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Evaluating Effort-Expenditure For Reward in Adults with Major Depressive Disorder and Obesity
Abstract
Converging evidence has suggested that disturbances in monetary reward processing may subserve the shared biosignature between major depressive disorder (MDD) and obesity. However, there remains a paucity of studies that have evaluated the deficits in specific subcomponents of reward functioning in populations with MDD and obesity comorbidity. We evaluated the association between effort-expenditure for monetary reward and neural activation in regions associated with reward-based decision making (i.e., the caudate nucleus, anterior cingulate cortex (ACC) and hippocampus) in people with MDD and obesity comorbidity. We acquired structural and functional magnetic resonance imaging (fMRI) in 12 participants and performed a spherical region-of-interest analysis (ROI) using previously defined peak MNI coordinates. A one-sample t-test was employed to compare ROI-specific blood-oxygen-level-dependent (BOLD) signal change during the task choice selection window (i.e., high-effort vs. low-effort task) of the effort-expenditure for reward task (EEfRT). We observed no change in activation of the caudate nucleus, ACC or hippocampus in participants with increased BMI when contrasting the high effort > low effort reward magnitude condition for the EEfRT. The findings from our exploratory study evaluated the disturbances in fundamental reward processes, including cost-benefit decision making, in people MDD and obesity. Future studies should further investigate this relationship with a larger sample size.
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Cognitive control and incentive sensitivity are related to overeating and obesity. Optimal white matter integrity is relevant for an efficient interaction among reward-related brain regions. However, its relationship with sensitivity to incentives remains controversial. The aim of this study was to assess the incentive sensitivity and its relationship to white matter integrity in normal-weight and overweight groups. Seventy-six young adults participated in this study: 31 were normal-weight (body mass index [BMI] 18.5 to < 25.0 kg/m², 14 females) and 45 were overweight (BMI ≥ 25.0 kg/m², 22 females). Incentive sensitivity was assessed using an antisaccade task that evaluates the effect of incentives (neutral, reward, and loss avoidance) on cognitive control performance. Diffusion tensor imaging studies were performed to assess white matter integrity. The relationship between white matter microstructure and incentive sensitivity was investigated through tract-based spatial statistics. Behavioral antisaccade results showed that normal-weight participants presented higher accuracy (78.0 vs. 66.7%, p = 0.01) for loss avoidance incentive compared to overweight participants. Diffusion tensor imaging analysis revealed a positive relationship between fractional anisotropy and loss avoidance accuracy in the normal-weight group (p < 0.05). No relationship reached significance in the overweight group. These results support the hypothesis that white matter integrity is relevant for performance in an incentivized antisaccade task.
Depression is a leading cause of burden of disease among young people. Current treatments are not uniformly effective, in part due to the heterogeneous nature of major depressive disorder (MDD). Refining MDD into more homogeneous subtypes is an important step towards identifying underlying pathophysiological mechanisms and improving treatment of young people. In adults, symptom-based subtypes of depression identified using data-driven methods mainly differed in patterns of neurovegetative symptoms (sleep and appetite/weight). These subtypes have been associated with differential biological mechanisms, including immuno-metabolic markers, genetics and brain alterations (mainly in the ventral striatum, medial orbitofrontal cortex, insular cortex, anterior cingulate cortex amygdala and hippocampus). K-means clustering was applied to individual depressive symptoms from the Quick Inventory of Depressive Symptoms (QIDS) in 275 young people (15–25 years old) with MDD to identify symptom-based subtypes, and in 244 young people from an independent dataset (a subsample of the STAR*D dataset). Cortical surface area and thickness and subcortical volume were compared between the subtypes and 100 healthy controls using structural MRI. Three subtypes were identified in the discovery dataset and replicated in the independent dataset; severe depression with increased appetite, severe depression with decreased appetite and severe insomnia, and moderate depression. The severe increased appetite subtype showed lower surface area in the anterior insula compared to both healthy controls. Our findings in young people replicate the previously identified symptom-based depression subtypes in adults. The structural alterations of the anterior insular cortex add to the existing evidence of different pathophysiological mechanisms involved in this subtype.
Current models of addiction biology highlight altered neural responses to non-drug rewards as a central feature of addiction. However, given that drugs of abuse can directly impact reward-related dopamine circuitry, it is difficult to determine the extent to which reward processing alterations are a trait feature of individuals with addictions, or primarily a consequence of exogenous drug exposure. Examining individuals with behavioral addictions is one promising approach for disentangling neural features of addiction from the direct effects of substance exposure. The current fMRI study compared neural responses during monetary reward processing between drug naïve young adults with a behavioral addiction, internet gaming disorder (IGD; n = 22), and healthy controls (n = 27) using a monetary incentive delay task. Relative to controls, individuals with IGD exhibited blunted caudate activity associated with loss magnitude at the outcome stage, but did not differ from controls in neural activity at other stages. These findings suggest that decreased loss sensitivity might be a critical feature of IGD, whereas alterations in gain processing may be less characteristic of individuals with IGD, relative to those with substance use disorders. Therefore, classic theories of altered reward processing in substance use disorders should be translated to behavioral addictions with caution.
The monetary incentive delay task breaks down reward processing into discrete stages for fMRI analysis. Here we look at anticipation of monetary gain and loss contrasted with neutral anticipation. We meta-analysed data from 15 original whole-brain group maps (n = 346) and report extensive areas of relative activation and deactivation throughout the whole brain. For both anticipation of gain and loss we report robust activation of the striatum, activation of key nodes of the putative salience network, including anterior cingulate and anterior insula, and more complex patterns of activation and deactivation in the central executive and default networks. On between-group comparison, we found significantly greater relative deactivation in the left inferior frontal gyrus associated with incentive valence. This meta-analysis provides a robust whole-brain map of a reward anticipation network in the healthy human brain.
Electronic supplementary material
The online version of this article (10.1007/s11065-018-9385-5) contains supplementary material, which is available to authorized users.
Background:
Obesity and depression are both highly prevalent public health disorders and evidence on their relationship is inconsistent. This study examined whether depressive symptoms are associated with current obesity, and further, whether obesity in turn is associated with an increased odds of depressive symptoms five years later after accounting for potential lifestyle confounders and depressive symptoms at baseline.
Methods:
Data were obtained from the 1958 British birth cohort (N = 9217 for cross-sectional and 7340 for prospective analysis). Clinical Interview Schedule-Revised and Mental Health Inventory-5 were used for screening depressive symptoms at ages 45 and 50 years, respectively. General and central obesity were defined using measurements of body mass index (BMI) and waist circumference (WC) at 45 years, respectively.
Results:
There was a cross-sectional association between depressive symptoms and obesity: participants with ≥2 depressive symptoms had 31% (95%CI 11% to 55%) higher odds of general and 26% higher odds of central obesity (95%CI 8% to 47%). In prospective analyses, both general and central obesity were associated with higher odds of depressive symptoms five years later among women but not in men (Pinteraction < 0.01). After adjustment for depressive symptoms at baseline, sociodemographic and lifestyle factors, women with general obesity had 38% (95% CI 7% to 77%) and women with central obesity 34% (95%CI 9% to 65%) higher odds of depression compared to others.
Conclusions:
Depressive symptoms are associated with concurrent obesity and related lifestyle factors among women and men in mid-life. Our study suggests that obesity in turn affects long-term risk of depressive symptoms in women but not in men, independently of concurrent associations, providing an important target group for the implementation of preventative strategies.
Individuals with obesity are often characterized by alterations in reward processing. This may affect how new information is used to update stimulus values during reinforcement-based learning. Here, we investigated obesity-related changes in non-food reinforcement processing, their impact on learning performance as well as the neural underpinnings of reinforcement-based learning in obesity. Nineteen individuals with obesity (BMI > = 30 kg/m², 10 female) and 23 lean control participants (BMI 18.5–24.9 kg/m², 11 female) performed a probabilistic learning task during functional magnetic resonance imaging (fMRI), in which they learned to choose between advantageous and disadvantageous choice options in separate monetary gain, loss, and neutral conditions. During learning individuals with obesity made a significantly lower number of correct choices and accumulated a significantly lower overall monetary outcome than lean control participants. FMRI analyses revealed aberrant medial prefrontal cortex responses to monetary losses in individuals with obesity. There were no significant group differences in the regional representation of prediction errors. However, we found evidence for increased functional connectivity between the ventral striatum and insula in individuals with obesity. The present results suggest that obesity is associated with aberrant value representations for monetary losses, alterations in functional connectivity during the processing of learning outcomes, as well as a decresased reinforcement-based learning performance. This may affect how new information is incorporated to adjust dysfunctional behavior and could be a factor contributing to the maintenance of dysfunctional eating behavior in obesity.
Electronic supplementary material
The online version of this article (10.1007/s11682-017-9786-8) contains supplementary material, which is available to authorized users.
Background: The association between body size, weight change and depression has not been systematically summarized, especially for underweight individuals.
Aims: To conduct a systematic review and a meta-analysis to examine the association between indices of body size, weight change and depression.
Method: A total of 183 studies were selected. Fully adjusted hazard ratios (HRs) or odds ratios (ORs) were extracted. A total of 76 studies contributed to data synthesis with a random-effect model, and subgroup analyses were conducted to evaluate the effect of potential moderators.
Results: In cohort studies, underweight at baseline increased the risk of subsequent depression (OR 1.16, 95% CI 1.08-1.24). Overweight (BMI 25-29.9 kg/m2) showed no statistically significant relationship with depression overall; however, the subgroup analyses presented different results according to sex (men: OR 0.84, 95% CI 0.72-0.97, women: OR 1.16, 95% CI 1.07-1.25). In cross-sectional designs, obesity with BMI over 40 kg/m2 showed a greater pooled OR than obesity over BMI 30 kg/m2.
Conclusion: Both underweight and obesity increase the risk of depression. The association between overweight and depression differs by sex.
Meta-analyses of genome-wide association studies (meta-GWASs) and candidate gene studies have identified genetic variants associated with cardiovascular diseases, metabolic diseases and mood disorders. Although previous efforts were successful for individual disease conditions (single disease), limited information exists on shared genetic risk between these disorders. This article presents a detailed review and analysis of cardiometabolic diseases risk (CMD-R) genes that are also associated with mood disorders. First, we reviewed meta-GWASs published until January 2016, for the diseases 'type 2 diabetes, coronary artery disease, hypertension' and/or for the risk factors 'blood pressure, obesity, plasma lipid levels, insulin and glucose related traits'. We then searched the literature for published associations of these CMD-R genes with mood disorders. We considered studies that reported a significant association of at least one of the CMD-R genes and 'depression' or 'depressive disorder' or 'depressive symptoms' or 'bipolar disorder' or 'lithium treatment response in bipolar disorder', or 'serotonin reuptake inhibitors treatment response in major depression'. Our review revealed 24 potential pleiotropic genes that are likely to be shared between mood disorders and CMD-Rs. These genes include MTHFR, CACNA1D, CACNB2, GNAS, ADRB1, NCAN, REST, FTO, POMC, BDNF, CREB, ITIH4, LEP, GSK3B, SLC18A1, TLR4, PPP1R1B, APOE, CRY2, HTR1A, ADRA2A, TCF7L2, MTNR1B and IGF1. A pathway analysis of these genes revealed significant pathways: corticotrophin-releasing hormone signaling, AMPK signaling, cAMP-mediated or G-protein coupled receptor signaling, axonal guidance signaling, serotonin or dopamine receptors signaling, dopamine-DARPP32 feedback in cAMP signaling, circadian rhythm signaling and leptin signaling. Our review provides insights into the shared biological mechanisms of mood disorders and cardiometabolic diseases.
Anhedonia, the reduced ability to experience pleasure in response to otherwise rewarding stimuli, is a core symptom of major depressive disorder (MDD). Although the posterior ventromedial prefrontal cortex (pVMPFC) and its functional connections have been consistently implicated in MDD, their roles in anhedonia remain poorly understood. Furthermore, it is unknown whether anhedonia is primarily associated with intrinsic 'resting-state' pVMPFC functional connectivity or an inability to modulate connectivity in a context-specific manner. To address these gaps, a pVMPFC region of interest was first identified using activation likelihood estimation meta-analysis. pVMPFC connectivity was then examined in relation to anhedonia and general distress symptoms of depression, using both resting-state and task-based functional magnetic resonance imaging involving pleasant music, in current MDD and healthy control groups. In MDD, pVMPFC connectivity was negatively correlated with anhedonia but not general distress during music listening in key reward- and emotion-processing regions, including nucleus accumbens, ventral tegmental area/substantia nigra, orbitofrontal cortex and insula, as well as fronto-temporal regions involved in tracking complex sound sequences, including middle temporal gyrus and inferior frontal gyrus. No such dissociations were observed in the healthy controls, and resting-state pVMPFC connectivity did not dissociate anhedonia from general distress in either group. Our findings demonstrate that anhedonia in MDD is associated with context-specific deficits in pVMPFC connectivity with the mesolimbic reward system when encountering pleasurable stimuli, rather than a static deficit in intrinsic resting-state connectivity. Critically, identification of functional circuits associated with anhedonia better characterizes MDD heterogeneity and may help track of one of its core symptoms.
Introduction:
Obesity is a common medical illness that is increasingly recognised as conferring risk of decline in cognitive performance, independent of other comorbid medical conditions. Individuals with mood disorders (bipolar disorder (BD) or major depressive disorder (MDD)) display an increased prevalence of both obesity and risk factors for cardiovascular diseases. Moreover, BD and MDD are associated with impairment in cognitive functioning across multiple domains. The independent contribution of obesity to cognitive decline in this population has not been explored. This study examines the impact of obesity on cognition by comparing neuropsychological performance in obese individuals, with or without a mood disorder before and after undergoing bariatric surgery.
Methods and analysis:
This study compares measures of declarative memory, executive functioning and attention in obese individuals (body mass index >35 kg/m(2)) with BD or MDD, and 2 control populations (obese individuals without a psychiatric illness and healthy non-obese controls) prior to and following bariatric surgery. Participants (ages 18-60) receive a psychiatric diagnosis via the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; SCID). Mood ratings, physical measurements, nutritional and health questionnaires are also administered. A standardised battery of neuropsychological tests aimed at establishing performance in areas of declarative memory, executive functioning and attention are administered. Warrington's Recognition Memory Task (RMT) and an N-Back Task are performed in a 3 T functional MRI to investigate patterns of neural activation during cognitive performance. Additionally, anatomical MRI data are obtained to investigate potential changes in neural structures. Baseline data will be analysed for between-group differences and later compared with postsurgical data to investigate cognitive change.
Ethics and dissemination:
This study has been approved by the Hamilton Integrated Research Ethics Board (09-3254). Results will be available in peer-reviewed scientific publications and scientific meetings presentations, and released in lay form to media.
Anhedonia is a prominent symptom in neuropsychiatric disorders, most markedly in major depressive disorder (MDD) and schizophrenia (SZ). Emerging evidence indicates an overlap in the neural substrates of anhedonia between MDD and SZ, which supported a transdiagnostic approach. Therefore, we used activation likelihood estimation (ALE) meta-analysis of functional magnetic resonance imaging studies in MDD and SZ to examine the neural bases of three subdomains of anhedonia: consummatory anhedonia, anticipatory anhedonia and emotional processing. ALE analysis focused specifically on MDD or SZ was used later to dissociate specific anhedonia-related neurobiological impairments from potential disease general impairments. ALE results revealed that consummatory anhedonia was associated with decreased activation in ventral basal ganglia areas, while anticipatory anhedonia was associated with more substrates in frontal-striatal networks except the ventral striatum, which included the dorsal anterior cingulate, middle frontal gyrus and medial frontal gyrus. MDD and SZ patients showed similar neurobiological impairments in anticipatory and consummatory anhedonia, but differences in the emotional experience task, which may also involve affective/mood general processing. These results support that anhedonia is characterized by alterations in reward processing and relies on frontal-striatal brain circuitry. The transdiagnostic approach is a promising way to reveal the overall neurobiological framework that contributes to anhedonia and could help to improve targeted treatment strategies.
Food is an innate reward stimulus related to energy homeostasis and survival, whereas money is considered a more general reward stimulus that gains a rewarding value through learning experiences. Although the underlying neural processing for both modalities of reward has been investigated independently from one another, a more detailed investigation of neural similarities and/ or differences between food and monetary reward is still missing. Here, we investigated the neural processing of food compared to monetary related rewards in 27 healthy, normal-weight women using functional magnetic resonance imaging (fMRI). We developed a task distinguishing between the anticipation and the receipt of either abstract food or monetary reward. Both tasks activated the ventral striatum during the expectation of a reward. Compared to money, greater food related activations were observed in prefrontal, parietal and central midline structures during the anticipation and lateral orbitofrontal cortex (lOFC) during the receipt of food reward. Furthermore, during the receipt of food reward, brain activation in the secondary taste cortex was positively related to the BMI. These results indicate that food dependent activations encompass to a greater extent brain regions involved in self-control and self-reflection during the anticipation and phylogenetically older parts of the lOFC during the receipt of reward.
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Mood disorders are common and debilitating conditions characterized in part by profound deficits in reward-related behavioural domains. A recent literature has identified important structural and functional alterations within the brain's reward circuitry - particularly in the ventral tegmental area-nucleus accumbens pathway - that are associated with symptoms such as anhedonia and aberrant reward-associated perception and memory. This Review synthesizes recent data from human and rodent studies from which emerges a circuit-level framework for understanding reward deficits in depression. We also discuss some of the molecular and cellular underpinnings of this framework, ranging from adaptations in glutamatergic synapses and neurotrophic factors to transcriptional and epigenetic mechanisms.
Anhedonia is a core feature of major depressive disorder (MDD), but the precise nature of anhedonic symptoms is unknown. Whereas anhedonia has traditionally been viewed as a deficit in the experience of pleasure, more recent evidence suggests that reduced anticipation and motivation may also be a core feature of this symptom. Here, we provide data from a study in MDD patients and healthy controls using a translational measure of reward motivation, the Effort Expenditure for Rewards Task (EEfRT or "effort"). This task offers subjects a series of trials where they may choose to expend more or less effort for the opportunity to win varying amounts of monetary rewards. We found that MDD patients were less willing to expend effort for rewards than controls. Additionally, we observed that patients were less able to effectively use information about magnitude and probability of rewards to guide their choice behavior. Finally, within the MDD patient group, duration of the current episode was a significant negative predictor of EEfRT task performance. These findings offer novel support for theoretical models proposing that anhedonia in MDD may reflect specific impairments in motivation and reward-based decision-making.
How does the brain translate information signaling potential rewards into motivation to get them? Motivation to obtain reward is thought to depend on the midbrain [particularly the ventral tegmental area (VTA)], the nucleus accumbens (NAcc), and the dorsolateral prefrontal cortex (dlPFC), but it is not clear how the interactions among these regions relate to reward-motivated behavior. To study the influence of motivation on these reward-responsive regions and on their interactions, we used dynamic causal modeling to analyze functional magnetic resonance imaging (fMRI) data from humans performing a simple task designed to isolate reward anticipation. The use of fMRI permitted the simultaneous measurement of multiple brain regions while human participants anticipated and prepared for opportunities to obtain reward, thus allowing characterization of how information about reward changes physiology underlying motivational drive. Furthermore, we modeled the impact of external reward cues on causal relationships within this network, thus elaborating a link between physiology, connectivity, and motivation. Specifically, our results indicated that dlPFC was the exclusive entry point of information about reward in this network, and that anticipated reward availability caused VTA activation only via its effect on the dlPFC. Anticipated reward thus increased dlPFC activation directly, whereas it influenced VTA and NAcc only indirectly, by enhancing intrinsically weak or inactive pathways from the dlPFC. Our findings of a directional prefrontal influence on dopaminergic regions during reward anticipation suggest a model in which the dlPFC integrates and transmits representations of reward to the mesolimbic and mesocortical dopamine systems, thereby initiating motivated behavior.
Motivational theories of choice focus on the influence of goal values and strength of reinforcement to explain behavior. By contrast relatively little is known concerning how the cost of an action, such as effort expended, contributes to a decision to act. Effort-based decision making addresses how we make an action choice based on an integration of action and goal values. Here we review behavioral and neurobiological data regarding the representation of effort as action cost, and how this impacts on decision making. Although organisms expend effort to obtain a desired reward there is a striking sensitivity to the amount of effort required, such that the net preference for an action decreases as effort cost increases. We discuss the contribution of the neurotransmitter dopamine (DA) toward overcoming response costs and in enhancing an animal's motivation toward effortful actions. We also consider the contribution of brain structures, including the basal ganglia and anterior cingulate cortex, in the internal generation of action involving a translation of reward expectation into effortful action.
To investigate the neural mechanisms of food motivation in children and adolescents, and examine brain activation differences between healthy weight (HW) and obese participants.
Ten HW children (ages 11-16; BMI < 85%ile) and 10 obese children (ages 10-17; BMI >95%ile) matched for age, gender and years of education.
Functional magnetic resonance imaging (fMRI) scans were conducted twice: when participants were hungry (pre-meal) and immediately after a standardized meal (post-meal). During the fMRI scans, the participants passively viewed blocked images of food, non-food (animals) and blurred baseline control.
Both groups of children showed brain activation to food images in the limbic and paralimbic regions (PFC/OFC). The obese group showed significantly greater activation to food pictures in the PFC (pre-meal) and OFC (post-meal) than the HW group. In addition, the obese group showed less post-meal reduction of activation (vs pre-meal) in the PFC, limbic and the reward-processing regions, including the nucleus accumbens.
Limbic and paralimbic activation in high food motivation states was noted in both groups of participants. However, obese children were hyper-responsive to food stimuli as compared with HW children. In addition, unlike HW children, brain activations in response to food stimuli in obese children failed to diminish significantly after eating. This study provides initial evidence that obesity, even among children, is associated with abnormalities in neural networks involved in food motivation, and that the origins of neural circuitry dysfunction associated with obesity may begin early in life.
Humans can acquire appropriate behaviors that maximize rewards on a trial-and-error basis. Recent electrophysiological and imaging studies have demonstrated that neural activity in the midbrain and ventral striatum encodes the error of reward prediction. However, it is yet to be examined whether the striatum is the main locus of reward-based behavioral learning. To address this, we conducted functional magnetic resonance imaging (fMRI) of a stochastic decision task involving monetary rewards, in which subjects had to learn behaviors involving different task difficulties that were controlled by probability. We performed a correlation analysis of fMRI data by using the explanatory variables derived from subject behaviors. We found that activity in the caudate nucleus was correlated with short-term reward and, furthermore, paralleled the magnitude of a subject's behavioral change during learning. In addition, we confirmed that this parallelism between learning and activity in the caudate nucleus is robustly maintained even when we vary task difficulty by controlling the probability. These findings suggest that the caudate nucleus is one of the main loci for reward-based behavioral learning.
There is significant association between obesity and depression. Naltrexone/Bupropion (NB) is indicated for treatment of overweight and obesity (BMI ≥27 kg/m² with a comorbidity or ≥30 kg/m²).
This post-hoc analysis examines safety and efficacy of NB and placebo among individuals with overweight or obesity who were also taking antidepressant therapy during the LIGHT trial (N=8910). Subjects were divided into four subgroups: NB + antidepressants (n=1150), NB without antidepressants (n=3300), placebo + antidepressants (n=1127) and placebo without antidepressants (n=3317).
Among subjects taking NB, the combined incidence of serious adverse events (AEs) and AEs leading to treatment discontinuation was not significantly different between those on antidepressants and those who were not.
The key weight-loss efficacy analyses were performed on NB or placebo-treated subjects who remained on study therapy through 104 weeks and who did or did not have documented antidepressant use at each of the baseline, week 52 and week 104 visits (Completers: N=1811; 47.0% female, 86.9% white, mean age of 61 years, mean baseline BMI 37.4 kg/m²). The mean adjusted weight change in subjects taking antidepressants was numerically, but not significantly greater for NB vs. placebo (-6.3% vs. -4.3%). For those subjects not on antidepressants, weight loss was significantly greater for NB vs. PL (-6.8% vs. -3.6%).
NB is generally well tolerated in patients with overweight or obesity who are on antidepressants and is effective in promoting weight loss regardless of antidepressant use. These results show that for patients on antidepressant therapy, NB may be an effective option for obesity management.
Objective
Converging evidence suggests abnormalities in monetary reward processing may underlie the shared pathophysiology between major depressive disorder and obesity. As such, there is a need to parse deficits in specific subcomponents of monetary reward functioning (i.e., valuation, learning and anticipation).
Methods
PsycINFO, Google Scholar and PubMed databases were searched for English-language articles published between database inception to June 6th, 2020. Studies were identified using the following search and medical search heading (MeSH) terms and search strings: (reward (valuation OR motivation OR anticipation OR learning OR functioning OR decision-making OR reinforcement)) AND ((obesity OR overweight OR obese).
Results
Findings were reviewed from 11 studies assessing the association between obesity and monetary reward processing. Four studies found significant differences in reward learning in individuals with obesity compared to normal-weight participants. Five studies found body mass index (BMI) to be predictive of willingness to expend effort (i.e., valuation) for a monetary reward. Three studies found changes in neural activations in the ventral striatum during anticipatory phases preceding receipt of a monetary reward in participants with obesity.
Conclusions
Participants with obesity demonstrated significantly poorer performance in task-based measures of reward learning, valuation, and anticipation, resulting in lower monetary reward outcomes across all studies compared to healthy controls. Notably, participants with obesity and comorbid depression performed worse than participants with no comorbid depression.
Limitations
There persists heterogeneity between studies with regards to inclusion of mood disorder populations and exclusion of psychiatric comorbidities in groups with obesity.
Aims: This study estimated the economic and humanistic burden associated with chronic non-communicable diseases (NCCDs) among adults with comorbid major depressive and/or any anxiety disorders (MDD and/or AAD).
Materials and Methods: A retrospective analysis was conducted using the Medical Expenditure Panel Survey data (2010-2015). The analytic cohort included adults (≥18 years) with MDD only (C1), AAD only (C2) or both (C3). The presence of either of 6 NCCDs (cardiovascular diseases (CVD), pulmonary disorders [PD], pain, hypercholesterolemia, diabetes and obesity) were assessed. Study outcomes included healthcare costs, activity limitations, and quality of life. Multivariate regressions were conducted in each of the 3 cohorts to evaluate the association between the presence of NCCDs and outcomes.
Results: The analytic sample included 9,160,465 patients: C1(4,391,738), C2(3,648,436), C3(1,120,292). Pain(59%) was the most common condition, followed by CVD (55%), hypercholesterolemia(50%), obesity(42%), PD(17%), and diabetes(14%). Mean annual healthcare costs were the greatest for C3($14,317), followed by C1($10,490) and C2($7,906). For C1: CVD was associated with the highest increment in annual costs($3,966) followed by pain($3,617). For C2: Diabetes was associated with the highest incremental annual costs($4,281) followed by PD($2,997). For C3: cost trends were similar to those seen in C2. NCCDs resulted in a significant decrease in physical quality of life across all cohorts. Pain was associated with a significantly higher likelihood of self-reported physical, social, cognitive, and activity limitations.
Conclusions: 60% of patients with MDD and/or AAD had at least one additional NCCD, which significantly increased the economic and humanistic burden. These findings are important for payers and clinicians in making treatment decisions. These results underscore the need for development of multi-pronged interventions which aim to improve quality of life and reduce activity limitations among patients with mental health disorders and NCCDs.
Background:
Anhedonia and abnormalities in reward behavior are core features of major depressive disorder (MDD). Convergent evidence indicates that overweight/obesity (OW), a highly prevalent condition in MDD, is independently associated with reward disturbances. We therefore aimed to investigate the moderating effect of OW on the willingness to expend efforts for reward in individuals with MDD and healthy controls (HC).
Methods:
Forty-one adults (HC n = 20, MDD n = 21) completed the Effort Expenditure for Rewards Task (EEfRT), clinical and cognitive measures. Anthropometric parameters were assessed in all participants, and an additional evaluation of laboratorial parameters were conducted solely on those with MDD. Individuals with MDD were all on vortioxetine monotherapy (10-20 mg/day).
Results:
Interactions between reward magnitude, group and OW were observed (χ2 = 9.192, p = 0.010); the OW-MDD group chose the hard task significantly less than normal weight (NW)-HC (p = 0.033) and OW-HC (p = 0.034), whereas there were no differences between NW-MDD and HCs. Within individuals with MDD, the proportion of hard task choices was more strongly correlated with body mass index (BMI) (r = -0.456, p = 0.043) and insulin resistance (HOMA2-IR) (r = -0.467, p = 0.038), than with depressive symptoms (r = 0.290, p = 0.214).
Conclusions:
OW significantly moderated the association between MDD and willingness to make efforts for rewards. These findings offer novel evidence on the potential role of metabolic factors on the basis of anhedonia, and for the heuristic models proposing a pathophysiological connection between mood and metabolic disorders.
The aim of this study was to assess the association between anhedonia and metabolic syndrome (MetS) in a well-characterized community sample of individuals with a current depressive episode. This is a cross-sectional study with young adults aged 24–30 years old. Depressive episode and the presence of anhedonia was assessed using the Mini International Neuropsychiatric Interview – Plus version (MINI Plus). The MetS was assessed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III). The sample included 931 subjects, being 22 had depression without anhedonia, whereas 55 had depression with anhedonia. MetS was more prevalent among subjects with depression and anhedonia (43.6%) when compared to individuals without anhedonia and population control group. Moreover, subjects with depression and anhedonia have a significant increase of levels of glucose, triglycerides, total-cholesterol and LDL-cholesterol, as well as significant decreased in the HDL-cholesterol level. The present study showed that individuals with depression and anhedonia present higher prevalence of MetS. Our study suggests that the use of the concept of anhedonia may contribute to a better understanding of the complex relationship between depression and metabolic syndrome.
Depression, together with insulin resistance, is increasingly prevalent among youth. These conditions have traditionally been compartmentalized, but recent evidence suggests that a shared brain motivational network underlies their co-occurrence. We posit that, in the context of depressive symptoms, insulin resistance is associated with aberrant structure and functional connectivity in the Anterior Cingulate Cortex (ACC) and hippocampus. This motivational neural circuit underlies dysfunctional behavioral responses and increased sensitivity to rewarding aspects of ingesting high calorie food that lead to disinhibition of eating even when satiated. To investigate this shared mechanism, we evaluated a sample of forty-two depressed and overweight (BMI > 85th%) youth aged 9 to 17. Using ACC and hippocampus structural and seed-based regions of interest, we investigated associations between insulin resistance, depression, structure (ACC thickness, and ACC and hippocampal area), and resting-state functional connectivity (RSFC). We predicted that aberrant associations among these neural and behavioral characteristics would be stronger in insulin resistant compared to insulin sensitive youth. We found that youth with greater insulin resistance had higher levels of anhedonia and more food seeking behaviors, reduced hippocampal and ACC volumes, and greater levels of ACC and hippocampal dysconnectivity to fronto-limbic reward networks at rest. For youth with high levels of insulin resistance, thinner ACC and smaller hippocampal volumes were associated with more severe depressive symptoms, whereas the opposite was true for youth with low levels of insulin resistance. The ACC-hippocampal motivational network that subserves depression and insulin resistance separately, may represent a critical neural interaction that link these syndromes together.
Background:
Obesity has been implicated in the pathophysiology of major depressive disorder (MDD), which prompted us to examine the possible association of obesity with cognitive function and brain structure in patients with MDD.
Methods:
Three hundred and seven patients with MDD and 294 healthy participants, matched for age, sex, ethnicity (Japanese), and handedness (right) were recruited for the study. Cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS). Gray and white matter structures were analyzed using voxel-based morphometry and diffusion tensor imaging in a subsample of patients (n = 114) whose magnetic resonance imaging (MRI) data were obtained using a 1.5 T MRI system.
Results:
Verbal memory, working memory, motor speed, attention, executive function, and BACS composite scores were lower for the MDD patients than for the healthy participants (p < 0.05). Among the patient group, working memory, motor speed, executive function, and BACS composite scores were lower in obese patients (body mass index ≥ 30, n = 17) than in non-obese patients (n = 290, p < 0.05, corrected). MRI determined frontal, temporal, thalamic, and hippocampal volumes, and white matter fractional anisotropy values in the internal capsule and left optic radiation were reduced in obese patients (n = 7) compared with non-obese patients (n = 107, p < 0.05, corrected).
Limitations:
Sample size for obese population was not very large.
Conclusions:
Obesity is associated with decreased cognitive function, reduced gray matter volume, and impaired white matter integrity in cognition-related brain areas in patients with MDD.
Background:
Two objectives of the NIMH Research Domain Criteria (RDoC) initiative are to identify (a) mechanisms that are common to multiple psychiatric disorders, and (b) mechanisms that are unique to specific psychiatric symptoms, and that reflect markers of differential risk for these symptoms. With respect to these objectives, a brain-behavior dimension that has received considerable attention and that is directly relevant to the Positive Valence Systems domain of the RDoC initiative involves reward processing.
Methods:
The present review paper first examines the relationship between reward processing and mood-related symptoms from an RDoC perspective. We then place this work in a larger context by examining the relationship between reward processing abnormalities and psychiatric symptoms defined broadly, including mood-related symptoms, schizophrenia, and addiction.
Results:
Our review suggests that reward hyposensitivity relates to a subtype of anhedonia characterized by motivational deficits in unipolar depression, and reward hypersensitivity relates to a cluster of hypo/manic symptoms characterized by excessive approach motivation in the context of bipolar disorder. Integrating this perspective with research on reward processing abnormalities in schizophrenia and addiction, we further argue that the principles of equifinality and multifinality may be preferable to a transdiagnostic perspective for conceptualizing the relationship between reward processing and psychiatric symptoms defined broadly.
Conclusion:
We propose that vulnerability to either motivational anhedonia or approach-related hypo/manic symptoms involve extreme and opposite profiles of reward processing. We further propose that an equifinality and multifinality perspective may serve as a useful framework for future research on reward processing abnormalities and psychiatric symptoms.
Depression and obesity are both highly prevalent and are leading public health problems. These foregoing disorders independently have great impact on morbidity and mortality affecting patients’ health and well-being as well as on the socioeconomic aspect of functional impairment and healthcare expenditure. Results from epidemiological studies, clinical trials and recent meta-analyses support the association between mood disorders and obesity as both frequently co-occur in all races of populations examined. It is now well-established through longitudinal studies that obesity is a risk factor for mood disorders and vice versa. In the current review, we aim to address the evidence regarding 4 questions: (1) does obesity moderate response to antidepressants among patients with depressive disorders?, (2) does the presence of depressive disorders moderate the progression or outcome of obesity?, (3) does treatment of obesity moderate outcomes among patients with depressive disorders?, and (4) does treatment of depressive disorders moderate outcomes of obesity? In order to improve the interpretability of the results we confined the evaluations to studies where patients met the criteria for depressive disorders or obesity (i.e. BMI > 30). Extant evidence supports the association between obesity and adverse health outcomes among individuals with depressive disorders. In addition, the treatment of one condition (i.e. obesity or depressive disorders) appears to improve the course of the other condition. It might be beneficial to check for the other condition in patients presenting with one condition and treatment should be administered to treat both conditions.
This article describes the National Institute of Mental Health's Research Domain Criteria (RDoC) initiative. The description includes background, rationale, goals, and the way the initiative has been developed and organized. The central RDoC concepts are summarized and the current matrix of constructs that have been vetted by workshops of extramural scientists is depicted. A number of theoretical and methodological issues that can arise in connection with the nature of RDoC constructs are highlighted: subjectivism and heterophenomenology, desynchrony and theoretical neutrality among units of analysis, theoretical reductionism, endophenotypes, biomarkers, neural circuits, construct “grain size,” and analytic challenges. The importance of linking RDoC constructs to psychiatric clinical problems is discussed. Some pragmatics of incorporating RDoC concepts into applications for NIMH research funding are considered, including sampling design.
The rapidly increasing prevalence of both obesity and depression represent two major public health concerns worldwide. But the evidence regarding the direction and strength of the association between these two disorders, for both adult men and women, are remain inconclusive. We systematically reviewed publications from five different databases: Pubmed, Embase, BIOSIS, CINAHL and PsychINFO. A total of 21 articles were included for the systematic review and 19 of them for the meta-analysis using a bias-adjusted (quality effect) model. This resulted in the inclusion of approximately 226063 (33.7% men) participants. Those who were depressed had a 37% (RR: 1.37, 95% CI: 1.17, 1.48) increased risk of being obese, and who were obese had a 18% increased risk of being depressed (RR: 1.18, 95% CI: 1.04, 1.35). Those who were depressed had a 2% (RD: 0.02, 95% CI: 0.01, 0.03) excess risk of obesity, however, the reciprocal associations were not significant. The association between overweight and depression was not found significant in either direction. Both men and women were at risk of obesity and depression bi-directionally. In sensitivity analyses bi-directional associations were more pronounced among young and middle aged adults and in studies with longer follow-up. The findings of this study suggest that the strength of the association is greater for the direction leading from depression to obesity and this link was more pronounced for young and middle aged women.
Objective:
Appetite and weight changes are common but variable diagnostic markers in major depressive disorder: some depressed individuals manifest increased appetite, while others lose their appetite. Many of the brain regions implicated in appetitive responses to food have also been implicated in depression. It is thus remarkable that there exists no published research comparing the neural responses to food stimuli of depressed patients with increased versus decreased appetites.
Method:
Using functional MRI, brain activity was compared in unmedicated depressed patients with increased or decreased appetite and healthy control subjects while viewing photographs of food and nonfood objects. The authors also measured how resting-state functional connectivity related to subjects' food pleasantness ratings.
Results:
Within putative reward regions, depressed participants with increased appetites exhibited greater hemodynamic activity to food stimuli than both those reporting appetite decreases and healthy control subjects. In contrast, depressed subjects experiencing appetite loss exhibited hypoactivation within a region of the mid-insula implicated in interoception, with no difference observed in this region between healthy subjects and those with depression-related appetite increases. Mid-insula activity was negatively correlated with food pleasantness ratings of depressed participants with increased appetites, and its functional connectivity to reward circuitry was positively correlated with food pleasantness ratings.
Conclusions:
Depression-related increases in appetite are associated with hyperactivation of putative mesocorticolimbic reward circuitry, while depression-related appetite loss is associated with hypoactivation of insular regions that support monitoring the body's physiological state. Importantly, the interactions among these regions also contribute to individual differences in the depression-related appetite changes.
Background:
Anhedonia, the loss of interest or pleasure in reward processing, is a hallmark feature of major depressive disorder (MDD), but its underlying neurobiological mechanism is largely unknown. The present study aimed to examine the underlying neural mechanism of reward-related decision-making in patients with MDD.
Method:
We examined behavioral and neural responses to rewards in patients with first-episode MDD (N=25) and healthy controls (N=25) using the Effort-Expenditure for Rewards Task (EEfRT). The task involved choices about possible rewards of varying magnitude and probability. We tested the hypothesis that individuals with MDD would exhibit a reduced neural response in reward-related brain structures involved in cost-benefit decision-making.
Results:
Compared with healthy controls, patients with MDD showed significantly weaker responses in the left caudate nucleus when contrasting the 'high reward'-'low reward' condition, and blunted responses in the left superior temporal gyrus and the right caudate nucleus when contrasting high and low probabilities. In addition, hard tasks chosen during high probability trials were negatively correlated with superior temporal gyrus activity in MDD patients, while the same choices were negatively correlated with caudate nucleus activity in healthy controls.
Conclusions:
These results indicate that reduced caudate nucleus and superior temporal gyrus activation may underpin abnormal cost-benefit decision-making in MDD.
Background:
An important step in obesity research involves identifying neurobiological underpinnings of nonfood reward processing unique to specific subgroups of obese individuals.
Methods:
Nineteen obese individuals seeking treatment for binge eating disorder (BED) were compared with 19 non-BED obese individuals (OB) and 19 lean control subjects (LC) while performing a monetary reward/loss task that parses anticipatory and outcome components during functional magnetic resonance imaging. Differences in regional activation were investigated in BED, OB, and LC groups during reward/loss prospect, anticipation, and notification.
Results:
Relative to the LC group, the OB group demonstrated increased ventral striatal and ventromedial prefrontal cortex activity during anticipatory phases. In contrast, the BED group relative to the OB group demonstrated diminished bilateral ventral striatal activity during anticipatory reward/loss processing. No differences were observed between the BED and LC groups in the ventral striatum.
Conclusions:
Heterogeneity exists among obese individuals with respect to the neural correlates of reward/loss processing. Neural differences in separable groups with obesity suggest that multiple, varying interventions might be important in optimizing prevention and treatment strategies for obesity.
Anhedonia, the lack of interest or pleasure in response to hedonic stimuli or experiences, is a cardinal symptom of depression. This deficit in hedonic processing has been posited to influence depressed individuals' motivation to engage in potentially rewarding experiences. Accumulating evidence indicates that hedonic processing is not a unitary construct but rather consists of an anticipatory and a consummatory phase. We examined how these components of hedonic processing influence motivation to obtain reward in participants diagnosed with major depression and in never-disordered controls. Thirty-eight currently depressed and 30 never-disordered control participants rated their liking of humorous and nonhumorous cartoons and then made a series of choices between viewing a cartoon from either group. Each choice was associated with a specified amount of effort participants would have to exert before viewing the chosen cartoon. Although depressed and control participants did not differ in their consummatory liking of the rewards, levels of reward liking predicted motivation to expend effort for the rewards only in the control participants; in the depressed participants, liking and motivation were dissociated. In the depressed group, levels of anticipatory anhedonia predicted motivation to exert effort for the rewards. These findings support the formulation that anhedonia is not a unitary construct and suggest that, for depressed individuals, deficits in motivation for reward are driven primarily by low anticipatory pleasure and not by decreased consummatory liking.
We found that development of obesity was coupled with emergence of a progressively worsening deficit in neural reward responses. Similar changes in reward homeostasis induced by cocaine or heroin are considered to be crucial in triggering the transition from casual to compulsive drug-taking. Accordingly, we detected compulsive-like feeding behavior in obese but not lean rats, measured as palatable food consumption that was resistant to disruption by an aversive conditioned stimulus. Striatal dopamine D2 receptors (D2Rs) were downregulated in obese rats, as has been reported in humans addicted to drugs. Moreover, lentivirus-mediated knockdown of striatal D2Rs rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with extended access to palatable high-fat food. These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.
Association between obesity and depression has repeatedly been established. For treatment and prevention purposes, it is important to acquire more insight into their longitudinal interaction.
To conduct a systematic review and meta-analysis on the longitudinal relationship between depression, overweight, and obesity and to identify possible influencing factors.
Studies were found using PubMed, PsycINFO, and EMBASE databases and selected on several criteria.
Studies examining the longitudinal bidirectional relation between depression and overweight (body mass index 25-29.99) or obesity (body mass index > or =30) were selected.
Unadjusted and adjusted odds ratios (ORs) were extracted or provided by the authors.
Overall, unadjusted ORs were calculated and subgroup analyses were performed for the 15 included studies (N = 58 745) to estimate the effect of possible moderators (sex, age, depression severity). Obesity at baseline increased the risk of onset of depression at follow-up (unadjusted OR, 1.55; 95% confidence interval [CI], 1.22-1.98; P < .001). This association was more pronounced among Americans than among Europeans (P = .05) and for depressive disorder than for depressive symptoms (P = .05). Overweight increased the risk of onset of depression at follow-up (unadjusted OR, 1.27; 95% CI, 1.07-1.51; P < .01). This association was statistically significant among adults (aged 20-59 years and > or =60 years) but not among younger persons (aged <20 years). Baseline depression (symptoms and disorder) was not predictive of overweight over time. However, depression increased the odds for developing obesity (OR, 1.58; 95% CI, 1.33-1.87; P < .001). Subgroup analyses did not reveal specific moderators of the association.
This meta-analysis confirms a reciprocal link between depression and obesity. Obesity was found to increase the risk of depression, most pronounced among Americans and for clinically diagnosed depression. In addition, depression was found to be predictive of developing obesity.
Having shown taxometrically that there exists a hypohedonic schizotypal taxon in a college population, J. J. Blanchard, S. W. Gangestad, S. A. Brown, and W. P. Horan (2000) suggested that P. E. Meehl erred in revising his 1962 theory by postulating a normal-range individual differences variable of hedonic capacity that potentiates schizotypy into schizophrenia. The aversive drift and secondary anhedonia of Meehl's theory imply that the schizotypal taxon will generate hypohedonic taxonicity in an adult population. Psychometrically measurable hedonic disposition (as distinguished from genetic primary hedonic capacity) is "dragged along" by the schizogene, especially in the social domain. To choose between causal interpretations, it could be ascertained whether the schizotypal anhedonic taxon is composed of individuals who are schizotaxic on the basis of psychophysiological, cognitive, and soft neurologic indicators.
Dopamine agonists have been implicated in causing compulsive behaviors in patients with Parkinson's disease (PD). These have included gambling, hypersexuality, hobbyism, and other repetitive, purposeless behaviors ("punding"). In this report, we describe 7 patients in whom compulsive eating developed in the context of pramipexole use. All of the affected patients had significant, undesired weight gain; 4 had other comorbid compulsive behaviors. In the 5 patients who lowered the dose of pramipexole or discontinued dopamine agonist treatment, the behavior remitted and no further weight gain occurred. Physicians should be aware that compulsive eating resulting in significant weight gain may occur in PD as a side-effect of dopamine agonist medications such as pramipexole. Given the known risks of the associated weight gain and obesity, further investigation is warranted.
The reinforcing effects of addictive drugs and palatable foods are regulated, at least in part, by a common biological mechanism. The reactivity or sensitivity of these brain reward regions have been found to correlate significantly with the risk for a variety of drug addictions. Sensitivity to Reward (STR) is conceptualised as a psycho-biological personality trait rooted firmly in the availability of dopamine in the mesocorticolimbic ('common reward') pathways, and as such is a good candidate for studying motivational factors and eating behaviours. The purpose of the present study was to examine whether STR was related to behaviours that contribute to excess body weight. Structural equation modelling procedures were used with a sample of healthy adult women (n=151). We hypothesised that STR would positively predict overeating and a preference for foods high in fat and sugar; and that these two behaviour would, in turn, predict a higher Body Mass Index. Results provided an excellent fit of the model to our data confirming our view that a personality trait like STR can only influence a physical condition like body weight indirectly by the way it co-varies with behaviours that contribute directly to variation in the outcome variable.
Anhedonia, the lack of reactivity to pleasurable stimuli, is a cardinal feature of depression that has received renewed interest as a potential endophenotype of this debilitating disease. The goal of the present study was to test the hypothesis that individuals with major depression are characterized by blunted reward responsiveness, particularly when anhedonic symptoms are prominent.
A probabilistic reward task rooted within signal-detection theory was utilized to objectively assess hedonic capacity in 23 unmedicated subjects meeting DSM-IV criteria for major depressive disorder (MDD) and 25 matched control subjects recruited from the community. Hedonic capacity was defined as reward responsiveness - i.e., the participants' propensity to modulate behavior as a function of reward.
Compared to controls, MDD subjects showed significantly reduced reward responsiveness. Trial-by-trial probability analyses revealed that MDD subjects, while responsive to delivery of single rewards, were impaired at integrating reinforcement history over time and expressing a response bias toward a more frequently rewarded cue in the absence of immediate reward. This selective impairment correlated with self-reported anhedonic symptoms, even after considering anxiety symptoms and general distress.
These findings indicate that MDD is characterized by an impaired tendency to modulate behavior as a function of prior reinforcements, and provides initial clues about which aspects of hedonic processing might be dysfunctional in depression.
Recent work suggests that obesity may adversely affect cognitive behavior. To examine this suggestion, the effects of feeding a standard chow diet, and either supplemental sugar or fat on the development of obesity and performance on a test of spatial learning, the Morris Water Maze (MWM), were assessed in young male Long-Evans rats. Rats given access to a sucrose solution or dietary fat in addition to the chow diet consumed approximately 10% more calories per day, gained more weight, and had larger epididymal fat pads than rats fed the chow diet alone. Moreover, rats fed the supplemental sucrose took significantly more time to find a hidden platform in the MWM than rats fed the chow diet alone or chow and supplemental fat. Additionally, when tested 10 days after the initial training trials, rats given sucrose displayed deficits in long-term spatial memory. After 6 weeks on the diets, fasting blood glucose and serum triglyceride concentrations were significantly higher in sucrose-fed rats than in rats eating only the standard diet. These results indicate that diet-induced obesity resulting from excess sucrose intake, but not fat intake, in young animals impairs spatial learning and memory. It is hypothesized that these deficits arise from metabolic insults that leave the brain vulnerable to alterations in insulin sensitivity and glucose metabolism.
Worth the “EEfRT”? The effort expenditure for rewards task as an objective measure of motivation and anhedonia
- Treadway