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17 pages, 2624 KiB  
Article
Cerebral Hemodynamics as a Diagnostic Bridge Between Mild Cognitive Impairment and Late-Life Depression: A Multimodal Approach Using Transcranial Doppler and MRI
by Sergiu-Florin Arnautu, Diana-Aurora Arnautu, Minodora Andor, Cristina Vacarescu, Dragos Cozma, Brenda-Cristina Bernad, Catalin Juratu, Adrian Tutelca and Catalin-Dragos Jianu
Life 2025, 15(8), 1246; https://doi.org/10.3390/life15081246 - 6 Aug 2025
Abstract
Background: Vascular dysfunction is increasingly recognized as a shared contributor to both cognitive impairment and late-life depression (LLD). However, the combined diagnostic value of cerebral hemodynamics, neuroimaging markers, and neuropsychological outcomes remains underexplored. This study aimed to investigate the associations be-tween transcranial Doppler [...] Read more.
Background: Vascular dysfunction is increasingly recognized as a shared contributor to both cognitive impairment and late-life depression (LLD). However, the combined diagnostic value of cerebral hemodynamics, neuroimaging markers, and neuropsychological outcomes remains underexplored. This study aimed to investigate the associations be-tween transcranial Doppler (TCD) ultrasound parameters, cognitive performance, and depressive symptoms in older adults with mild cognitive impairment (MCI) and LLD. Importantly, we evaluated the integrative value of TCD-derived indices alongside MRI-confirmed white matter lesions (WMLs) and standardized neurocognitive and affective assessments. Methods: In this cross-sectional study, 96 older adults were enrolled including 78 cognitively unimpaired individuals and 18 with MCI. All participants underwent structured clinical, neuropsychological, and imaging evaluations including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS-15), MRI-based Fazekas scoring of WMLs, and TCD ultrasonography of the middle cerebral artery. Hemodynamic variables included mean blood flow velocity (MBFV), end-diastolic velocity (EDV), pulsatility index (PI), and resistive index (RI). Logistic regression and receiver operating characteristic (ROC) analyses were used to identify independent predictors of MCI. Results: Participants with MCI showed significantly lower MBFV and EDV, and higher PI and RI (p < 0.05 for all) compared with cognitively unimpaired participants. In multivariate analysis, lower MBFV (OR = 0.64, p = 0.02) and EDV (OR = 0.70, p = 0.03), and higher PI (OR = 3.2, p < 0.01) and RI (OR = 1.9, p < 0.01) remained independently associated with MCI. ROC analysis revealed excellent discriminative performance for RI (AUC = 0.919) and MBFV (AUC = 0.879). Furthermore, PI correlated positively with depressive symptom severity, while RI was inversely related to the GDS-15 scores. Conclusions: Our findings underscore the diagnostic utility of TCD-derived hemodynamic parameters—particularly RI and MBFV—in identifying early vascular contributions to cognitive and affective dysfunction in older adults. The integration of TCD with MRI-confirmed WML assessment and standardized cognitive/mood measures represents a novel and clinically practical multi-modal approach for neurovascular profiling in aging populations. Full article
(This article belongs to the Special Issue Intracerebral Hemorrhage: Advances and Perspectives)
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12 pages, 738 KiB  
Article
Impact of the COVID-19 Pandemic on the Emotional Health of Children Under 6 Years in Washington, DC
by Tom Kariyil, Miranda Gabriel, Kavya Sanghavi and Elizabeth M. Chawla
Children 2025, 12(8), 981; https://doi.org/10.3390/children12080981 - 26 Jul 2025
Viewed by 231
Abstract
Background/Objective: A growing body of international research continues to show evidence of worsening youth mental health since the beginning of the COVID-19 global pandemic, yet very little research in this area has included young children under 6 years. Given the potential impact of [...] Read more.
Background/Objective: A growing body of international research continues to show evidence of worsening youth mental health since the beginning of the COVID-19 global pandemic, yet very little research in this area has included young children under 6 years. Given the potential impact of early life stress during this critical period of development, it is crucial to better understand the effects on this age group. The objective of this study was to better understand the impact of the COVID-19 pandemic on the emotional health of very young children. Methods: This study utilized retrospective chart review of primary care records to compare the prevalence of markers of stress in two cohorts of children under the age of 6 years, comparing children presenting for care prior to the pandemic (1 April 2019–31 March 2020; control period) with those presenting for care during the first year of the pandemic (1 April 2020–31 March 2021; study period) in a large pediatric primary care clinic in Washington, DC, USA. Based on power calculations, charts of 200 patients from each cohort were reviewed and prevalence of stress markers were summarized using counts and percentages and compared between groups using chi-squared tests. Multivariable logistic regression models were also conducted for each domain adjusting for age, gender, and insurance type. Results: Overall, sleep difficulties were significantly more prevalent during the pandemic period compared to the control period (14% vs. 6.5%, p = 0.013). In addition, signs of stress presented differently across age groups. For example, during the pandemic period toddlers (13–35 months) were 13 times more likely (OR = 13, 95% CI [2.82, 60.4], p < 0.001) and preschool-aged children (36–71 months) were 18.5 times more likely (OR = 18.5, 95% CI [4.0, 86], p < 0.001) than infants to present with behavior problems, indicating substantially higher risk of externalizing symptoms in older children compared to infants. Toddlers were less likely than infants to present with mood changes (e.g., fussiness or crying) (OR = 0.15, 95% CI [0.03, 0.65], p = 0.011). In addition, toddlers (OR = 0.55, 95% CI [0.31, 0.97], p = 0.038) and preschool-aged children (OR = 0.15, 95% CI [0.06, 0.4], p < 0.001) were also less likely to present with feeding difficulties compared to infants. Conclusions: One of the very few studies of young children under 6 years (including infants) during the COVID-19 pandemic, this study found that even very young children experienced stress during the pandemic. Signs of emotional stress were identified in a primary care office during routine care, highlighting an important opportunity for early intervention and/or prevention, such as counseling and resources for caregivers, in settings where young children are already presenting for routine care. Full article
(This article belongs to the Special Issue Stress and Stress Resilience in Children and Adolescents: 2nd Edition)
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31 pages, 5415 KiB  
Review
Psychopharmacological Therapy Positively Modulates Disease Activity in Inflammatory Bowel Disease: A Systematic Review
by Federica Di Vincenzo, Antonio Maria D’Onofrio, Angelo Del Gaudio, Elena Chiera, Gaspare Filippo Ferrajoli, Francesco Pesaresi, Alessio Simonetti, Marianna Mazza, Georgios Demetrios Kotzalidis, Mauro Pettorruso, Giovanni Martinotti, Loris Riccardo Lopetuso, Antonio Gasbarrini, Gabriele Sani, Gionata Fiorino, Franco Scaldaferri and Giovanni Camardese
Int. J. Mol. Sci. 2025, 26(13), 6514; https://doi.org/10.3390/ijms26136514 - 6 Jul 2025
Viewed by 884
Abstract
Depression, anxiety, and perceived stress are common comorbidities in patients with inflammatory bowel disease (IBD) and may negatively influence the disease course. Likewise, severe IBD may contribute to the development or worsening of psychiatric symptoms. Despite the established relevance of the gut–brain axis [...] Read more.
Depression, anxiety, and perceived stress are common comorbidities in patients with inflammatory bowel disease (IBD) and may negatively influence the disease course. Likewise, severe IBD may contribute to the development or worsening of psychiatric symptoms. Despite the established relevance of the gut–brain axis and frequent use of psychotropic medications in IBD patients, limited evidence exists regarding the effects of psychiatric treatments on gastrointestinal disease activity. Therefore, the aim of this systematic review is to evaluate the effectiveness of psychiatric therapies on gastrointestinal symptoms and disease activity in patients with IBD. The work was conducted in accordance with PRISMA guidelines. Searches were performed across PubMed, Web of Science, and Scopus up to July 2024. Eligible studies evaluated the effectiveness of psychiatric medications—including antidepressants, antipsychotics, anxiolytics, sedative-hypnotics, mood stabilizers, anticonvulsants, and others—on at least one gastrointestinal outcome in patients with IBD. Outcomes included changes in commonly used clinical and endoscopic scores for Crohn’s disease (CD) and ulcerative colitis (UC), number of bowel movements, stool consistency, presence of blood in stool, severity of abdominal pain, as well as in surrogate markers of disease activity following treatment. Out of 8513 initially identified articles, 22 studies involving 45,572 IBD patients met the inclusion criteria. Antidepressants, particularly bupropion, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and duloxetine, were associated with improvements in IBD activity scores, including Crohn’s Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD, Mayo score and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) for UC. Case reports highlighted potential benefits of pregabalin and lithium carbonate, respectively, showed by the reduction in clinical and endoscopic score of disease activity for pregabalin and improvement of UC symptoms for lithium carbonate, while topiramate showed limited efficacy. Clonidine and naltrexone determined the reductions in clinical and endoscopic score of disease activity, including CDAI and Crohn’s disease endoscopy index severity score (CDEIS) for CD and Disease Activity Index (DAI) for UC. Despite the limited data and study heterogeneity, antidepressants, naltrexone, and clonidine were associated with improvements in IBD activity. Larger, prospective studies are needed to confirm the therapeutic potential of psychiatric medications in modulating IBD activity and to guide integrated clinical management. Full article
(This article belongs to the Section Molecular Immunology)
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21 pages, 1089 KiB  
Review
Salivary Biomarkers as a Predictive Factor in Anxiety, Depression, and Stress
by Dana Gabriela Budala, Ionut Luchian, Dragos Ioan Virvescu, Teona Tudorici, Vlad Constantin, Zinovia Surlari, Oana Butnaru, Dan Nicolae Bosinceanu, Cosmin Bida and Monica Hancianu
Curr. Issues Mol. Biol. 2025, 47(7), 488; https://doi.org/10.3390/cimb47070488 - 26 Jun 2025
Viewed by 1012
Abstract
Anxiety and depression are highly prevalent mental health disorders often associated with dysregulation of neuroendocrine and immune systems, particularly the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic–adrenal–medullary (SAM) system. Recent research highlights the potential of salivary biomarkers to serve as non-invasive indicators for psychological [...] Read more.
Anxiety and depression are highly prevalent mental health disorders often associated with dysregulation of neuroendocrine and immune systems, particularly the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic–adrenal–medullary (SAM) system. Recent research highlights the potential of salivary biomarkers to serve as non-invasive indicators for psychological distress. This narrative review synthesizes current evidence on key salivary biomarkers, cortisol, alpha-amylase (sAA), secretory immunoglobulin A (sIgA), chromogranin A (CgA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), brain-derived neurotrophic factor (BDNF), and salivary microRNAs (miRNAs), in relation to anxiety, depression, and stress. A comprehensive literature search (2010–2025) was conducted using multiple databases and relevant MeSH terms. The review reveals consistent associations between these salivary analytes and stress-related disorders, reflecting changes in neuroendocrine activity, immune response, and neuroplasticity. Cortisol and sAA mirror acute stress reactivity, while cytokines and CRP indicate chronic inflammation. BDNF and miRNAs provide insight into neuroplastic dysfunction and gene regulation. Despite promising results, limitations such as variability in sampling methods and biomarker specificity remain. In conclusion, salivary biomarkers offer a promising avenue for early detection, monitoring, and personalization of treatment in mood and anxiety disorders. Conclusions: Cortisol and alpha-amylase serve as the principal markers of acute stress response, whereas cytokines such as IL-6 and TNF-α, together with CRP, indicate chronic inflammation associated with extended emotional distress. Full article
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32 pages, 704 KiB  
Review
A Comprehensive Scoping Review on Diet and Nutrition in Relation to Long COVID-19 Symptoms and Recovery
by Galya Bigman, Marius Emil Rusu, Nicole Shelawala, John D. Sorkin, Brock A. Beamer and Alice S. Ryan
Nutrients 2025, 17(11), 1802; https://doi.org/10.3390/nu17111802 - 26 May 2025
Cited by 2 | Viewed by 2316
Abstract
Background/Objectives: Long COVID-19 is characterized by persistent symptoms lasting three months or more following SARS-CoV-2 infection. Nutrition has emerged as a modifiable factor influencing recovery trajectories and symptom burden; however, existing evidence remains fragmented across diverse study designs and populations. This scoping review [...] Read more.
Background/Objectives: Long COVID-19 is characterized by persistent symptoms lasting three months or more following SARS-CoV-2 infection. Nutrition has emerged as a modifiable factor influencing recovery trajectories and symptom burden; however, existing evidence remains fragmented across diverse study designs and populations. This scoping review synthesized global evidence on the role of diet and nutrition in managing long COVID-19 symptoms and supporting recovery. Methods: Following PRISMA-ScR and Joanna Briggs Institute guidelines for scoping reviews, we searched major biomedical databases for studies published between 2020 and 2025. Eligible studies examined dietary intake, nutritional status, or nutrition-related interventions in adults with long COVID-19. Results: After duplicates were removed, 1808 records were screened, resulting in 50 studies that met the inclusion criteria—27 intervention studies and 23 observational studies. Nutritional exposures included micronutrients (e.g., vitamins D, K2), amino acids (e.g., L-arginine), multinutrient formulations, microbiota-targeted therapies (e.g., probiotics, synbiotics), nutritional status, diet quality, and whole-diet patterns (e.g., the Mediterranean diet). Approximately 76% of studies reported improvements in long COVID-19-related symptoms such as fatigue, mood disturbances, physical function, and markers of inflammation. Conclusions: Diet and nutrition may support long COVID-19 recovery by targeting inflammation and the gut microbiome to alleviate symptoms and improve functional outcomes. Well-powered trials of whole-diet approaches, combined with targeted supplementation, are needed to confirm their potential as scalable, accessible tools for post-COVID-19 recovery and management. Full article
(This article belongs to the Section Nutritional Epidemiology)
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16 pages, 1423 KiB  
Article
Frontal Transcranial Direct Current Stimulation in Moderate to Severe Depression: Clinical and Neurophysiological Findings from a Pilot Study
by Florin Zamfirache, Gabriela Prundaru, Cristina Dumitru and Beatrice Mihaela Radu
Brain Sci. 2025, 15(6), 540; https://doi.org/10.3390/brainsci15060540 - 22 May 2025
Viewed by 903
Abstract
Background/Objectives: Transcranial Direct Current Stimulation (tDCS) has proven to be a promising intervention for major depressive disorder (MDD). Even so, the specific neurophysiological mechanisms underlying its therapeutic effects, particularly regarding frontal EEG markers, remain insufficiently understood. This pilot study investigated both the [...] Read more.
Background/Objectives: Transcranial Direct Current Stimulation (tDCS) has proven to be a promising intervention for major depressive disorder (MDD). Even so, the specific neurophysiological mechanisms underlying its therapeutic effects, particularly regarding frontal EEG markers, remain insufficiently understood. This pilot study investigated both the clinical efficacy and neurophysiological impact of frontal tDCS in individuals with mild to severe depression, with particular focus on mood changes and alterations in Frontal Alpha Asymmetry (FAA), Beta Symmetry, and Theta/Alpha Ratios at the F3 and F4 electrode sites. Methods: A total of thirty–one participants were enrolled and completed a standardized Flow Neuroscience tDCS protocol targeting the dorsolateral prefrontal cortex using a bilateral F3/F4 montage. The intervention included an active phase of five stimulations per week for three weeks, followed by a Strengthening Phase with two stimulations per week. Clinical outcomes were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS), while neurophysiological changes were evaluated via standardized quantitative EEG (QEEG) recordings obtained before and after the treatment course. Among the participants, fourteen individuals had a baseline MADRS score of ≥20, indicating moderate to severe depressive symptoms. Results: Following tDCS treatment, significant reductions in MADRS scores were observed across the cohort, with clinical response rates notably higher in the moderate/severe group (71.4%) compared to the mild depression group (20.0%). Neurophysiological effects were modest: no significant changes were detected in FAA or Beta Symmetry measures. However, a substantial reduction in the Theta/Alpha Ratio at F4 was found in participants with moderate to severe depression (p = 0.018, Cohen’s d = −0.72), suggesting enhanced frontal cortical activation associated with clinical improvement. Conclusions: These findings indicate that frontal tDCS is effective in reducing depressive symptoms, particularly in cases of moderate to severe depression. While improvements in FAA and Beta Symmetry were not significant, changes in the Theta/Alpha Ratio at F4 point toward dynamic neurophysiological reorganization potentially linked to therapeutic outcomes. The Theta/Alpha Ratio may serve as a promising biomarker for tracking tDCS response, whereas other EEG metrics might represent more stable trait characteristics. Future research should prioritize individualized stimulation protocols and incorporate more sensitive neurophysiological assessments, including functional connectivity analyses and task-evoked EEG paradigms, to understand the mechanisms underlying clinical improvements. Full article
(This article belongs to the Special Issue Advances in Non-Invasive Brain Stimulation)
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25 pages, 2404 KiB  
Article
Network Pharmacology-Guided Evaluation of Ginger and Cornelian Cherry Extracts Against Depression and Metabolic Dysfunction in Estrogen-Deficient Chronic Stressed Rats
by Nara Lee, Ting Zhang, Hanbin Joe and Sunmin Park
Int. J. Mol. Sci. 2025, 26(10), 4829; https://doi.org/10.3390/ijms26104829 - 18 May 2025
Viewed by 893
Abstract
This study investigated the therapeutic effects of water extracts from Zingiber officinale Roscoe (ginger) and Cornus officinalis Siebold and Zucc. fruits (COF) water extracts on depression-like behavior and metabolic dysfunction in estrogen-deficient rats exposed to chronic mild stress (CMS). Network pharmacology analysis identified [...] Read more.
This study investigated the therapeutic effects of water extracts from Zingiber officinale Roscoe (ginger) and Cornus officinalis Siebold and Zucc. fruits (COF) water extracts on depression-like behavior and metabolic dysfunction in estrogen-deficient rats exposed to chronic mild stress (CMS). Network pharmacology analysis identified three bioactive compounds in ginger and four in COF, with 11 overlapping targets linked to both depression and metabolic pathways, primarily involving NR3C1, HTR2A, MAOA, and SLC6A4 genes associated with hypothalamic–pituitary–adrenal (HPA) axis regulation and neurotransmitter modulation. Ovariectomized rats received 200 mg/kg/day of ginger or COF extracts for 7 weeks, with a 4-week CMS protocol initiated at week 3. Both extracts significantly improved depression-like behaviors, memory performance, glucose tolerance, lipid profiles, and bone mineral density, normalized HPA axis markers (corticosterone and ACTH), and increased hippocampal serotonin and dopamine levels. Ginger demonstrated greater efficacy in improving memory and metabolic outcomes compared to COF. Molecular docking further validated these findings, revealing strong and stable interactions between key phytochemicals—such as hydroxygenkwanin and telocinobufagin—and target proteins MAOA, HTR2A, and NR3C1, supporting their mechanistic role in stress and mood regulation. These results support supplementing ginger and COF extracts as promising botanical interventions for estrogen-deficiency-related mood and metabolic disorders, with potential clinical application at a human-equivalent dose of 1.5 g/day. Full article
(This article belongs to the Special Issue Medicinal Plants and Bioactive Compounds in Health and Disease)
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19 pages, 1052 KiB  
Review
Nutrition and Neuroinflammation: Are Middle-Aged Women in the Red Zone?
by Veronique Bernier, Angeline Chatelan, Camille Point and Mélanie Strauss
Nutrients 2025, 17(10), 1607; https://doi.org/10.3390/nu17101607 - 8 May 2025
Viewed by 2376
Abstract
Women exhibit unique vulnerabilities in health, especially regarding mental health and neurodegenerative diseases. Biological, hormonal, and metabolic differences contribute to sex-specific risks that remain underrepresented in clinical studies. Diseases such as major depressive disorder (MDD) and Alzheimer’s disease (AD) are more prevalent in [...] Read more.
Women exhibit unique vulnerabilities in health, especially regarding mental health and neurodegenerative diseases. Biological, hormonal, and metabolic differences contribute to sex-specific risks that remain underrepresented in clinical studies. Diseases such as major depressive disorder (MDD) and Alzheimer’s disease (AD) are more prevalent in women and may be influenced by hormonal transitions, particularly during menopause. Chronic low-grade inflammation is emerging as a shared mechanism underlying both conditions, and this inflammatory state can be worsened by dietary habits. During menopause, mood and sleep disturbances can influence dietary behavior, leading to enhanced snacking and consumption of high-glycemic and comfort foods. Such foods, low in nutritional value, promote weight gain and elevated inflammatory markers. Their consumption combined (or not) with a preexisting Western diet pattern—already linked to inflammation—could reinforce systemic inflammation involving the gut–brain axis. Moreover, the symptoms “per se” could act on inflammation as well. Peripheral inflammation may cross the blood–brain barrier, sustaining mood disorders and promoting neurodegenerative changes. Finally, MDD and AD are both associated with conditions such as obesity and diabetes, which occur more frequently in women. The review highlights how menopause-related changes in mood, sleep, and diet may heighten susceptibility to mental and neurodegenerative diseases. Full article
(This article belongs to the Special Issue Implications of Diet and the Gut Microbiome in Neuroinflammation)
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12 pages, 254 KiB  
Article
Beyond “Fire” and “Ashes”: The Influence of Trait Characteristics on the Response to Mood Stabilizers in Bipolar Disorders
by Alfonso Tortorella, Francesca Scopetta, Gianmarco Cinesi, Ilaria Baldini, Antonio Russo, Kety Amantini, Filippo De Giorgi and Giulia Menculini
Brain Sci. 2025, 15(5), 490; https://doi.org/10.3390/brainsci15050490 - 7 May 2025
Viewed by 534
Abstract
Background: The present study aimed to investigate the clinical correlates of treatment response to mood stabilizers in patients with bipolar disorder (BD), with a specific focus on trait-related characteristics such as impulsivity and affective temperaments. Methods: In- and outpatients diagnosed with BD were [...] Read more.
Background: The present study aimed to investigate the clinical correlates of treatment response to mood stabilizers in patients with bipolar disorder (BD), with a specific focus on trait-related characteristics such as impulsivity and affective temperaments. Methods: In- and outpatients diagnosed with BD were recruited at the Section of Psychiatry of the General Hospital/University of Perugia. Socio-demographic, clinical, and current psychopathological characteristics were collected. The treatment response was retrospectively assessed using the Alda Scale. Trait characteristics were evaluated through the Barratt Impulsiveness Scale (BIS-11) and the Brief Temperament Evaluation of Memphis, Pisa, and San Diego—Münster version (briefTEMPS-M). Bivariate analyses and a general linear model were employed to analyze the correlates of treatment response to mood stabilizers. Results: Among the investigated variables, trait impulsivity showed a significant negative association with treatment response. A similar effect was observed for depressive temperament, while other affective temperaments were not significantly associated with treatment outcomes. Patients with good treatment responses exhibited higher illness duration and lower severity of BD, higher prevalence of comorbid anxiety disorders, lower diurnal variation in depressive symptoms, and lower functional impairment in autonomy and occupational domains. The main limitations of this study were represented by the small sample size, the retrospective assessment of treatment response, and the inclusion of patients from a single center. Conclusions: The present findings suggest that impulsivity and depressive temperament should be investigated as potential predictors of poor response to mood stabilizers in BD. These trait dimensions, together with other clinical markers, may serve as useful targets for patient stratification and the development of personalized treatment strategies. Full article
19 pages, 5849 KiB  
Article
Folic Acid Mitigates Sertraline-Induced Liver Damage in Adult Female Albino Rats During Pregnancy and Postpartum: A Biochemical and Histological Study
by Ayman A. Refai, Mohammad I. Jumaa, Einas M. Yousef, Ala M. Aljehani, Rana Ahmed Alduraywish, Mohamed R. Elkabary, Safaa M. Hanafy, Hanan S. Seleem and Eman S. El-Roghy
Medicina 2025, 61(4), 751; https://doi.org/10.3390/medicina61040751 - 18 Apr 2025
Viewed by 852
Abstract
Background and Objectives: Sertraline is a selective serotonin reuptake inhibitor (SSRI) that is frequently prescribed during pregnancy to treat mood disorders. Studies indicate that chronic use of sertraline is associated with elevated liver enzymes, oxidative stress, and histological alterations in the liver. Folic [...] Read more.
Background and Objectives: Sertraline is a selective serotonin reuptake inhibitor (SSRI) that is frequently prescribed during pregnancy to treat mood disorders. Studies indicate that chronic use of sertraline is associated with elevated liver enzymes, oxidative stress, and histological alterations in the liver. Folic acid, a recommended supplement currently used during the first trimester of pregnancy, has antioxidant and anti-inflammatory effects. Hence, folic acid might be a potential protective agent against sertraline-induced liver injury. The current study aimed to investigate the possible hepatotoxic effects of sertraline administration during pregnancy and early postpartum. In addition, we sought to evaluate the potential protective effects of folic acid supplementation in alleviating any sertraline-induced liver damage. Materials and Methods: Eighty pregnant albino rats were randomly divided into four groups: control, folic acid-treated, sertraline-treated, and folic acid–sertraline-treated. Each group was divided into rats euthanized immediately after giving birth (0 h) or 14 days postpartum. Biochemical, histological, and immunohistochemical evaluations of liver function and structure were conducted. Results: Administration of sertraline was associated with a significant increase in hepatic enzymes (ALT and AST) and disrupted lipid profile (elevated cholesterol, triglycerides, and LDL-c) compared to the control group. Increased apoptosis was evidenced by increased caspase 3 expression and histological alterations, including vacuolation and inflammatory infiltrates, in sertraline-treated rats. Folic acid supplementation effectively mitigated these effects by preserving liver architecture, normalizing biochemical markers (ALT, AST, and lipid profile changes), and reducing apoptotic activity (lower caspase 3 expression). Conclusions: Folic acid mitigated sertraline-induced hepatic damage in pregnant rats. This suggests the potential benefits of using folic acid during the whole duration of pregnancy in patients treated with sertraline. Full article
(This article belongs to the Topic Human Anatomy and Pathophysiology, 3rd Edition)
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15 pages, 2092 KiB  
Systematic Review
Non-Severe Hypophosphatemia in Older Patients: A Systematic Review
by Luca Barbarossa, Martina Zandonà, Maria Luisa Garo, Ribal Bou Mjahed and Patrizia D’Amelio
Nutrients 2025, 17(8), 1354; https://doi.org/10.3390/nu17081354 - 16 Apr 2025
Viewed by 1029
Abstract
Background/Objectives: Phosphorus plays a fundamental role in cellular and extracellular metabolism, contributing to nucleic acid synthesis, enzymatic activity, neurologic function, and skeletal mineralization. Despite its significance, non-severe hypophosphatemia (HP) remains largely asymptomatic and underdiagnosed, with limited data on its prevalence in the general [...] Read more.
Background/Objectives: Phosphorus plays a fundamental role in cellular and extracellular metabolism, contributing to nucleic acid synthesis, enzymatic activity, neurologic function, and skeletal mineralization. Despite its significance, non-severe hypophosphatemia (HP) remains largely asymptomatic and underdiagnosed, with limited data on its prevalence in the general population. Most studies focus on specific subgroups, such as critically ill or dialysis patients, while the impact of mild HP in older adults, a potentially vulnerable demographic, is not well understood. The objective of this systematic review is to investigate the prevalence and clinical implications of non-severe HP in older adults. Methods: The study followed PRISMA guidelines to assess HP in patients aged ≥ 65 years without critical illnesses or genetic disorders. A systematic search was conducted in PubMed, Web of Science, and Scopus (March 2024). Eligible studies included RCTs and prospective/retrospective studies, excluding cancer-related studies or insufficient phosphate data. Results: We identified 1350 articles, with 26 meeting eligibility criteria. Ultimately, eight studies involving 26,548 patients were included, with an HP prevalence of 12.5%. Studies reveal a higher prevalence of HP in frail individuals, particularly those with increased frailty scores, and an association between HP and cognitive decline, depressed mood, falls, and chronic comorbidities. HP was also prevalent in infectious diseases, especially bacterial pneumonia, with longer hospital stays and increased mortality rates. Malnutrition was significantly more common in HP patients, characterized by weight loss and poor nutritional status. Furthermore, HP increased fall risk during hospitalization and worsened outcomes after coronary artery bypass graft surgery, including higher mortality and graft failure rates, underscoring its clinical importance. Discussion: This review identified that non-severe hypophosphatemia (HP) is associated with conditions such as frailty, cognitive decline, and an increased risk of falls. The evidence suggests that low phosphate levels may negatively impact health, increasing mortality and the risk of adverse clinical outcomes. Despite limitations in diagnostic criteria and sample variability, the findings indicate that HP can be a useful marker for identifying patients at risk of health deterioration. Further research is needed to clearly define the management and treatment of HP in this vulnerable population. Full article
(This article belongs to the Special Issue Addressing Malnutrition in the Aging Population)
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21 pages, 3647 KiB  
Article
Systemic Responses Towards Oxy-Inflammation, Hormones, and Mood in Breast Cancer Survivors: Preliminary Evidences from Dragon Boat Endurance Race
by Michela Montorsi, Alessandra Vezzoli, Federica Mrakic Sposta, Maristella Gussoni, Andrea Brizzolari, Gerardo Bosco, Cinzia Dellanoce, Alessandra Barassi, Barbara Picconi, Cristina Ranuncoli and Simona Mrakic Sposta
J. Clin. Med. 2025, 14(7), 2532; https://doi.org/10.3390/jcm14072532 - 7 Apr 2025
Cited by 1 | Viewed by 1098
Abstract
Background/Objectives: Endurance exercise increases oxygen demand and, when not balanced by antioxidant defenses, consequently, oxidative stress and inflammatory cytokines increase too. In breast cancer survivors (BCS), post-treatment, physical capacity decreases, lowering life quality. Dragon boat (DB) paddling has shown benefits in reducing lymphedema [...] Read more.
Background/Objectives: Endurance exercise increases oxygen demand and, when not balanced by antioxidant defenses, consequently, oxidative stress and inflammatory cytokines increase too. In breast cancer survivors (BCS), post-treatment, physical capacity decreases, lowering life quality. Dragon boat (DB) paddling has shown benefits in reducing lymphedema and improving psychological well-being. This study aimed at non-invasively investigating in BCS, by means of saliva and urine samples, the systemic responses to oxy-inflammation, and appetite hormones after a DB endurance race. Methods: 15 BCS and 15 healthy women (5 (CTR) who performed the DB race too) were studied. BCS and CTR were monitored pre- and post-race. Reactive oxygen species (ROS) production, total antioxidant capacity (TAC), lipid peroxidation (8-iso), DNA oxidation (8-OH-dG), nitric oxide metabolites (NOx), inflammation markers (IL-6-10 and TNFα), appetite hormones, electrolytes concentration, psychometric, and physical scales were assessed. Results: At rest, compared to healthy women, BCS showed a significant increase in oxy-inflammation biomarkers. BCS showed a general increase in oxy-inflammation parameters compared to CTR after the DB race. In BCS, there were the following results: ROS: +80%; lipid peroxidation: +103%; DNA oxidation: +44%; interleukins-6: +179%; IL-10: +55%; TNFα: +9%, NOx: +60% increases and unbalanced appetite hormones: leptin (−32%); and ghrelin (+53%). Moreover, the dragon boat offered a holistic approach to recovery, addressing emotional and social needs supporting belonging, love, and esteem needs, reported to be about 56% of the motivations in this activity, while post-race the following increased: a sense of fatigue (+55%); tiredness (48%); a cold sensation (+15%); and +32% pain. Conclusions: This study provided evidence that, in BCS, a DB endurance race produces an important imbalance in the oxy-inflammation state, at the same time being accompanied by a positive impact on subjective mood and general wellness. Future studies should focus on long-term effects. Full article
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19 pages, 967 KiB  
Article
Depression in Diarrhea-Predominant IBS Patients: Exploring the Link Between Gut Barrier Dysfunction and Erythrocyte Polyunsaturated Fatty Acid Levels
by Michele Linsalata, Laura Prospero, Antonia Ignazzi, Giuseppe Riezzo, Benedetta D’Attoma, Domenica Mallardi, Francesco Goscilo, Maria Notarnicola, Valentina De Nunzio, Giuliano Pinto and Francesco Russo
J. Clin. Med. 2025, 14(7), 2483; https://doi.org/10.3390/jcm14072483 - 5 Apr 2025
Viewed by 770
Abstract
Background: Patients with irritable bowel syndrome (IBS) often experience comorbid psychological conditions, notably depression and anxiety. Evidence suggests that these conditions are linked to gut barrier dysfunction, dysbiosis, and chronic inflammation. All these factors are central to IBS pathophysiology and mood disturbances. [...] Read more.
Background: Patients with irritable bowel syndrome (IBS) often experience comorbid psychological conditions, notably depression and anxiety. Evidence suggests that these conditions are linked to gut barrier dysfunction, dysbiosis, and chronic inflammation. All these factors are central to IBS pathophysiology and mood disturbances. Polyunsaturated fatty acids (PUFAs) play crucial roles in modulating inflammation and depression. This study examined the associations among intestinal permeability, PUFA profiles, low-grade inflammation, and depression severity in IBS patients with diarrhea (IBS-D). Methods: Forty-three IBS-D patients (7 men, 36 women; 44.56 ± 1.52 years) were categorized into depressed (IBS-D(d+)) and non-depressed (IBS-D(d−)) groups according to scores on the depression subscale of the Symptom Checklist-90-Revised (SCL-90-R). Biomarkers of small intestinal permeability (s-IP) were assessed in urine and blood, alongside erythrocyte membrane PUFA composition, dysbiosis, and inflammation indices. Results: IBS-D (d+) patients exhibited elevated s-IP and altered PUFA metabolism compared to their IBS-D (d−) counterparts. Additionally, in the first group, omega-3 PUFA concentrations inversely correlated with s-IP biomarkers, while the omega-6/omega-3 ratio showed a positive correlation. Moreover, depression severity is significantly associated with s-IP markers and omega-3 PUFA levels. Lastly, IBS-D (d+) patients exhibited higher levels of dysbiosis and pro-inflammatory cytokines than IBS-D (d−) patients. Conclusions: These findings highlight the interplay between intestinal barrier integrity and PUFA metabolism in IBS-D patients with depression, suggesting that s-IP markers and erythrocyte PUFA profiles could represent novel therapeutic targets for managing depression in this population. This study was registered on ClinicalTrials.gov (NCT03423069), with a date of registration of 30 January 2018. Full article
(This article belongs to the Special Issue New Insights into Irritable Bowel Syndrome)
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18 pages, 2553 KiB  
Article
Novel ABCD1 and MTHFSD Variants in Taiwanese Bipolar Disorder: A Genetic Association Study
by Yi-Guang Wang, Chih-Chung Huang, Ta-Chuan Yeh, Wan-Ting Chen, Wei-Chou Chang, Ajeet B. Singh, Chin-Bin Yeh, Yi-Jen Hung, Kuo-Sheng Hung and Hsin-An Chang
Medicina 2025, 61(3), 486; https://doi.org/10.3390/medicina61030486 - 11 Mar 2025
Viewed by 943
Abstract
Background and Objectives: In recent years, bipolar disorder (BD), a multifaceted mood disorder marked by severe episodic mood fluctuations, has been shown to have an impact on disability-adjusted life years (DALYs). The increasing prevalence of BD highlights the need for better diagnostic tools, [...] Read more.
Background and Objectives: In recent years, bipolar disorder (BD), a multifaceted mood disorder marked by severe episodic mood fluctuations, has been shown to have an impact on disability-adjusted life years (DALYs). The increasing prevalence of BD highlights the need for better diagnostic tools, particularly those involving genetic insights. Genetic association studies can play a crucial role in identifying variations linked to BD, shedding light on its genetic underpinnings and potential therapeutic targets. This study aimed to identify novel genetic variants associated with BD in the Taiwanese Han population and to elucidate their potential roles in disease pathogenesis. Materials and Methods: Genotyping was conducted using the Taiwan Precision Medicine Array (TPM Array) on 128 BD patients and 26,122 control subjects. Following quality control, 280,177 single nucleotide polymorphisms (SNPs) were analyzed via chi-square tests, and linkage disequilibrium (LD) analyses were employed to examine the associations among key SNPs. Results: Eleven SNPs reached significance (p < 10−5), with the variant rs11156606 in the ABCD1 gene—implicated in fatty acid metabolism—emerging as a prominent finding. LD analysis revealed that rs11156606 is strongly linked with rs73640819, located in the 3′ untranslated region, suggesting a regulatory role in gene expression. Additionally, rs3829533 in the MTHFSD gene was found to be in strong LD with the missense variants rs3751800 and rs3751801, indicating potential alterations in protein function. Conclusion: These findings enhance the genetic understanding of BD within a Taiwanese cohort by identifying novel risk-associated variants and support the potential for using these markers in early diagnosis and targeted therapeutic strategies. Full article
(This article belongs to the Section Psychiatry)
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35 pages, 1868 KiB  
Review
Impact of Vegan and Vegetarian Diets on Neurological Health: A Critical Review
by Vicente Javier Clemente-Suárez, Laura Redondo-Flórez, Alexandra Martín-Rodríguez, Agustín Curiel-Regueros, Alejandro Rubio-Zarapuz and José Francisco Tornero-Aguilera
Nutrients 2025, 17(5), 884; https://doi.org/10.3390/nu17050884 - 28 Feb 2025
Cited by 6 | Viewed by 19121
Abstract
Background/Objectives: The global shift towards vegan and vegetarian diets has garnered attention for their ethical, environmental, and potential health benefits. These diets are often rich in phytonutrients and antioxidants, which have been associated with lower levels of inflammatory markers, such as C-reactive protein [...] Read more.
Background/Objectives: The global shift towards vegan and vegetarian diets has garnered attention for their ethical, environmental, and potential health benefits. These diets are often rich in phytonutrients and antioxidants, which have been associated with lower levels of inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6), suggesting a potential protective effect against systemic inflammation and oxidative stress. However, despite these benefits, concerns remain regarding their impact on neurological health due to the possible deficiencies of critical nutrients such as vitamin B12, DHA, EPA, and iron. This review critically evaluates the influence of these dietary patterns on neurological outcomes, emphasizing their nutritional composition, potential deficiencies, and their interplay with inflammation and oxidative stress. Methods: A systematic review of the literature published between 2010 and 2023 was conducted, focusing on studies that explore the relationship between vegan and vegetarian diets and neurological health. Key nutrients such as vitamin B12, omega-3 fatty acids, iron, and zinc were analyzed alongside antinutritional factors and their effects on the nervous system. Results: Evidence suggests that vegan and vegetarian diets, when well planned, can be rich in phytonutrients and antioxidants, which have been associated with lower levels of inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6). These findings indicate a potential role in reducing systemic inflammation and oxidative stress, both of which are linked to neurodegenerative diseases. However, deficiencies in critical nutrients such as vitamin B12, DHA, EPA, and iron have been consistently associated with an increased risk of cognitive decline, mood disturbances, and neurodegenerative disorders. Additionally, the presence of antinutritional factors like phytates and oxalates may further impair nutrient absorption, necessitating careful dietary planning and supplementation. Conclusions: While plant-based diets provide anti-inflammatory and antioxidant benefits, their neurological implications depend on nutrient adequacy. Proper planning, supplementation, and food preparation techniques are essential to mitigate risks and enhance cognitive health. Further research is needed to explore long-term neurological outcomes and optimize dietary strategies. Full article
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