Search Results (2,068)

Heavy metals are a major toxicological concern due to their adverse effects on human health, particularly in children exposed to contaminated areas. This study evaluated biomarkers of exposure in 253 children aged 6 to 12 from Magangue, Achi, and Arjona (Bolivar, Colombia), analyzing their relationship with neurotoxicity and hematological markers. The mean Pb concentrations at the study sites were 1.98 µg/g (Magangue) > 1.51 µg/g (Achi) > 1.24 µg/g (Arjona). A similar pattern was observed for Cd concentrations for Magangue (0.39 µg/g) > Achi (0.36 µg/g) > Arjona (0.14 µg/g). In contrast, Se concentrations followed a different trend for Arjona (0.29 µg/g) > Magangue (0.21 µg/g) > Achi (0.16 µg/g). The proportion of Se/Pb molar ratios > 1 was higher in Arjona (3.8%) than in Magangue (0.9%) and Achi (2.0%). For Se/Cd ratios, values > 1 were also more frequent in Arjona (70.7%), exceeding 20% in the other two locations. Significant differences were found among locations in red and white blood cell parameters and platelet indices. Neurotransmitter-related biomarkers, including serotonin, monoamine oxidase A (MAO-A), and acetylcholinesterase levels, also varied by location. Principal component analysis showed that Pb and Cd had high loadings on the same component as PLT, WBC, and RDW, and while Se loaded together with HGB, PDW, MCHC, MCH, and MCV, suggesting distinct hematological patterns associated with each element. Multiple linear regression analysis demonstrated a statistically significant inverse association between hair Pb levels and serotonin concentrations. Although MAO-A and Cd showed negative β coefficients, these associations were not statistically significant after adjustment. These findings highlight the potential impact of toxic element exposure on key hematological and neurochemical parameters in children, suggesting early biological alterations that may compromise health and neurodevelopment. Full article

Hormonal contraceptives (HCs) are widely used and generally well tolerated; however, their neuroendocrinological effects remain underappreciated in clinical decision-making. Beyond ovulation suppression, HCs influence brain function by modulating key neurotransmitters such as GABA, serotonin, and dopamine, as well as neurosteroids like allopregnanolone and β-endorphin. These interactions help explain why some users experience mood swings, anxiety, or changes in sexual desire, while others report improvements in well-being. In this narrative review, we explore how different estrogenic and progestin components affect central pathways involved in emotional regulation and cognition. Evidence suggests that estradiol or estetrol-based formulations combined with anti-androgenic progestins like drospirenone or nomegestrol acetate may offer a more favourable neuroendocrine profile, particularly in women with a history of mood disorders or hormonal sensitivity. Understanding these neuroendocrine mechanisms may support more personalized contraceptive choices, particularly in women with mood disorders and hormonal vulnerability. Full article

Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on cognitive function through β-amyloid (Aβ) deposition and multi-omics profiling. We evaluated six male Mn-exposed workers (median age 63, exposure duration 31 years) and five historical controls (median age: 60 years), all of whom had undergone brain PET scans. Exposed individuals showed significantly higher Aβ deposition in exposed individuals (p < 0.05). The average annual cumulative respirable Mn was 329.23 ± 516.39 µg/m³ (geometric mean 118.59), and plasma Mn levels were significantly elevated in the exposed group (0.704 ± 0.2 ng/mL) compared to controls (0.397 ± 0.18 in controls). Results: LC-MS/MS-based pathway analyses revealed disruptions in olfactory signaling, mitochondrial fatty acid β-oxidation, biogenic amine synthesis, transmembrane transport, and choline metabolism. Simoa analysis showed notable alterations in ADRD-related plasma biomarkers. Protein microarray revealed significant differences (p < 0.05) in antibodies targeting neuronal and autoimmune proteins, including Aβ (25–35), GFAP, serotonin, NOVA1, and Siglec-1/CD169. Conclusion: These findings suggest Mn exposure is associated with neurodegenerative biomarker alterations and disrupted biological pathways relevant to cognitive decline. Full article

Sedation and anesthesia are essential for ensuring animal welfare during surgical procedures such as hernia repair in swine. However, the number of sedative and anesthetic agents officially approved for livestock use remained limited. This study evaluated the sedative efficacy and serotonergic effects of a romifidine/ketamine/diazepam protocol, with and without the addition of tramadol, in swine undergoing umbilical hernia repair. Sixty-six crossbred Large White swine were randomly allocated to three groups: LL (lidocaine 4 mg/kg by infiltration), LT (lidocaine 2 mg/kg by infiltration + tramadol 2 mg/kg intraperitoneally), and TT (lidocaine2 mg/kg by infiltration + tramadol 4 mg/kg intraperitoneally). The physiological parameters heart rate, arterial pressure, oxygen saturation, rectal body temperature, and respiratory rate were assessed. The depth of intraoperative anesthesia and postoperative sedation was assessed using an ordinal scoring system (0–3). Plasma serotonin (5-HT) concentration was measured at baseline and 24 h post-surgery. Physiological parameters remained within species-specific reference ranges throughout the procedure. Anesthesia depth scores significantly decreased over time in all groups (p ≤ 0.001), with the tramadol-treated groups (LT and TT) showing more prolonged deeper anesthesia. Postoperative sedation was significantly higher in the TT group (p ≤ 0.001). Serotonin concentration decreased in LL, increased in LT, and remained stable in TT. These findings suggest that tramadol may enhance sedation and recovery, potentially through serotonergic modulation. Moreover, serotonin could serve as a physiological marker warranting further investigation in future studies of anesthetic protocols in veterinary medicine. Full article

Background: Mental health issues among medical students have gained increasing attention globally, with studies indicating a high prevalence of psychological disorders within this population. The use of antidepressants and anti-anxiety medications has become a common response to these mental health challenges. However, it is crucial to understand the extent of their usage and associated effects on students’ mental health and academic performance. This cross-sectional study explored the use of antidepressants and anti-anxiety drugs and their impact on the mental health of medical students in Saudi Arabia. Methods: A cross-sectional survey of 561 medical students from 34 universities was conducted between March and July 2024. An anonymous online questionnaire was used to collect sociodemographic, mental health, and medication usage-related information. Results: Most of the participants were female (71.5%) and aged 21–25 years (62.7%). Approximately 23.8% of them used antidepressants, 5.6% reported using anti-anxiety medications, and 14.0% used both types of medication. Among the medication users, 71.7% were using selective serotonin reuptake inhibitors (SSRIs), and 28.3% were using other medications. Adverse drug reactions were reported by 58.8% of the participants, and 39.6% changed drugs with inadequate efficacy. Notably, 49.0% of the respondents who have ever used medications discontinued their medication without consulting a healthcare professional. Despite these challenges, 62.0% of the participants felt that their medications had a positive impact on their academic performance, 73.4% believed that the benefits outweighed the drawbacks, and 76.2% expressed a willingness to continue taking their medication. In particular, 77.6% agreed that treatment with these drugs could prevent mental breakdowns. Sleep duration, physical activity, and family history of psychiatric disorders were significantly associated with medication use, with p values of 0.002, 0.014, and 0.042, respectively. Conclusions: These results shed light on the need to understand the prescribing practices of antidepressant and anti-anxiety drugs among medical students while promoting the appropriate use of these medications among the students. There is a need to incorporate mental health interventions into counseling services and awareness programs to support students. Future longitudinal studies are needed to explore long-term trends. Full article

Background/Objectives: Selective serotonin reuptake inhibitors (SSRIs), widely prescribed for anxiety disorders, may negatively impact the gut microbiota, contributing to dysbiosis. Considering the gut–brain axis’s importance in mental health, probiotics could represent an effective adjunctive strategy. This study evaluated the effects of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on microbiota composition, metabolic activity, and immune markers in fecal samples from patients with anxiety on SSRIs, using the SHIME^® (Simulator of the Human Intestinal Microbial Ecosystem) model. Methods: The fecal microbiotas of four patients using sertraline or escitalopram were inoculated in SHIME^® reactors simulating the ascending colon. After stabilization, a 14-day probiotic intervention was performed. Microbial composition was assessed by 16S rRNA sequencing. Short-chain fatty acids (SCFAs), ammonia, and GABA were measured, along with the prebiotic index (PI). Intestinal barrier integrity was evaluated via transepithelial electrical resistance (TEER), and cytokine levels (IL-6, IL-8, IL-10, TNF-α) were analyzed using a Caco-2/THP-1 co-culture system. The statistical design employed in this study for the analysis of prebiotic index, metabolites, intestinal barrier integrity and cytokines levels was a repeated measures ANOVA, complemented by post hoc Tukey’s tests to assess differences across treatment groups. For the 16S rRNA sequencing data, alpha diversity was assessed using multiple metrics, including the Shannon, Simpson, and Fisher indices to evaluate species diversity, and the Chao1 and ACE indices to estimate species richness. Beta diversity, which measures microbiota similarity across groups, was analyzed using weighted and unweighted UniFrac distances. To assess significant differences in beta diversity between groups, a permutational multivariate analysis of variance (PERMANOVA) was performed using the Adonis test. Results: Probiotic supplementation increased Bifidobacterium and Lactobacillus, and decreased Klebsiella and Bacteroides. Beta diversity was significantly altered, while alpha diversity remained unchanged. SCFA levels increased after 7 days. Ammonia levels dropped, and PI values rose. TEER values indicated enhanced barrier integrity. IL-8 and TNF-α decreased, while IL-6 increased. GABA levels remained unchanged. Conclusions: The probiotic combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 modulated gut microbiota composition, metabolic activity, and inflammatory responses in samples from individuals with anxiety on SSRIs, supporting its potential as an adjunctive strategy to mitigate antidepressant-associated dysbiosis. However, limitations—including the small pooled-donor sample, the absence of a healthy control group, and a lack of significant GABA modulation—should be considered when interpreting the findings. Although the SHIME^® model is considered a gold standard for microbiota studies, further clinical trials are necessary to confirm these promising results. Full article

Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This review explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective of this review is to elucidate how seizures disrupt critical physiological systems, especially the brainstem, heart, and lungs, contributing to SUDEP, with emphasis on respiratory control failure and autonomic instability. Methods: The literature from experimental models, clinical observations, neuroimaging studies, and genetic analyses was systematically examined. Results: SUDEP is frequently preceded by generalized tonic–clonic seizures, which trigger central and obstructive apnea, hypoventilation, and cardiac arrhythmias. Brainstem dysfunction, particularly in areas such as the pre-Bötzinger complex and nucleus tractus solitarius, plays a central role. Genetic mutations affecting ion channels (e.g., SCN1A, KCNQ1) and neurotransmitter imbalances (notably serotonin and GABA) exacerbate autonomic dysregulation. Risk is compounded by a prone sleeping position, reduced arousal capacity, and impaired ventilatory responses. Conclusions: SUDEP arises from a cascade of interrelated failures in respiratory and cardiac regulation initiated by seizure activity. The recognition of modifiable risk factors, implementation of monitoring technologies, and targeted therapies such as serotonergic agents may reduce mortality. Multidisciplinary approaches integrating neurology, cardiology, and respiratory medicine are essential for effective prevention strategies. Full article

The serotonergic system, originating in the raphe nuclei, differentially modulates the dorsal and ventral hippocampus, which are implicated in cognition and emotion, respectively. Emerging evidence from rodent models (e.g., neonatal ventral hippocampal lesion, pharmacological NMDA receptor antagonist exposure) and human postmortem studies indicates dorsoventral serotonergic alterations in schizophrenia. These data include elevated 5-HT1A receptor expression in the dorsal hippocampus, linking serotonergic hypofunction to cognitive deficits, and hyperactive 5-HT2A/3 receptor signaling and denser serotonergic innervation in the ventral hippocampus driving local hyperexcitability associated with psychosis and stress responsivity. These dorsoventral serotonergic alterations are shown to disrupt the excitation–inhibition balance, impair synaptic plasticity, and disturb network oscillations, as established by in vivo electrophysiology and functional imaging. Synthesizing these multi-level findings, we propose a novel “dorsoventral serotonin imbalance” model of schizophrenia, in which ventral hyperactivation predominantly contributes to psychotic symptoms and dorsal hypoactivity underlies cognitive deficits. We further highlight promising preclinical evidence that selective targeting of region- and receptor-specific targeting, using both pharmacological agents and emerging delivery technologies, may offer novel therapeutic opportunities enabling symptom-specific strategies in schizophrenia. Full article

The gut microbiota and its interaction with the nervous system through the gut–brain axis (MGB) have been the subject of growing interest in biomedical research. It has been proposed that modulation of microbiota using probiotics could offer a promising therapeutic alternative for mood regulation and the treatment of anxiety and depression disorders. The findings indicate that several probiotic strains, such as Lactobacillus and Bifidobacterium, have demonstrated anxiolytic and antidepressant effects in pre and clinical studies. These effects seem to be mediated by the regulation of the hypothalamic–pituitary–adrenal axis (HPA), the synthesis of neurotransmitters such as serotonin (5-HT) and Gamma-amino-butyric acid (GABA), as well as the modulation of systemic inflammation. However, the lack of standardization in dosing and strain selection, in addition to the scarcity of large-scale clinical studies, limit the applicability of these findings in clinical therapy. Additional research is required to establish standardized therapeutic protocols and better understand the role of probiotics in mental health. The aim of this narrative review is to discuss the relationship between the gut microbiota and the MGB axis in the context of anxiety and depression disorders, the underlying neurobiological mechanisms, as well as the preclinical evidence for the effect of probiotics in modulating these disorders. In this way, an exhaustive search was carried out in scientific databases including PubMed, ScienceDirect, Scopus, and Web of Science. Preclinical research evaluating the effects of different probiotic strains in animal models during chronic treatment was selected, excluding those studies that did not provide access to the full text. Full article

Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impressions include personification of an unknown presence, strong chest pressure sensation, and intense fear resulting from subjective interaction with the unfolding nightmare. While the mechanism underlying skeletal muscle atonia is known, the physiology of hallucinations remains unclear. Their complex etiology involves interactions among various membrane receptor systems and neurotransmitters, which leads to altered neuronal functionality and disruptions in sensory perception. According to current knowledge, serotonergic activation of 5-hydroxytryptamine-receptor-2A (5-HT2A)-associated pathways plays a critical role in promoting hallucinogenesis during SP. Furthermore, they share similarities with psychedelic-substance-induced ones (i.e., LSD, psilocybin, and 2,5-dimethoxy-4-iodoamphetamine). These compounds also target the 5-HT2A receptor; however, their molecular mechanism varies from serotonin-induced ones. The current review discusses the intracellular signaling pathways responsible for promoting hallucinations in SP, highlighting the critical role of β-arrestin-2. We propose that the β-arrestin-2 signaling pathway does not directly induce hallucinations but creates a state of network susceptibility that facilitates their abrupt emergence in sensory areas. Understanding the molecular basis of serotonergic hallucinations and gaining better insight into 5-HT2A-receptor-dependent pathways may prove crucial in the treatment of multifactorial neuropsychiatric disorders associated with the dysfunctional activity of serotonin receptors. Full article

Hypoxia can adversely affect multiple organ systems. This study investigated the impact of intermittent hypoxia on serotonin levels and depression-like behaviors across distinct neuroanatomical regions. Sixteen adult female Wistar albino rats were divided into two groups: control (n = 8) and hypoxia (n = 8). The hypoxia group was exposed to a simulated altitude of 3000 for 5 h daily over 14 days. Behavioral assessments included locomotor activity (open field test) and depression-like behaviors (forced swimming test). Serotonin levels were quantified via ELISA in the prefrontal cortex, striatum, thalamus, hypothalamus, hippocampus, and serum. Intermittent hypoxia did not alter locomotor activity (p > 0.05) but significantly increased depression-like behavior (p < 0.05), accompanied by a pronounced reduction in swimming behavior (p < 0.0001), a marker associated with serotonergic function. Serotonin levels were significantly reduced in the prefrontal cortex (p < 0.005) and striatum (p < 0.05), while no changes were observed in other regions or serum (p > 0.05). These findings demonstrate that intermittent hypoxia induces depression-like behaviors and region-specific serotonin depletion, particularly in the prefrontal cortex and striatum. This underscores the need to evaluate hypoxia-related brain health implications in conditions such as sleep apnea and acute mountain sickness. Full article

Depression in cancer survivors is commonly treated with serotonin and norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine. These drugs alleviate depressive symptoms by inhibiting the reuptake of serotonin and norepinephrine. However, a novel approach has emerged with the development of trans-2-phenylcyclopropylamine (PCPA)–drug conjugates that inhibit lysine-specific demethylase 1 (LSD1), which is a biomarker and molecular target for cancer therapy. LSD1 inhibition can effectively suppress cancer cell proliferation. Nuc01 is a novel PCPA–drug conjugate designed as a prodrug of venlafaxine. In vivo studies showed that Nuc01 dose-dependently reduced immobility time in the tail suspension test in mice, outperforming desmethylvenlafaxine. This suggests that Nuc01 may act as a potent triple reuptake inhibitor, potentially offering enhanced efficacy in the treatment of depression. Additionally, in vitro studies demonstrated that Nuc01 effectively occupies the PCPA binding site within LSD1 (IC₅₀ = 530 nm) and inhibits the proliferation of MDA-MB-231 cancer cells (IC₅₀ = 1130 nm). These findings suggest that Nuc01 may function as an LSD1 inhibitor with potential anticancer properties. Collectively, the data indicate that Nuc01 appears to exhibit dual functional characteristics: acting as a triple reuptake inhibitor potentially applicable for depression treatment and as an LSD1 inhibitor demonstrating anticancer potential. Full article

Background: Anabolic–androgenic steroids (AASs) are commonly used for performance enhancement but have been linked to significant neurobiological consequences. This review explores the impact of AASs on neurochemical pathways, cognitive function, and psychiatric disorders, highlighting their potential neurotoxicity. Methods: A narrative review of current literature was conducted to examine AASs-induced alterations in neurotransmitter systems, structural and functional brain changes, and associated psychiatric conditions. The interplay between AASs use and other substances was also considered. Results: Chronic AASs exposure affects serotonin and dopamine systems, contributing to mood disorders, aggression, and cognitive deficits. Structural and functional changes in the prefrontal cortex and limbic regions suggest long-term neurotoxicity. AASs use is associated with increased risks of depression, anxiety, and psychosis, potentially driven by hormonal dysregulation and neuroinflammation. Co-occurring substance use exacerbates neurocognitive impairments and behavioral disturbances. Discussion: While evidence supports the link between AASs use and neurotoxicity, gaps remain in understanding the precise mechanisms and long-term effects. Identifying biomarkers of brain damage and developing targeted interventions are crucial for mitigating risks. Increased awareness among medical professionals and policymakers is essential to address AASs-related neuropsychiatric consequences. Conclusions: AASs abuse poses significant risks to brain health, necessitating further research and prevention efforts. Evidence-based strategies are needed to educate the public, enhance early detection, and develop effective interventions to reduce the neuropsychiatric burden of AASs use. Full article

Serotoninomics is an expanding field that focuses on the comprehensive study of the serotoninergic system, including serotonin’s biosynthesis, metabolism, and regulation, as well as related scientific methodologies 5-hydroxytryptamine (5-HT). This field explores serotonin’s complex roles in various physiological and pathological contexts. The essential amino acid tryptophan (Trp) is a precursor for several metabolic and catabolic pathways, with the kynurenine (KYN) pathway being particularly significant, representing about 95% of Trp metabolism. In contrast, only a small portion (1–2%) of dietary Trp enters the serotonin pathway. Anthranilic acid (AA), a metabolite in the KYN pathway, has emerged as a potential biomarker and therapeutic target for schizophrenia. Elevated serum AA levels in patients with schizophrenia have been associated with neurotoxic effects and disruptions in neurotransmission, suggesting AA’s critical role in the disorder’s pathophysiology. Furthermore, the 5-HT_2A receptor’s involvement is particularly noteworthy, especially in relation to schizophrenia’s positive symptoms. Recent findings indicate that 5-HT_2A receptor hyperactivity is linked to positive symptoms of schizophrenia, such as hallucinations and delusions. This study investigates serotoninomics’ implications for neuropsychiatric disorders, focusing on AA in schizophrenia and analysing recent research on serotonin signalling pathways and AA’s neurochemical effects. Understanding the roles of the 5-HT_2A receptor and AA in neuropsychiatric disorders could lead to the development of more precise and less invasive diagnostic tools, specific therapeutic strategies, and improved clinical outcomes. Ongoing research is essential to uncover these pathways’ exact mechanisms and therapeutic potential, thereby advancing personalised medicine and innovative treatments in neuropsychiatry. Full article

Background: Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder characterized by recurrent episodes of intense nausea and vomiting. Despite increasing awareness, a standardized treatment approach remains lacking in pediatric populations. Lifestyle factors and anxiety are common triggers, yet their systematic management has not been fully incorporated into therapeutic strategies. Objective: To evaluate the effectiveness of lifestyle modifications and selective serotonin reuptake inhibitors (SSRIs) in the management of pediatric CVS and to compare their outcomes with standard cyproheptadine prophylaxis. Methods: This retrospective study included 119 patients aged 1.2–17.5 years who were diagnosed with CVS according to Rome IV criteria between September 2021 and January 2025. Clinical, psychiatric, and lifestyle data were retrieved from the university’s digital medical records. Patients were grouped according to treatment modality: cyproheptadine, SSRI, or acute attack management alone. Treatment success at 12 weeks was defined as complete cessation of vomiting episodes or absence of hospitalization, prolonged attacks, and school/work absenteeism. Results: Anxiety symptoms were present in 78.2% of patients. SSRIs were prescribed to 34 patients with moderate to severe anxiety, all of whom achieved treatment success. Lifestyle adherence was observed in 73.9% and was found to be a predictor of treatment success. Cyproheptadine was administered to 66 patients but did not provide additional benefit over effective lifestyle modification. Six patients discontinued cyproheptadine due to drowsiness or weight gain. Conclusions: Lifestyle interventions significantly improve outcomes in pediatric CVS. SSRIs represent a safe and effective prophylactic option for patients with comorbid anxiety or poor adherence to behavioral recommendations. These findings support the integration of psychosocial and lifestyle-based strategies into standard CVS treatment protocols. Full article