Search Results (859)

Background/Objectives: We investigated whether ingestion of caffeine (~1 h before) was beneficial to subsequent morning (~07:30 h) mood, reactive agility, and cognitive measures in naïve-mild habitual caffeine consumers. Methods: A total of 150 recreationally active males were recruited, of whom 51 participated and completed six sessions as follows: (i) three familiarization sessions of all procedures at 12:00 h, and (ii) three experimental conditions. Participants completed caffeine and placebo trials under double-blind conditions, together with an open-label no-pill control trial using the stratified block randomization method based on baseline performance, which were counterbalanced in a crossover design into either caffeine (CAFF, 300 mg or 2.5–5.3 mg·kg⁻¹ body weight), placebo (PLAC), or no-pill control (NoPill), both ingested at ~06:30 h. For each experimental session, on arrival at the laboratory, questions on sleep, mood states, and caffeine withdrawal were asked. A battery of cognitive performance tests was then administered (trail-making test, Rey’s auditory verbal learning test, and Stroop word–colour interference test). At 30 min of rest and after a 5 min warm-up on a treadmill with associated stretches, rectal and mean skin temperatures (T_r and T_sk) were measured. Thereafter, two 90 s reactive agility tests (RATs) were undertaken, with average movement time(s) and contact number per light recorded. Data were analyzed using a general linear model with repeated measures, but the RAT measures were run as ANCOVA with mass used as a covariate. Results: The battery of cognitive tests showed no significant main effects for condition, whether the body mass of the participants was considered or not. There were no significant main effects of the experimental condition for RAT variables. There was a main effect for “light position”, for mean movement time values (p < 0.001, η²_p = 0.508), and cognitive–motor efficiency (contacts·s⁻¹, p < 0.001, η²_p = 0.582), where pairwise analysis showed mean movement times as higher, and cognitive–motor efficiency values indicating a lower rate of successful responses during movement for lights 1 and 5 (the furthest from the start point corresponding to light 3), rather than lights 2, 3 and 4. There were no significant interactions for condition and light for any of the variables. Conclusions: Early morning ingestion of 300 mg of caffeine had no effect on the battery of cognitive or reactive agility test measures in the population of naïve-mild habitual caffeine consumers. Caffeine ingestion had no effect on T_r, T_sk, mood, or caffeine withdrawal symptom scores, as well as tiredness or alertness, with or without consideration for body mass. Full article

Background and Objectives: This methodology-focused narrative review synthesizes the eye-tracking literature in bipolar disorder (BD) to evaluate the utility of such technology in identifying potential state or trait biomarkers for BD. Methods: A PubMed and Scopus search was performed from database inception to August 2026. Eligible studies included adults with BD or individuals at high-risk for BD compared with healthy controls (HCs) that used at least one quantitative eye-tracking paradigm and reported extractable quantitative outcomes. Studies were grouped into eight paradigms: free-viewing task (FVT), antisaccade (AS), prosaccade (PS), memory-guided saccade (MGS), smooth pursuit eye movements (SPEM), vergence, binocular rivalry (BR), and eye-blink rate (EBR). Findings were synthesized narratively based on study designs and outcome measures. Results: 24 studies met inclusion criteria. FVT and PS were the most frequently represented paradigms (n = 8 each), followed by AS (n = 7), BR (n = 4), and SPEM (n = 3); MGS, vergence, and EBR were each represented by one report. Findings from FVT, AS, and PS were inconsistent; the study designs, stimulus types, mood states during the study, and outcome measures of studies with these paradigms were diverse. BR alternation rate was consistently slower in BD across three studies. SPEM deficits were more closely associated with psychotic features. Evidence from single studies of MGS, vergence, and EBR limits their interpretations. Conclusions: Eye-tracking paradigms are promising tools for studying cognitive, affective, perceptual, sensorimotor, and reward-related presentations of BD. However, the field needs standardized protocols that include eye-tracking paradigms, mood states, symptom severity, outcome measures, study samples, and comparison groups to examine the utility of eye-tracking technology in BD. Full article

Perioperative neurocognitive disorders (PND) encompass a spectrum of cognitive impairments occurring across the surgical period and are associated with significant morbidity, delayed recovery, and reduced quality of life. Although established risk factors include advanced age, cardiovascular disease, and preexisting cognitive impairment, the contribution of mood disorders to PND susceptibility remains incompletely understood. This review systematically examines the neurobiological overlap between mood disorders, particularly major depressive disorder (MDD) and bipolar disorder, and PND, with emphasis on shared biomolecular mechanisms. We identify convergent pathophysiologic pathways including hypothalamic–pituitary–adrenal (HPA) axis dysregulation, chronic neuroinflammation, NF-κB-mediated cytokine signaling, microglial priming, tryptophan–kynurenine pathway dysregulation, and brain-derived neurotrophic factor (BDNF) suppression. These mechanisms collectively suggest that patients with preexisting mood disorders may enter surgery in a biologically sensitized neuroimmune state, lowering the threshold for exaggerated neuroinflammatory responses and postoperative cognitive dysfunction. Recognition of mood disorders as modifiable perioperative vulnerability states may inform preoperative risk stratification, guide anesthetic and analgesic management, and support the development of targeted interventions to reduce postoperative cognitive complications and improve surgical outcomes. Full article

This study investigated the effects of human–calf interactions on psychophysiological and emotional responses in humans. Thirty healthy adults (mean age: 25 ± 1.3 years) participated in four distinct 3 min activities with a Holstein calf: (1) watching a 2D video of a calf (video observation), (2) observing a calf directly (direct observation), (3) feeding a calf, and (4) grooming a calf. Electroencephalogram (EEG) measurements were recorded from the prefrontal, frontal, parietal, and occipital lobes during each activity. Participants’ emotional states were assessed using the Profile of Mood States (POMS) questionnaire before and after the sessions. Results showed that relative alpha power spectra, indicative of relaxation and resting states, significantly increased during both direct and video observation of the calf compared to feeding or grooming activities (p < 0.05). Relative beta power, associated with concentration and alertness without stress, was also elevated during the observation conditions relative to grooming (p = 0.044). Furthermore, POMS scores revealed a significant reduction in total mood disturbance after calf-related activities, particularly following observation (both video and direct) and grooming (p = 0.004). These findings suggest that brief interactions with calves may promote relaxation, enhance attention, reduce stress, and improve emotional well-being in healthy adults. The results provide preliminary evidence that may inform future research on the development of animal-assisted activity programs. Full article

The regular practice of physical exercise is often associated with promoting benefits for practitioners. In recent decades, street running has become popular worldwide, with most participants being recreational runners who engage in the activity primarily to promote health, well-being, leisure, and quality of life, although some also participate with competitive goals. Among the psychological aspects related to exercise, studies have shown that some individuals may become susceptible to “exercise dependence,” a condition in which exercise takes a central role in a person’s life. As a result, individuals may exhibit characteristics such as excessive training, injuries; weight control issues, withdrawal symptoms when unable to exercise and even problems in social relationships when exercise is exclusively prioritized. Background/Objectives: The aim of this study was to investigate and analyze levels of susceptibility to running dependence and its relationship with exercise volume and mood states (tension, depression, anger, vigor, fatigue, and mental confusion). Methods: This was a quantitative cross-sectional study involving 761 regular Brazilian runners (59.8% male and 40.2% female) who consented to participate and answered the Sociodemographic Questionnaire, the Escala de Dependência de Corrida (EDC), a Brazilian Portuguese adaptation of the Negative Addiction Scale (NAS), and the Brunel Mood Scale (BRUMS). The analysis plan was conducted through descriptive statistics (mean, standard deviation, median, 1st and 3rd quartiles, interquartile range, and 95% confidence intervals) and inferential statistics (Spearman’s Correlation and Kruskal–Wallis Test). In all tests, the significance level adopted was p < 0.05. Results: The sample was divided into three groups of susceptibility to exercise dependence: low (37.6%), moderate (36.4%), and high (26%). Scores indicative of greater susceptibility to exercise dependence showed positive correlations with running practice volume (years of experience, weekly training frequency, weekly training duration, and weekly mileage), as well as with vigor. Although a statistically significant correlation was also observed for tension, its magnitude was trivial (rs = 0.080). Comparisons using the Kruskal–Wallis test showed that higher susceptibility levels were associated with greater running volumes and higher raw vigor scores, whereas no significant group differences were observed for the remaining mood states. Conclusions: Higher susceptibility to exercise dependence was associated with greater running volume and higher raw vigor scores. No consistent associations were observed with negative mood states, except for a trivial correlation with tension. These findings suggest that greater susceptibility to exercise dependence among runners was primarily associated with higher raw vigor scores rather than with broader alterations in mood states. Full article

Background: Primary care providers are increasingly using screening programs to identify patients at risk of mental disorders. Early diagnosis of bipolar disorder type I (BDI) is essential for a better outcome. Endophenotypes are an important subtype of biomarkers. Furthermore, previous studies show anxiety trait as a possible BDI endophenotype, but there is a lack of replication. Objective: Our study evaluates the presence of anxiety trait and bipolarity risk in bipolar disorder type I first-degree relatives (FDR). Methods: We evaluated 219 participants (119 healthy controls, 68 healthy FDR and 32 affective unipolar FDR), including sociodemographic data, psychiatric history, Spielberg’s State and Trait Anxiety Inventory (STAI), General Health Questionnaire, Beck Depression Inventory, and Mood Disorder Questionnaire (MDQ) scores as a measure of bipolarity risk. Results: In our sample, affective unipolar BDI’s first-degree relatives showed the highest scores in STAI anxiety trait compared to healthy controls and BDI’s healthy first-degree relatives. STAI-Trait only correlated significantly with bipolarity risk (MDQ) in the unipolar affective first-degree relatives subgroup. Conclusions: Although further investigation is warranted, trait anxiety is a potential endophenotype for BDI. It exhibits high heritability and confers an increased lifetime risk for unipolar affective disorder and a predisposition toward bipolarity. Full article

This study investigated the acute effects of guarana supplementation on cognitive, technical, physiological, and psychological responses in soccer players prior to, during, and following high-intensity 4 vs. 4 small-sided games (SSGs). Thirty-two male amateur soccer players (20.1 ± 2.9 years) completed a randomized, double-blind, placebo-controlled crossover trial involving guarana (300 mg) and placebo, separated by a 7-day washout. After a 70 min absorption period, participants performed the Trail Making Test (TMT-A/B) and Loughborough Soccer Passing Test (LSPT) before and after a 20 min SSG protocol. Heart rate (HR), HR recovery, perceived physical exertion, perceived mental exertion, mood state, and 24 h wellness were assessed. Guarana significantly improved TMT-A performance compared with placebo (p = 0.005, η²p = 0.05), whereas no significant differences were observed for TMT-B (p = 0.08, η²p = 0.02). A significant Group × Time interaction was found for total LSPT performance time (p = 0.01, η²p = 0.06), driven by a significant technical performance optimization at pre-exercise (p < 0.01) that dissipated post-exercise (p > 0.05). Guarana significantly increased mean exercise HR (p < 0.05) and slowed early recovery kinetics (p < 0.05) without altering perceived physical exertion (p > 0.05). Concurrently, it significantly reduced perceived mental exertion (p < 0.01) and attenuated Total Mood Disturbance (p < 0.001). No significant between condition variations were noted for 24 h wellness indices (p > 0.05). These findings suggest that acute low-dose guarana administration may improve basic attentional readiness and was associated with improved pre-exercise technical performance, although this performance advantage was attenuated following high-intensity physical exertion. Full article

Background/Objectives: Large-scale dysfunction in the default mode (DMN), salience (SN), and central executive (CEN) networks characterises conditions affecting affective, cognitive, and autonomic regulation. Chronic low back pain (CLBP) shows hyperactive salience signalling, disrupted DMN processing, and impaired executive regulation. Chiropractic adjustments modulate cortical excitability, yet whether these extend to oscillatory reorganisation is unknown. This exploratory secondary analysis aimed to determine whether chiropractic care is associated with frequency- and network-specific changes in source-localised EEG connectivity within and between the DMN, SN, and CEN in adults with CLBP. Methods: Seventy-six adults with CLBP were randomised to chiropractic plus usual care (n = 38) or usual care alone (n = 38). EEG was recorded during resting-state and SEP paradigms at baseline, post-intervention, and four weeks. Source activity was reconstructed with sLORETA and PLI computed across theta, alpha, beta, and gamma bands. For each condition, Fisher-z network-mean PLI was analysed in separate network-by-band linear mixed-effects models with Group, Session, and their interaction as fixed effects and a random intercept for a unique participant identifier; ROI-level changes were examined with cluster-based permutation tests, with inference at the connected-component level. Results: Resting-state alpha-band connectivity within the default mode network was higher in the chiropractic group both immediately after care and at four-week follow-up (both $q<0.001$), alongside additional frequency- and network-specific effects. Region-level analyses identified a distributed alpha-band network spanning most triple-network regions, in which resting-state connectivity increased in the chiropractic group after care ($p_{FWE}=0.003$; Holm-adjusted $p=0.042$). For the somatosensory evoked recordings, no network-level interaction survived multiple-comparison correction; the distributed connectivity changes identified in exploratory region-level analyses are therefore considered preliminary. Conclusions: Chiropractic adjustments are associated with frequency-specific changes in resting-state connectivity within the DMN, SN, and CEN. These findings are hypothesis-generating and require confirmation in adequately powered, pre-registered trials before they can be interpreted as a neurophysiological basis for improvements in pain, mood, fatigue, sleep, or quality of life. Full article

Post-stroke epilepsy (PSE) is one of the most common long-term neurological complications of stroke and represents a major contributor to disability, reduced quality of life, and increased healthcare burden. Although numerous risk factors and biomarkers have been proposed, many current risk models still emphasize lesion-related predictors and do not fully account for the temporal evolution of post-stroke network excitability. This narrative review aims to examine post-stroke epileptogenesis as a dynamic process of network reconfiguration and to summarize current evidence on biological, neurophysiological, imaging, and clinical biomarkers across different stages following stroke. A structured narrative review of the literature was performed using major biomedical databases. Studies addressing mechanisms of post-stroke epileptogenesis, biomarkers, network dysfunction, neuroinflammation, EEG findings, neuroimaging correlates, and longitudinal monitoring strategies were evaluated and synthesized qualitatively. Evidence suggests that post-stroke epileptogenesis is driven by complex interactions among structural injury, neuroinflammation, blood–brain barrier dysfunction, neurotransmitter imbalance, maladaptive plasticity, and large-scale network reorganization. Importantly, many biomarkers demonstrate substantial temporal variability, and their clinical significance depends on the stage of recovery and the evolving state of brain networks. Emerging data indicate that sleep disturbances, stress, mood disorders, metabolic factors, and other state-dependent influences may further modulate seizure susceptibility after stroke. Post-stroke epileptogenesis may be better conceptualized as a dynamic process of network instability rather than a fixed consequence of focal brain damage. It is proposed that the post-stroke brain can transiently or persistently enter an “irritable brain state”, characterized by increased vulnerability to pathological synchronization under the influence of biological and behavioral modulators. This framework may facilitate the development of longitudinal biomarker strategies and personalized monitoring approaches in future research. However, it should be emphasized that the “irritable brain state” remains a conceptual and hypothesis-generating construct; no validated diagnostic criteria exist, and prospective evidence demonstrating that interventions targeting this state reduce the incidence of post-stroke epilepsy is currently lacking. Full article

Background: Perinatal brain network alterations, including changes in resting-state functional connectivity (rsFC), may increase vulnerability for perinatal mood and anxiety disorders (PMAD). The Fronto-Parietal Network (FPN), the Default-Mode Network (DMN), and the Salience Network (SN) are interconnected networks implicated in mood disorders. However, these networks’ role in perinatal neuroplasticity and PMAD remains unclear. Methods: This pilot study prospectively followed twenty-two women from preconception to postpartum. Participants completed anxiety and depression questionnaires and underwent fMRI scans at preconception and postpartum. The FPN, DMN, and SN were defined and average connectivity of each network was determined. Differences in connectivity from preconception to postpartum within each network and to each network at the whole-brain level were computed. Results: While connectivity within the FPN, DMN, and SN did not show significant changes from preconception to postpartum, we found increased rsFC from the left anterior prefrontal cortex to the DMN, and decreased rsFC from the right ventral posterior cingulate cortex to the FPN, from preconception to postpartum. Bilateral supplementary motor areas (SMAs) showed increased connectivity to the FPN from preconception to postpartum, and this change in connectivity was negatively correlated with anxiety scores during pregnancy. Right SMA connectivity to the FPN at preconception showed positive association with postpartum depression scores (p < 0.05 for all comparisons). Conclusions: RsFC perinatal-related changes were demonstrated in cognitive and motor regions connected to the DMN and FPN. Among women with perinatal depressive and anxiety symptoms, changes in SMA rsFC to the FPN from preconception to postpartum were observed, indicating possible roles in PMAD. Full article

Background/Objectives: Botanical nootropics are increasingly sought as natural alternatives to synthetic stimulants. Mangifera indica leaf extract, standardized to the polyphenol mangiferin, has shown promise in regulating brain activity and enhancing cognitive performance. This study aimed to replicate, in an independent cohort, the acute cognitive benefits of a soluble mango leaf extract (Zynamite^® S) following a previous proof-of-concept trial. Methods: In a double-blind, randomized, placebo-controlled crossover trial, 88 healthy young adults (aged 18–25) received either a single 100 mg dose of Zynamite^® S or a matched placebo. Cognitive performance was assessed using the Trail Making Test (TMT), Digit Symbol Substitution Test (DSST), and Stroop Color-Word Test. Emotional states were assessed via the Profile of Mood States (POMS) at baseline, and then at 30 min, 3 h, and 5 h post-ingestion. Results: Zynamite^® S supplementation resulted in the replication of previous findings, with significant improvements in mental processing speed, attention, and cognitive flexibility (p < 0.05). Notably, this trial identified a rapid onset of action, with significant cognitive and mood improvements detectable as early on as 30 min post-dose and a sustained duration of the effect with benefits observed up to 5 h post-administration. Mood assessments confirmed an overall improvement in emotional balance (p < 0.05) by reducing tension, mental fatigue, and low mood during the completion of cognitive-demanding tasks. Conclusions: These findings reproduce the acute benefits of Zynamite^® S in a healthy young adult population, including a rapid onset of effects and a sustained improvement in cognitive performance and mood over a 5 h window. Full article

Post-traumatic stress disorder (PTSD) is a severe condition triggered by traumatic exposure, characterized by symptoms like trauma re-experiencing, avoidance, mood alterations, hypervigilance, and sleep disturbances. While its exact mechanisms remain uncertain, PTSD involves dysregulation across neurobiological systems underlying fear conditioning, threat appraisal, executive control, and stress response. Although research highlights the sympathetic–adreno–medullary (SAM) system and the hypothalamic–pituitary–adrenal (HPA) axis, findings on stress-related mediators remain inconsistent regarding their precise contributions over time. To address this, we propose a hypothetical model viewing PTSD as a multistable system shifting from physiological to pathological steady states. We assume that intense, repeated emotional stress triggers spike activation in the amygdala, driving an amygdala–locus coeruleus loop into a high-activation state via reciprocal excitation, mediated by corticotropin-releasing hormone (CRH) and noradrenaline. This sequentially alters amygdala–hippocampus and prefrontal cortex loops, reinforcing fear expression and impairing extinction. This model is consistent with key features of PTSD, including its higher prevalence among females, increased glucocorticoid receptor sensitivity, the frequently observed hypocortisolism, and the partial efficacy of serotonin and norepinephrine reuptake inhibitor (SNRI) and CRH receptor antagonists. While requiring experimental validation, this framework connects molecular, circuit, and behavioral data to help identify novel interventions for restoring adaptive stress-response dynamics. Full article

Though perinatal mental health has been frequently examined in the context of maternal depression, research has minimally explored the degree to which a partner’s perinatal mental diagnosis influences perinatal mood and anxiety disorder incidence. Drawing on Bowen’s Family Systems Theory, we examine co-occurring symptoms of postpartum depression and anxiety (PPD/A) and support dynamics within couples through a cross-sectional mixed-methods study. In the summer of 2024, birthing and non-birthing caregivers (n = 907) across the United States completed a survey including a modified Edinburgh Postnatal Depression Scale (EPDS) and additional questions about partner support, screening, and communication. Post-survey interviews (n = 17) revealed further insight into the relational dynamics of co-occurring PPD/A symptoms among couples. Survey analyses indicated correlations between birthing and non-birthing partner experiences of PPD/A. Further, co-occurrence was associated with diminished emotional support and increased distress for birthing parents. Participants who desired more partner support or felt afraid to express their feelings had significantly higher EPDS scores. Qualitative findings reinforced these patterns, highlighting the roles of relational strain, gender norms, and lack of systemic support for perinatal mental health. Findings suggest couple-based screening practices and interventions that recognize the bidirectional emotional impact of PPD/A may hold promise for improving outcomes across the entire family system. Full article

Depressive symptoms are highly prevalent among individuals with substance use disorders, particularly opioid use disorder (OUD), yet their clinical meaning is often difficult to determine. In routine practice, these symptoms are commonly interpreted within a binary framework, either as manifestations of an independent mood disorder or as substance-induced states related to intoxication, withdrawal, or early abstinence. Although clinically useful, this distinction may not fully capture a third configuration in which depressive psychopathology emerges within the chronic addictive process itself. This Perspective proposes a tripartite model of depressive states in OUD informed primarily by clinical and dimensional studies conducted in populations with heroin use disorder. First, substance-induced depression refers to mood symptoms temporally linked to the acute or subacute pharmacological effects of substances and generally expected to improve with stabilization or sustained abstinence. Second, an independent mood disorder may coexist with OUD, with particular attention warranted for bipolar-spectrum presentations characterized by affective instability, cyclothymic or irritable temperaments, mixed features, and mood-related patterns of substance use. Third, addiction-related depression describes a persistent depressive configuration associated with reward dysregulation, hypophoria, motivational depletion, cognitive inefficiency, and the Worthlessness/Being Trapped dimension identified primarily in dimensional studies of heroin use disorder. These configurations should not be regarded as rigid or mutually exclusive categories, but as longitudinal clinical formulations that may predominate at different stages of the addictive trajectory. Distinguishing among them may improve diagnostic clarity and support a hierarchical clinical approach in which stabilization of OUD is generally an initial therapeutic priority, while antidepressant and mood-stabilizing interventions are guided by symptom severity, temporal course, psychopathological organization, and evidence of an independent mood disorder. Full article

Background and Objective: Depression is frequent in Parkinson’s disease (PD), but it is unclear how mood changes and impacts patient’s quality of life (QoL) over time. Our objective was to analyze the frequency of depression and mood changes in people with PD (PwP) over 5 years of follow-up, comparing it with a control group, as well as its relationship with the patients’ QoL. Patients and Methods: PwP and healthy controls (HC) recruited from the COPPADIS cohort from January/2016 to November/2017 were included in this 5-year follow-up study. Mood was assessed by the Beck Depression Inventory II (BDI-II), and participants were classified as having major depression, minor depression, subthreshold depression, or non-depression at baseline and at 2, 4, and 5 years of follow-up. Correlation analysis and linear regression models were applied. Results: The BDI-II total score increased from 8.1 ± 6.2 at baseline to 10.3 ± 8.1 at the 5-year follow-up visit in PwP (p < 0.0001) but not in HC (from 4.1 ± 5.2 to 4.0 ± 5.7 [p = 0.896]). The prevalence of depression remained around 50–54% in the PwP group and 21–25% in the HC group throughout the follow-up period, but the mood state showed variability for each patient between visits. Patients’ QoL was associated with the depressive state throughout the entire follow-up period (p < 0.0001). Worsening QoL, sleep, longer disease duration, and an increase in neuropsychiatric symptoms were identified as independent factors associated with a worsening of mood over time in PwP (N = 348). Conclusions: Mood change over time in PwP is associated with QoL. Full article