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Current Topics in Behavioral... 2022Drug addiction has been defined as a chronically relapsing disorder that is characterized by a compulsion to seek and take a drug or stimulus, the loss of control in... (Review)
Review
Drug addiction has been defined as a chronically relapsing disorder that is characterized by a compulsion to seek and take a drug or stimulus, the loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug or stimulus is prevented, a component of which is anhedonia. The present review explores a heuristic framework for understanding the role of anhedonia in addiction, in which anhedonia is a key component of hyperkatifeia (conceptualized as the potentiated intensity of negative emotional/motivational symptoms during drug withdrawal) and negative reinforcement in addiction. The neural substrates that mediate such anhedonia and crosstalk between elements of hyperkatifeia that contribute to anhedonia are then explored, including crosstalk between physical pain and emotional pain systems. The present review explores current knowledge of neurochemical neurocircuitry changes that are associated with conditioned hyperkatifeia/anhedonia. The overall hypothesis is that the shift in motivation toward negative reinforcement in addiction reflects the allostatic misregulation of hedonic tone, such that drug taking makes anhedonia worse during the process of seeking temporary relief by compulsive drug taking, thereby perpetuating the addiction cycle and hedonic comorbidities that are associated with addiction.
Topics: Anhedonia; Brain; Humans; Pain; Reinforcement, Psychology; Substance-Related Disorders
PubMed: 35112332
DOI: 10.1007/7854_2021_288 -
Current Topics in Behavioral... 2022Anhedonia reflects a reduced ability to engage in previously pleasurable activities and has been reported in children as young as 3 years of age. It manifests early and...
Anhedonia reflects a reduced ability to engage in previously pleasurable activities and has been reported in children as young as 3 years of age. It manifests early and is a strong predictor of psychiatric disease onset and progression over the course of development and into adulthood. However, little is known about its mechanistic origins, particularly in childhood and adolescence. In this chapter, we provide a socio-cognitive model of the development of anhedonia. This model is substantiated by past literature presented in this chapter to account for how the individual trajectories of emotion knowledge, autobiographical memory, and self-concept representations contribute to the onset, persistence, and progression of anhedonia from early childhood through adolescence.
Topics: Adolescent; Adult; Anhedonia; Attention; Child; Child, Preschool; Emotions; Humans; Memory, Episodic; Mental Disorders
PubMed: 35585464
DOI: 10.1007/7854_2022_356 -
Current Topics in Behavioral... 2022Anhedonia, the reduction of pleasure and reward-seeking behavior, is a transdiagnostic construct associated with a range of important health outcomes. As with other... (Review)
Review
Anhedonia, the reduction of pleasure and reward-seeking behavior, is a transdiagnostic construct associated with a range of important health outcomes. As with other psychiatric disorders, anhedonia is a relatively common, though understudied, feature of posttraumatic stress disorder (PTSD) that is not adequately targeted by existing treatments. The purpose of this review is to describe the current state of the literature on anhedonia in PTSD and highlight areas for future research based on gaps in the existing evidence base. First, we review evidence for anhedonia symptoms as a distinct PTSD symptom factor and its associations with psychiatric comorbidity, disease trajectory, and quality of life outcomes, as well as describe theories that seek to explain the occurrence of anhedonia among individuals with PTSD. Second, we review evidence for behavioral and neural alterations in reward processing and circuitry, a marker of anhedonia, among individuals with PTSD and in animal models relevant to this disorder. Finally, we discuss key gaps in our understanding of anhedonia in PTSD and suggest areas for future research. Specifically, the timing of anhedonia symptom development and underlying circuit dysfunction in the trauma response trajectory, as well as potential differential associations of facets of anhedonia on clinical outcomes, remain unclear. Additionally, further research is needed to determine potential moderators of anhedonia, as well as the efficacy and effectiveness of psychotherapeutic, psychopharmacological, and device-based interventions targeting anhedonia among individuals with PTSD. A more thorough understanding of these topics will ultimately improve prevention and intervention efforts for PTSD.
Topics: Anhedonia; Animals; Humans; Phenotype; Prevalence; Quality of Life; Stress Disorders, Post-Traumatic
PubMed: 34907507
DOI: 10.1007/7854_2021_292 -
CNS Neuroscience & Therapeutics Jul 2018Anhedonia, as a dysregulation of the reward circuit, is present in both Major Depressive Disorder (MDD) and schizophrenia (SZ). (Review)
Review
BACKGROUND
Anhedonia, as a dysregulation of the reward circuit, is present in both Major Depressive Disorder (MDD) and schizophrenia (SZ).
AIMS
To elucidate the clinical and neurobiological differences between schizophrenia (SZ) and depression (MDD) in regard to anhedonia, while reconciling the challenges and benefits of assessing anhedonia as a transdiagnostic feature under the Research Domain Criteria (RDoC) framework.
METHODS
In this review, we summarize data from publications examining anhedonia or its underlying reward deficits in SZ and MDD. A literature search was conducted in OVID Medline, PsycINFO and EMBASE databases between 2000 and 2017.
RESULTS
While certain subgroups share commonalities, there are also important differences. SZ may be characterized by a disorganization, rather than a deficiency, in reward processing and cognitive function, including inappropriate energy expenditure and focus on irrelevant cues. In contrast, MDD has been characterized by deficits in anticipatory pleasure, development of reward associations, and integration of information from past experience. Understanding the roles of neurotransmitters and aberrant brain circuitry is necessary to appreciate differences in reward function in SZ and MDD.
CONCLUSION
Anhedonia as a clinical presentation of reward circuit dysregulation is an important and relatively undertreated symptom of both SZ and MDD. In order to improve patient outcomes and quality of life, it is important to consider how anhedonia fits into both diagnoses.
Topics: Anhedonia; Depression; Humans; Schizophrenia; Schizophrenic Psychology
PubMed: 29687627
DOI: 10.1111/cns.12854 -
Harvard Review of Psychiatry 2020Depression is both prevalent and costly, and many individuals do not adequately respond to existing psychopharmacological and behavioral interventions. The current... (Review)
Review
Depression is both prevalent and costly, and many individuals do not adequately respond to existing psychopharmacological and behavioral interventions. The current article describes the use of neuroscience in augmenting behavioral interventions for depression in two primary areas: anhedonia and cognitive deficits/biases. Neuroscience research has increased our understanding of the neural bases of reward processing and regulation of positive affect, and anhedonia among depressed samples can be related to deficits in each of these domains. Treatments that specifically target reward processing and regulation of positive affect in order to reduce anhedonia represent a recent advance in the field. Depression is also associated with aberrant processes relating to working memory, autobiographical memory, attentional bias, and interpretive bias. Neuroscience findings have increasingly been leveraged to augment the efficacy of cognitive-training and bias-modification interventions in these domains. The use of neuroscience to inform the development and augmentation of behavioral interventions for depression is a promising avenue of continued research.
Topics: Affect; Anhedonia; Attention; Behavior Therapy; Brain; Cognition; Depressive Disorder; Humans; Memory, Short-Term; Neurosciences; Randomized Controlled Trials as Topic; Reward
PubMed: 31913979
DOI: 10.1097/HRP.0000000000000241 -
Current Topics in Behavioral... 2022This chapter discusses how the complex concept of anhedonia can be operationalized and studied in preclinical models. It provides information about the development of...
This chapter discusses how the complex concept of anhedonia can be operationalized and studied in preclinical models. It provides information about the development of anhedonia in the context of early-life adversity, and the power of preclinical models to tease out the diverse molecular, epigenetic, and network mechanisms that are responsible for anhedonia-like behaviors.Specifically, we first discuss the term anhedonia, reviewing the conceptual components underlying reward-related behaviors and distinguish anhedonia pertaining to deficits in motivational versus consummatory behaviors. We then describe the repertoire of experimental approaches employed to study anhedonia-like behaviors in preclinical models, and the progressive refinement over the past decade of both experimental instruments (e.g., chemogenetics, optogenetics) and conceptual constructs (salience, valence, conflict). We follow with an overview of the state of current knowledge of brain circuits, nodes, and projections that execute distinct aspects of hedonic-like behaviors, as well as neurotransmitters, modulators, and receptors involved in the generation of anhedonia-like behaviors. Finally, we discuss the special case of anhedonia that arises following early-life adversity as an eloquent example enabling the study of causality, mechanisms, and sex dependence of anhedonia.Together, this chapter highlights the power, potential, and limitations of using preclinical models to advance our understanding of the origin and mechanisms of anhedonia and to discover potential targets for its prevention and mitigation.
Topics: Anhedonia; Humans; Motivation; Reward
PubMed: 35156184
DOI: 10.1007/7854_2021_299 -
The International Journal of... Apr 2022Mood disorders, especially depression, are a major cause of human disability. The loss of pleasure (anhedonia) is a common, severely debilitating symptom of clinical...
Mood disorders, especially depression, are a major cause of human disability. The loss of pleasure (anhedonia) is a common, severely debilitating symptom of clinical depression. Experimental animal models are widely used to better understand depression pathogenesis and to develop novel antidepressant therapies. In rodents, various experimental models of anhedonia have already been developed and extensively validated. Complementing rodent studies, the zebrafish (Danio rerio) is emerging as a powerful model organism to assess pathobiological mechanisms of affective disorders, including depression. Here, we critically discuss the potential of zebrafish for modeling anhedonia and studying its molecular mechanisms and translational implications.
Topics: Anhedonia; Animals; Antidepressive Agents; Behavior, Animal; Disease Models, Animal; Zebrafish
PubMed: 34918075
DOI: 10.1093/ijnp/pyab092 -
The British Journal of Clinical... Jun 2022Anhedonia, or reward system dysfunction, is associated with poorer treatment outcomes among depressed individuals. The role of anhedonia in treatment engagement,... (Review)
Review
Anhedonia, or reward system dysfunction, is associated with poorer treatment outcomes among depressed individuals. The role of anhedonia in treatment engagement, however, has not yet been explored. We review research on components of reward functioning impaired in depression, including effort valuation, reward anticipation, initial responsiveness, reward learning, reward probability, and reward delay, highlighting potential barriers to treatment engagement associated with these components. We then propose interventions to improve treatment initiation and continuation by addressing deficits in each component of reward functioning, focusing on modifications of existing evidence-based interventions to meet the needs of individuals with heightened anhedonia. We describe potential settings for these interventions and times at which they can be delivered during the process of referring individuals to mental health treatment, conducting intakes or assessments, and providing treatment. Additionally, we note the advantages of using screening processes already in place in primary care, workplace, school, and online settings to identify individuals with heightened anhedonia who may benefit from these interventions. We conclude with suggestions for future research on the impact of anhedonia on treatment engagement and the efficacy of interventions to address it. PRACTITIONER POINTS: Many depressed individuals who might benefit from treatment do not initiate it or discontinue early. One barrier to treatment engagement may be anhedonia, a core symptom of depression characterized by loss of interest or pleasure in usual activities. We describe brief interventions to improve treatment engagement in individuals with anhedonia that can be implemented during the referral process or early in treatment. We argue that interventions aiming to improve treatment engagement in depressed individuals that target anhedonia may be particularly effective.
Topics: Anhedonia; Depression; Humans; Pleasure; Psychotherapy; Reward
PubMed: 34625993
DOI: 10.1111/bjc.12335 -
Aiding and Abetting Anhedonia: Impact of Inflammation on the Brain and Pharmacological Implications.Pharmacological Reviews Jul 2021Exogenous administration of inflammatory stimuli to humans and laboratory animals and chronic endogenous inflammatory states lead to motivational deficits and ultimately... (Review)
Review
Exogenous administration of inflammatory stimuli to humans and laboratory animals and chronic endogenous inflammatory states lead to motivational deficits and ultimately anhedonia, a core and disabling symptom of depression present in multiple other psychiatric disorders. Inflammation impacts neurotransmitter systems and neurocircuits in subcortical brain regions including the ventral striatum, which serves as an integration point for reward processing and motivational decision-making. Many mechanisms contribute to these effects of inflammation, including decreased synthesis, release and reuptake of dopamine, increased synaptic and extrasynaptic glutamate, and activation of kynurenine pathway metabolites including quinolinic acid. Neuroimaging data indicate that these inflammation-induced neurotransmitter effects manifest as decreased activation of ventral striatum and decreased functional connectivity in reward circuitry involving ventral striatum and ventromedial prefrontal cortex. Neurocircuitry changes in turn mediate nuanced effects on motivation that include decreased willingness to expend effort for reward while maintaining the ability to experience reward. Taken together, the data reveal an inflammation-induced pathophysiologic phenotype that is agnostic to diagnosis. Given the many mechanisms involved, this phenotype represents an opportunity for development of novel and/or repurposed pharmacological strategies that target inflammation and associated cellular and systemic immunometabolic changes and their downstream effects on the brain. To date, clinical trials have failed to capitalize on the unique nature of this transdiagnostic phenotype, leaving the field bereft of interpretable data for meaningful clinical application. However, novel trial designs incorporating established targets in the brain and/or periphery using relevant outcome variables (e.g., anhedonia) are the future of targeted therapy in psychiatry. SIGNIFICANCE STATEMENT: Emerging understanding of mechanisms by which peripheral inflammation can affect the brain and behavior has created unprecedented opportunities for development of pharmacological strategies to treat deficits in motivation including anhedonia, a core and disabling symptom of depression well represented in multiple psychiatric disorders. Mechanisms include inflammation and cellular and systemic immunometabolism and alterations in dopamine, glutamate, and kynurenine metabolites, revealing a target-rich environment that nevertheless has yet to be fully exploited by current clinical trial designs and drugs employed.
Topics: Anhedonia; Animals; Brain; Humans; Inflammation; Motivation; Reward
PubMed: 34285088
DOI: 10.1124/pharmrev.120.000043 -
Journal of Affective Disorders Nov 2023The external behavioural manifestations and internal neural mechanisms of anhedonia are sexually dimorphic. This study aimed to explore the sex differences in the...
OBJECTIVE
The external behavioural manifestations and internal neural mechanisms of anhedonia are sexually dimorphic. This study aimed to explore the sex differences in the regional brain neuroimaging features of anhedonia in the context of major depressive disorder (MDD).
METHOD
The resting-fMRI by applying amplitude of low-frequency fluctuation (ALFF) method was estimated in 414 patients with MDD (281 high anhedonia [HA], 133 low anhedonia [LA]) and 213 healthy controls (HC). The effects of two factors in patients with MDD were analysed using a 2 (sex: male, female) × 2 (group: HA, LA) ANOVA concerning the brain regions in which statistical differences were identified between patients with MDD and HC. We followed up with patients with HA at baseline, and 43 patients completed a second fMRI scan in remission. Paired t-test was performed to compare the ALFF values of anhedonia-related brain regions between the baseline and remission periods.
RESULTS
For the sex-by-group interaction, the bilateral insula, right hippocampus, right post cingulum cortex, and left putamen showed significant differences. Furthermore, the abnormally elevated ALFF values in anhedonia-related brain regions at baseline decreased in remission.
CONCLUSION
Our findings point to the fact that the females showed unique patterns of anhedonia-related brain activity compared to males, which may have clinical implications for interfering with the anhedonia symptoms in MDD. Using task fMRI, we can further examine the distinct characteristics between consumption anhedonia and anticipation anhedonia in MDD.
Topics: Female; Humans; Male; Depressive Disorder, Major; Anhedonia; Sex Characteristics; Magnetic Resonance Imaging; Brain
PubMed: 37591350
DOI: 10.1016/j.jad.2023.08.083