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PloS One 2020Insight into motivational processes may be gained by examining measures of willingness to exert effort for rewards, which have been linked to neuropsychiatric symptoms...
Insight into motivational processes may be gained by examining measures of willingness to exert effort for rewards, which have been linked to neuropsychiatric symptoms of anhedonia and apathy. However, while much work has focused on the development of models of motivation based on classic tasks of externally-generated levels of effort for reward, there has been less focus on the question of self-generated motivation or volition. We developed a task that aims to capture separate measures of self-generated and externally-generated motivation, with two task variants for physical and cognitive effort, and sought to test and validate this measure in two populations of healthy volunteers (N = 27 and N = 28). Similar to previous reports, a sigmoid function represented a better overall fit to the effort-reward data than a linear or Weibull model. Individual sigmoid function shapes were governed by two free parameters: bias (the amount of reward needed for effort initiation) and reward insensitivity (the amount of increase in reward needed to accelerate effort expenditure). For both physical and cognitive effort, bias was higher in the self-generated condition, indicating reduced self-generated volitional effort initiation, compared to externally-generated effort initiation, across effort domains. Bias against initial effort initiation in the self-generated condition was related to a specific dimensional measure of anticipatory anhedonia. For physical effort only, reward insensitivity was also higher in the self-generated condition compared to the externally-generated motivation condition, indicating lower self-generated effort acceleration. This work provides a novel objective measure of self-generated motivation that may provide insights into mechanisms of anhedonia and related symptoms.
Topics: Adult; Anhedonia; Apathy; Bias; Cognition; Decision Making; Female; Healthy Volunteers; Humans; Male; Middle Aged; Motivation; Reward; Volition
PubMed: 32428020
DOI: 10.1371/journal.pone.0232949 -
Brain, Behavior, and Immunity Jan 2021Depression has been associated with low-grade elevation of plasma cytokines (e.g. interleukin-6, IL-6; tumor necrosis factor alpha, TNFα) in both cross-sectional and...
BACKGROUND
Depression has been associated with low-grade elevation of plasma cytokines (e.g. interleukin-6, IL-6; tumor necrosis factor alpha, TNFα) in both cross-sectional and longitudinal studies in adults. Preclinical and clinical studies also suggest that IL-6 and TNFα elevation are associated with anhedonia. However, few studies have examined longitudinal relationships between cytokines and depression/anhedonia in clinically depressed samples, particularly adolescents.
METHODS
Thirty-six adolescents with a depressive disorder receiving standard-of-care community treatment were assessed at a baseline and a follow-up timepoint. Self-report and clinical measures of depression and anhedonia, along with plasma IL-6 and TNFα levels, were obtained at both timepoints. Baseline cytokine measures were examined in association with baseline and follow-up clinical measures. On an exploratory basis, change in clinical measures over time was examined in relation to change in cytokine levels over time.
RESULTS
Higher baseline TNFα levels predicted higher follow-up depression severity after approximately four months (controlling for baseline depression). Higher baseline TNFα levels also associated positively with baseline anhedonia and predicted higher anhedonia at follow-up (controlling for baseline anhedonia). No association was found between change in clinical measures and change in cytokine levels over time.
CONCLUSIONS
Among adolescents receiving standard-of-care community treatment for depression, higher levels of TNFα predicted greater depressive symptoms at 4-month follow-up, suggesting this cytokine may be used to help identify patients in need of more intensive treatment. Elevated TNFα levels were also associated with concurrent and future anhedonia symptoms, suggesting a specific mechanism in which TNFα affects depression trajectories. Future studies should examine the relationships between cytokine levels and depression/anhedonia symptoms at multiple timepoints in larger cohorts of depressed adolescents.
Topics: Adolescent; Adult; Anhedonia; Cross-Sectional Studies; Cytokines; Depression; Humans; Interleukin-6; Longitudinal Studies; Tumor Necrosis Factor-alpha
PubMed: 32919038
DOI: 10.1016/j.bbi.2020.09.004 -
Cureus Apr 2020Escalating cannabis use may be linked to decreased motivation and anhedonia, which are symptoms of depression. Adolescent cannabis users with subthreshold depressive... (Review)
Review
Escalating cannabis use may be linked to decreased motivation and anhedonia, which are symptoms of depression. Adolescent cannabis users with subthreshold depressive symptoms such as reduced motivation may be susceptible to the development of significant anhedonia in addition to impaired emotional development. The main issue regarding depression within the context of cannabis use is whether or not there is a neurobiological basis linking the two variables. A Medical Subject Headings (MeSH) function PubMed search using the keywords "cannabis, depression, adolescence, endocannabinoid, and temperament" returned 1,109 articles. Data were included from studies that satisfied the following criteria: (i) published within the last 10 years (older studies were included based on relevance), (ii) on adolescent subjects (animal or human), (iii) published in English, (iv) journal articles, systematic reviews, meta-analyses, clinical trials, observational studies (animal or human), (v) on subjects who had unipolar depression with no comorbidities, and (vi) on subjects who used cannabis [with no confounding variables such as the use of ethanol, nicotine, cocaine, lysergic acid diethylamide (LSD), and heroin; and no medical conditions such as comorbid psychosis, mania, or autism]. Depressive symptoms in cannabinoid users were a common co-occurrence partly explained by pleiotropic linkage of genetic locus identified on chromosome 11q23.1-q23.2 and comprises the gene sequence nuclear cell adhesion molecule 1-tetratricopeptide repeat domain 12-ankyrin repeat and kinase domain containing 1-dopamine receptor D2 (NCAM1-TTC12-ANKK1-DRD2). The relationship between the two is not invariant and is influenced by polymorphic DRD, endocannabinoid receptor (CNR), and 5-HT genes. Anhedonia seemed to be the most important symptom. Cannabinoid-induced long-term neuroplastic changes, particularly in the dorsal striatum, is a possible mechanism resulting in anhedonia and long-term effects on motivation.
PubMed: 32455076
DOI: 10.7759/cureus.7759 -
Psychological Medicine Jul 2023Anhedonia is apparent in different mental disorders and is suggested to be related to dysfunctions in the reward system and/or affect regulation. It may hence be a...
BACKGROUND
Anhedonia is apparent in different mental disorders and is suggested to be related to dysfunctions in the reward system and/or affect regulation. It may hence be a common underlying feature associated with symptom severity of mental disorders.
METHODS
We constructed a cross-sectional graphical Least Absolute Shrinkage and Selection Operator (LASSO) network and a relative importance network to estimate the relationships between anhedonia severity and the severity of symptom clusters of major depressive disorder (MDD), anxiety sensitivity (AS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) in a sample of Dutch adult psychiatric patients ( = 557).
RESULTS
Both these networks revealed anhedonia severity and depression symptom severity as central to the network. Results suggest that anhedonia severity may be predictive of the severity of symptom clusters of MDD, AS, ADHD, and ASD. MDD symptom severity may be predictive of AS and ADHD symptom severity.
CONCLUSIONS
The results suggest that anhedonia may serve as a common underlying transdiagnostic psychopathology feature, predictive of the severity of symptom clusters of depression, AS, ADHD, and ASD. Thus, anhedonia may be associated with the high comorbidity between these symptom clusters and disorders. If our results will be replicated in future studies, it is recommended for clinicians to be more vigilant about screening for anhedonia and/or depression severity in individuals diagnosed with an anxiety disorder, ADHD and/or ASD.
Topics: Adult; Humans; Anhedonia; Depressive Disorder, Major; Autism Spectrum Disorder; Syndrome; Cross-Sectional Studies; Attention Deficit Disorder with Hyperactivity
PubMed: 35348051
DOI: 10.1017/S0033291722000575 -
Journal of Neural Transmission (Vienna,... Sep 2023The brain is built with hemispheric asymmetries in structure and function to enable fast neuronal processing. In neuroimaging studies, several mental disorders have been... (Review)
Review
The brain is built with hemispheric asymmetries in structure and function to enable fast neuronal processing. In neuroimaging studies, several mental disorders have been associated with altered or attenuated hemispheric asymmetries. However, the exact mechanism linking asymmetries and disorders is not known. Here, studies in animal models of mental disorders render important insights into the etiology and neuronal alterations associated with both disorders and atypical asymmetry. In this review, the current literature of animal studies in rats and mice focusing on anxiety and fear, anhedonia and despair, addiction or substance misuse, neurodegenerative disorders as well as stress exposure, and atypical hemispheric asymmetries is summarized. Results indicate overall increased right-hemispheric neuronal activity and a left-sided behavioral bias associated with symptoms of anxiety, fear, anhedonia, behavioral despair as well as stress exposure. Addiction behavior is associated with right-sided bias and transgenic models of Alzheimer's disease indicate an asymmetrical accumulation of fibrillar plaques. Most studies focused on changes in the bilateral amygdala and frontal cortex. Across studies, two crucial factors influencing atypical asymmetries arose independently of the disorder modeled: sex and developmental age. In conclusion, animal models of mental disorders demonstrate atypical hemispheric asymmetries similar to findings in patients. Particularly, increased left-sided behavior and greater right-hemispheric activity were found across models applying stress-based paradigms. However, sex- and age-dependent effects on atypical hemispheric asymmetries are present that require further investigation. Animal models enable the analysis of hemispheric changes on the molecular level which may be most effective to detect early alterations.
Topics: Rats; Animals; Mice; Rodentia; Anhedonia; Brain; Neuroimaging; Mental Disorders; Functional Laterality; Magnetic Resonance Imaging
PubMed: 36842091
DOI: 10.1007/s00702-023-02610-z -
Complex Psychiatry 2023Chronic stress-related illnesses such as major depressive disorder and post-traumatic stress disorder share symptomatology, including anxiety, anhedonia, and...
INTRODUCTION
Chronic stress-related illnesses such as major depressive disorder and post-traumatic stress disorder share symptomatology, including anxiety, anhedonia, and helplessness. Across disorders, neurotoxic dysregulated glutamate (Glu) signaling may underlie symptom emergence. Current first-line antidepressant drugs, which do not directly target Glu signaling, fail to provide adequate benefit for many patients and are associated with high relapse rates. Riluzole modulates glutamatergic neurotransmission by increasing metabolic cycling and modulating signal transduction. Clinical studies exploring riluzole's efficacy in stress-related disorders have provided varied results. However, the utility of riluzole for treating specific symptom dimensions or as a prophylactic treatment has not been comprehensively assessed.
METHODS
We investigated whether chronic prophylactic riluzole (∼12-15 mg/kg/day p.o.) could prevent the emergence of behavioral deficits induced by unpredictable chronic mild stress (UCMS) in mice. We assessed (i) anxiety-like behavior using the elevated-plus maze, open-field test, and novelty-suppressed feeding, (ii) mixed anxiety/anhedonia-like behavior in the novelty-induced hypophagia test, and (iii) anhedonia-like behavior using the sucrose consumption test. Z-scoring summarized changes across tests measuring similar dimensions. In a separate learned helplessness (LH) cohort, we investigated whether chronic prophylactic riluzole treatment could block the development of helplessness-like behavior.
RESULTS
UCMS induced an elevation in anhedonia-like behavior and overall behavioral emotionality that was blocked by prophylactic riluzole. In the LH cohort, prophylactic riluzole blocked the development of helplessness-like behavior.
DISCUSSION/CONCLUSION
This study supports the utility of riluzole as a prophylactic medication for preventing anhedonia and helplessness symptoms associated with stress-related disorders.
PubMed: 37101541
DOI: 10.1159/000529534 -
The American Journal of Psychiatry May 2021Preclinical studies point to the KCNQ2/3 potassium channel as a novel target for the treatment of depression and anhedonia, a reduced ability to experience pleasure. The... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Preclinical studies point to the KCNQ2/3 potassium channel as a novel target for the treatment of depression and anhedonia, a reduced ability to experience pleasure. The authors conducted the first randomized placebo-controlled trial testing the effect of the KCNQ2/3 positive modulator ezogabine on reward circuit activity and clinical outcomes in patients with depression.
METHODS
Depressed individuals (N=45) with elevated levels of anhedonia were assigned to a 5-week treatment period with ezogabine (900 mg/day; N=21) or placebo (N=24). Participants underwent functional MRI during a reward flanker task at baseline and following treatment. Clinical measures of depression and anhedonia were collected at weekly visits. The primary endpoint was the change from baseline to week 5 in ventral striatum activation during reward anticipation. Secondary endpoints included depression and anhedonia severity as measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Snaith-Hamilton Pleasure Scale (SHAPS), respectively.
RESULTS
The study did not meet its primary neuroimaging endpoint. Participants in the ezogabine group showed a numerical increase in ventral striatum response to reward anticipation following treatment compared with participants in the placebo group from baseline to week 5. Compared with placebo, ezogabine was associated with a significantly larger improvement in MADRS and SHAPS scores and other clinical endpoints. Ezogabine was well tolerated, and no serious adverse events occurred.
CONCLUSIONS
The study did not meet its primary neuroimaging endpoint, although the effect of treatment was significant on several secondary clinical endpoints. In aggregate, the findings may suggest that future studies of the KCNQ2/3 channel as a novel treatment target for depression and anhedonia are warranted.
Topics: Adult; Anhedonia; Carbamates; Depressive Disorder; Depressive Disorder, Major; Double-Blind Method; Female; Functional Neuroimaging; Humans; KCNQ2 Potassium Channel; KCNQ3 Potassium Channel; Magnetic Resonance Imaging; Male; Membrane Transport Modulators; Middle Aged; Phenylenediamines; Reward; Ventral Striatum
PubMed: 33653118
DOI: 10.1176/appi.ajp.2020.20050653 -
CNS Neuroscience & Therapeutics Nov 2019Anhedonia is a transdiagnostic psychopathological dimension, consisting in the impaired ability to experience pleasure. In order to further our understanding of its... (Review)
Review
INTRODUCTION
Anhedonia 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.
METHODS
We 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.
RESULTS
All 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.
CONCLUSIONS
Anhedonia 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.
Topics: Anhedonia; Animals; Brain; Clinical Trials as Topic; Endophenotypes; Humans; Mental Disorders; Reward; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation
PubMed: 31638332
DOI: 10.1111/cns.13230 -
Frontiers in Psychiatry 2021Anhedonia is considered as one of the five dimensions of negative symptoms and mainly refers to the reduction of the capacity of feeling pleasure. Increasing evidence...
Anhedonia is considered as one of the five dimensions of negative symptoms and mainly refers to the reduction of the capacity of feeling pleasure. Increasing evidence suggests that anhedonia in schizophrenia may be partly explained by cognitive impairment. However, the associations between specific cognitive impairment and anhedonia are not fully investigated. The purpose of this study was to examine anticipatory anhedonia, consummatory anhedonia, and their cognitive associations in schizophrenia. A total number of 100 patients with schizophrenia and 67 healthy volunteers were recruited. The clinical symptoms of schizophrenia were assessed. Anticipatory pleasure, consummatory pleasure, and cognitive functions of each participant were measured. Multiple linear regression analysis was performed to investigate the influencing factors of anhedonia in schizophrenia. The results showed no significant differences in sex, age, education year, body mass index (BMI), and marital status between the schizophrenia group and healthy control group (all > 0.05). Both anticipatory and consummatory pleasure in the schizophrenia group were significantly lower than those in the healthy control group (all < 0.05). Immediate memory, visual spanning, language, attention, and delayed memory were significantly poorer in the schizophrenia group (all < 0.05). The results showed that language deficit is an independent risk factor for anticipatory anhedonia ( = 0.265, = 0.008, 95% 0.038-0.244), while delayed memory deficit is an independent risk factor for consummatory anhedonia ( = 0.391, < 0.001, 95% 0.085-0.237). To the best of our knowledge, this is the first study that reported the specific cognitive associations of anhedonia in schizophrenia. The findings have added new evidence on the influencing factors of anhedonia and provided clues for the associations between clinical manifestations of schizophrenia.
PubMed: 34925093
DOI: 10.3389/fpsyt.2021.762216 -
Schizophrenia Bulletin Oct 2021Dysfunction in the neural circuits underlying salience signaling is implicated in symptoms of psychosis and may predict conversion to a psychotic disorder in youth at...
Dysfunction in the neural circuits underlying salience signaling is implicated in symptoms of psychosis and may predict conversion to a psychotic disorder in youth at clinical high risk (CHR) for psychosis. Additionally, negative symptom severity, including consummatory and anticipatory aspects of anhedonia, may predict functional outcome in individuals with schizophrenia-spectrum disorders. However, it is unclear whether anhedonia is related to the ability to attribute incentive salience to stimuli (through reinforcement learning [RL]) and whether measures of anhedonia and RL predict functional outcome in a younger, help-seeking population. We administered the Salience Attribution Test (SAT) to 33 participants who met criteria for either CHR or a recent-onset psychotic disorder and 29 help-seeking youth with nonpsychotic disorders. In the SAT, participants must identify relevant and irrelevant stimulus dimensions and be sensitive to different reinforcement probabilities for the 2 levels of the relevant dimension ("adaptive salience"). Adaptive salience attribution was positively related to both consummatory pleasure and functioning in the full sample. Analyses also revealed an indirect effect of adaptive salience on the relation between consummatory pleasure and both role (αβ = .22, 95% CI = 0.02, 0.48) and social functioning (αβ = .14, 95% CI = 0.02, 0.30). These findings suggest a distinct pathway to poor global functioning in help-seeking youth, via impaired reward sensitivity and RL.
Topics: Adolescent; Anhedonia; Depression; Female; Humans; Male; Patient Acceptance of Health Care; Psychosocial Functioning; Psychotic Disorders; Reinforcement, Psychology; Risk
PubMed: 34240217
DOI: 10.1093/schbul/sbab075