-
Bipolar Disorders Jun 2024Bipolar depression is the major cause of morbidity in patients with bipolar disorder. It affects psychosocial functioning and markedly impairs occupational productivity....
BACKGROUND
Bipolar depression is the major cause of morbidity in patients with bipolar disorder. It affects psychosocial functioning and markedly impairs occupational productivity. Anhedonia is one of the most debilitating symptoms of depression contributing to treatment resistance. It correlates with suicidality, low quality of life, social withdrawal, and poor treatment response. Currently, there is no approved treatment specifically targeting anhedonia. Emerging evidence suggests that ketamine possesses anti-anhedonic properties in individuals with depression.
OBJECTIVES
The aim of this naturalistic open-label study was to investigate the effect of add-on ketamine treatment on anhedonia in treatment resistant bipolar depression.
METHODS
Our main interest was the change in patient-reported (Snaith-Hamilton Pleasure Scale) and rater-based anhedonia measure (Montgomery-Åsberg Depression Rating Scale-anhedonia subscale). The secondary aim was to analyze the score change in three Inventory of Depressive Symptomatology-Self Report (IDS-SR) domains: mood/cognition, anxiety/somatic, and sleep. Patients underwent assessments at several time points, including baseline, after the third, fifth, and seventh ketamine infusions. Additionally, a follow-up assessment was conducted 1 week following the final ketamine administration.
RESULTS
We found improvement in anhedonia symptoms according to both patient-reported and rater-based measures. The improvement in IDS-SR domains was most prominent in anxiety/somatic factor and mood/cognition factor, improvement in sleep factor was not observed. No serious adverse events occurred.
CONCLUSION
Add-on ketamine seems to be a good choice for the treatment of anhedonia in treatment resistant bipolar depression. It also showed a good effect in reducing symptoms of anxiety in this group of patients. Considering unmet needs and the detrimental effect of anhedonia and anxiety, more studies are needed on ketamine treatment in resistant bipolar depression.
Topics: Humans; Ketamine; Bipolar Disorder; Anhedonia; Male; Adult; Female; Middle Aged; Depressive Disorder, Treatment-Resistant; Psychiatric Status Rating Scales
PubMed: 38311367
DOI: 10.1111/bdi.13409 -
Journal of Affective Disorders Jul 2024Major depressive disorder (MDD) is a heterogeneous group of mood disorders. A prominent symptom domain is anhedonia narrowly defined as a loss of interest and ability to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Major depressive disorder (MDD) is a heterogeneous group of mood disorders. A prominent symptom domain is anhedonia narrowly defined as a loss of interest and ability to experience pleasure. Anhedonia is associated with depressive symptom severity, MDD prognosis, and suicidality. We perform a systematic review and meta-analysis of extant literature investigating the effects of anhedonia on health-related quality of life (HRQoL) and functional outcomes in persons with MDD.
METHODS
A literature search was conducted on PubMed, OVID databases, and SCOPUS for published articles from inception to November 2023, reporting on anhedonia and patient-reported outcomes in persons with MDD. The reported correlation coefficients between anhedonia and self-reported measures of both HRQoL and functional outcomes were pooled using a random effects model.
RESULTS
We identified 20 studies that investigated anhedonia with HRQoL and/or functional outcomes in MDD. Anhedonia as measured by the Snaith-Hamilton Pleasure Scale (SHAPS) scores had a statistically significant correlation with patient-reported HRQoL (r = -0.41 [95 % CI = -0.60, -0.18]) and functional impairment (r = 0.39 [95 % CI = 0.22, 0.54]).
LIMITATIONS
These preliminary results primarily investigate correlations with consummatory anhedonia and do not distinguish differences in anticipatory anhedonia, reward valuation or reward learning; therefore, these results require replication.
CONCLUSIONS
Persons with MDD experiencing symptoms of anhedonia are more likely to have worse prognosis including physical, psychological, and social functioning deficits. Anhedonia serves as an important predictor and target for future therapeutic and preventative tools in persons with MDD.
Topics: Humans; Anhedonia; Depressive Disorder, Major; Quality of Life
PubMed: 38657767
DOI: 10.1016/j.jad.2024.04.086 -
BMC Psychiatry Nov 2023Anhedonia is a core symptom in patients with unipolar and bipolar depression. However, sex-specific markers reflecting biological heterogeneity are lacking. Emerging...
BACKGROUND
Anhedonia is a core symptom in patients with unipolar and bipolar depression. However, sex-specific markers reflecting biological heterogeneity are lacking. Emerging evidence suggests that sex differences in immune-inflammatory markers and lipoprotein profiles are associated with anhedonia.
METHODS
The demographic and clinical data, immune-inflammatory markers (CD3, CD4, and CD8), and lipoprotein profiles [TC, TG, LDL-C, HDL-C, lipoprotein(a) Lp (a)] of 227 patients with unipolar and bipolar depression were collected. The Hamilton Depression Rating Scale (HAMD) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess depression and anhedonia symptoms. Data were analyzed using ANOVA, logistic regression, and receiver operating characteristic curves.
RESULTS
Male patients in the anhedonia group had higher levels of CD3, CD4, and CD8, and lower levels of Lp (a) than the non-anhedonia group, while no significant difference was identified in female patients with and without anhedonia. Logistic regression analysis showed that CD3, CD4, CD8, and Lp (a) levels were associated with anhedonia in male patients. Furthermore, the combination of CD3, CD4, CD8, and Lp (a) had the strongest predictive value for distinguishing anhedonia in male patients than individual parameters.
CONCLUSIONS
We identified sex-specific associations between immune-inflammatory markers, lipoprotein profiles, and anhedonia in patients with unipolar and bipolar depression. The combination of CD3, CD4, CD8, and Lp (a) might be a possible biomarker for identifying anhedonia in male patients with unipolar and bipolar depression.
Topics: Humans; Male; Female; Anhedonia; Bipolar Disorder; Pleasure; Lipoproteins; Biomarkers
PubMed: 38012724
DOI: 10.1186/s12888-023-05378-4 -
Behaviour Research and Therapy Oct 2023This cluster randomised controlled trial examined the effectiveness of universal school-based mindfulness training (MT; vs. passive control) to lower anhedonia and... (Randomized Controlled Trial)
Randomized Controlled Trial
The effect of universal school-based mindfulness on anhedonia and emotional distress and its underlying mechanisms: A cluster randomised controlled trial via experience sampling in secondary schools.
This cluster randomised controlled trial examined the effectiveness of universal school-based mindfulness training (MT; vs. passive control) to lower anhedonia and emotional distress among mid-adolescents (15-18 years). It further examined three potential mechanisms: dampening of positive emotions, non-acceptance/suppression of negative emotions, and perceived social pressure not to experience/express negative emotions. Adolescents (n = 136, n = 95) participated in three assessment points (before, after and two/three months after the in-class MT), consisting of Experience Sampling (ES) assessments and self-report questionnaires (SRQs) to corroborate the ES assessments. Analyses were based on general linear modelling and multilevel modelling. Overall, no evidence was found for a significant beneficial and long-lasting impact of the MT on adolescents' mental health. Importantly, some barriers inherently linked to universal MT approaches (low engagement in and mixed attitudes towards the MT) may have tempered the effectiveness of the MT in the current trial. Further research should prioritise overcoming these barriers to optimise programme implementation. Additionally, given the potential complex interplay of moderators at micro- (home practice), meso- (school climate), and macro-level (broader context), research should simultaneously focus on alternative ways of delivering MT at schools to strengthen adolescents' mental health.
Topics: Adolescent; Humans; Mindfulness; Anhedonia; Ecological Momentary Assessment; Emotions; Schools; Psychological Distress
PubMed: 37797436
DOI: 10.1016/j.brat.2023.104405 -
Journal of Ethnopharmacology Dec 2023Artemisia annua L. (Asteraceae) has been used as an antipyretic and anti-parasitic drug in traditional medicine for more than 2000 years. It has also been prescribed to...
ETHNOPHARMACOLOGICAL RELEVANCE
Artemisia annua L. (Asteraceae) has been used as an antipyretic and anti-parasitic drug in traditional medicine for more than 2000 years. It has also been prescribed to treat symptoms caused by deficiency of Yin, which might be observed in menopausal state from the point of view of traditional medicine.
AIM OF THE STUDY
We hypothesized that A. annua might be useful for treating menopausal disorders with less adverse effects than hormone replacement therapy. Thus, the aim of the present study was to investigate effects of A. annua on postmenopausal symptoms of ovariectomized (OVX) mice.
MATERIALS AND METHODS
OVX mice were employed as a model for postmenopausal disorders. Mice were treated with a water extract of A. annua (EAA; 30, 100 or 300 mg/kg, p.o.) or 17β-estradiol (E2; 0.5 mg/kg, s.c.) for 8 weeks. Open field test (OFT), novel object recognition task (NOR), Y-maze test, elevated plus maze test (EPM), splash test and tail suspension test (TST) were conducted to determine whether EAA could ameliorate postmenopausal symptoms. Phosphorylated levels of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and glycogen synthase kinase-3β (GSK-3β), β-catenin and expression level of synaptophysin in the cortex and hippocampus were evaluated by Western blot analysis.
RESULTS
EAA treatment significantly increased the discrimination index in NOR, decreased the time in closed arm than in open arm in EPM, increased grooming time in splash test, and decreased immobility time in TST, as did E2 treatment. In addition, decreased phosphorylation levels of ERK, Akt, GSK-3β, and β-catenin and expression levels of synaptophysin in the cortex and hippocampus after OVX were reversed by administration of EAA and E2.
CONCLUSION
These results suggest that A. annua can ameliorate postmenopausal symptoms such as cognitive dysfunction, anxiety, anhedonia, and depression by activating ERK, Akt, and GSK-3β/β-catenin signaling pathway and hippocampal synaptic plasticity, and that A. annua would be a novel treatment for postmenopausal symptoms.
Topics: Mice; Animals; Proto-Oncogene Proteins c-akt; Glycogen Synthase Kinase 3 beta; beta Catenin; Synaptophysin; Artemisia annua; Postmenopause; Extracellular Signal-Regulated MAP Kinases
PubMed: 37331451
DOI: 10.1016/j.jep.2023.116800 -
Appetite Nov 2023high-calorie and sugar-sweetened food is considered more pleasant food. People with anhedonia symptoms have difficulties experiencing pleasure in daily activities....
INTRODUCTION
high-calorie and sugar-sweetened food is considered more pleasant food. People with anhedonia symptoms have difficulties experiencing pleasure in daily activities. However, is still unclear if anhedonia symptomatology increases palatable food consumption in the Chilean Adults sample.
OBJECTIVE
to explore food networks in the Chilean Adults sample and in people with anhedonia symptom.
METHODS
the sample was recruited through digital platforms. Pregnant or lactating women and subjects under pharmacological treatment or psychotherapy were excluded. A total of 1242 subjects, 76.6% women, with a mean age of 30.7 (SD 9.3) and who were highly educated, participated in the study. Data were collected through an online survey. A questionnaire on food consumption based on daily and weekly frequency was used, as well as the Snaith-Hamilton Pleasure Scale to measure anhedonia symptoms. We employed the Gaussian graph model (GGM) to analyze food consumption as networks. We started with the total sample, and then we repeated the analysis on a subsample with anhedonia symptoms, and next on a subsample with exclusively food-related anhedonia.
RESULTS
in the total sample, a positive and strong relationship was observed between fruits and vegetables, as well as a negative association with the triad of sugar-sweetened beverages, fast food, and fried food. The network in anhedonic subjects shows that "pasta, rice & potatoes" and "bread" have a stronger association and a more central place in the network compared those without anhedonia symptoms.
CONCLUSIONS
Subjects with anhedonia symptoms have a more central consumption of foods with a high or medium glycemic index compared to subjects without anhedonia symptoms, which could trigger the development of chronic diet-related diseases.
PubMed: 37704006
DOI: 10.1016/j.appet.2023.107042 -
Heliyon May 2024Infectious diseases can contribute to substance abuse. Here, a fatal case of borreliosis and substance abuse is reported. This patient had a history of multiple tick...
BACKGROUND
Infectious diseases can contribute to substance abuse. Here, a fatal case of borreliosis and substance abuse is reported. This patient had a history of multiple tick bites and increasing multisystem symptoms, yet diagnosis and treatment were delayed. He experimented with multiple substances including phencyclidine (PCP), an N-methyl-d-aspartate (NMDA) receptor antagonist that opposes NMDA agonism caused by infection. During PCP withdrawal, he committed one homicide, two assaults, and suicide.
METHODS
Brain tissue was obtained from autopsy and stained for microglial activation and quinolinic acid (QA). Immunoflouresence (IFA) and fluorescence hybridization (FISH) were used to identify the presence of pathogens in autopsy tissue.
RESULTS
Autopsy tissue evaluation demonstrated in the pancreas by IFA and heart by IFA and FISH. Activated microglia and QA were found in the brain, indicating neuroinflammation. It is postulated that PCP withdrawal may exacerbate symptoms produced by -induced biochemical imbalances in the brain. This combination may have greatly increased his acute homicidal and suicidal risk. Patient databases also demonstrated the risk of homicide or suicide in patients diagnosed with borreliosis and confirmed multiple symptoms in these patients, including chronic pain, anxiety, and anhedonia.
CONCLUSIONS
Late-stage borreliosis is associated with multiple symptoms that may contribute to an increased risk of substance abuse and addictive disorders. More effective diagnosis and treatment of borreliosis, and attention to substance abuse potential may help reduce associated morbidity and mortality in patients with borreliosis, particularly in endemic areas.
PubMed: 38779029
DOI: 10.1016/j.heliyon.2024.e31159 -
Cellular and Molecular Life Sciences :... Sep 2023Major depressive disorder (MDD) is a pervasive and devastating mental disease. Broad spectrum histone deacetylase (HDAC) inhibitors are considered to have potential for...
Major depressive disorder (MDD) is a pervasive and devastating mental disease. Broad spectrum histone deacetylase (HDAC) inhibitors are considered to have potential for the treatment of depressive phenotype in mice. However, due to its non-specific inhibition, it has extensive side effects and can not be used in clinical treatment of MDD. Therefore, finding specific HDAC subtypes that play a major role in the etiology of MDD is the key to develop corresponding specific inhibitors as antidepressants in the future. Copy number variation in HDAC9 gene is thought to be associated with the etiology of some psychiatric disorders. Herein, we found that HDAC9 was highly expressed in the hippocampus of chronic restraint stress (CRS) mouse model of depression. Upregulation of HDAC9 expression in hippocampal neurons of mice induced depression-like phenotypes, including anhedonia, helplessness, decreased dendritic spine density, and neuronal hypoexcitability. Moreover, knockdown or knockout of HDAC9 in hippocampal neurons alleviated depression-like phenotypes caused by chronic restraint stress (CRS) in WT mice. Importantly, using immunoprecipitation-mass spectrometry (IP-MS), we further found that Annexin A2 (ANXA2) was coupled to and deacetylated by HDAC9. This coupling resulted in the inhibition of ubiquitinated ANXA2 degradation and then mediates depression-like behavior. Overall, we discovered a previously unrecognized role for HDAC9 in hippocampal neurons in the pathogenesis of depression, indicating that inhibition of HDAC9 might be a promising clinical strategy for the treatment of depressive disorders.
Topics: Animals; Mice; Annexin A2; Depression; Depressive Disorder, Major; DNA Copy Number Variations; Hippocampus; Histone Deacetylase Inhibitors; Histone Deacetylases; Up-Regulation
PubMed: 37690046
DOI: 10.1007/s00018-023-04945-y -
Translational Psychiatry Sep 2023Selective serotonin reuptake inhibitors (SSRI) are common first-line treatments for major depression. However, a significant number of depressed patients do not respond...
Selective serotonin reuptake inhibitors (SSRI) are common first-line treatments for major depression. However, a significant number of depressed patients do not respond adequately to these pharmacological treatments. In the present preclinical study, we demonstrate that organic cation transporter 2 (OCT2), an atypical monoamine transporter, contributes to the effects of SSRI by regulating the routing of the essential amino acid tryptophan to the brain. Contrarily to wild-type mice, OCT2-invalidated mice failed to respond to prolonged fluoxetine treatment in a chronic depression model induced by corticosterone exposure recapitulating core symptoms of depression, i.e., anhedonia, social withdrawal, anxiety, and memory impairment. After corticosterone and fluoxetine treatment, the levels of tryptophan and its metabolites serotonin and kynurenine were decreased in the brain of OCT2 mutant mice compared to wild-type mice and reciprocally tryptophan and kynurenine levels were increased in mutants' plasma. OCT2 was detected by immunofluorescence in several structures at the blood-cerebrospinal fluid (CSF) or brain-CSF interface. Tryptophan supplementation during fluoxetine treatment increased brain concentrations of tryptophan and, more discreetly, of 5-HT in wild-type and OCT2 mutant mice. Importantly, tryptophan supplementation improved the sensitivity to fluoxetine treatment of OCT2 mutant mice, impacting chiefly anhedonia and short-term memory. Western blot analysis showed that glycogen synthase kinase-3β (GSK3β) and mammalian/mechanistic target of rapamycin (mTOR) intracellular signaling was impaired in OCT2 mutant mice brain after corticosterone and fluoxetine treatment and, conversely, tryptophan supplementation recruited selectively the mTOR protein complex 2. This study provides the first evidence of the physiological relevance of OCT2-mediated tryptophan transport, and its biological consequences on serotonin homeostasis in the brain and SSRI efficacy.
Topics: Animals; Mice; Anhedonia; Antidepressive Agents; Brain; Corticosterone; Depressive Disorder, Major; Fluoxetine; Kynurenine; Organic Cation Transporter 2; Selective Serotonin Reuptake Inhibitors; Serotonin; Tryptophan
PubMed: 37775532
DOI: 10.1038/s41398-023-02596-y -
Trials Jan 2024Anhedonia, which is defined as the inability to feel pleasure, is considered a core symptom of major depressive disorder (MDD). It can lead to several adverse outcomes...
Active versus sham DLPFC-NAc rTMS for depressed adolescents with anhedonia using resting-state functional magnetic resonance imaging (fMRI): a study protocol for a randomized placebo-controlled trial.
BACKGROUND
Anhedonia, which is defined as the inability to feel pleasure, is considered a core symptom of major depressive disorder (MDD). It can lead to several adverse outcomes in adolescents, including heightened disease severity, resistance to antidepressants, recurrence of MDD, and even suicide. Specifically, patients who suffer from anhedonia may exhibit a limited response to selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT). Previous researches have revealed a link between anhedonia and abnormalities within the reward circuitry, making the nucleus accumbens (NAc) a potential target for treatment. However, since the NAc is deep within the brain, repetitive transcranial magnetic stimulation (rTMS) has the potential to modulate this specific region. Recent advances have enabled treatment technology to precisely target the left dorsolateral prefrontal cortex (DLPFC) and modify the functional connectivity (FC) between DLPFC and NAc in adolescent patients with anhedonia. Therefore, we plan to conduct a study to explore the safety and effectiveness of using resting-state functional connectivity magnetic resonance imaging (fcMRI)-guided rTMS to alleviate anhedonia in adolescents diagnosed with MDD.
METHODS
The aim of this article is to provide a study protocol for a parallel-group randomized, double-blind, placebo-controlled experiment. The study will involve 88 participants who will be randomly assigned to receive either active rTMS or sham rTMS. The primary object is to measure the percentage change in the severity of anhedonia, using the Snaith-Hamilton Pleasure Scale (SHAPS). The assessment will be conducted from the baseline to 8-week post-treatment period. The secondary outcome includes encompassing fMRI measurements, scores on the 17-item Hamilton Rating Scale for Depression (HAMD-17), the Montgomery Asberg Depression Rating Scale (MADRS), the Chinese Version of Temporal Experience of Pleasure Scale (CV-TEPS), and the Chinese Version of Beck Scale for Suicide Ideation (BSI-CV). The Clinical Global Impression (CGI) scores will also be taken into account, and adverse events will be monitored. These evaluations will be conducted at baseline, as well as at 1, 2, 4, and 8 weeks.
DISCUSSION
If the hypothesis of the current study is confirmed, (fcMRI)-guided rTMS could be a powerful tool to alleviate the core symptoms of MDD and provide essential data to explore the mechanism of anhedonia.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05544071. Registered on 16 September 2022.
Topics: Humans; Adolescent; Transcranial Magnetic Stimulation; Dorsolateral Prefrontal Cortex; Depressive Disorder, Major; Anhedonia; Magnetic Resonance Imaging; Prefrontal Cortex; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38218932
DOI: 10.1186/s13063-023-07814-y