Anhedonia is one of the core features of the negative symptoms of schizophrenia and can be extremely burdensome. Our study applied resting-state functional magnetic resonance imaging (fMRI)-based support vector regression (SVR) to predict anhedonia in patients with first-episode schizophrenia (FES) and analysed the correlation between the wavelet-based amplitude low-frequency fluctuation (wavelet-ALFF) of the main brain region and anhedonia. We recruited 31 patients with FES and 33 healthy controls (HCs) from the Affiliated Brain Hospital of Guangzhou Medical University. All subjects completed the Temporal Experience of Pleasure Scale (TEPS) and received resting-state fMRI (rs-fMRI). We used the wavelet-ALFF method and SVR to analyse the data. Patients with FES had lower consummatory pleasure scores than healthy subjects (t = -2.71, P<0.01). FES displays variable wavelet-ALFF in a wide range of cerebral cortices (P<0.05, GFR corrected). The SVR analysis showed that wavelet-ALFF, based primarily on the right putamen (r = 0.40, P<0.05) and right superior occipital gyrus (r = -0.39, P<0.05), was effective in predicting consummatory pleasure scores with an accuracy of 56.43 %. Our study shows that abnormal spontaneous neural activity in FES may be related to the state of consummatory anhedonia in FES. Wavelet-ALFF changes in the right putamen and superior occipital gyrus may be a biological feature of FES with anhedonia and could serve as a potential biological marker of FES with anhedonia.

BACKGROUND: Current clinical studies have indicated that major depressive disorder (MDD) with adverse childhood experiences (ACEs) is associated with greater anhedonia. However, little is known about whether the change in reward sensitivity among young MDD individuals with ACEs are related to anhedonia.
METHODS: We evaluated anhedonia and ACEs of each patient. Then, we performed Iowa gambling task during EEG to measure the reward positivity (RewP) and its difference (ΔRewP) in 86 MDD patients (31 with no or one ACE and 55 with two or more ACEs) and 44 healthy controls (HCs). Furthermore, we constructed a mediation model to assessed whether aberrant ΔRewP could mediate the relationship between ACEs and anhedonia.
RESULTS: Compared with healthy controls and MDD patients with no or one ACE, MDD patients with two or more ACEs had the most severe symptoms of anhedonia and impaired decision-making, and showed significantly reduced reward sensitivity (most blunted ΔRewP). More importantly, ΔRewP mediated relationship between ACEs and anhedonia in MDD.
CONCLUSIONS: We found that the ΔRewP partially mediates the association between ACEs and anhedonia in MDD patients, which provides evidence for the neurobiological basis of abnormal changes in the reward system in MDD individuals with early adverse experiences.

Chronic predator stress (CPS) is an important and ecologically relevant tool for inducing anhedonia in animals, but the neural circuits underlying the associated neurobiological changes remain to be identified. Using cell-type-specific manipulations, we found that corticotropin-releasing hormone (CRH) neurons in the medial subthalamic nucleus (mSTN) enhance struggle behaviors in inescapable situations and lead to anhedonia, predominately through projections to the external globus pallidus (GPe). Recordings of in vivo neuronal activity revealed that CPS distorted mSTN-CRH neuronal responsivity to negative and positive stimuli, which may underlie CPS-induced behavioral despair and anhedonia. Furthermore, we discovered presynaptic inputs from the bed nucleus of the stria terminalis (BNST) to mSTN-CRH neurons projecting to the GPe that were enhanced following CPS, and these inputs may mediate such behaviors. This study identifies a neurocircuitry that co-regulates escape response and anhedonia in response to predator stress. This new understanding of the neural basis of defensive behavior in response to predator stress will likely benefit our understanding of neuropsychiatric diseases.

Social touch has a vital role in human development and psychological well-being. However, there is a lack of measures assessing individual differences in social touch experiences and attitudes, especially under Eastern cultures. This study developed the Social Touch Experiences and Attitudes Questionnaire - Chinese version (STEAQ-C) and examined its psychometric properties with healthy young Chinese adults. In Study 1, an item pool was generated and principal component analysis (PCA) was used to identify the factor structure of the STEAQ. Study 2 recruited an independent sample and examined its reliability and validity. Network analysis further explored the interrelations between social touch and a variety of subclinical traits and symptoms. PCA identified four factors of the STEAQ-C, relating to childhood touch experiences, current touch with intimate partners, with family and friends, and with unfamiliar people. Study 2 confirmed the four-factor structure and upheld its internal consistency and stability. Positive attitudes towards and greater experiences of social touch were negatively correlated with sensory over-responsiveness and sensory hyposensitivity, as well as childhood trauma particularly emotional neglect, supporting the convergent validity. Evidence of criterion-related validity was accrued via its concurrent and predictive associations with secure attachment style, higher levels of social competence, and lower levels of social anxiety. Network analysis highlighted altered perception of social touch may be a shared feature for psychiatric conditions with social dysfunctions (e.g., autism, social anxiety and negative schizotypy). The newly-developed STEAQ-C may be a timely tool in assessing social touch experiences and attitudes under Eastern cultures.

Anhedonia and motivational impairments are cardinal features of depression, against which conventional antidepressants demonstrate limited efficacy. Preclinical investigations and extant clinical trial data substantiate the promise of opioid receptor modulators in addressing anhedonia, depression, and anxiety. While synthetic opioid agents like dezocine are conventionally employed for analgesia, their distinctive pharmacological profile has engendered interest in their potential antidepressant properties and translational applications. Herein, we present a case in which persistent bupropion treatment was ineffective. However, the incidental administration of a single low-dose intravenous injection of dezocine resulted in a rapid and sustained amelioration of depressive symptoms, particularly anhedonia and motivational deficits. Our findings posit a potentially novel role for the \"legacy drug\" dezocine.

Empirical findings suggested that anhedonia, a reduced capability to access pleasure and a core symptom in both schizophrenia and the major depressive disorder, can be present in people with high levels of social anhedonia and people with subsyndromal depression. Few studies have adopted a multidimensional framework to investigate anhedonia in these subclinical samples. We recruited 35 participants with high social anhedonia (SA), 53 participants with subsyndromal depression (SD), 20 participants with co-occurrence of both traits (CO), and 47 participants with low levels of both traits (CN) to complete a self-report questionnaire capturing the pleasure experience, and the Monetary Incentives Delay (MID) Task and the Social Incentives Delay (SID) Task capturing the motivation of reward. Results indicated that people with SA, SD and CO exhibited lower abstract anticipatory pleasure compared to CN. Moreover, people with SD and CO exhibited specific impairment in response to social incentives. Together, our findings characterized the multidimensional features of anhedonia performances of subclinical samples with SA, SD and CO, which may contribute to the formulation of early identification of at-risk groups.

BACKGROUND: Anhedonia is a core symptom of depression that is closely related to prognosis and treatment outcomes. However, accurate and efficient treatments for anhedonia are lacking, mandating a deeper understanding of the underlying mechanisms.
METHODS: A total of 303 patients diagnosed with depression and anhedonia were assessed by the Snaith-Hamilton Pleasure Scale (SHAPS) and magnetic resonance imaging (MRI). The patients were categorized into a low-anhedonia group and a high-anhedonia group using the K-means algorithm. A data-driven approach was used to explore the differences in brain structure and function with different degrees of anhedonia based on MATLAB. A random forest model was used exploratorily to test the predictive ability of differences in brain structure and function on anhedonia in depression.
RESULTS: Structural and functional differences were apparent in several brain regions of patients with depression and high-level anhedonia, including in the temporal lobe, paracingulate gyrus, superior frontal gyrus, inferior occipital gyrus, right insular gyrus, and superior parietal lobule. And changes in these brain regions were significantly correlated with scores of SHAPS.
CONCLUSIONS: These brain regions may be useful as biomarkers that provide a more objective assessment of anhedonia in depression, laying the foundation for precision medicine in this treatment-resistant, relatively poor prognosis group.

OBJECTIVE: Anhedonia is a critical diagnostic symptom of major depressive disorder (MDD), being associated with poor prognosis. Understanding the neural mechanisms underlying anhedonia is of great significance for individuals with MDD, and it encourages the search for objective indicators that can reliably identify anhedonia.
METHODS: A predictive model used connectome-based predictive modeling (CPM) for anhedonia symptoms was developed by utilizing pre-treatment functional connectivity (FC) data from 59 patients with MDD. Node-based FC analysis was employed to compare differences in FC patterns between melancholic and non-melancholic MDD patients. The support vector machines (SVM) method was then applied for classifying these two subtypes of MDD patients.
RESULTS: CPM could successfully predict anhedonia symptoms in MDD patients (positive network: r = 0.4719, p < 0.0020, mean squared error = 23.5125, 5000 iterations). Compared to non-melancholic MDD patients, melancholic MDD patients showed decreased FC between the left cingulate gyrus and the right parahippocampus gyrus (p_bonferroni = 0.0303). This distinct FC pattern effectively discriminated between melancholic and non-melancholic MDD patients, achieving a sensitivity of 93.54%, specificity of 67.86%, and an overall accuracy of 81.36% using the SVM method.
CONCLUSIONS: This study successfully established a network model for predicting anhedonia symptoms in MDD based on FC, as well as a classification model to differentiate between melancholic and non-melancholic MDD patients. These findings provide guidance for clinical treatment.

UNASSIGNED: Post-COVID-19 condition (PCC), also known as \"long COVID,\" is characterized by persistent symptoms, negatively affecting the well-being of individuals with PCC. Anhedonia (i.e. reduced capacity for pleasure) and compromised psychosocial functioning are notable symptoms in those with PCC. We aimed to provide insights to understand the effects of anhedonia and impaired psychosocial functioning of individuals with PCC.
UNASSIGNED: This post-hoc analysis used data from an 8-week, double-blind, randomized, placebo-controlled trial which evaluated vortioxetine for cognitive deficits in individuals with PCC (Clinicaltrials.gov Identifier: NCT05047952). A total of 147 eligible participants were randomly assigned to receive vortioxetine or matching placebo over eight weeks of double-blind treatment. Our study investigated the relationship between anhedonia, assessed by the Snaith-Hamilton Pleasure Scale (SHAPS), and psychosocial functioning, measured with the Post-COVID Functional Status (PCFS) scale. The analysis was conducted using a generalized linear model, with adjustments for relevant covariates such as age, sex, education, suspected versus confirmed COVID diagnosis, MDD diagnosis, and alcohol consumption.
UNASSIGNED: Of the 147 participants, 143 participants had available baseline data for analysis. We observed that baseline PCFS score was statistically significantly positively correlated to baseline SHAPS score (β = 0.070, p = 0.045, 95% CI).
UNASSIGNED: Our analysis revealed a significant relationship between measures of anhedonia and psychosocial functioning in adults with PCC. Strategies that aim to improve patient-reported outcomes with PCC need to prioritize the prevention and treatment of hedonic disturbances in patients experiencing PCC.

Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals\' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS, which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving unaltered improvement in the FST and TST. Mechanically, we found that ISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicating decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. The present findings further expand the potential role of ER stress in depression and provide important details for a therapeutic path forward for PERK inhibitors in mood disorders.