth (16-21 years, 92% female), BOLD signal changes were detected following naltrexone in the nucleus accumbens during PFV (Δ%BOLD -0.08 ± 0.03; Cohen's d -1.06, p = 0.048) and anterior cingulate cortex during MID (Δ%BOLD 0.06 ± 0.03; Cohen's d 1.25, p = 0.086). fMRI detected acute reward pathway modulation in this small sample of adolescents with binge/purge ED. If validated in future, larger trials, task-based Δ%BOLD detected by fMRI may serve as a pharmacodynamic biomarker of opioid antagonism to facilitate the development of novel therapeutics targeting the reward pathway, enable quantitative pharmacology trials, and inform drug dosing. https://clinicaltrials.gov/ct2/show/NCT04935931, NCT#04935931.

Dental Health Services Victoria value-based health care principles for oral health models of care.

Efforts to progress oral healthcare reform can be challenging with competing interests of governments and service providers to achieve the intended outcomes. The value-based health care approach has been adopted in many areas of healthcare but has had limited applications to oral healthcare systems. Dental Health Services Victoria, an Australian state government funded entity, commenced its journey to value-based health care in 2016, to shift away from traditional dental service models that reward activity and volume towards a stronger emphasis on value and outcomes. To maintain the value-based health care agenda focus, Dental Health Services Victoria developed three key principles, which can be adopted by other organisations engaged in reforming oral healthcare, to improve the oral health for the population it serves. In 2018, Dental Health Services Victoria developed a value-based health care framework, which has informed strategic organisation priorities for action. In 2023, the following three key principles are identified as being essential to support the operationalisation and development of effective models of oral healthcare: Principle 1 - Care is co-designed with the person or population Principle 2 - Prevention and early intervention are prioritised. Principle 3 - Consistent measurement of health outcomes and costs are embedded. The exploration of the three key principles is an important communication tool to translate value-based health care into practice with key stakeholders. Further work is required to socialise them to within dental teams. Organisations looking to commence the value-based health care agenda can apply Dental Health Services Victoria's three key principles as a first step.

Oxytocin administration enhances pleasantness and neural responses to gentle stroking but not moderate pressure social touch by increasing peripheral concentrations.

Social touch constitutes a key component of human social relationships, although in some conditions with social dysfunction, such as autism, it can be perceived as unpleasant. We have previously shown that intranasal administration of oxytocin facilitates the pleasantness of social touch and activation of brain reward and social processing regions, although it is unclear if it influences responses to gentle stroking touch mediated by cutaneous C-touch fibers or pressure touch mediated by other types of fibers. Additionally, it is unclear whether endogenous oxytocin acts via direct entry into the brain or by increased peripheral blood concentrations. In a randomized controlled design, we compared effects of intranasal (direct entry into the brain and increased peripheral concentrations) and oral (only peripheral increases) oxytocin on behavioral and neural responses to social touch targeting C-touch (gentle-stroking) or other (medium pressure without stroking) cutaneous receptors. Although both types of touch were perceived as pleasant, intranasal and oral oxytocin equivalently enhanced pleasantness ratings and responses of reward, orbitofrontal cortex, and social processing, superior temporal sulcus, regions only to gentle-stroking not medium pressure touch. Furthermore, increased blood oxytocin concentrations predicted the pleasantness of gentle stroking touch. The specificity of neural effects of oxytocin on C-touch targeted gentle stroking touch were confirmed by time-course extraction and classification analysis. Increased peripheral concentrations of oxytocin primarily modulate its behavioral and neural responses to gentle social touch mediated by C-touch fibers. Findings have potential implications for using oxytocin therapeutically in conditions where social touch is unpleasant. Key Technological Projects of Guangdong Province grant 2018B030335001. NCT05265806.

Revisiting placebo

The placebo effect refers to the phenomenon in which a treatment or intervention that is not inherently therapeutic, such as a sugar pill or saline injection, can produce a measurable improvement in a patient's symptoms or condition. The exact mechanisms behind the placebo effect are not well understood, but it is thought to involve the release of endorphins, the body's natural pain-relieving chemicals, and the activation of the brain's reward and pain-regulation systems. This article reviews recent research into the efficacy of the placebo in general practice.

Insulin Resistance and Glycated Hemoglobin in Obesity Are Associated With Preference for Sugar-Sweetened Yogurt: A Pilot Study.

Insulin resistance is associated with elevated activation of food reward, which should be associated with an increased reinforcing value of food. Research has also shown that sugar is a macronutrient strongly associated with reward and reinforcing value of food. This research is designed to assess whether insulin resistance is associated with a stronger preference for sugar-sweetened, thus elevating blood glucose responses in obese people with varying degrees of insulin resistance. Thirteen people with obesity (body mass index, 39.1 kg/m 2 ; range, 30.0-45.1 kg/m 2 ) with varying degrees of insulin resistance (Homeostatic Model Assessment of Insulin Resistance, 5.2; range, 0.7-11.6) consumed novel flavored-colored yogurts that were sweetened with either sugar or monkfruit daily for 6 days to assess whether when given the choice of sugar-sweetened versus monkfruit-sweetened yogurts to consume, participants preferred sugar-sweetened yogurts. Participants consumed a greater amount ( p = .009) and percentage ( p = .04) of sugar-sweetened yogurt earned than monkfruit-sweetened yogurt. The percent of sugar-sweetened versus monkfruit-sweetened yogurt consumed in relationship to amount earned was related to insulin resistance ( r = 0.64, p = .019), glycated hemoglobin ( r = 0.61, p = .027), insulin ( r = 0.58, p = .007), and glucose ( r = 0.56, p = .048). Insulin resistance is associated with preference for sugar-sweetened foods in participants with obesity, which may make it hard to make dietary changes. Research is needed to assess whether treatments that improve insulin resistance also change the preference for sugar-sweetened or high-glycemic-index foods.