UNASSIGNED: Despite significant progress in our understanding of depression, prevalence rates have substantially increased in recent years. Thus, there is an imperative need for more cost-effective and scalable mental health treatment options, including digital interventions that minimize therapist burden.
UNASSIGNED: This study focuses on a fully automated digital implementation of behavioral activation (BA)-a core behavioral component of cognitive behavioral therapy for depression. We examine the efficacy of a 1-month fully automated SMS text message-based BA intervention for reducing depressive symptoms and anhedonia.
UNASSIGNED: To this end, adults reporting at least moderate current depressive symptoms (8-item Patient Health Questionnaire score ≥10) were recruited online across the United States and randomized to one of three conditions: enjoyable activities (ie, BA), healthy activities (ie, an active control condition), and passive control (ie, no contact). Participants randomized to enjoyable and healthy activities received daily SMS text messages prompting them to complete 2 activities per day; participants also provided a daily report on the number and enjoyment of activities completed the prior day.
UNASSIGNED: A total of 126 adults (mean age 32.46, SD 7.41 years) with current moderate depressive symptoms (mean score 16.53, SD 3.90) were recruited. Participants in the enjoyable activities condition (BA; n=39) experienced significantly greater reductions in depressive symptoms compared to participants in the passive condition (n=46). Participants in both active conditions-enjoyable activities and healthy activities (n=41)-reported reduced symptoms of anxiety compared to those in the control condition.
UNASSIGNED: These findings provide preliminary evidence regarding the efficacy of a fully automated digital BA intervention for depression and anxiety symptoms. Moreover, reminders to complete healthy activities may be a promising intervention for reducing anxiety symptoms.

Emotion studies have commonly reported impaired emotional processing in individuals with heightened anhedonic depressive symptoms, as typically measured by collecting single subjective ratings for a given emotional cue. However, the interindividual variation in moment-to-moment emotional reactivity, and associated time-varying brain networks recruitment as emotions are unfolding, remains unclear. In this study, we filled this gap by using the unique temporal characteristics of music to investigate behavioural and brain network dynamics as a function of anhedonic depressive symptoms severity. Thirty-one neurotypical participants aged 18-30 years completed anhedonic depression questionnaires and then continuously rated happy, neutral and sad pieces of music whilst undergoing MRI scanning. Using a unique combination of dynamic approaches to behavioural (i.e., emotion dynamics) and fMRI (i.e., leading eigenvector dynamics analysis; LEiDA) data analysis, we found that participants higher in anhedonic depressive symptoms exhibited increased recruitment of attentional networks and blunted emotional response to both happy and sad musical excerpts. Anhedonic depression mediated the relationship between attentional networks recruitment and emotional blunting, and the elevated recruitment of attentional networks during emotional pieces of music carried over into subsequent neutral music. Future studies are needed to investigate whether these findings could be generalised to a clinical population (i.e., major depressive disorder).

暂无摘要。

Anhedonia, the reduced ability to experience pleasure, is a prevalent symptom in various psychiatric disorders, but has not been investigated in dermatological conditions, particularly those characterized by chronic itch. This study aimed to examine the prevalence and clinical correlates of anhedonia in patients with chronic itch. A cross-sectional study was conducted in 137 patients with chronic itch, classified according to the International Forum for the Study of Itch (IFSI) classification. Anhedonia was assessed using the Snaith-Hamilton Pleasure Scale (SHAPS) and Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS). Itch severity, quality of life, and psychological distress were assessed using the Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), ItchyQoL, and Hospital Anxiety and Depression Scale (HADS), respectively. The mean SHAPS score was 1.0 ± 1.7 points, and the mean ACIPS total score was 76.9 ± 16.2 points. In the study sample, 13.1% of patients were identified as anhedonic, with a higher prevalence observed in those with severe and very severe itch. Anhedonia was significantly correlated with itch severity (R = 0.2, p=0.02 for 24 h VASmean and SHAPS; R = 0.2, p = 0.01 for 24 h VASmax and SHAPS), anxiety symptoms (R = 0.3, p < 0.001 for SHAPS and HADS-anxiety), depression symptoms (R = 0.4, p < 0.001 for SHAPS and HADS-depression), and impairment in quality of life (R = 0.2, p = 0.014 for SHAPS and ItchyQoL). Anhedonia is a significant and prevalent aspect of psychological distress in patients with chronic itch. Addressing this symptom may not only improve patients\' overall mental health but also enhance the effectiveness of treatments for chronic itch. Future research is needed to elucidate further the mechanisms underlying the relationship between anhedonia and chronic itch and to develop targeted interventions for this population.

Dynamic brain immune function in individuals with posttraumatic stress disorder is rarely studied, despite evidence of peripheral immune dysfunction. Positron emission tomography brain imaging using the radiotracer [11C]PBR28 was used to measure the 18-kDa translocator protein (TSPO), a microglial marker, at baseline and 3 h after administration of lipopolysaccharide (LPS), a potent immune activator. Data were acquired in 15 individuals with PTSD and 15 age-matched controls. The PTSD group exhibited a significantly lower magnitude LPS-induced increase in TSPO availability in an a priori prefrontal-limbic circuit compared to controls. Greater anhedonic symptoms in the PTSD group were associated with a more suppressed neuroimmune response. In addition, while a reduced granulocyte-macrophage colony-stimulating factor response to LPS was observed in the PTSD group, other measured cytokine responses and self-reported sickness symptoms did not differ between groups; these findings highlight group differences in central-peripheral immune system relationships. The results of this study provide evidence of a suppressed microglia-mediated neuroimmune response to a direct immune system insult in individuals with PTSD that is associated with the severity of symptoms. They also provide further support to an emerging literature challenging traditional concepts of microglial and immune function in psychiatric disease.

BACKGROUND: Chronic Gulf War Illness (GWI) is characterized by cognitive and mood impairments, as well as persistent neuroinflammation and oxidative stress. This study aimed to investigate the efficacy of Epidiolex®, a Food and Drug Administration (FDA)-approved cannabidiol (CBD), in improving brain function in a rat model of chronic GWI.
METHODS: Six months after exposure to low doses of GWI-related chemicals [pyridostigmine bromide, N,N-diethyl-meta-toluamide (DEET), and permethrin (PER)] along with moderate stress, rats with chronic GWI were administered either vehicle (VEH) or CBD (20 mg/kg, oral) for 16 weeks. Neurobehavioral tests were conducted on 11 weeks after treatment initiation to evaluate the performance of rats in tasks related to associative recognition memory, object location memory, pattern separation, and sucrose preference. The effect of CBD on hyperalgesia was also examined. The brain tissues were processed for immunohistochemical and molecular studies following behavioral tests.
RESULTS: GWI rats treated with VEH exhibited impairments in all cognitive tasks and anhedonia, whereas CBD-treated GWI rats showed improvements in all cognitive tasks and no anhedonia. Additionally, CBD treatment alleviated hyperalgesia in GWI rats. Analysis of hippocampal tissues from VEH-treated rats revealed astrocyte hypertrophy and increased percentages of activated microglia presenting NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) complexes as well as elevated levels of proteins involved in NLRP3 inflammasome activation and Janus kinase/signal transducers and activators of the transcription (JAK/STAT) signaling. Furthermore, there were increased concentrations of proinflammatory and oxidative stress markers along with decreased neurogenesis. In contrast, the hippocampus from CBD-treated GWI rats displayed reduced levels of proteins mediating the activation of NLRP3 inflammasomes and JAK/STAT signaling, normalized concentrations of proinflammatory cytokines and oxidative stress markers, and improved neurogenesis. Notably, CBD treatment did not alter the concentration of endogenous cannabinoid anandamide in the hippocampus.
CONCLUSIONS: The use of an FDA-approved CBD (Epidiolex®) has been shown to effectively alleviate cognitive and mood impairments as well as hyperalgesia associated with chronic GWI. Importantly, the improvements observed in rats with chronic GWI in this study were attributed to the ability of CBD to significantly suppress signaling pathways that perpetuate chronic neuroinflammation.

UNASSIGNED: Frontline antidepressants such as selective serotonin reuptake inhibitors (SSRIs) leave many patients with unmet treatment needs. Moreover, even when SSRIs reduce depressive symptoms, anhedonia, the loss of pleasure to previously rewarding activities, often remains unabated. This state of affairs is disheartening and calls for the development of medications to more directly treat anhedonia. The atypical psychedelic 3,4-methylenedioxymethamphetamine (MDMA) might have promise as a prohedonic medication given its efficacious applications for treatment-resistant post-traumatic stress disorder and comorbid depression. However, in addition to its prosocial effects as an entactogen, MDMA is also associated with neurotoxic cognitive deficits. The present studies were designed to examine the relative potency of MDMA in female and male rats across three distinct behavioral domains to assist in defining a preclinical profile of MDMA as a candidate prohedonic therapeutic.
UNASSIGNED: First, signal detection metrics of reward responsivity were examined using the touchscreen probabilistic reward task (PRT), a reverse-translated assay used to objectively quantify anhedonic phenotypes in humans. Second, to probe potential cognitive deficits, touchscreen-based assays of psychomotor vigilance and delayed matching-to-position were used to examine attentional processes and short-term spatial memory, respectively. Finally, MDMA\'s entactogenic effects were studied via pairwise assessments of social interaction facilitated by machine-learning analyses.
UNASSIGNED: Findings show (1) dose-dependent increases in reward responsivity as quantified by the PRT, (2) dose-dependent deficits in attention and short-term memory, and (3) dose-dependent increases in aspects of prosocial interaction in male but not female subjects. Neither the desirable (prohedonic) nor undesirable (cognition disruptive) effects of MDMA persisted beyond 24 h.
UNASSIGNED: The present results characterize MDMA as a promising prohedonic treatment, notwithstanding some liability for short-lived cognitive impairment following acute administration.

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.

BACKGROUND: Anhedonia is characterized by a reduced ability to anticipate, experience, and/or learn about pleasure. This phenomenon has a transdiagnostic nature and is one of the key symptoms of mood disorders, schizophrenia, addictions, and somatic conditions.
OBJECTIVE: To evaluate the genetic architecture of anhedonia and its overlap with other mental disorders and somatic conditions.
METHODS: We performed a genome-wide association study of anhedonia on a sample of 4,520 individuals from a Russian non-clinical population. Using the available summary statistics, we calculated polygenic risk scores (PRS) to investigate the genetic relationship between anhedonia and other psychiatric or somatic phenotypes.
RESULTS: No variants with a genome-wide significant association were identified. PRS for major depression, bipolar disorder, and schizophrenia were significantly associated with anhedonia. Conversely, no significant associations were found between PRS for anxiety and anhedonia, which aligns well with existing clinical evidence. None of the PRS for somatic phenotypes attained a significance level after correction for multiple comparisons. A nominal significance for the anhedonia association was determined for omega-3 fatty acids, type 2 diabetes mellitus, and Crohn\'s disease.
CONCLUSIONS: Anhedonia has a complex polygenic architecture, and its presence in somatic diseases or normal conditions may be due to a genetic predisposition to mood disorders or schizophrenia.
UNASSIGNED: Ангедония характеризуется снижением способности предвосхищать, испытывать и/или усваивать удовольствие. Этот феномен имеет трансдиагностическую природу и является одним из ключевых симптомов расстройств настроения, шизофрении, аддикций и соматических состояний.
UNASSIGNED: Оценить генетическую архитектуру ангедонии и её перекрытие с другими психическими расстройствами и соматическими состояниями.
UNASSIGNED: Проведено исследование полногеномного поиска ассоциаций ангедонии на выборке из 4 520 человек из российской неклинической популяции. Используя доступную сводную статистику, мы рассчитали шкалы полигенного риска (polygenic risk scores, PRS), чтобы исследовать генетическую связь между ангедонией и другими психиатрическими или соматическими фенотипами.
UNASSIGNED: Не было идентифицировано ни одного варианта, достигшего полногеномного уровня значимости. PRS для депрессии, биполярного расстройства и шизофрении были значимо ассоциированы с ангедонией. И наоборот, не обнаружено значимых ассоциаций между PRS для тревожных расстройств и ангедонии, что хорошо согласуется с существующими клиническими данными. Ни один из PRS для соматических фенотипов не достиг уровня значимости после коррекции на множественные сравнения. При номинальном уровне значимости ассоциация с ангедонией выявлена для PRS ω-3 жирных кислот, сахарного диабета 2-го типа и болезни Крона.
UNASSIGNED: Ангедония имеет сложную полигенную архитектуру, в связи с чем её присутствие при соматических заболеваниях или нормальных состояниях может быть обусловлено генетической предрасположенностью к расстройствам настроения или шизофрении.

Social anhedonia is a hallmark symptom of schizophrenia. Discrepancies in anticipated versus consummatory pleasure for non-social stimuli are well-documented. Thus, a similar emotional paradox may underlie social anhedonia. If so, our understanding of social anhedonia-including how to treat it in schizophrenia-could be enhanced. This project used a 5-day experience sampling method (ESM) to measure discrepancies between anticipated and consummatory pleasure for real-world social activities in people with schizophrenia and healthy controls (n = 30/group). ESM results were compared to laboratory assessments of negative symptoms and neurocognition. The schizophrenia group exhibited similar levels of anticipated and consummatory social pleasure as controls throughout daily life, and both groups were accurate in their short-term predictions of pleasure. Clinical interviews revealed those with schizophrenia showed significant deficits in long-term social pleasure prediction (i.e., a 1-week timeframe). Thus, people with schizophrenia may exhibit differences in ability to predict pleasure in the short-term versus the long-term. Negative symptoms and neurocognition were related to anticipated, but not consummatory, social pleasure, suggesting anhedonia is driven by deficits in thinking about pleasure, rather than inability to experience pleasure. Clinical implications include focusing on building upon short-term ability to predict pleasure in therapy to increase social motivation in schizophrenia.