Dysfunctional Reward Research Articles

Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons

Energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system andcan promote reward dysfunctions, compulsive feeding, and weight gain. Yet the mechanisms by which nutrients influence the MCL circuitry remain elusive. Here, we show that nutritional triglycerides (TGs), a conserved post-prandial metabolic signature among mammals, can be metabolized within the MCL system and modulate DA-associated behaviors by gating the activity of dopamine receptor subtype 2 (DRD2)-expressing neurons through a mechanism that involves the action of the lipoprotein lipase (LPL). Further, we show that in humans, post-prandial TG excursions modulate brain responses to food cues in individuals carrying a genetic risk for reduced DRD2 signaling. Collectively, these findings unveil a novel mechanism by which dietary TGs directly alter signaling in the reward circuit to regulate behavior, thereby providing a new mechanistic basis by which energy-rich diets may lead to (mal)adaptations in DA signaling that underlie reward deficit and compulsive behavior.

Associations of neural processing of reward with posttraumatic stress disorder and secondary psychotic symptoms in trauma-affected refugees

ABSTRACT Background: Psychological traumatic experiences can lead to posttraumatic stress disorder (PTSD). Secondary psychotic symptoms are not common but may occur. Objectives: Since psychotic symptoms of schizophrenia have been related to aberrant reward processing in the striatum, using the same paradigm we investigate whether the same finding extends to psychotic and anhedonic symptoms in PTSD. Methods: A total of 70 male refugees: 18 PTSD patients with no secondary psychotic symptoms (PTSD-NSP), 21 PTSD patients with secondary psychotic symptoms (PTSD-SP), and 31 healthy controls (RHC) were interviewed and scanned with functional magnetic resonance imaging (fMRI) during a monetary incentive delay task. Using region of interest analysis of the prefrontal cortex and ventral striatum, we investigated reward-related activity. Results: Compared to RHC, participants with PTSD had decreased neural activity during monetary reward. Also, participants with PTSD-SP exhibited decreased activity in the associative striatum relative to participants with PTSD-NSP during processing of motivational reward anticipation which correlated with severity of psychotic symptoms. However, the difference between the two PTSD groups disappeared when PTSD severity and trauma exposure were accounted for. Conclusions: Anhedonia and secondary psychotic symptoms in PTSD are characterized by dysfunctional reward consumption and anticipation processing, respectively. The latter may reflect a mechanism by which abnormal reward signals in the basal ganglia facilitates psychotic symptoms across psychiatric conditions.

Reduced Reward Responsiveness in Women With Moderate - to - Severe Premenstrual Syndrome: Evidence From a Probabilistic Reward Task.

Nearly 50% of women of reproductive age worldwide experience premenstrual syndrome (PMS). Women with PMS exhibit low positive affect and low frontal electroencephalography asymmetry scores, both of which are associated with reward processing. These findings suggest that women with PMS may exhibit deficiencies in reward processing. A probabilistic reward task based on signal detection approach was used to assess reward responsiveness in 30 women with moderate-to-severe PMS and 31 controls without PMS. The results revealed that in the late luteal phase, the women with moderate-to-severe PMS exhibited lower response bias and lower hit rate toward more frequently rewarded stimuli (rich stimuli) than the controls. By contrast, the response bias and hit rate did not differ between the two groups in the follicular phase. The group differences still remained after controlling for anhedonic symptoms. Furthermore, trial-by-trial probability analyses revealed that women with moderate-to-severe PMS exhibited a trend of having a higher miss rate for rich stimuli than the controls. In particular, when a rich stimulus was preceded by an infrequently rewarded stimulus (a rewarded lean stimulus), participants in the PMS group exhibited a trend for higher miss rate than those in the control group in the late luteal and follicular phases. However, group differences in the probability analyses were nonsignificant after controlling for anhedonic symptoms. These results provide preliminary evidence that women with moderate-to-severe PMS exhibit dysfunctional reward responsiveness and impaired ability to modulate their behavior as a function of prior reinforcement.

Reward processing electrophysiology in schizophrenia: Effects of age and illness phase

BackgroundReward processing abnormalities may underlie characteristic pleasure and motivational impairments in schizophrenia. Some neural measures of reward processing show age-related modulation, highlighting the importance of considering age effects on reward sensitivity. We compared event-related potentials (ERPs) reflecting reward anticipation (stimulus-preceding negativity, SPN) and evaluation (reward positivity, RewP; late positive potential, LPP) across individuals with schizophrenia (SZ) and healthy controls (HC), with an emphasis on examining the effects of chronological age, brain age (i.e., predicted age based on neurobiological measures), and illness phase. MethodsSubjects underwent EEG while completing a slot-machine task for which rewards were not dependent on performance accuracy, speed, or response preparation. Slot-machine task EEG responses were compared between 54 SZ and 54 HC individuals, ages 19 to 65. Reward-related ERPs were analyzed with respect to chronological age, categorically-defined illness phase (early; ESZ versus chronic schizophrenia; CSZ), and were used to model brain age relative to chronological age. ResultsIllness phase-focused analyses indicated there were no group differences in average SPN or RewP amplitudes. However, a group × reward outcome interaction revealed that ESZ differed from HC in later outcome processing, reflected by greater LPP responses following loss versus reward (a reversal of the HC pattern). While brain age estimates did not differ among groups, depressive symptoms in SZ were associated with older brain age estimates while controlling for negative symptoms. ConclusionsESZ and CSZ did not differ from HC in reward anticipation or early outcome processing during a cognitively undemanding reward task, highlighting areas of preserved functioning. However, ESZ showed altered later reward outcome evaluation, pointing to selective reward deficits during the early illness phase of schizophrenia. Further, an association between ERP-derived brain age and depressive symptoms in SZ extends prior findings linking depression with reward-related ERP blunting. Taken together, both illness phase and age may impact reward processing among SZ, and brain aging may offer a promising, novel marker of reward dysfunction that warrants further study.

The Dopamine Receptor Subtype 2 (DRD2) Regulates the Central Reinforcing Actions of Dietary Lipids in Humans and Rodents

Emerging evidence suggests that energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system and can promote the development of compulsive-like feeding, reward dysfunction, and ultimately weight gain. Yet the mechanisms by which metabolic signals influence MCL circuitry to control behavior remain poorly understood. Circulating triglycerides (TG) are a conserved post-prandial metabolic signature among mammals and high plasma TG are associated with reduced reward responsiveness in humans. Here, we show that the TG-processing enzyme lipoprotein lipase (LPL) is enriched throughout the MCL of both mouse and human, including DA-releasing neurons in the ventral tegmental area and DA-receptive neurons in the striatum. Using brain-specific TG delivery in mice, we show that nutritional TG are metabolized within the MCL system where they acutely control D2 DA receptor (DRD2) signaling. We also show that TG are directly reinforcing in mice, and that central TG sensing relies on LPL activity in the MCL. Likewise, in humans, post-prandial TG excursions modulate brain response to food cues in MCL with the direction of the association determined by a DRD2 dependent genotype. Collectively, these findings reveal a mechanism by which dietary TG directly alter MCL signaling to regulate behavior, providing a new mechanistic basis by which energy-rich diets can lead to adaptations in DA signaling that underlie compulsive behavior.

Posttraumatic Stress Disorder is associated with altered reward mechanisms during the anticipation and the outcome of monetary incentive cues.

Recent studies suggest that Posttraumatic Stress Disorder (PTSD) might be associated with dysfunctional reward circuitry. However, further research is needed to understand the key role of the reward system in PTSD symptomatology. Twenty participants with PTSD and 21 Trauma-Exposed matched Controls (TECs) completed the Monetary Incentive Delay (MID) task during an MRI session. Reaction times (RTs) and hit rates were recorded. Brain activity was investigated during the anticipation and the outcome of monetary gains and losses. During the anticipation of monetary loss, PTSD participants had higher RTs than TECs. However, the groups did not differ at the neurofunctional level. During successful avoidance of monetary loss, PTSD patients showed higher activation than TECs in the left caudate nucleus. During the anticipation of monetary gains, no differences in RTs were found between groups. PTSD patients had specific activations in the right amygdala, nucleus accumbens, putamen, and middle frontal gyrus (p<0.05 family-wise error (FWE)-corrected), while TECs had specific activation in the anterior cingulate cortex. When obtaining monetary gains, PTSD patients had specific activation in the caudate nucleus, while TECs had specific activations in the right hypothalamus, subthalamic nucleus, and left inferior frontal gyrus. For the first time, functional brain activation during both the anticipation and the outcome of monetary rewards is reported altered in PTSD patients. These alterations might be associated with the complex symptomatology of PTSD.

Anhedonia across borders: Transdiagnostic relevance of reward dysfunction for noninvasive brain stimulation endophenotypes.

IntroductionAnhedonia is a transdiagnostic psychopathological dimension, consisting in the impaired ability to experience pleasure. In order to further our understanding of its neural correlates and to explore its potential relevance as a predictor of treatment response, in this article we systematically reviewed studies involving anhedonia and neuromodulation interventions, across different disorders.MethodsWe included seven studies fulfilling inclusion/exclusion criteria and involving different measures of anticipatory and consummatory anhedonia, as well as different noninvasive brain stimulation interventions (transcranial magnetic stimulation and transcranial direct current stimulation). Studies not exploring hedonic measures or not involving neuromodulation intervention were excluded.ResultsAll the included studies entailed the use of rTMS protocols in one of the diverse prefrontal targets. The limited amount of studies and the heterogeneity of stimulation protocols did not allow to draw any conclusion with regard to the efficacy of rTMS in the treatment of transnosographic anhedonia. A potential for anhedonia in dissecting possible endophenotypes of different psychopathological conditions preliminarily emerged.ConclusionsAnhedonia is an underexplored condition in neuromodulation trials. It may represent a valuable transdiagnostic dimension that requires further examination in order to discover new clinical predictors for treatment response.

Neural Sensitivity to Social and Monetary Reward in Depression: Clarifying General and Domain-Specific Deficits.

Reward dysfunction is thought to be play a critical role in the pathogenesis of depression. Multiple studies have linked depression to abnormal neural sensitivity to monetary rewards, but it remains unclear whether this reward dysfunction is generalizable to other rewards types. The current study begins to address this gap by assessing abnormal sensitivity to both monetary and social rewards in relation to depressive symptoms. We recorded event-related potentials (ERPs) during two incentive delay tasks, one with monetary reward and one with social reward. Both tasks were administered within the same sample, enabling a direct comparison of reward types. ERPs elicited by social and nonsocial rewards were morphologically similar across several stages of processing: cue salience, outcome anticipation, early outcome evaluation, outcome salience. Moderation analyses showed depression was linked with a pattern of general deficits across social and monetary rewards, specifically for the stages of outcome anticipation (stimulus-preceding negativity) and outcome salience (feedback-P3); self-reported reward sensitivity was generally associated with early outcome evaluation (reward positivity). Regression analyses modeling task-specific variance, however, showed a unique association between depression and outcome salience for social rewards, controlling for monetary rewards. The findings from this study underscore the importance of assessing neural sensitivity to multiple reward types in depression, particularly social reward. Characterizing the profile of reward functioning in depression across reward types may help to link laboratory-based deficits to relatively global vs. focal difficulties in real-world functioning.

Effects of Marijuana Use on Brain Circuitry and Depressive Symptoms in Adolescents With Bipolar Disorder

Substance use is highly prevalent in youth with bipolar disorder (BD), with up to 50 percent developing a co-occurring substance use disorder. Little is known about how substance use alters depressive symptom severity in BD. Fronto-limbic brain circuitry modulated by the endocannabinoid system is a primary neurobiological system implicated in reward dysfunction in depression and addiction. This pilot study examined differences in depressive symptom severity, resting-state functional connectivity (rsfc), and reward function in adolescents with bipolar depression with (BD-C) and without (BD-NC) a history of cannabis use relative to healthy control (HC) subjects.

Brain Reward Function after Chronic and Binge Methamphetamine Regimens in Mice Expressing the HIV-1 TAT Protein.

Methamphetamine abuse and human immunodeficiency virus (HIV) are common comorbidities. HIV-associated proteins, such as the regulatory protein TAT, may contribute to brain reward dysfunction, inducing an altered sensitivity to methamphetamine reward and/or withdrawal in this population. These studies examined the combined effects of TAT protein expression and, chronic and binge methamphetamine regimens on brain reward function. Transgenic mice with inducible brain expression of the TAT protein were exposed to either saline, a chronic, or a binge methamphetamine regimen. TAT expression was induced via doxycycline treatment during the last week of methamphetamine exposure. Brain reward function was assessed daily throughout the regimens, using the intracranial self-stimulation procedure, and after a subsequent acute methamphetamine challenge. Both methamphetamine regimens induced withdrawal-related decreases in reward function. TAT expression substantially, but not significantly increased the withdrawal associated with exposure to the binge regimen compared to the chronic regimen, but did not alter the response to acute methamphetamine challenge. TAT expression also led to persistent changes in adenosine 2B receptor expression in the caudate putamen, regardless of methamphetamine exposure. These results suggest that TAT expression may differentially affect brain reward function, dependent on the pattern of methamphetamine exposure. The subtle effects observed in these studies highlight that longer-term TAT expression, or its induction at earlier stages of methamphetamine exposure, may be more consequential at inducing behavioral and neurochemical effects.

Neural Response to Rewards, Stress and Sleep Interact to Prospectively Predict Depressive Symptoms in Adolescent Girls

Blunted reward processing both characterizes major depressive disorder and predicts increases in depressive symptoms. However, little is known about the interaction between blunted reward processing and other risk factors in relation to increases in depressive symptoms. Stressful life events and sleep problems are prominent risk factors that contribute to the etiopathogenesis of depression and have been linked to reward dysfunction; these factors may interact with reward dysfunction to predict increased depressive symptoms. In a large sample of 8- to 14-year-old adolescent girls, the current study examined how blunted reward processing, stressful life events, and sleep problems at baseline interacted to predict increases in depressive symptoms 1 year later. Reward processing was indexed by the reward positivity (RewP), an event-related potential elicited during a simple monetary reward paradigm (i.e., Doors task). Two-way interactions confirmed that a blunted RewP predicted increased depressive symptoms at (a) high levels of stress but not average or low levels of stress, and (b) high and average levels of sleep problems but not low levels of sleep problems. Finally, a 3-way interaction confirmed that a blunted RewP predicted increased depressive symptoms at high levels of stress and sleep problems but not average or low levels of stress and sleep problems. Thus, adolescents characterized by low reward response (i.e., blunted RewP) were at an increased risk of developing depressive symptoms if they experienced increased stressful life events or sleep problems; moreover, risk was greatest among adolescents characterized by all 3.

Buprenorphine prevents stress-induced blunting of nucleus accumbens dopamine response and approach behavior to food reward in mice

Alterations to the mesolimbic dopamine (DA) system are thought to underlie dysfunctional reward processing in stress-related psychiatric disorders. Using in vivio microdialysis in awake freely moving mice, we assessed the effects of stress on the motivational and neurochemical correlates underlying conditioned approach behavior for palatable food in the non-deprived mouse. Mice trained to approach and consume food in a familiar environment exhibited a 30% increase in nucleus accumbens shell (AcbSh) extracellular dopamine levels coincident with approach towards and consumption of the food reward. This effect was not observed in mice that were presented with the food in an unfamiliar environment or were exposed for the first time and were region specific. The addition of an acute environmental stressor (bright light and novel scent) during food exposure decreased DA release and delayed approach to the food. The disruptive impact of acute novelty stress on DA levels and approach behavior was reversed in animals pretreated with buprenorphine, an opioid drug with antidepressant-like and anxiolytic effects. Together, these data indicate that exposure to mild stress reduces incentive drive to approach palatable food via alterations in AcbSh dopamine responsiveness to food reward. Moreover, they implicate the brain opioid system as a potential pharmacological target for counteracting behavioral and neurochemical elements associated with stress.

Food cue reactivity in food addiction: A functional magnetic resonance imaging study

BackgroundWhile neuroimaging studies have revealed that reward dysfunction may similarly contribute to obesity and addiction, no prior studies have examined neural responses in individuals who meet the “clinical” food addiction phenotype. MethodsWomen (n = 44) with overweight and obesity, nearly half of whom (n = 20) met criteria for moderate-to-severe Yale Food Addiction Scale 2.0 (YFAS 2.0) food addiction, participated in a functional magnetic resonance imaging cue reactivity task. Participants viewed images of highly processed foods, minimally processed foods, and household objects while thinking about how much they wanted each item. Differences in neural responses by YFAS 2.0 food addiction to highly processed and minimally processed food cues were investigated. ResultsThere was a significant interaction between participant group and neural response in the right superior frontal gyrus to highly versus minimally processed food cues (r = 0.57). Individuals with YFAS 2.0 food addiction exhibited modest, elevated responses in the superior frontal gyrus for highly processed food images and more robust, decreased activations for minimally processed food cues, whereas participants in the control group showed the opposite responses in this region. Across all participants, the household items elicited greater activation than the food cues in regions associated with interoceptive awareness and visuospatial attention (e.g., insula, inferior frontal gyrus, inferior parietal lobe). ConclusionsWomen with overweight or obesity and YFAS 2.0 food addiction, compared to those with only overweight or obesity, exhibited differential responses to highly and minimally processed food cues in a region previously associated with cue-induced craving in persons with a substance-use disorder. Overall, the present work provides further support for the utility of the food addiction phenotype within overweight and obesity.

Bidirectional Associations Between Stress and Reward Processing in Children and Adolescents: A Longitudinal Neuroimaging Study

BackgroundAberrations in both neural reward processing and stress reactivity are associated with increased risk for mental illness; yet, how these two factors relate to each other remains unclear. Several studies suggest that stress exposure impacts reward function, thus increasing risk for psychopathology. However, the alternative hypothesis, in which reward dysfunction impacts stress reactivity, has been rarely examined. The current study aimed to test both hypotheses using a longitudinal design. MethodsParticipants were 38 children (23 girls; 61%) from a prospective cohort study. A standard stress-exposure measure was collected at 7 years of age. Children performed a well-validated imaging reward paradigm at age 10, and a standardized acute psychological stress laboratory protocol was administered both at age 10 and at age 13. Structural equation modeling was used to examine bidirectional associations between stress and neural response to reward anticipation. ResultsHigher exposure to stressful life events at age 7 predicted lower neural response to reward anticipation in regions of the basal ganglia at age 10, which included ventral caudate, nucleus accumbens, putamen, and globus pallidus. Lower response to reward anticipation in medial prefrontal and anterior cingulate cortex predicted higher stress reactivity at age 13. ConclusionsOur findings provide support for bidirectional associations between stress and reward processing, in that stress may impact reward anticipation, but also in that reduced reward anticipation may increase susceptibility to stress.

Aerobic Exercise Reduced Body Weight through Midbrain-striatal Dopaminergic Plasticity in Obese Mice

PURPOSE: Previous research indicates that midbrain-striatal dopaminergic disruption is associated with obesity and involved in feeding behavior and voluntary physical activity. Since the action of exercise on midbrain-striatal dopamine, it may be an effective strategy to improve physical inactivity and overeating induced by food reward dysfunction in obesity. We therefore explored the mechanisms. METHODS: Male C57BL/6 mice were randomly divided into control group (C, n=12), exercise group(CE, n=12)fed a normal diet (13% fat), and an additional group (H, n=40) fed a high fat diet (51% fat). Obese mice in H were further divided into obesity group (O, n=12) and obesity + exercise group (OE, n=12). The CE and OE mice underwent treadmill exercise (5-13 m/min, about 58%-75% VO2max, 50 min/d, 5 d/wk for 8 wks). The food preference test and open-field test were used to assess food reward, and voluntary physical activity. Tyrosine hydroxylase (TH)+ neurons were detected by immunohistochemistry, and the expression of TH protein in midbrain-striatum were measured by western blot. RESULTS: Body weight of OE was 15.2% lower than that of O (P < 0.01). Sucrose preference, physical activity level and time were decreased by 25.8%, 46.77% and 37.56% in O compare to C (P < 0.05, P < 0.01, P < 0.01), but were 18.2%, 37.28% and 26.35% higher, respectively, in OE than O (P < 0.05). TH+ cells in substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) decreased by 15.41% and 18.45%, respectively, in O compare to C (P < 0.05), but increased by 12.62% and 15.53% in OE compare to O (P < 0.05). TH+ fibers in dorsal striatum nucleus accumbens were 16.36% and 17.48% lower in O than C (P < 0.05), but was 12.54% and 14.13% higher in OE vs. O (P < 0.05). In addition, the expression of TH protein in midbrain and striatum decreased by 18.46% (P < 0.05) and 16.35% (P < 0.05) in O compared with C, but increased by 12.23% and 11.58% in OE compare to O (P < 0.05). CONCLUSIONS: The aerobic exercise inhibits body weight gain, improves food reward and voluntary physical activity in obese mice. The exercise-induced midbrain-striatal dopaminergic plasticity may be one of the important mechanisms for this adaptation.

Peer Victimization and Dysfunctional Reward Processing: ERP and Behavioral Responses to Social and Monetary Rewards.

Peer victimization (or bullying) is a known risk factor for depression, especially among youth. However, the mechanisms connecting victimization experience to depression symptoms remains unknown. As depression is known to be associated with neural blunting to monetary rewards, aberrant responsiveness to social rewards may be a key deficit connecting socially stressful experiences with later depression. We, therefore, sought to determine whether adolescents’ experiences with social stress would be related to their current response to social rewards over less socially relevant monetary rewards. Neural responses to monetary and social rewards were measured using event-related potentials (ERPs) to peer acceptance and rejection feedback (Island Getaway task) and to monetary reward and loss feedback (Doors task) in a sample of 56 late adolescents/emerging young adults followed longitudinally since preschool. In the Island Getaway task, participants voted whether to “keep” or “kick out” each co-player, providing an index of prosocial behavior, and then received feedback about how each player voted for the participant. Analyses tested whether early and recent peer victimization was related to response to rewards (peer acceptance or monetary gains), residualized for response to losses (peer rejection or monetary losses) using the reward positivity (RewP) component. Findings indicated that both experiencing greater early and greater recent peer victimization were significantly associated with participants casting fewer votes to keep other adolescents (“Keep” votes) and that greater early peer victimization was associated with reduced neural response to peer acceptance. Early and recent peer victimization were significantly more associated with neural response to social than monetary rewards. Together, these findings suggest that socially injurious experiences such as peer victimization, especially those occurring early in childhood, relate to two distinct but important findings: that early victimization is associated with later reduced response to peer acceptance, and is associated with later tendency to reject peers. Findings also suggest that there is evidence of specificity to reward processing of different types; thus, future research should expand studies of reward processing beyond monetary rewards to account for the possibility that individual differences may be related to other, more relevant, reward types.

Patients With Obsessive-Compulsive Disorder Exhibit Deficits in Consummatory but Not Anticipatory Pleasure.

Background: Reward dysfunctions have been reported in obsessive-compulsive disorder (OCD), which implicates a high possibility of anhedonia for this disease. However, several components of anhedonia, such as consummatory and anticipatory pleasure, has not been substantially studied in OCD patients.Methods: The Chinese version of the Temporal Experience of Pleasure Scale (CV-TEPS) was used to evaluate both the consummatory and anticipatory pleasure in 130 OCD patients, 89 major depressive disorder (MDD) patients, and 95 healthy controls (HCs). The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Beck Depression Inventory (BDI) were scored for assessing the severity of obsessive and compulsive symptoms and depressive symptoms, respectively. Analyses of covariance (ANCOVA) were used to compare the differences of anhedonia among the three groups with the severity of depression controlled. Regression analyses were also used to analyze the relationship between consummatory and anticipatory pleasure and clinical variables in OCD patients.Results: After controlling for the effect of depression, there were significant differences in TEPS scores among the three groups (p < 0.05). Compared with HCs, OCD patients had lower scores on the consummatory subscale, but not the anticipatory subscale, of the TEPS. MDD patients had lower scores on both the consummatory and anticipatory subscales than HCs.Conclusion: OCD patients exhibit deficits in consummatory but not anticipatory pleasure, which is distinct from MDD patients.

Development and Initial Tests of Reward Re-Training: A Novel Treatment For Reward Dysfunction

Development and Initial Tests of Reward Re-Training: A Novel Treatment For Reward Dysfunction

Blunted Reward Sensitivity and Trait Disinhibition Interact to Predict Substance Use Problems.

Reward deficit models of addiction posit weaknesses in reward sensitivity to be promotive of substance dependence, while the externalizing spectrum model views substance problems as arising in large part from a general disinhibitory liability. The current study sought to integrate these perspectives by testing for separate and interactive associations of disinhibition and reward dysfunction with interview-assessed substance use disorders (SUDs). Community and college adults (N = 199) completed a scale measure of trait disinhibition and performed a gambling-feedback task yielding a neural index of reward sensitivity, the 'Reward Positivity' (RewP). Disinhibition and blunted RewP independently predicted SUDs, and also operated synergistically, such that participants - in particular, men - with high levels of disinhibition together with blunted RewP exhibited especially severe substance problems. Though limited by its cross-sectional design, this work provides new information about the interplay of disinhibition, reward processing, and gender in SUDs and suggests important directions for future research.

Dysfunction of the Mesolimbic Circuit to Food Odors in Women With Anorexia and Bulimia Nervosa: A fMRI Study.

Brain reward dysfunction in eating disorders has been widely reported. However, whether the neural correlates of hedonic and motivational experiences related to food cues are differentially affected in anorexia nervosa of restrictive type (ANr), bulimia nervosa (BN), and healthy control (HC) participants remains unknown. Here, 39 women (14 ANr, 13 BN, and 12 HC) underwent fMRI while smelling food or non-food odors in hunger and satiety states during liking and wanting tasks. ANr and BN patients reported less desire to eat odor-cued food and odor-cued high energy-density food (EDF), respectively. ANr patients exhibited lower ventral tegmental area (VTA) activation than BN patients to food odors when rating their desire to eat, suggesting altered incentive salience attribution to food odors. Compared with HC participants, BN patients exhibited decreased activation of the caudate nucleus to food odors in the hunger state during the wanting task. Both patient groups also showed reduced activation of the anterior ventral pallidum and insula in response to high EDF odors in the hunger state during the wanting task. These findings indicate that brain activation within the food reward-regulating circuit differentiates the three groups. ANr patients further exhibited lower activation of the precuneus than other participants, suggesting a possible role of body image distortion in ANr. Our study highlights that food odors are relevant sensory probes to gain better insight into the dysfunction of the mesolimbic and striatal circuitry involved in food reward processing in patients with EDs.