-
Cell Reports Aug 2021Astrocytic contributions to neuroinflammation are widely implicated in disease, but they remain incompletely explored. We assess medial prefrontal cortex (PFC) and...
Astrocytic contributions to neuroinflammation are widely implicated in disease, but they remain incompletely explored. We assess medial prefrontal cortex (PFC) and visual cortex (VCX) astrocyte and whole-tissue gene expression changes in mice following peripherally induced neuroinflammation triggered by a systemic bacterial endotoxin, lipopolysaccharide, which produces sickness-related behaviors, including anhedonia. Neuroinflammation-mediated behavioral changes and astrocyte-specific gene expression alterations peak when anhedonia is greatest and then reverse to normal. Notably, region-specific molecular identities of PFC and VCX astrocytes are largely maintained during reactivity changes. Gene pathway analyses reveal alterations of diverse cell signaling pathways, including changes in cell-cell interactions of multiple cell types that may underlie the central effects of neuroinflammation. Certain astrocyte molecular signatures accompanying neuroinflammation are shared with changes reported in Alzheimer's disease and mouse models. However, we find no evidence of altered neuronal survival or function in the PFC even when neuroinflammation-induced astrocyte reactivity and behavioral changes are significant.
Topics: Alzheimer Disease; Anhedonia; Animals; Astrocytes; Cell Communication; Cerebral Cortex; Inflammation; Lipopolysaccharides; Mice, Inbred C57BL; Neurons; Phenotype; Pyramidal Cells; Transcription, Genetic; Mice
PubMed: 34380036
DOI: 10.1016/j.celrep.2021.109508 -
Canadian Journal of Psychiatry. Revue... May 2018
Topics: Anhedonia; Biomarkers; Cognitive Dysfunction; Depressive Disorder, Major; Humans; Precision Medicine; Sleep Wake Disorders
PubMed: 29278937
DOI: 10.1177/0706743717748883 -
Epilepsy & Behavior : E&B Mar 2023Anhedonia, the impaired ability to experience pleasure, is a core feature of major depressive disorder, one of the most common comorbidities in epilepsy. It is also...
BACKGROUND
Anhedonia, the impaired ability to experience pleasure, is a core feature of major depressive disorder, one of the most common comorbidities in epilepsy. It is also reported as a clinical feature independent of depression in a number of other neurological conditions. This study aimed to establish the prevalence of anhedonia in a sample of people with epilepsy, with and without a diagnosis of depression, and to examine the clinical and demographic characteristics of those who present with this symptom.
METHODS
A consecutive sample of 211 people (118 female, 93 male, mean age 38.09 years) completed the Snaith-Hamilton Pleasure Scale (SHAPS) to determine the presence of anhedonia and the Hospital Anxiety and Depression Scale to determine levels of anxiety and depression. The majority of patients had focal epilepsy (n = 165), and the remaining patients had generalized epilepsy (n = 22), or unclassified epilepsy (n = 24). Sixteen percent of the sample had a clinical diagnosis of depression at the time of the study.
RESULTS
Over one in three of the sample (35%) reported significant anhedonia on the SHAPS. While these patients were more likely to have a diagnosis of depression (p < 0.01), 30% of people without a diagnosis of depression also reported significant anhedonia. Difficulties gaining pleasure on 12 of the 14 items on the SHAPS were associated with cognitive difficulties, with those reporting an inability to feel pleasure on the item scoring significantly lower on tests of cognitive function than those who were able to gain pleasure. Of the three cognitive domains examined (overall intellectual ability, verbal memory, and processing speed), a poor memory had the strongest relationship; with lower memory function associated with an impaired ability to experience pleasure on 9 of the 14 items.
CONCLUSION
While anhedonia is well recognized as a feature of depression, our data suggests that it can be present in up to a third of people with epilepsy who do not have a diagnosis of depression. Cognitive difficulties, particularly impaired memory function may mediate some features of anhedonia. The implications of these findings for the clinical management of anhedonia in people with epilepsy are discussed.
Topics: Humans; Male; Female; Adult; Anhedonia; Depressive Disorder, Major; Pleasure; Epilepsy
PubMed: 36443164
DOI: 10.1016/j.yebeh.2022.108966 -
Molecular Psychiatry Oct 2022Increased inflammation in major depressive disorder (MDD) has been associated with low functional connectivity (FC) in corticostriatal reward circuits and symptoms of... (Randomized Controlled Trial)
Randomized Controlled Trial
Functional connectivity in reward circuitry and symptoms of anhedonia as therapeutic targets in depression with high inflammation: evidence from a dopamine challenge study.
Increased inflammation in major depressive disorder (MDD) has been associated with low functional connectivity (FC) in corticostriatal reward circuits and symptoms of anhedonia, relationships which may involve the impact of inflammation on synthesis and release of dopamine. To test this hypothesis while establishing a platform to examine target engagement of potential therapies in patients with increased inflammation, medically stable unmedicated adult MDD outpatients enrolled to have a range of inflammation (as indexed by plasma C-reactive protein [CRP] levels) were studied at two visits involving acute challenge with the dopamine precursor levodopa (L-DOPA; 250 mg) and placebo (double-blind, randomized order ~1-week apart). The primary outcome of resting-state (rs)FC in a classic ventral striatum to ventromedial prefrontal cortex reward circuit was calculated using a targeted, a priori approach. Data available both pre- and post-challenge (n = 31/40) established stability of rsFC across visits and determined CRP > 2 mg/L as a cut-point for patients exhibiting positive FC responses (post minus pre) to L-DOPA versus placebo (p < 0.01). Higher post-L-DOPA FC in patients with CRP > 2 mg/L was confirmed in all patients (n = 40) where rsFC data were available post-challenge (B = 0.15, p = 0.006), and in those with task-based (tb)FC during reward anticipation (B = 0.15, p = 0.013). While effort-based motivation outside the scanner positively correlated with rsFC independent of treatment or CRP, change in anhedonia scores negatively correlated with rsFC after L-DOPA only in patients with CRP > 2 mg/L (r = -0.56, p = 0.012). FC in reward circuitry should be further validated in larger samples as a biomarker of target engagement for potential treatments including dopaminergic agents in MDD patients with increased inflammation.
Topics: Adult; Humans; Anhedonia; Dopamine; Depressive Disorder, Major; Neural Pathways; Depression; Levodopa; Magnetic Resonance Imaging; Reward; Inflammation
PubMed: 35927580
DOI: 10.1038/s41380-022-01715-3 -
Current Topics in Behavioral... 2022Anhedonia, or the decreased ability to experience pleasure, is a cardinal symptom of major depression that commonly occurs within other forms of psychopathology.... (Review)
Review
Anhedonia, or the decreased ability to experience pleasure, is a cardinal symptom of major depression that commonly occurs within other forms of psychopathology. Supportive of long-held theory that anhedonia represents a genetically influenced vulnerability marker for depression, evidence from twin studies suggests that it is moderately-largely heritable. However, the genomic sources of this heritability are just beginning to be understood. In this review, we survey what is known about the genomic architecture underlying anhedonia and related constructs. We briefly review twin and initial candidate gene studies before focusing on genome-wide association study (GWAS) and polygenic efforts. As large samples are needed to reliably detect the small effects that typically characterize common genetic variants, the study of anhedonia and related phenotypes conflicts with current genomic research requirements and frameworks that prioritize sample size over precise phenotyping. This has resulted in few and underpowered studies of anhedonia-related constructs that have largely failed to reliably identify individual variants. Nonetheless, the polygenic architecture of anhedonia-related constructs identified in these studies has genetic overlap with depression and schizophrenia as well as related brain structure (e.g., striatal volume), providing important clues to etiology that may usefully guide refinement in nosology. As we await the accumulation of larger samples for more well-powered GWAS of reward-related constructs, novel analytic techniques that leverage GWAS summary statistics (e.g., genomic structural equation modeling) may currently be used to help characterize how the genomic architecture of anhedonia is shared and distinct from that underlying other constructs (e.g., depression, neuroticism, anxiety).
Topics: Anhedonia; Depressive Disorder, Major; Genome-Wide Association Study; Genomics; Humans; Reward
PubMed: 35152374
DOI: 10.1007/7854_2021_293 -
Journal of Affective Disorders Feb 2019Despite the fact that higher levels of anxiety and anhedonia in Major Depressive Disorder (MDD) are linked to poorer treatment outcomes, mechanisms contributing to these...
BACKGROUND
Despite the fact that higher levels of anxiety and anhedonia in Major Depressive Disorder (MDD) are linked to poorer treatment outcomes, mechanisms contributing to these clinical presentations remain unclear. Neuroticism, impaired cognitive control, and blunted reward learning may be critical processes involved in MDD and may help to explain symptoms of anxiety and anhedonia.
METHODS
Using baseline data from patients with early-onset MDD (N = 296) in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) trial, we conducted a path analysis to model relationships between neuroticism, cognitive control, and reward learning to levels of anxiety and anhedonia.
RESULTS
Neuroticism was positively associated with both anhedonia (standardized coefficient = 0.26, p < .001) and anxiety (standardized coefficient = 0.40, p < .001). Cognitive control was negatively associated with anxiety (standardized coefficient = -0.18, p < .05). Reward learning was not significantly associated with either anxiety or anhedonia.
LIMITATIONS
Extraneous variables not included in the model may have even more influence in explaining symptoms of anxiety and anhedonia. Restricted range in these variables may have attenuated some of the hypothesized relationships. Most important, because this was a cross-sectional analysis in a currently depressed sample, we cannot draw any causal conclusions without experimental and longitudinal data.
CONCLUSIONS
These cross-sectional findings suggest that neuroticism may contribute to anxiety and anhedonia in patients with early onset and either chronic or recurrent MDD, while enhanced cognitive control may protect against anxiety.
Topics: Adult; Anhedonia; Antidepressive Agents; Anxiety Disorders; Cognition; Cross-Sectional Studies; Depressive Disorder, Major; Female; Humans; Learning; Male; Middle Aged; Neuroticism; Reward; Treatment Outcome
PubMed: 30699849
DOI: 10.1016/j.jad.2018.11.072 -
Archives of Psychiatric Nursing Jun 2013Anhedonia presents itself in a myriad of disease processes. To further develop our understanding of anhedonia and effective ways to manage it, the concept requires clear... (Review)
Review
Anhedonia presents itself in a myriad of disease processes. To further develop our understanding of anhedonia and effective ways to manage it, the concept requires clear boundaries. This paper critically examined the current scientific literature and conducted a concept analysis of anhedonia to provide a more accurate and lucid understanding of the concept. As part of the concept analysis, this paper also provides model, borderline, related, and contrary examples of anhedonia.
Topics: Anhedonia; Humans; Motivation; Personal Satisfaction
PubMed: 23706888
DOI: 10.1016/j.apnu.2013.02.001 -
Annual Review of Clinical Psychology 2014Depression is a significant public health problem, but its etiology and pathophysiology remain poorly understood. Such incomplete understanding likely arises from the... (Review)
Review
Depression is a significant public health problem, but its etiology and pathophysiology remain poorly understood. Such incomplete understanding likely arises from the fact that depression encompasses a heterogeneous set of disorders. To overcome these limitations, renewed interest in intermediate phenotypes (endophenotypes) has resurfaced, and anhedonia has emerged as one of the most promising endophenotypes of depression. Here, a heuristic model is presented postulating that anhedonia arises from dysfunctional interactions between stress and brain reward systems. To this end, we review and integrate three bodies of independent literature investigating the role of (a) anhedonia, (b) dopamine, and (c) stress in depression. In a fourth section, we summarize animal data indicating that stress negatively affects mesocorticolimbic dopaminergic pathways critically implicated in incentive motivation and reinforcement learning. In the last section, we provide a synthesis of these four literatures, present initial evidence consistent with our model, and discuss directions for future research.
Topics: Anhedonia; Depressive Disorder; Humans; Models, Psychological; Stress, Psychological
PubMed: 24471371
DOI: 10.1146/annurev-clinpsy-050212-185606 -
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 -
Translational Psychiatry Aug 2020Fatigue and anhedonia are commonly reported, co-occurring clinical symptoms associated with chronic illnesses. Fatigue is a multidimensional construct that is defined as... (Review)
Review
Fatigue and anhedonia are commonly reported, co-occurring clinical symptoms associated with chronic illnesses. Fatigue is a multidimensional construct that is defined as a distressing, persistent, subjective sense of physical, cognitive, or emotional tiredness that interferes with usual functioning. Anhedonia is a component of depressive disorders and other psychiatric conditions, such as schizophrenia, and is defined by the reduced ability to experience pleasure. Both symptoms greatly affect the health-related quality of life of patients with chronic illnesses. Although fatigue and anhedonia are commonly associated with each other, understanding the differences between the two constructs is necessary for diagnosis and clinical treatment. A scoping review was conducted based on published guidance, starting with a comprehensive search of existing literature to understand the similarities and differences between fatigue and anhedonia. An initial search of PubMed using fatigue and anhedonia as medical subject headings yielded a total of 5254 articles. A complete full-text review of the final 21 articles was conducted to find articles that treated both constructs similarly and articles that presented fatigue and anhedonia as distinct constructs. About 60% of the reviewed articles consider both constructs as distinct, but a considerable number of the reviewed articles found these constructs indistinguishable. Nomenclature and biology were two themes from the reviewed articles supporting the idea that anhedonia and fatigue are indistinguishable constructs. The information generated from this review is clinically relevant to optimize the management of fatigue related to anhedonia from other fatigue subtypes.
Topics: Anhedonia; Emotions; Fatigue; Humans; Quality of Life; Schizophrenia
PubMed: 32769967
DOI: 10.1038/s41398-020-00960-w