Search Results (43)

Maternal exposure to infectious agents has been associated with an increased risk of mental disorders in offspring, such as autism spectrum disorder. Evidence suggests that maternal immune responses during infection can significantly impact the neurodevelopment of the offspring, potentially affecting central nervous system functions in the future. Inulin is an indigestible soluble fiber that acts as a prebiotic. It promotes the production of short-chain fatty acids, such as butyrate, which can help inhibit the production of pro-inflammatory cytokines. Thus, this study aims to investigate whether inulin treatment during pregnancy can mitigate or reduce the impact of maternal immune activation (MIA) on the neurodevelopment of the offspring. Swiss mice were used in a dose–response study to evaluate the protective effects of inulin against maternal exposure to soluble Toxoplasma gondii antigen. Adult offspring of both sexes underwent behavioral assessments, and their gut microbiota was characterized. Both males and females in the soluble T. gondii antigen (STAg) group exhibited reduced sociability, as evidenced by the three-chamber social interaction test. Moreover, co-treatment with inulin mitigated this effect. Additionally, anhedonia was observed only in female offspring from the MIA group, but treatment with 1% and 3% inulin also mitigated this effect. The analysis of fecal microbiota showed significant differences between the STAg and inulin treatments at both the family and genus levels. Therefore, inulin appears to have a potential protective effect on the neurodevelopment of the offspring exposed to maternal antigenic challenges during pregnancy mediated by offspring microbiome modulations. Full article

This study aimed to assess the association between four depression subtypes and health-related symptoms. Although it was expected that there would be asymmetry across the associations between depression subtypes and health, that relationship had not been previously reported. Data on the core diagnostic symptoms of depression and four depression subtypes, plus health-related outcomes, were collected from a sample of 301 community participants who completed standardised self-report questionnaires. Results indicated that Somatic Depression and Depressed Mood were most consistently associated with poorer outcomes across physical, emotional, and social domains, while Cognitive Depression and Anhedonia subtypes showed weaker associations. An exploratory network analysis identified Social Functioning and Depressed Mood as central nodes, indicating that affective disturbance and social wellbeing are key pathways through which depression relates to wider health outcomes. In conclusion, these results confirmed the heterogeneity of depression, as well as indicating that certain symptom clusters carry disproportionate weight in predicting health outcomes, thus exhibiting an asymmetrical pattern of associations between depression and health. Full article

Social isolation and loneliness represent critical psychosocial stressors associated with profound hormonal dysregulation and adverse behavioral outcomes. This review synthesizes current evidence on neuroendocrine mechanisms linking perceived and objective social disconnection to health consequences, emphasizing hypothalamic–pituitary–adrenal axis dysfunction, altered glucocorticoid signaling, and inflammatory pathways. Loneliness activates conserved transcriptional responses with upregulated proinflammatory gene expression and downregulated antiviral responses, mediated through sustained cortisol elevation and glucocorticoid resistance. Neural circuit alterations in reward processing, particularly the ventral tegmental area-nucleus accumbens pathway, contribute to anhedonia, social withdrawal, and cognitive decline. Sex differences in neuroendocrine responses reveal distinct hormonal profiles and circuit-specific adaptations. Emerging interventions targeting oxytocin and arginine vasopressin systems, alongside behavioral approaches addressing loneliness-induced cognitive biases, show promise. Critical research gaps include a mechanistic understanding of epigenetic modifications, sex-specific therapeutic responses, and translational applications across diverse populations. Understanding the endocrine–behavior interface in social disconnection offers opportunities for targeted interventions addressing this growing public health challenge. Full article

Central nervous system (CNS) cryptococcosis caused by Cryptococcus neoformans is a severe opportunistic infection that primarily affects individuals with impaired cellular immunity. Although the classic presentation includes headache, fever, and meningeal signs, chronically immunosuppressed patients may develop atypical neuropsychiatric manifestations, leading to diagnostic delays. We report the case of a 53-year-old man with rheumatoid arthritis (RA) receiving long-term prednisolone and etanercept therapy, who presented with a 7-day history of depressive mood, anhedonia, social withdrawal, irritability, and progressive confusion. Neurological examination revealed disorientation without focal deficits. Brain imaging showed only mild cortical atrophy, and cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, low glucose, and elevated protein levels. Multiplex PCR (FilmArray^®) of CSF identified Cryptococcus neoformans, CSF positive to C. neoformans. The patient was treated with liposomal amphotericin B followed by fluconazole, resulting in gradual improvement of both neurological and psychiatric symptoms. This case highlights an unusual presentation of CNS cryptococcosis in a non-HIV immunosuppressed patient with RA, emphasizing that acute psychiatric or cognitive changes can be the predominant manifestation. Clinicians should consider fungal infections in the differential diagnosis of acute neuropsychiatric symptoms in patients receiving chronic corticosteroid and biologic therapy. Early recognition and molecular diagnosis can facilitate timely antifungal treatment, potentially improving prognosis and reducing morbidity associated with delayed therapy. This report underscores the importance of awareness of atypical presentations of opportunistic infections in immunosuppressed populations. Full article

Background: Nursing students face emotional and psychological challenges stemming from early clinical exposure, intense academic pressure, and persistent social stigmas. These stressors can contribute to mental health deterioration and increase the risk of suicidal thoughts and behavior. Objective: To evaluate the psychosocial context and identify risk and protective factors contributing to suicidal behavior in undergraduate nursing students. Methods: This cross-sectional study included 433 undergraduate nursing students and utilized validated psychological instruments to assess suicidal behavior, emotional distress, impulsivity, anhedonia, mental health, and perceived social support. Data were analyzed using descriptive statistics, bivariate tests, exploratory factor analysis, and multivariate modeling to identify key predictors of suicidal behavior. Network visualization was used to integrate significant point-biserial correlations with factor loadings. Results: Among 433 nursing students (77.8% women, 93.8% cisgender, mean age 19), 15.2% showed clinically significant suicidal risk. Suicidal behavior was more frequent among women and students living away from home (p < 0.05). Higher levels of impulsivity, ADHD symptoms, and especially moderate-to-severe hopelessness (p < 0.001) were strongly associated. Hazardous alcohol use was also a significant risk factor (p < 0.01), while strong material and emotional support showed a protective effect (p < 0.05). Two psychological dimensions, emotional distress/impulsivity and hopelessness/low support, explained most of the variance. Conclusions: 1 in 7 nursing students show clinically relevant suicidal risk, particularly those with heightened hopelessness, emotional dysregulation or hazardous alcohol use. Protective social support plays a key mitigating role. These results underline the urgent need for tailored mental health interventions that specifically address emotional regulation and hopelessness, while reinforcing social support systems within nursing education contexts. Full article

Chronic stress alters hypothalamic–pituitary–adrenal (HPA) axis function, affecting corticosterone regulation and adaptive responses. Understanding individual variability in stress adaptation requires identifying distinct HPA axis response patterns. Here, we assessed HPA axis sensitivity in male C57BL6 mice exposed to 30 days of chronic social defeat stress (CSDS). Negative feedback integrity was evaluated using the dexamethasone suppression test (DST), with corticosterone measured after saline or low-dose dexamethasone administration at days 10 and 30. Behavioral testing (open field, elevated plus maze, social interaction test, partition, social defeat, forced swimming test, sucrose preference test) and qPCR analysis of HPA-axis-related genes in the hypothalamus (Crh, Crhr1, Crhbp, Fkbp5, Nr3c1), pituitary (Pomc, Crhr1, Nr3c1, Nr3c2), and adrenal glands (Cyp11a1, Cyp11b1, Hsd11b1, Mc2r, Star, Fkbp5, Nr3c1) were performed. K-means cluster analysis identified three distinct response profiles differing in baseline and dexamethasone-suppressed corticosterone levels. Clusters also exhibited differences in behavioral phenotypes and HPA axis gene expression. Cluster 1 showed low basal corticosterone and an abnormal dexamethasone suppression response, without significant Crh or Crhbp dysregulation in the hypothalamus. Cluster 2 exhibited elevated basal corticosterone, a blunted dexamethasone response, anhedonia, and reduced immobility in the forced swim test; increased Crh and reduced Fkbp5 suggested enhanced glucocorticoid receptor sensitivity and sustained hypercortisolemia. Cluster 3, characterized by normal basal corticosterone and normal dexamethasone response, displayed upregulation of Crh and Crhbp, consistent with balanced and potentially adaptive HPA axis regulation under chronic stress. These results demonstrate that corticosterone response heterogeneity reflects distinct adaptive trajectories under chronic stress. Identifying behavioral and molecular markers of these strategies may advance understanding of stress vulnerability and resilience mechanisms, with implications for stress-related disorders. Full article

Background: Absence epilepsy is a common pediatric neurological disorder characterized by brief seizures and lapses in awareness. The relationship between anxiety and absence epilepsy is multifaceted. This study aims to investigate neurobehavioral signs directly and indirectly related to anxiety and potential sex differences in aged WAG/Rij rats, a well-established animal model of absence epilepsy. Methods: A battery of behavioral tests was conducted to assess various aspects of neurobehavior, including anxiety (elevated plus maze), anhedonia (sucrose preference), social function, and associative learning (fear conditioning). Multidimensional metrics assessed cognition, motor function, and exploration strategies, prioritizing anxiety as a key influencing factor. Results: Electroencephalogram (EEG) phenotyping was used to identify epileptic and non-epileptic rats. Traditional anxiety measures in the elevated plus maze did not reveal significant differences between groups. However, the Anxiety Composite Index revealed higher autonomic reactivity in non-epileptic females. Cognitive assessments showed no epilepsy- or sex-related differences in overall learning performance. Females exhibited superior avoidance learning compared males. Among epileptic males, those with poor learning performance also displayed higher anxiety-avoidance scores. Rats with high anxiety levels showed enhanced socio-affective reactivity and passive coping, with no effect on exploratory learning. Conclusions: Our findings highlight the importance of sex-specific analyses and physiological measures in epilepsy research. Neurobehavioral comorbidities in WAG/Rij rat model are significantly influenced by anxiety-like behavioral phenotype. Enhanced phenotyping of rat models of absence epilepsy can improve its translational value in understanding epilepsy-associated psychiatric disorders. Full article

Background/Objectives: Autism spectrum disorder is a psychological condition characterized by symptoms such as repetitive stereotypic behaviors and social interaction/communication difficulties. It is known that omega-3 deficiency during brain maturation may cause learning disabilities and motor impairment. Therefore, we examined the effects of omega-3 treatment during gestation and/or lactation on autism-related behavioral and molecular deficits in a valproic acid (VPA)-rat model. Methods: Female Wistar rats were divided into five groups: control, VPA (500 mg/kg at G12.5), VPA+omega-3 (gestation), VPA+omega-3 (lactation), and VPA+omega-3 (gestation + lactation). The omega-3 supplement was dissolved in drinking water and offered for consumption daily during gestation and/or lactation. After the treatment period, behavioral tests were performed. The rats were then sacrificed, and inflammatory cytokines, parvalbumin, and glutamate decarboxylase-67 (GAD67) levels in the prefrontal cortex and hippocampus were examined. Results: Prenatal VPA administration increased repetitive behaviors, decreased sociability, impaired memory, and induced anhedonia. The behavioral and neurochemical effects of VPA exposure were more severe in males than in females. Early maternal omega-3 treatments rescued these behavioral changes. The treatments also reversed prenatal VPA-induced neuroinflammation. Lastly, GAD67 and parvalbumin decreases in these brain regions were mitigated by the treatments, the therapeutic effects of which were more pronounced in males. In terms of efficacy, the treatment groups ranked as follows: “gestation + lactation” > “gestation” > “lactation”. Conclusions: Maternal omega-3 supplementation—especially when administered throughout gestation and lactation—provides significant protection against behavioral and neurochemical deficits associated with prenatal VPA exposure. Early omega-3 intake may serve as a valuable complementary strategy in autism intervention. Full article

Background: Anhedonia, defined as the diminished capacity to experience pleasure, represents a core negative symptom in first-episode psychosis (FEP) with profound implications for functional outcomes and long-term prognosis. Despite its clinical significance, comprehensive understanding of anhedonia prevalence, underlying mechanisms, and optimal intervention strategies in early psychosis remains limited. Objectives: To systematically examine the prevalence and characteristics of anhedonia in FEP patients, explore neurobiological mechanisms, identify clinical correlates and predictive factors, and evaluate intervention efficacy. Methods: Following PRISMA 2020 guidelines, we conducted comprehensive searches across PubMed, Embase, PsycINFO, and Web of Science databases from January 1990 to June 2025. Studies examining anhedonia and negative symptoms in FEP patients (≤24 months from onset) using validated assessment instruments were included. Quality assessment was performed using appropriate tools for study design. Results: Twenty-one studies comprising 3847 FEP patients met inclusion criteria. Anhedonia prevalence ranged from 30% at 10-year follow-up to 53% during acute phases, demonstrating persistent motivational deficits across illness trajectory. Factor analytic studies consistently supported five-factor negative symptom models with anhedonia as a discrete dimension. Neuroimaging investigations revealed consistent alterations in reward processing circuits, including ventral striatum hypofunction and altered network connectivity patterns. Social anhedonia demonstrated stronger associations with functional outcomes compared to other domains. Epigenetic mechanisms involving oxytocin receptor methylation showed gender-specific associations with anhedonia severity. Conventional antipsychotic treatments showed limited efficacy for anhedonia improvement, while targeted psychosocial interventions demonstrated preliminary promise. Conclusions: Anhedonia showed high prevalence (30–53%) across FEP populations with substantial clinical burden (13-fold increased odds vs. general population). Meta-analysis revealed large effect sizes for anhedonia severity in FEP vs. controls (d = 0.83) and strong negative correlations with functional outcomes (r =·−0.82). Neuroimaging demonstrated consistent ventral striatum dysfunction and altered network connectivity. Social anhedonia emerged as the strongest predictor of functional outcomes, with independent suicide risk associations. Conventional antipsychotics showed limited efficacy, while behavioral activation approaches demonstrated preliminary promise. These findings support anhedonia as a distinct treatment target requiring specialized assessment and intervention protocols in early psychosis care. Full article

Background: The present study focuses on the development and validation of the Self-Perceived Anhedonia Scale for Adults (SPAS-A), a novel instrument designed to assess pleasure deficits across multiple dimensions of anhedonia, including social, physical, cognitive, and emotional facets. The study aimed to establish the psychometric properties of the scale, including its reliability and validity. Materials and methods: All the data were collected from a sample of 600 participants between February 2024 and November 2024 via Google Forms. Results: Factorial analysis, including Exploratory Factor Analysis and Principal Component Analysis, revealed a four-factor structure, accounting for 72.4% of the total variance, which demonstrated a coherent and multidimensional representation of anhedonia. The reliability of the scale was further supported by high Cronbach’s Alpha values for each subscale, with social anhedonia showing an exceptional value of 0.916, followed by emotional (0.905), cognitive (0.900), and physical (0.873) anhedonia. Conclusions: These findings indicate that SPAS-A is a reliable and valid tool for assessing pleasure deficits in adults, providing a comprehensive measure of anhedonia that can be utilized in both clinical and research settings. Future studies could benefit from longitudinal designs and more diverse samples to better understand the temporal and cultural variability of anhedonia. Full article

Background/Objectives: Negative symptoms (NSs) significantly impair the outcome of schizophrenia, primarily due to their effect on quality of life and their resistance to pharmacological treatments. Several scales have been developed to assess the various dimensions of NSs, including avolition, anhedonia, alogia, social withdrawal, and blunted affect. While observer-rated scales are the most commonly used, self-assessment tools remain underutilized. However, self-assessments offer a promising approach for gaining insights into the personal experiences of individuals. The objective of this review was to identify and report the psychometric properties of self-assessment scales for NSs that are relevant for both research and clinical practice, with a focus on tools that assess multiple domains of NSs in order to support comprehensive evaluations and tailored therapeutic strategies. Methods: We conducted an exhaustive literature review following PRISMA guidelines to identify self-evaluation scales that evaluate several domains of NSs in the MEDLINE and Web of Science databases. The COSMIN checklist was used to assess the methodological quality of each tool. Results: Our review identified five self-assessment scales. Among these, two scales received a Grade A recommendation for use in clinical or research practice: the Self-evaluation Negative Symptom (SNS), which assesses the five domains of NSs, and the Motivation And Pleasure Scale Self-report (MAP-SR), which evaluates anhedonia, avolition, and social withdrawal. Conclusions: The SNS and the MAP-SR are the only tools with sufficient psychometric properties, making them reliable for use in both research and clinical practice. Despite the development of self-assessment tools for NSs, their integration into research and clinical settings remains limited, highlighting the need for increased utilization to enhance the understanding and management of these symptoms. Full article

Background: There is a high rate of depressive symptoms such as irritability, anhedonia, fatigue, and hypersomnia in patients with type 2 diabetes mellitus (T2DM). However, the causes and underlying mechanisms of the comorbidity of depression and diabetes remain unknown. Methods: For the first time, we identified Decidual protein induced by progesterone 1 (Depp1), also known as DEPP autophagy regulator 1, as a hub gene in both depression and T2DM models. Depp1 levels were increased in the mPFC but not in other brain regions, such as the hippocampus or nucleus accumbens, according to Western blot and PCR assays. Results: Glucose dysregulation and synaptic loss occur in both depression and T2DM. The typical hyperglycemia in T2DM was observed in two models of depression, namely, chronic social defeat stress (CSDS) and chronic restraint stress (CRS). Hyperglycemia, which occurred in T2DM, was observed, and metabolomics data clearly showed the perturbation of glucose levels and glucose metabolism in the medial prefrontal cortex (mPFC). Decreased protein levels of BDNF and PSD95 suggested significant synaptic loss in depressed and diabetic mice. Conclusion: These findings suggest that the comorbidity of depression and diabetes is involved in the dysfunction of Depp1 in the mPFC. Full article

Post-translational modifications of proteins via palmitoylation, a thioester linkage of a 16-carbon fatty acid to a cysteine residue, reversibly increases their affinity for cholesterol-rich lipid rafts in membranes, changing their function. Little is known about how altered palmitoylation affects function at the systemic level and contributes to CNS pathology. However, recent studies suggested a role for the downregulation of palmitoyl acetyltransferase (DHHC) 21 gene expression in the development of Major Depressive Disorder (MDD)-like syndrome. Here, we sought to investigate how susceptibility (sucrose preference below 65%) or resilience (sucrose preference > 65%) to stress-induced anhedonia affects DHHC gene expression in the hippocampus of C57BL/6J mice during the phase of spontaneous recovery from anhedonia. Because MDD is a recurrent disorder, it is important to understand the molecular mechanisms underlying not only the symptomatic phase of the disease but also a state of temporary remission. Indeed, molecular changes associated with the application of pharmacotherapy at the remission stage are currently not well understood. Therefore, we used a mouse model of chronic stress to address these questions. The stress protocol consisted of rat exposure, social defeat, restraint stress, and tail suspension. Mice from the stress group were not treated, received imipramine via drinking water (7 mg/kg/day), or received intraperitoneal injections of dicholine succinate (DS; 25 mg/kg/day) starting 7 days prior to stress and continuing during a 14-day stress procedure. Controls were either untreated or treated with either of the two drugs. At the 1st after-stress week, sucrose preference, forced swim, novel cage, and fear-conditioning tests were carried out; the sucrose test and 5-day Morris water maze test followed by a sacrifice of mice on post-stress day 31 for all mice were performed. Transcriptome Illumina analysis of hippocampi was carried out. Using the RT-PCR, the hippocampal gene expression of Dhhc3, Dhhc7, Dhhc8, Dhhc13, Dhhc14, and Dhhc21 was studied. We found that chronic stress lowered sucrose preference in a subgroup of mice that also exhibited prolonged floating behavior, behavioral invigoration, and impaired contextual fear conditioning, while auditory conditioning was unaltered. At the remission phase, no changes in the sucrose test were found, and the acquisition of the Morris water maze was unchanged in all groups. In anhedonic, but not resilient animals, Dhhc8 expression was lowered, and the expression of Dhhc14 was increased. Antidepressant treatment with either drug partially preserved gene expression changes and behavioral abnormalities. Our data suggest that Dhhc8 and Dhhc14 are likely to be implicated in the mechanisms of depression at the remission stage, serving as targets for preventive therapy. Full article

Introduction: The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines depression as a persistent period of sadness or a reduced interest in everyday activities lasting at least two weeks. Anhedonia, a key symptom of depression, is notable for its significance and is regarded as the second most important factor related to non-somatic issues, following closely behind a depressed mood. This study primarily investigates how excessive or problematic use of Internet-connected devices affects the mood and emotions of young people, with a specific emphasis on anhedonia. Additionally, it explores associated socio-behavioral changes and examines the interaction between IA and depression. Methods: This systematic review was conducted following PRISMA international guidelines. Searches were performed in PubMed, Cochrane Library (Clinical Trials section), Scopus, Embase, PsycInfo, and grey literature sources like Google Scholar. A predefined search strategy using Boolean operators was employed, and two researchers independently selected papers, with a third researcher resolving any discrepancies. Manual reviews were conducted to minimize selection bias. Results: Out of 3812 records, 7 studies were included. The findings suggest that social anhedonia correlates with higher levels of IA, particularly among adolescents and young adults. In some studies, loneliness was identified as a mediator between social anhedonia and social functioning, indicating a complex interplay of emotional factors. Other investigations revealed that increased screen time is associated with a heightened risk of developing addiction-related behaviors. Practical Implications and Conclusions: This review highlights the key role of anhedonia in the development of Internet addiction (IA) among young people, particularly through its impact on emotional regulation and social interactions. Addressing psychological and environmental factors is essential for developing targeted strategies to prevent and manage IA and its related mental health challenges. Full article

Evidence indicates that chronic social stress plays a significant role in the development of cancer and depression. Although their association is recognized, the precise physiological mechanism remains unknown. In our previous work, we observed that OF1 males subjected to chronic social defiance exhibited anhedonia, and those who developed tumors in the lung showed anxiety-associated behaviors. In this study, we observed that tumor-bearing OF1 mice presented higher levels of 3-HK, and this increase may be due to IDO. No differences in hippocampal catecholamine levels were observed. Our results suggest that a systemic tumor can induce molecular changes in the hippocampal kynurenine pathway that may impact behavior. Full article