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Frontiers in Psychiatry 2024Anhedonia is a core symptom of depression characterized by a diminished ability to experience pleasure. Currently available treatments for depression often fall short in...
BACKGROUND
Anhedonia is a core symptom of depression characterized by a diminished ability to experience pleasure. Currently available treatments for depression often fall short in adequately addressing anhedonia that often presents as a chronic and debilitating symptom. Ketamine is known to possess antianhedonic properties.
METHODS
This analysis of a naturalistic observational study of treatment-resistant depression inpatients (n=28) analyzed antianhedonic response patterns measured by Snaith-Hamilton Pleasure Scale and changes in Inventory of Depressive Symptomatology in responders (n=6) and non-responders (n=22) stratified per Montgomery-Åsberg Depression Rating Scale during short-term ketamine treatment.
RESULTS
Results show that responders significantly improve in anhedonia over time (p=0.0084) and at the 7th infusion and follow-up (both p<0.05). Non-responders reported significant reduction in anhedonia over time (p=0.0011) and at the 5th, 7th infusion and at the follow-up (all p's<0.05). Non-responders were also observed to improve significantly in self-reported depression at the 7th infusion (p=0.0219) but not at the follow-up.
DISCUSSION
There is no complete overlap between change in depressive symptoms and anhedonia. Therefore, it might be assumed ketamine alleviates anhedonia as an individual symptom domain regardless of formal treatment outcome.
PubMed: 38439794
DOI: 10.3389/fpsyt.2024.1334293 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Oct 2023At present, the doctor-patient relationship is tense. The prevalence of negative emotions, such as depression and anxiety, among healthcare workers is increasing every...
OBJECTIVES
At present, the doctor-patient relationship is tense. The prevalence of negative emotions, such as depression and anxiety, among healthcare workers is increasing every year. Negative attitudes of medical workers toward mental problems may aggravate the doctor-patient conflict and psychological problems of medical workers. This study aims to explore the complex network relationships between outpatient medical workers' attitudes toward mental problems, doctor-patient relationships, and their depression/anxiety levels.
METHODS
A total of 578 outpatient medical staff from the Second Xiangya Hospital of Central South University (167 males, 411 females) completed questionnaires on their attitudes toward mental problems, doctor-patient relationships, and depression/anxiety symptoms. Network analysis was conducted separately to construct the "attitude towards mental problems-doctor-patient relationship network" and "depression-anxiety related network".
RESULTS
The edge between "M15 (insulting words)" and "D8 (waste time)" showed the strongest strength in the "attitude towards mental problems-doctor-patient relationship network", and "M15 (insulting words)" had the highest bridge strength in the network. For the analysis of emotional variables, "P1 (anhedonia)" showed the most obvious association with "D10 (communication difficulties)" in the doctor-patient relationship and "M2 (poor quality of life)" in the psychiatric attitudes, and "P1 (anhedonia)" was the key bridge symptom in the network.
CONCLUSIONS
The "insulting words" may be an intervention target for medical workers' attitudes toward mental problems. The "anhedonia" in depression is the potential symptom that needs to be treated. Intervention targeting these variables may be beneficial to improve the mental health level of medical workers and the doctor-patient relationship.
Topics: Female; Male; Humans; Anhedonia; Depression; Physician-Patient Relations; Quality of Life; Anxiety; Health Personnel
PubMed: 38432880
DOI: 10.11817/j.issn.1672-7347.2023.230115 -
CNS Neuroscience & Therapeutics Mar 2024Noninvasive brain stimulation (NIBS) techniques are a promising tool for treating the negative symptoms of schizophrenia. Growing evidence suggests that different... (Meta-Analysis)
Meta-Analysis
Is it more effective for anhedonia and avolition? A systematic review and meta-analysis of non-invasive brain stimulation interventions for negative symptoms in schizophrenia.
BACKGROUND
Noninvasive brain stimulation (NIBS) techniques are a promising tool for treating the negative symptoms of schizophrenia. Growing evidence suggests that different dimensions of negative symptoms have partly distinct underlying pathophysiological mechanisms. Previous randomized controlled trials (RCTs) have shown inconsistent impacts of NIBS across dimensions.
OBJECTIVE
This systematic review and meta-analysis evaluated the effects of NIBS on general negative symptoms, and on specific domains, including blunted affect, alogia, asociality, anhedonia, and avolition.
DATA SOURCES
PubMed, Web of Science, Embase, Cochrane CENTRAL, PsycINFO, OpenGrey, and Clinicaltrials.gov from the first date available to October, 2023.
RESULTS
Among 1049 studies, we identified eight high-quality RCTs. NIBS significantly affects general negative symptoms (SMD = -0.54, 95% CI [-0.88, -0.21]) and all five domains (SMD = -0.32 to -0.63). Among dimensions, better effects have been shown for improvement of avolition (SMD = -0.47, 95% CI [-0.81, -0.13]) and anhedonia (SMD = -0.63, 95% CI [-0.98, -0.28]). Subgroup analyses of studies that applied once daily stimulation or >10 sessions showed significantly reduced negative symptom severity.
CONCLUSION
NIBS exerts distinct effects across multiple dimensions of negative symptom, with treatment effects related to stimulation frequency and total sessions. These results need to be confirmed in dedicated studies.
Topics: Humans; Anhedonia; Brain; PubMed; Schizophrenia; Electric Stimulation Therapy
PubMed: 38432851
DOI: 10.1111/cns.14645 -
NPJ Digital Medicine Mar 2024While digital phenotyping provides opportunities for unobtrusive, real-time mental health assessments, the integration of its modalities is not trivial due to high...
While digital phenotyping provides opportunities for unobtrusive, real-time mental health assessments, the integration of its modalities is not trivial due to high dimensionalities and discrepancies in sampling frequencies. We provide an integrated pipeline that solves these issues by transforming all modalities to the same time unit, applying temporal independent component analysis (ICA) to high-dimensional modalities, and fusing the modalities with linear mixed-effects models. We applied our approach to integrate high-quality, daily self-report data with BiAffect keyboard dynamics derived from a clinical suicidality sample of mental health outpatients. Applying the ICA to the self-report data (104 participants, 5712 days of data) revealed components related to well-being, anhedonia, and irritability and social dysfunction. Mixed-effects models (55 participants, 1794 days) showed that less phone movement while typing was associated with more anhedonia (β = -0.12, p = 0.00030). We consider this method to be widely applicable to dense, longitudinal digital phenotyping data.
PubMed: 38429434
DOI: 10.1038/s41746-024-01048-1 -
Scientific Reports Mar 2024Upon both acute and prolonged alcohol intake, the brain undergoes a metabolic shift associated with increased acetate metabolism and reduced glucose metabolism, which...
Upon both acute and prolonged alcohol intake, the brain undergoes a metabolic shift associated with increased acetate metabolism and reduced glucose metabolism, which persists during abstinence, putatively leading to energy depletion in the brain. This study evaluates the efficacy of ketogenic treatments to rescue psychiatric and neurochemical alterations during long-term alcohol withdrawal. Female mice were intermittently exposed to alcohol vapor or air for three weeks, during which mice were introduced to either a ketogenic diet (KD), control diet supplemented with ketone ester (KE) or remained on control diet (CD). Withdrawal symptoms were assessed over a period of four weeks followed by re-exposure using several behavioral and biochemical tests. Alcohol-exposed mice fed CD displayed long-lasting depressive-like symptoms measured by saccharin preference and tail suspension, as well as decreased norepinephrine levels and serotonin turnover in the hippocampus. Both KD and KE rescued anhedonia for up to three weeks of abstinence. KD mice showed higher latency to first immobility in the tail suspension test, as well as lower plasma cholesterol levels. Our findings show promising effects of nutritional ketosis in ameliorating alcohol withdrawal symptoms in mice. KD seemed to better rescue these symptoms compared to KE.
Topics: Mice; Female; Animals; Substance Withdrawal Syndrome; Alcoholism; Mice, Inbred C57BL; Ethanol; Ketones; Ketosis
PubMed: 38429369
DOI: 10.1038/s41598-024-55310-3 -
Translational Psychiatry Mar 2024Chronic stress is the primary environmental risk factor for major depressive disorder (MDD), and there is compelling evidence that neuroinflammation is the major...
Chronic stress is the primary environmental risk factor for major depressive disorder (MDD), and there is compelling evidence that neuroinflammation is the major pathomechanism linking chronic stress to MDD. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a negative regulator of MAPK signaling pathways involved in cellular stress responses, survival, and neuroinflammation. We examined the possible contributions of MKP-1 to stress-induced MDD by comparing depression-like behaviors (anhedonia, motor retardation, behavioral despair), neuroinflammatory marker expression, and MAPK signaling pathways among rats exposed to chronic unpredictable mild stress (CUMS), overexpressing MKP-1 in the hippocampus, and CUMS-exposed rats underexpressing MKP-1 in the hippocampus. Rats exposed to CUMS exhibited MKP-1 overexpression, greater numbers of activated microglia, and enhanced expressions of neuroinflammatory markers (interleukin [IL]-6, [IL]-1β, tumor necrosis factor [TNF]-ɑ, and decreased phosphorylation levels of ERK and p38 in the hippocampus as well as anhedonia in the sucrose preference test, motor retardation in the open field, and greater immobility (despair) in the forced swimming tests. These signs of neuroinflammation and depression-like behaviors and phosphorylation levels of ERK and p38 were also observed in rats overexpressing MKP-1 without CUMS exposure, while CUMS-induced neuroinflammation, microglial activation, phosphorylation levels of ERK and p38, and depression-like behaviors were significantly reversed by MKP-1 knockdown. Moreover, MKP-1 knockdown promoted the activation of the MAPK isoform ERK, implying that the antidepressant-like effects of MKP-1 knockdown may be mediated by the ERK pathway disinhibition. These findings suggested that hippocampal MKP-1 is an essential regulator of stress-induced neuroinflammation and a promising target for antidepressant development.
Topics: Animals; Rats; Anhedonia; Antidepressive Agents; Depression; Depressive Disorder, Major; Disease Models, Animal; Down-Regulation; Hippocampus; Interleukin-6; Neuroinflammatory Diseases; Stress, Psychological; Tumor Necrosis Factor-alpha
PubMed: 38424085
DOI: 10.1038/s41398-024-02846-7 -
Trends in Cognitive Sciences Jun 2024Anhedonia is a reduction in enjoyment, motivation, or interest. It is common across mental health disorders and a harbinger of poor treatment outcomes. The enjoyment... (Review)
Review
Anhedonia is a reduction in enjoyment, motivation, or interest. It is common across mental health disorders and a harbinger of poor treatment outcomes. The enjoyment aspect, termed 'consummatory anhedonia', in particular poses fundamental questions about how the brain constructs rewards: what processes determine how intensely a reward is experienced? Here, we outline limitations of existing computational conceptualisations of consummatory anhedonia. We then suggest a richer reinforcement learning (RL) account of consummatory anhedonia with a reconceptualisation of subjective hedonic experience in terms of goal progress. This accounts qualitatively for the impact of stress, dysfunctional cognitions, and maladaptive beliefs on hedonic experience. The model also offers new views on the treatments for anhedonia.
Topics: Humans; Anhedonia; Reward; Reinforcement, Psychology; Models, Psychological; Brain; Motivation
PubMed: 38423829
DOI: 10.1016/j.tics.2024.01.006 -
Psychiatria Polska Feb 2024Fibromyalgia (FM) is often comorbid with psychiatric disorders. Moreover, several studies show that psychiatric disorders may be linked to the severity and impact of FM....
OBJECTIVES
Fibromyalgia (FM) is often comorbid with psychiatric disorders. Moreover, several studies show that psychiatric disorders may be linked to the severity and impact of FM. Therefore, the study described in the article had two main goals: (1) to explore various psychopathological symptom dimensions in patients with fibromyalgia and secondly, (2) to examine the links between psychopathology and response to treatment with serotonin and norepinephrine reuptake inhibitors (SNRI).
METHODS
This cross-sectional study was performed between December 2020 and November 2022. The definition of resistance to SNRI was <30% reduction of pain after ≥8 weeks of treatment. 30 FM subjects responsive to SNRI (FM T[+]), 32 patients non-responsive to SNRI (FM T[-]) and 30 healthy controls were enrolled. Participants were examined by physicians and completed self-report tools to evaluate levels of depression (Quick Inventory of Depressive Symptomatology, Hospital Anxiety and Depression Scale), anxiety (State and Trait Anxiety Inventory), anhedonia (Snaith-Hamilton Pleasure Scale), bipolar symptoms (Mood Disorder Questionnaire, Hypomania Checklist), and dissociation (Dissociative Experiences Scale - Revised). ANOVA analysis and a series of simple logistic regressions were used to examine the associations between psychopathological variables and response to SNRI.
RESULTS
FM T[-] vs. FM T[+] showed higher levels of: depression, state and trait anxiety and anhedonia as well as higher proportion of scores indicating the presence of anxiety disorder. Increased severity of depression, anxiety and anhedonia were predictors of resistance to SNRI.
CONCLUSIONS
Modifiable psychopathological symptoms vary in FM T[+] vs. FM T[-] and are predictors of resistance to SNRI. Psychological assessment should be integrated into standard care for FM patients.
PubMed: 38421347
DOI: 10.12740/PP/OnlineFirst/176000 -
Frontiers in Cellular Neuroscience 2024Post-infection syndromes are characterised by fatigue, muscle pain, anhedonia, and cognitive impairment; mechanistic studies exploring these syndromes have focussed on...
INTRODUCTION
Post-infection syndromes are characterised by fatigue, muscle pain, anhedonia, and cognitive impairment; mechanistic studies exploring these syndromes have focussed on pathways downstream of Toll-like receptor (TLR) 4 activation. Here, we investigated the mechanistic interplay between behaviour, metabolism, and inflammation downstream of TLR-7 activation compared to TLR-4 activation in male and female CD1 mice.
METHODS
Animals received either a TLR-4 (LPS; 0.83 mg/kg) or TLR-7 (R848, 5 mg/kg) agonist, or saline, and behaviour was analysed in an Open Field (OF) at 24 h ( = 20/group). Plasma, liver, and prefrontal cortex (PFC) were collected for gene expression analysis at 24 h and 1H-NMR metabolomics.
RESULTS
TLR-4 and TLR-7 activation decreased distance travelled and rearing in the OF, but activation of each receptor induced distinct cytokine responses and metabolome profiles. LPS increased IL-1β expression and CXCL1 in the PFC, but TLR7 activation did not and strongly induced PFC CXCL10 expression. Thus, TLR7 induced sickness behaviour is independent of IL-1β expression. In both cases, the behavioural response to TLR activation was sexually dimorphic: females were more resilient. However, dissociation was observed between the resilient female mice behaviour and the levels of gene cytokine expression, which was, in general, higher in the female mice. However, the metabolic shifts induced by immune activation were better correlated with the sex-dependent behavioural dimorphisms; increased levels of antioxidant potential in the female brain are intrinsic male/female metabolome differences. A common feature of both TLR4 and TLR7 activation was an increase in N-acetyl aspartate (NAA) in the PFC, which is likely be an allostatic response to the challenges as sickness behaviour is inversely correlated with NAA levels.
DISCUSSION
The results highlight how the cytokine profile induced by one PAMP cannot be extrapolated to another, but they do reveal how the manipulation of the conserved metabolome response might afford a more generic approach to the treatment of post-infection syndromes.
PubMed: 38414751
DOI: 10.3389/fncel.2024.1345441 -
BMC Psychiatry Feb 2024Mood disorders are strongly associated with melatonin disturbances. However, it is unclear whether there is a difference in melatonin concentrations and melatonin...
BACKGROUND
Mood disorders are strongly associated with melatonin disturbances. However, it is unclear whether there is a difference in melatonin concentrations and melatonin circadian rhythm profiles between depression and bipolar disorder. In addition, the relationship between anhedonia, a common symptom of affective disorders, and its melatonin circadian rhythm remains under-investigated.
METHODS
Thirty-four patients with depression disorder, 20 patients diagnosed with bipolar disorder and 21 healthy controls participated in this study. The Revised Physical Anhedonia Scale (RPAS) was performed to assess anhedonia. Saliva samples were collected from all subjects at fixed time points (a total of 14 points) in two consecutive days for measuring the melatonin concentrations to fit circadian rhythms of subjects. Melatonin circadian rhythms were compared between the three groups using ANOVA. Partial correlation analysis and linear regression analysis were used to explore the correlation between melatonin rhythm variables and anhedonia.
RESULTS
We found that the peak phase of melatonin in the depression group was significantly advanced compared to the control group (P < 0.001) and the bipolar disorder group (P = 0.004). The peak phase of melatonin and RPAS showed a negative correlation (P = 0.003) in depression patients, which was also demonstrated in the multiple linear regression model (B=-2.47, P = 0.006).
CONCLUSIONS
These results suggest that circadian rhythms of melatonin are differentiated in depression and bipolar disorder and correlate with anhedonia in depression. Future research needs to explore the neurobiological mechanisms linking anhedonia and melatonin circadian rhythms in depressed patients.
Topics: Humans; Mood Disorders; Anhedonia; Melatonin; Cross-Sectional Studies; Circadian Rhythm
PubMed: 38413912
DOI: 10.1186/s12888-024-05606-5