Search Results (293)

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

Post-traumatic stress disorder (PTSD) has traditionally been viewed as a psychiatric disorder of fear, memory, and emotional regulation. However, growing evidence implicates systemic and neuroinflammation as key contributors. Individuals with PTSD often exhibit elevated blood levels of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and C-reactive protein, indicating immune dysregulation. Dysfunctions in the hypothalamic–pituitary–adrenal (HPA) axis marked by reduced cortisol levels impair the body’s ability to regulate inflammation, allowing persistent immune activation. Circulating cytokines cross a weakened blood–brain barrier and activate microglia, which release additional inflammatory mediators. This neuroinflammatory loop can damage brain circuits critical to emotion processing including the hippocampus, amygdala, and prefrontal cortex, and disrupt neurotransmitter systems like serotonin and glutamate, potentially explaining PTSD symptoms such as hyperarousal and persistent fear memories. Rodent models of PTSD show similar inflammatory profiles, reinforcing the role of neuroinflammation in disease pathology. Bromo-epi-androsterone (BEA), a synthetic analog of dehydroepiandrosterone (DHEA), has shown potent anti-inflammatory effects in clinical trials, significantly reducing IL-1β, IL-6, and TNF-α. By modulating immune activity, BEA represents a promising candidate for mitigating neuroinflammation and its downstream effects in PTSD. These findings support the rationale for initiating clinical trials of BEA as a novel therapeutic intervention for PTSD. Full article

Despite the known impacts of weaning on animal health, the underlying molecular mechanisms remain unclear, particularly how psychological and nutritional stress differentially affect gut health and immune function over time. This study hypothesized that early weaning exerts distinct short- and long-term effects on lamb stress physiology, immunity, and gut health, mediated by specific molecular pathways. Twelve pairs of full-sibling male Hu sheep lambs were assigned to control (CON) or early-weaned (EW) groups. Plasma stress/immune markers were dynamically monitored, and intestinal morphology, antioxidant capacity, apoptosis, and transcriptomic profiles were analyzed at 5 and 28 days post-weaning. Early weaning triggered transient psychological stress, elevating hypothalamic–pituitary–adrenal (HPA) axis hormones (cortisol, catecholamines) and inflammatory cytokines (TNF-α) within 1 day (p < 0.05); however, stress responses were transient and recovered by 7 days post-weaning. Sustained intestinal remodeling was observed in EW lambs, featuring reduced ileal villus height, increased crypt depth (p < 0.05), and oxidative damage (MDA levels doubled vs. CON; p < 0.01). Compensatory epithelial adaptation included increased crypt depth but paradoxically reduced villus tip apoptosis. The transcriptome analysis revealed significant changes in gene expression related to immune function, fat digestion, and metabolism. Key DEGs included APOA4, linked to lipid transport adaptation; NOS2, associated with nitric oxide-mediated immune–metabolic crosstalk; and mitochondrial gene COX1, reflecting energy metabolism dysregulation. Protein–protein interaction analysis revealed NOS2 as a hub gene interacting with IDO1 and CXCL11, connecting oxidative stress to immune cell recruitment. Early weaning exerts minimal lasting psychological stress but drives persistent gut dysfunction through transcriptome-mediated changes in metabolic and immune pathways, highlighting key genes such as APOA4, NOS2, and COX1 as potential regulators of these effects. Full article

Background: Borderline personality disorder (BPD) is a severe psychiatric condition characterised by emotional instability, impulsivity, interpersonal dysfunction, and self-injurious behaviours. Despite growing clinical interest, the neuropsychological mechanisms underlying these symptoms are still not fully understood. This review aims to summarise findings from neuroimaging, psychophysiological, and neurodevelopmental studies in order to clarify the neurobiological and physiological basis of BPD, with a particular focus on emotional dysregulation and implications for the treatment of adolescents. Methods: A narrative review was conducted, integrating results from longitudinal neurodevelopmental studies, functional and structural neuroimaging research (e.g. FMRI and PET), and psychophysiological assessments (e.g., heart rate variability and cortisol reactivity). Studies were selected based on their contribution to understanding the neural correlates of BPD symptom dimensions, particularly emotion dysregulation, impulsivity, interpersonal dysfunction, and self-harm. Results: Findings suggest that early reductions in amygdala volume, as early as age 13 predict later BPD symptoms. Hyperactivity of the amygdala, combined with hypoactivity in the prefrontal cortex, underlies deficits in emotion regulation. Orbitofrontal abnormalities correlate with impulsivity, while disruptions in the default mode network and oxytocin signaling are related to interpersonal dysfunction. Self-injurious behaviour appears to serve a neuropsychological function in regulating emotional pain and trauma-related arousal. This is linked to disruption of the hypothalamic-pituitary-adrenal (HPA) axis and structural brain alterations. The Unified Protocol for Adolescents (UP-A) was more effective to Mentalization-Based Therapy for Adolescents (MBT-A) at reducing emotional dysregulation compared, though challenges in treating identity disturbance and relational difficulties remain. Discussion: The reviewed evidence suggests that BPD has its in early neurodevelopmental vulnerability and is sustained by maladaptive neurophysiological processes. Emotional dysregulation emerges as a central transdiagnostic mechanism. Self-harm may serve as a strategy for regulating emotions in response to trauma-related neural dysregulation. These findings advocate for the integration of neuroscience into psychotherapeutic practice, including the application of neuromodulation techniques and psychophysiological monitoring. Conclusions: A comprehensive understanding of BPD requires a neuropsychologically informed framework. Personalised treatment approaches combining pharmacotherapy, brain-based interventions, and developmentally adapted psychotherapies—particularly DBT, psychodynamic therapy, and trauma-informed care—are essential. Future research should prioritise interdisciplinary, longitudinal studies to further bridge the gap between neurobiological findings and clinical innovation. Full article

Suicidality, encompassing suicidal ideation, attempts, and completed suicide, continues to be a significant public health concern globally. Traditional research has emphasized genetic, neurobiological, and psychosocial factors; however, recent findings suggest that gut microbiota may play a crucial role in influencing suicidal behavior. The gut microbiota impacts neuroinflammation, neurotransmitter metabolism, and the hypothalamic–pituitary–adrenal (HPA) axis, all of which are associated with psychiatric disorders linked to suicidality. This review gathers current evidence on the gut–brain axis, investigating the role of microbiota in suicidality through mechanisms such as immune system modulation, serotonin regulation, and the stress response. We also consider the potential of microbiota-targeted interventions, such as probiotics and dietary changes, as innovative therapeutic strategies. Despite the accumulating evidence, research in this field remains limited, emphasizing the urgent need for further investigation to clarify the causal relationship between gut microbiota and suicidality. Full article

The hypothalamic-pituitary-adrenal (HPA) axis plays an important regulatory role in inflammatory responses to systemic or local infection in the host. A high-calorie diet, which can aggravate pediatric pneumonia and delay recovery, is intimately associated with HPA axis disorder; however, its underlying mechanisms remain unknown. This study examined whether the mechanism by which a high-calorie diet aggravates pneumonia is related to HPA axis disorder. In this study, juvenile rats were fed a high-calorie diet and/or nebulized with lipopolysaccharide (LPS) for model construction. Our data shows that a high-calorie diet increases interleukin-1 beta(IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels in lung tissues and aggravates LPS-induced inflammatory injury in the lungs of juvenile rats. Additionally, we found that a high-calorie diet decreases the expression level of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in juvenile rats with pneumonia, resulting in HPA axis disorder. Hypothalamus proteomics and Western blot results proved that a high-calorie diet upregulated the expression level of hypothalamus hypoxia-inducible factor-1 alpha (HIF-1α) in juvenile rats with pneumonia, and this mechanism is associated with reduced HIF-1α ubiquitination. We further observed that HPA axis disorder was significantly abated and inflammatory damage in rat lung tissues was significantly alleviated after in vivo HIF-1α pathway inhibition. This shows that pneumonia aggravation by a high-calorie diet is associated with interference in the HIF-1α-mediated HPA axis. A high-calorie diet boosts HIF-1α signaling in the hypothalamus and exacerbates LPS-induced pneumonia by disrupting the HPA axis. This sheds light on lung inflammation and strengthens the lung-brain connection. Full article

Magnesium is an essential mineral involved in hundreds of biochemical reactions, with particular relevance to maintaining neural homeostasis, modulating neurotransmitter systems, and regulating inflammatory and oxidative stress mechanisms. This comprehensive review aims to evaluate the potential role of magnesium in the pathophysiology and treatment of three prevalent neurological and psychiatric disorders—depression, migraine, and Alzheimer’s disease—as well as its broader implications for cognitive health. Current research suggests that magnesium deficiency is associated with the development of depression, as magnesium influences glutamatergic and GABAergic neurotransmission, as well as the activity of the hypothalamic–pituitary–adrenal (HPA) axis, both of which play critical roles in stress responses and mood regulation. Additionally, magnesium’s anti-inflammatory properties may contribute to the alleviation of depressive symptoms. In the context of migraine’s pathophysiology, magnesium plays a role in regulating cerebral vascular tone, modulating the trigeminovascular system, and reducing neuronal hyperexcitability, which may explain the observed correlation between magnesium levels and the incidence of migraines. Regarding Alzheimer’s disease, preclinical and epidemiological studies suggest that magnesium may contribute to modulating neurodegenerative processes and preserving cognitive function; however, due to the heterogeneity of the current findings, further longitudinal and interventional studies are necessary to determine its precise clinical relevance. This review aims to enhance the understanding of the relationship between magnesium and these disorders through a narrative review of relevant clinical studies. The findings may provide insights into the potential therapeutic applications of magnesium and guide the future directions of the research into the prevention and treatment of depression, migraine, and Alzheimer’s disease and overall cognitive health. Full article

A dysregulated hypothalamic–pituitary–adrenal (HPA) axis in patients with type 2 diabetes (T2D), a condition preceded by prediabetes, has been shown to exacerbate the hyperglycaemic state, increasing the risk of depression. However, HPA axis activity in a prediabetic state—as well as whether the prediabetic state affects HPA axis regulation—is not fully understood. This study investigated the activity of the HPA axis in selected biomarkers and hormones related to HPA axis regulation in individuals with prediabetes. The study used samples obtained from adults aged between 25 and 45 of all ethnicities from the King Edward VIII Hospital. The samples were divided into three groups—non-prediabetic (NPD) (n = 40), prediabetic (PD) (n = 40), and T2D (n = 40)—based on the participant’s glycated haemoglobin percentage. The cortisol (CORT), adrenocorticotropic hormone (ACTH), insulin, epinephrine (EPI), and norepinephrine (NE) concentrations of the samples were measured. The plasma CORT and ACTH concentrations in the PD group were higher compared to the NPD group. Plasma insulin concentration was increased only in the T2D group. There was also an increase in the plasma epinephrine concentration in the T2D group as compared to the NPD and PD groups. These observations collectively suggest that prediabetes is associated with heightened HPA axis activity and may alter HPA axis regulation, which may cause an altered stress response. Full article

Background: Childhood neglect is a pervasive yet often overlooked form of maltreatment that exerts profound and lasting effects on neurodevelopment. Unlike other types of abuse, neglect is characterized by the absence of essential stimuli and caregiving, which are critical for normal brain maturation, particularly in regions involved in executive function. Objective: This narrative review aims to critically explore the neurobiological mechanisms through which early-life neglect impairs the development of executive functions. Special emphasis is placed on alterations in brain structure and function, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, and emerging epigenetic evidence. Methods: A comprehensive literature search (170 articles) was conducted across PubMed, Scopus, Web of Science, and PsycINFO, including studies published between 1 January 2000 to 31 March 2025. Relevant empirical and review articles were selected based on methodological rigor, relevance to executive functioning, and focus on child neglect. Results: Evidence reveals that neglect disrupts key neural circuits, particularly those involving the prefrontal cortex and amygdala, leading to deficits in attention, working memory, impulse control, and cognitive flexibility. Chronic stress associated with neglect also induces HPA axis dysregulation and elevated cortisol levels, which further compromise neural plasticity. Additionally, epigenetic modifications appear to mediate long-term cognitive and emotional consequences. Conclusions: Childhood neglect represents a distinct and critical risk factor for executive dysfunction. Understanding the neurodevelopmental consequences of neglect is essential for developing targeted prevention strategies and therapeutic interventions aimed at supporting cognitive resilience in affected populations. Full article

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

Organisms respond to environmental stress primarily through the autonomic nervous system and hypothalamic–pituitary–adrenal (HPA) axis, regulating metabolism, psychological states, and immune function and modulating memory, reward processing, and immune responses. The HPA axis plays a central role in stress response, exhibiting distinct activation patterns under acute versus chronic social defeat stress. However, differences in physiological impacts and regulatory pathways between these stress conditions remain understudied. This study integrates RNA sequencing and behavioral analyses to reveal that acute social defeat stress triggers transient anxiety-like behaviors, accompanied by systemic inflammation and immediate-early gene (IEG) activation. In contrast, chronic social defeat stress induces long-term behavioral and physiological alterations, including neurotransmitter imbalance (e.g., reduced GABA and increased glutamate), sustained activation of maladaptive pathways (e.g., IL-17 signaling), and disrupted corticosterone synthesis. These findings highlight the dynamic regulatory role of the HPA axis under varying stress conditions, providing novel insights into mental health disorders such as anxiety and depression. The study identifies potential therapeutic targets to mitigate chronic social defeat stress effects and offers a theoretical foundation for personalized interventions. Full article

Background/Objectives: Child abuse is a pervasive global issue with significant implications for the physical, emotional, and psychological well-being of victims. This review highlights the clinical, molecular, and therapeutic dimensions of child abuse, emphasizing its long-term impact and the need for interdisciplinary approaches. Early exposure to abuse activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to chronic cortisol release and subsequent neuroplastic changes in brain regions such as the hippocampus, amygdala, and prefrontal cortex. These molecular alterations, including epigenetic modifications and inflammatory responses, contribute to the heightened risk of psychiatric disorders and chronic illnesses in survivors. Clinically, child abuse presents with diverse manifestations ranging from physical injuries to psychological and developmental disorders, making timely diagnosis challenging. Methods: A multidisciplinary approach involving thorough clinical evaluation, detailed histories, and collaboration with child protection services is essential for accurate diagnosis and effective intervention. Results: Recent advances in molecular biology have identified biomarkers, such as stress-related hormones and epigenetic changes, which provide novel insights into the physiological impact of abuse and potential targets for therapeutic intervention. Current treatment strategies prioritize the child’s safety, psychological well-being, and prevention of further abuse. Trauma-focused cognitive behavioral therapy and family-centered interventions are pivotal in promoting recovery and resilience. Conclusions: Emerging research focuses on integrating molecular findings with clinical practice, utilizing digital health tools, and leveraging big data to develop predictive models and personalized treatments. Interdisciplinary collaboration remains crucial to translating research into policy and practice, ultimately aiming to mitigate the impact of child abuse and improve outcomes for survivors. Full article

Background/Objectives: Dimethyl trisulfide (DMTS) is a naturally occurring polysulfide with known antioxidant and neuroprotective properties. DMTS is a lipophilic transient receptor potential ankyrin 1 (TRPA1) ligand that reaches the central nervous system (CNS). Its role in the CNS, particularly regarding depression-like behaviour, has yet to be explored. This study investigates the influence of DMTS on stress responses and whether this effect is mediated through the TRPA1 ion channel, known for its role in stress adaptation. Using a mouse model involving three-week exposure, we examined the impact of DMTS on depression-like behaviour and anxiety and identified the involved brain regions. Methods: Our methods involved testing both Trpa1-wild-type and gene-knockout mice under CUMS conditions and DMTS treatment. DMTS was administered intraperitoneally at a dose of 30 mg/kg on days 16 and 20 of the 21-day CUMS protocol—in hourly injections seven times to ensure sustained exposure. Various behavioural assessments—including the open field, marble burying, tail suspension, forced swim, and sucrose preference tests—were performed to evaluate anxiety and depression-like behaviour. Additionally, we measured body weight changes and the relative weights of the thymus and adrenal glands, while serum levels of corticosterone and adrenocorticotropic hormone were quantified via ELISA. FOSB (FBJ murine osteosarcoma viral oncogene homolog B) immunohistochemistry was utilised to assess chronic neuronal activation in stress-relevant brain areas. Results: Results showed that CUMS induces depression-like behaviour, with the response being modulated by the TRPA1 status and that DMTS treatment significantly reduced these effects when TRPA1 channels were functional. DMTS also mitigated thymus involution due to hypothalamic–pituitary–adrenal (HPA) axis dysregulation. Conclusions: Overall, DMTS appears to relieve depressive and anxiety symptoms through TRPA1-mediated pathways, suggesting its potential as a dietary supplement or adjunct therapy for depression and anxiety. Full article

: Depression, commonly known as unipolar affective disorder, is one of the most prevalent mental illnesses in contemporary society, affecting individuals to varying degrees. Tea is one of the three major non-alcoholic beverages globally; it has a rich history of consumption and is associated with numerous health and nutritional benefits. This review systematically summarizes the antidepressant effects of various bioactive compounds found in tea, drawing upon research findings in the field of tea’s functional health. It elucidates the impact of tea’s bioactive components on the hypothalamic–pituitary–adrenal (HPA) axis, the nervous system, the immune system, intestinal microflora, and the monoaminergic system, among other physiological sites, to achieve antidepressant effects. These effects primarily involve enhancing neural signaling pathways, regulating neural signaling molecule levels, and reducing neuroinflammation. Tea may normalize the body’s nervous system by bolstering immune function, alleviating or eliminating cellular inflammation to maintain healthy homeostasis, or improving intestinal flora and mitigating stress to prevent or treat depressive disorders. Additionally, the potential social support derived from tea-drinking activities, such as cultural rituals and interpersonal communication, may contribute to its antidepressant effects. This review discusses and analyzes the current research status regarding the antidepressant effects of tea and highlights that tea and its active ingredients can be utilized to prevent and alleviate depression. Full article

Anxiety disorders are among the most common psychiatric conditions that significantly impair one’s quality of life and place a significant burden on healthcare systems. Conventional treatments have certain restraints, such as potential side effects and limited efficacy. Τhe underlying pathophysiological mechanisms of anxiety are not fully understood. A comprehensive literature search was performed in MEDLINE and Scopus databases for original English-language articles published between January 2014 and December 2024. Study selection, data extraction, and screening were independently carried out by multiple investigators using predefined criteria. Our review aimed to help better comprehend the molecular basis of anxiety, focusing on the hypothalamic–pituitary–adrenal (HPA) axis, serotonergic signaling, and gamma-aminobutyric acid (GABA) neurotransmission. In addition, we addressed the role of epigenetics and pharmacogenomics in personalized treatment. Although novel anxiety treatments are promising, they are predominantly preclinical and highly heterogeneous, which poses a challenge to achieving reliable therapeutic efficacy. Our findings could potentially contribute to the development of new therapeutic interventions. Further research is warranted, especially in human subjects, with an aim to combine genetic and epigenetic profiles to refine treatment approaches and develop innovative therapeutics. Full article