Search Results (51)

Background/Objectives: Insomnia is highly prevalent among patients with asthma and has been associated with systemic inflammation, reduced lung function, and increased mortality. This study investigated whether insomnia mediates the relationship between asthma control and psychosocial dysfunction, including social anhedonia and functional impairment. Methods: This cross-sectional study included 153 adults with physician-diagnosed asthma classified as controlled (n = 51) or uncontrolled (n = 102) according to the Asthma Control Test (ACT). Insomnia severity was assessed using the Athens Insomnia Scale (AIS), social anhedonia using the Revised Social Anhedonia Scale (RSAS), psychological distress using DASS-21, and functional impairment using the Functioning Assessment Short Test (FAST). Results: Uncontrolled asthma was associated with significantly higher insomnia severity and greater depression, anxiety, and stress levels (all p < 0.001). Asthma control emerged as the strongest independent predictor of insomnia severity (β = −0.451, p < 0.001). Although asthma control was not directly associated with social anhedonia or functional impairment, insomnia significantly mediated these relationships. The indirect effect of asthma control on social anhedonia via insomnia was significant (B = −0.1162, 95% CI [−0.2384, −0.0029]), as was the indirect effect on functional impairment (B = −0.4953, 95% CI [−0.8656, −0.1038]). Spirometric indices were not independently associated with psychosocial outcomes. Conclusions: Insomnia may represent an important intermediary process linking poor asthma control to psychosocial dysfunction. These findings highlight the clinical importance of assessing sleep disturbances in asthma patients and suggest that insomnia may contribute to broader psychosocial impairment beyond respiratory symptoms alone. Full article

Background: Subclinical psychological symptoms—such as low mood, perceived stress, and poor sleep—affect a large portion of the population and can impair quality of life despite remaining below clinical thresholds. The gut–brain axis has emerged as a promising target for interventions that support emotional and psychological resilience. Probiotics and postbiotics are gaining attention for their potential to modulate mood and stress via microbiome-related mechanisms, but human evidence remains limited, particularly in non-clinical populations. Objectives: We aimed to assess the effects of a two-strain combination of live microorganisms alongside a two-strain combination of heat-treated inactivated microorganisms on outcomes associated with anxiety, mood, perceived stress, and quality of life in healthy adults experiencing mild stress. Methods: This study was conducted in two parts. In Part I, a randomized, double-blind, placebo-controlled study, 100 participants were randomized to receive either a blend of live microorganisms (Bifidobacterium longum CECT 7347 and Lactobacillus rhamnosus CECT 8361) or an identical placebo once daily for 12 weeks. In Part II, a pilot feasibility study, a subset of eight placebo non-responders from Part I received the heat-inactivated preparation of the same bacterial strains in a 6-week trial extension phase. For Parts I and II, the primary outcome was the change in the Hamilton Anxiety Rating Scale (HAM-A). Secondary outcomes included measures of mood (Beck Depression Inventory (BDI); Patient Health Questionnaire-9 (PHQ-9)), stress (state and trait anxiety inventory (STAI); Perceived Stress Scale (PSS)), sleep (Pittsburgh Sleep Quality Index (PSQI)), quality of life (36-item Short Form Survey (SF-36)), gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale (GSRS)), salivary cortisol and microbiome modulation. Results: In Part I, there were no significant effects of the live blend on the HAM-A, indicating that the primary endpoint was not met. In addition, no significant effects were seen on the STAI or PSS scores when compared to the placebo. However, participants consuming the live blend trended toward a reduction in total PHQ-9 scores compared to placebo (p = 0.089), whilst preliminary exploratory analyses suggested an improvement in anhedonia (p = 0.045). Furthermore, there was a significant improvement in the vitality domain of the SF-36 compared to placebo (p = 0.017). On microbiome analysis, it was noted that consumption of the live blend was linked to the preservation of butyrate-producing bacteria, particularly members of the Pseudoflavonifractor genus and the Clostridium SGB6179 species. Furthermore, the abundance of B. longum species was found to be inversely associated with the total PSS Scores. In Part II, supplementation with the inactivated preparation resulted in significant within-group improvements for the vitality (p = 0.006) and social functioning (p = 0.010) domains of the SF-36 and improvements in PSS scores compared to baseline (p = 0.050). Conclusions: Supplementation with either the dual-strain live or inactivated formulations was associated with significant improvements in the vitality domain of the SF-36, whilst participants receiving the inactivated formulation demonstrated lower perceived stress and improved social functioning compared to baseline. Overall, the findings from this pilot study suggest that these two biotic consortia are well-tolerated and may be associated with improvements in measures of vitality in individuals with subclinical psychological symptoms. The subtle observations detected for stress and anhedonia suggest that further well-powered trials are needed to better characterize these findings, potentially in populations with greater baseline symptomatology. Full article

Chronic social isolation (CSIS) is a form of psychosocial stressor strongly associated with the development of depression. Preclinical studies demonstrated that CSIS induces behavioral phenotypes resembling human depression, including anhedonia, behavioral despair and anxiety. This review summarizes proteomic-driven discoveries characterizing hippocampal non-synaptic mitochondria (NSM) and synaptosomal fractions containing synaptic mitochondria from adult male rats exposed to six weeks of CSIS, an animal model of depression, compared to controls. The compartment-specific proteomic alterations reveal mechanisms underlying mitochondrial dysregulation, providing molecular insights into the depression-like phenotype. Hippocampal NSM exhibit changes in energy metabolism-related proteins, including components of the tricarboxylic acid cycle and oxidative phosphorylation, as well as mitochondrial transport proteins and alterations in chaperones, structural and translational proteins, and monoamine oxidase, further elucidating how these proteomic changes contribute to mitochondrial dysregulation. In contrast, synaptosomal proteomics reveal predominantly increased protein abundance associated with energy metabolism, signaling, cytoskeletal organization, protein quality control, and vesicle trafficking, suggesting compensatory adaptations. Together, these findings highlight compartment-specific mitochondrial proteomic changes that may underlie depression-like behaviors and represent potential targets for therapeutic intervention. Full article

Background: Anhedonia denotes a reduced capacity of experiencing pleasure, which is often reported by individuals with psychiatric disorders such as depression and polysubstance use disorders. Since anhedonia is a critical factor influencing the well-being of psychiatric and general populations, it is important to investigate predictors of anhedonia. Method: We conducted a survey in N = 300 young adults aged 18 to 30 (M = 25.45, SD = 3.66). As predictors of anhedonia, we examined polysubstance use, problems with social media use, coping styles, and mindfulness. We controlled for age, gender, education, and the frequency of leisure activities. Results: Together, the predictors explained 20% of the variance in anhedonia. We found a positive association of polysubstance use with anhedonia, indicating that the more substances individuals consumed, the more anhedonia they reported. Problems with social media were not significantly related to anhedonia. Concerning coping styles, individuals with a more problem-focused coping style (e.g., planning) reported significantly lower levels of anhedonia, whereas emotion-focused coping (e.g., seeking social support) was unrelated to anhedonia. Mindfulness negatively correlated with anhedonia. Conclusions: The present study adds to research on behavioral and dispositional predictors of anhedonia and underlines the positive impact of mindfulness and problem-focused coping on anhedonia. Full article

Background: Resistant major depression (RMD) is characterized by persistent depressive symptoms despite adequate pharmacological treatment, leading to functional impairment and increased physical comorbidity. Lifestyle interventions, particularly physical activity, are promising adjuncts, yet factors influencing engagement remain poorly understood. Methods: A purposive sampling approach and thematic analysis informed by a socioecological framework were employed to explore participants’ lived experiences after completing a 12-week supervised combined exercise program. Semi-structured interviews were thematically analyzed. Results: Engagement was influenced by three main themes: intrapersonal (symptoms, lifestyle, medication, program expectations), interpersonal (family, peers, healthcare professionals), and environmental (program location, schedule, session design) factors. Motivation was shaped by emotional, physical, and social goals, while barriers included fatigue, anhedonia, and side effects of medication. Conclusions: Engagement in exercise interventions for RMD is shaped by the interaction of personal, social, and environmental factors. Understanding lived experiences can inform the design of person-centered, sustainable interventions. Full article

Reward motivation adaptation is defined as the extent to which the willingness to exert effort varies as a function of incentive salience, encompassing both motivational (‘wanting’) and hedonic (‘liking’) components. Although reduced reward motivation has been reported in subclinical depression and anhedonia, it remains unclear whether impaired adaptation is a general feature of subclinical depression or is more evident when depressive symptoms co-occur with anhedonia. We addressed this question in two behavioral studies using a task that systematically varied effort–reward ratios. Study 1 contrasted three screening-based groups: individuals with elevated social anhedonia, individuals with subclinical depression without high social anhedonia, and controls with low levels of both, and found no clear group differences in reward motivation adaptation across effort–reward conditions. Study 2 focused on female participants with subclinical depression who also showed higher levels of anhedonia, compared with non-depressed controls. In this sample, the subclinical depression group showed lower overall reward motivation and indications of reduced ‘liking’ adaptation. In conclusion, these findings suggest that deficits in reward motivation adaptation were not clearly observable when subclinical depression or social anhedonia were considered in isolation, but may emerge when depressive status and broader measures of anhedonia co-occur, though this pattern requires confirmation in larger and more diverse samples. Full article

Background/Objectives: Autism is a complex neurodevelopmental condition characterized by social and cognitive impairments, with growing evidence implicating neuroinflammation, disrupted autophagy, apoptosis, GABAergic dysfunction, and gut permeability in its pathophysiology. Thus, this study aimed to evaluate the independent and combined effects of intermittent fasting (IF) and the next-generation probiotic Akkermansia muciniphila on behavioral outcomes and molecular markers in prenatal valproic acid (VPA)-induced autism model. Methods: Male rat offspring were allocated into five groups (n = 8 per group): control, VPA, IF, probiotic, and IF + probiotic. The groups other than the control group were exposed to 500 mg/kg VPA prenatally to establish an autism model. Intermittent fasting (16:8 time-restricted feeding) and Akkermansia muciniphila (1 × 10⁹ cfu/day) were applied for 30 days. Behavioral tests (stereotypy, social interaction, memory, and anhedonia) were performed during the last eight days of the treatment period, and the rats were sacrificed the following day for collection of brain tissue and serum samples. Proinflammatory, apoptotic, autophagic, and GABAergic markers were measured in the prefrontal cortex and hippocampus, while zonulin levels were measured in the serum. Data were analyzed using one-way ANOVA followed by Tukey’s post-hoc test. Results: Prenatal VPA exposure worsened all behavioral and molecular parameters. All treatments improved stereotypy, social interaction, and memory, whereas anhedonia improved only in the combined treatment group. The treatments also decreased neuroinflammation and apoptosis-related imbalance while enhancing autophagy and GABAergic markers. In terms of apoptosis- and autophagy-related markers, the IF-only and probiotic-only treatments were effective in the prefrontal cortex, while the IF + probiotic treatment showed its effect in both brain regions. Lastly, all treatments were successful in alleviating elevated serum zonulin levels. Conclusions: Intermittent fasting and Akkermansia muciniphila alleviate VPA-induced behavioral and neurobiological impairments. The combined treatment, in particular, offers stronger and multi-targeted therapeutic potential. Full article

Background: Late-onset depression (LOD) represents a distinct clinical and biological phenotype emerging in the context of global population ageing. This study aims to synthesize current evidence on the epidemiology, risk factors, mechanistic pathways, and therapeutic approaches of LOD, integrating biological, psychological, and social dimensions. Methods: This narrative review synthesizes recent evidence across epidemiology, clinical symptomatology, neurobiology, and treatment. Where conceptually appropriate or empirically overlapping, we incorporate findings from the broader late-life depression (LLD) literature. Results: LOD emerges (as a distinct clinical and biological entity in later life) as a clinically and biologically meaningful presentation of depression in later life, representing a minority of depressive cases. It is defined by prominent apathy, psychomotor slowing, and cognitive impairment, and is closely linked to frailty, medical comorbidity, and heightened dementia risk. Pathophysiological mechanisms converge on vascular, inflammatory, oxidative, and neuroplasticity pathways, while psychosocial adversity further shapes onset and course. Treatment prioritizes efficacy and tolerability amid multiple morbidity; SSRIs and SNRIs are first-line, with pro-dopaminergic or dual-action agents addressing anhedonia and apathy, and neuromodulation or augmentation strategies reserved for resistance. Integrative approaches combining pharmacotherapy, psychotherapy, and lifestyle interventions are essential to optimize outcomes in aging populations. Conclusions: Late-onset depression (is a distinct, biologically and psychosocially driven disorder) represents a biologically and psychosocially enriched subtype in its own within the spectrum of late-life depression, requiring integrated, personalized care. Addressing neurovascular mechanisms, psychosocial adversity, and prevention through coordinated geriatric and psychiatric strategies may improve outcomes in aging populations. Full article

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