Search Results (91)

Background: Wilson’s disease (WD) is a rare autosomal recessive disorder characterized by abnormal copper metabolism and accumulation in the liver and brain. While hepatic and neurological manifestations are well-recognized, psychiatric symptoms remain underdiagnosed and frequently precede other clinical signs, leading to delayed diagnosis and poorer outcomes. Objective: This opinion paper aims to explore the emerging understanding of psychiatric features in WD, particularly mood disturbances and their overlap with bipolar spectrum disorders, through a translational lens. Opinion: Psychiatric manifestations—including irritability, aggression, disinhibition, and mood instability—are observed in up to 100% of symptomatic WD patients. Accumulated copper induces oxidative stress and astrocyte dysfunction, which may disrupt neural circuits involved in emotion regulation. There is increasing evidence of shared pathophysiological mechanisms between WD and bipolar disorder, including redox imbalance and circadian rhythm dysregulation. Future Directions: The timely recognition of psychiatric symptoms is essential. Future research should investigate biomarkers of early psychiatric involvement, evaluate psychotropic medication safety in WD, and implement psychoeducational strategies to improve adherence and quality of life. A translational approach can foster individualized interventions and provide insights into broader mood disorders. Full article

Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder that not only affects attention and behavior but is also intricately linked with sleep disturbances and immune system dysregulation. Recent research highlights that individuals with ADHD frequently experience sleep problems, which in turn exacerbate ADHD symptoms and contribute to cognitive and emotional difficulties. Immunological alterations, including elevated proinflammatory cytokines and hypothalamic–pituitary–adrenal axis dysfunction, have been observed among ADHD patients, suggesting a biological interplay between inflammation, sleep, and neurodevelopment. Genetic and environmental factors further modulate these relationships, influencing the onset and progression of the disorder. Thus, there is a need to find a key connecting such topics and the most vulnerable subjects in order to contribute towards a more personalized approach. This review examines the complex relationships between sleep, immunology, and ADHD, and explores the underlying mechanisms that involve circadian rhythm genes, neuroinflammation, and neurotransmitter imbalances. Our review outlines therapeutic strategies, emphasizing the importance of integrated pharmacological, behavioral, and lifestyle interventions to improve sleep quality, regulate immune responses, and ultimately enhance the overall management of ADHD. Full article

Background/Objectives: Dyslexia and dysgraphia are common childhood neurodevelopmental disorders characterized by persistent reading and writing difficulties, despite normal intelligence and access to education. While typically described as cognitive–linguistic deficits, emerging research suggests potential links to orofacial dysfunction and emotional regulation issues. This study examines associations between stomatognathic anomalies, emotional dysregulation, and early indicators of dyslexia-dysgraphia risk in preschool children, aiming to strengthen early screening and intervention strategies. Methods: A cross-sectional case–control study included 689 Romanian children aged 5–7 from 11 kindergartens. Screening involved the ACTIV-BURLEA psychometric battery to evaluate language, motor, and cognitive abilities. Clinical assessments targeted dental arch form, occlusal balance, and tongue and lip function. Emotional regulation was evaluated using a standardized child behavior scale. Thirty-two children were identified as at risk for dyslexia-dysgraphia and followed longitudinally, and then compared to matched controls. Statistical analysis employed chi-square tests, Pearson correlations, t-tests, and logistic regression. Results: At follow-up, 74.19% of at-risk children received confirmed diagnoses. Tongue dysfunction (TD) (OR = 4.81, p = 0.06) and emotional dysregulation (ED) (OR = 3.94, p = 0.09) emerged as key risk indicators, though not statistically significant. Tongue dysfunction (TD) correlated with school avoidance (r = 0.76, p < 0.01), while occlusal anomalies (OAs) correlated with emotional distress (ED) (r = 0.64, p < 0.05). Conclusions: The findings suggest that early dyslexia-dysgraphia risk involves orofacial and emotional components. Tongue dysfunction (TD), occlusal disturbances (OA), and emotional dysregulation (ED) may offer important clinical markers. Integrating dental and emotional assessments into preschool screening may improve early identification and enable personalized intervention. Full article

Post-traumatic stress disorder (PTSD) is a chronic mental health condition resulting from exposure to traumatic events. It is associated with long-term neurobiological changes and disturbances in emotional regulation. Understanding the sociodemographic profiles, biomarkers, and emotional control in patients with PTSD helps to better comprehend the impact of the disorder on the body and its clinical course. An analysis of biomarkers such as Interleukin-18 (IL-18), Inositol-Requiring Enzyme 1 (IRE1), Phosphorylated Extracellular Signal-Regulated Kinase (pERK), and Activating Transcription Factor–6 (ATF-6) in PTSD patients with varying durations of illness (≤5 years and >5 years) and a control group without PTSD revealed significant differences. Patients with recently diagnosed PTSD (≤5 years) showed markedly elevated levels of inflammatory and cellular stress markers, indicating an intense neuroinflammatory response during the acute phase of the disorder. In the chronic PTSD group (>5 years), the levels of these biomarkers were lower than in the recently diagnosed group, but still significantly higher than in the control group. An opposite trend was observed regarding the suppression of negative emotions, as measured by the Courtauld Emotional Control Scale (CECS): individuals with chronic PTSD exhibited a significantly greater suppression of anger, depression, and anxiety than those with recent PTSD or healthy controls. Correlations between biomarkers were strongest in individuals with chronic PTSD, suggesting a persistent neuroinflammatory dysfunction. However, the relationships between biomarkers and emotional suppression varied depending on the stage of PTSD. These findings highlight the critical role of PTSD duration in shaping the neurobiological and emotional mechanisms of the disorder, which may have important implications for therapeutic strategies and patient monitoring. Full article

Background/Objectives: Atypical sensory processing is increasingly recognized as a transdiagnostic dimension of neurodevelopmental disorders (NDDs), with critical implications for emotional and behavioral regulation. This study aimed to identify distinct sensory profiles in preschool children with NDDs and to examine their associations with emotional–behavioral and cognitive/developmental functioning. Methods: A total of 263 children (aged 21–71 months) diagnosed with autism spectrum disorder (ASD), language disorder (LD), or other NDDs (ONDD) were recruited. Sensory processing was assessed using the SPM-P, emotional–behavioral functioning was assessed via the CBCL 1½–5, and cognitive/developmental levels were assessed through standardized instruments. Latent profile analysis (LPA) was conducted to identify sensory subtypes. Group comparisons and multinomial logistic regression were used to examine profile characteristics and predictors of profile membership. Results: Three sensory profiles emerged: (1) Multisystemic Sensory Dysfunction (20.1%), characterized by pervasive sensory and emotional difficulties, primarily observed in ASD; (2) Typical Sensory Processing (44.9%), showing normative sensory and emotional functioning, predominantly LD; and (3) Mixed Subclinical Sensory Processing (35%), with subclinical-range scores across multiple sensory and emotional domains, spanning all diagnoses. Higher cognitive functioning and fewer internalizing symptoms significantly predicted membership in the typical profile. A gradient of symptom severity was observed across profiles, with the Multisystemic group showing the most pronounced emotional–behavioral impairments. Conclusions: Distinct sensory–emotional phenotypes were identified across diagnostic categories, supporting a dimensional model of neurodevelopment. Sensory profiles were strongly associated with emotional functioning, independently of diagnostic status. Early sensory assessment may therefore offer clinically meaningful insights into emotional vulnerability and inform targeted interventions in preschool populations with NDDs. 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

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

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

Plateau environments present unique mental health challenges owing to stressors including hypoxia, low temperatures, and intense ultraviolet (UV) radiation. These factors induce structural and functional alterations in the gut microbiota, disrupting gut-brain axis homeostasis and contributing to the higher prevalence of depression in plateau regions relative to flatland areas. For example, studies report that 28.6% of Tibetan adults and 29.2% of children/adolescents on the Qinghai-Tibet Plateau experience depression, with increasing evidence linking this trend to alterations in the gut microbiota. Dysbiosis contributes to depression through three interconnected mechanisms: (1) Neurotransmitter imbalance: Reduced bacterial diversity impairs serotonin synthesis, disrupting emotional regulation. (2) Immune dysregulation: Compromised gut barrier function allows bacterial metabolites to trigger systemic inflammation via toll-like receptor signaling pathways. (3) Metabolic dysfunction: Decreased short-chain fatty acid levels weaken neuroprotection and exacerbate hypothalamic-pituitary-adrenal axis stress responses. Current interventions—including dietary fiber, probiotics, and fecal microbiota transplantation—aim to restore microbiota balance and increase short-chain fatty acids, alleviating depressive symptoms. However, key knowledge gaps remain in understanding the underlying mechanisms and generating population-specific data. In conclusion, existing evidence indicates an association between plateau environments, the gut microbiota, and depression, but causal relationships and underlying mechanisms require further empirical investigation. Integrating multiomics technologies to systematically explore interactions among high-altitude environments, the microbiota and the brain will facilitate the development of precision therapies such as personalized nutrition and tailored probiotics to protect mental health in high-altitude populations. Full article

Toll-like receptors (TLRs) comprise an evolutionarily conserved family of pattern recognition receptors that detect microbial-associated molecular patterns and endogenous danger signals to orchestrate innate immune responses. While traditionally positioned at the frontline of host defense, accumulating evidence suggests that TLRs are at the nexus of immuno-metabolic regulation and central nervous system (CNS) homeostasis. They regulate a wide range of immune and non-immune functions, such as cytokine and chemokine signaling, and play key roles in modulating synaptic plasticity, neurogenesis, and neuronal survival. However, alterations in TLR signaling can drive a sustained pro-inflammatory state, mitochondrial dysfunction, and oxidative stress, which are highly associated with the disruption of emotional and cognitive functions and the pathogenesis of psychiatric disorders. In this review, we integrate findings from molecular to organismal levels to illustrate the diverse roles of TLRs in regulating emotion, cognition, metabolic balance, and gut–brain interactions. We also explore emerging molecular targets with the potential to guide the development of more effective therapeutic interventions. Full article

Public speaking anxiety, which is closely related to social anxiety, is a crucial factor in the development of adolescents. It affects their ability to regulate their emotions and irrational beliefs, which in turn shapes their relationships and academic success. The purpose of this present study is two-fold: (a) to develop a valid and reliable measurement tool for public speaking anxiety for adolescents, and (b) to determine the mediating role of dysfunctional emotion regulation on the effect of irrational beliefs on public speaking anxiety. To achieve this, data were collected through face-to-face interviews from a total of 1231 adolescent students, including 642 girls (age, $\overline{X}$ = 14.96) and 589 boys ($\overline{X}$ = 14.99), aged between 12 and 17 years old in five stages. Data collection was based on the Public Speaking Anxiety Scale (PSAS) (developed in the current study), the Irrational Beliefs Scale (IBS), the Regulation of Emotions Questionnaire (REQ) and the Social Anxiety Scale for Adolescents (SAS-A). Data were analysed through SPSS, AMOS, JAMOVI, G-POWER and Microsoft Excel programmes. This study concludes that the Public Speaking Anxiety Scale (PSAS) has demonstrated both valid and reliable psychometric properties. The findings of this study further reveal that internal dysfunctional emotion regulation plays a partial mediating role in the effect of irrational beliefs on public speaking anxiety, and that external dysfunctional emotion regulation, on the contrary, did not have a mediating role in the effect of irrational beliefs on public speaking anxiety. Full article

Background: Borderline Personality Disorder (BPD) is a debilitating mental health condition characterized by emotional dysregulation and interpersonal dysfunction, with perceived social rejection exacerbating these issues. Emerging evidence suggests that a single session of transcranial direct current stimulation (tDCS) over the right ventrolateral prefrontal cortex (rVLPFC) may decrease the unique tendency of BPD patients to feel rejected even when socially included during a laboratory task. Objectives: This protocol outlines a double-blind, sham-controlled study evaluating the longitudinal effects of repeated anodal tDCS over the right ventrolateral prefrontal cortex (rVLPFC) on rejection-related emotions (RRE) during real-life social interactions in individuals with BPD. Methods: Sixty BPD patients will be randomized to receive real or sham tDCS across 10 daily sessions, coupled with an ecological momentary assessment (EMA) protocol capturing emotional and behavioral responses to real-life social interactions over four timepoints: baseline, during treatment, ten days post-treatment, and three months post-treatment. Primary outcomes include changes in RRE, with exploratory analyses examining feelings of social connection, aggressive tendencies, trust toward others, and interpersonal and affective dynamics. Multilevel modeling will assess temporal and group-level effects. Expected Results and Impact: This study aims to establish the efficacy of tDCS in reducing BPD patients’ negative emotional response in real-life social situations and to determine whether such effects are maintained in time. The findings could advance the clinical application of tDCS as an adjunctive intervention to alleviate social–emotional impairments in BPD, addressing gaps in current treatment approaches and guiding future research into the neural mechanisms of social emotion regulation. Full article

Depression is a multifactorial psychiatric condition with complex pathophysiology, increasingly linked to neuroinflammatory processes. The present review explores the role of neuroinflammation in depression, focusing on glial cell activation, cytokine signaling, blood–brain barrier dysfunction, and disruptions in neurotransmitter systems. The article highlights how inflammatory mediators influence brain regions implicated in mood regulation, such as the hippocampus, amygdala, and prefrontal cortex. The review further discusses the involvement of the hypothalamic–pituitary–adrenal (HPA) axis, oxidative stress, and the kynurenine pathway, providing mechanistic insights into how chronic inflammation may underlie emotional and cognitive symptoms of depression. The bidirectional relationship between inflammation and depressive symptoms is emphasized, along with the role of peripheral immune responses and systemic stress. By integrating molecular, cellular, and neuroendocrine perspectives, this review supports the growing field of immunopsychiatry and lays the foundation for novel diagnostic biomarkers and anti-inflammatory treatment approaches in depression. Further research in this field holds promise for developing more effective and personalized interventions for individuals suffering from depression. Full article

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity. Adolescents with ADHD have an elevated risk of developing Internet Gaming Disorder (IGD), a condition involving excessive gaming that disrupts daily life. IGD is linked to traits such as low frustration tolerance and sensation-seeking, with comorbid conditions like anxiety and depression further increasing vulnerability. Gaming frequently serves as a coping strategy due to emotional regulation difficulties. The dynamics within family units and peer relationships play a pivotal role, with dysfunctional environments heightening the risks and positive interactions serving as protective factors. Methods: This scoping review analyzed empirical studies published in the last decade exploring the association between ADHD, Problematic Internet Use (PIU), or IGD, focusing on neurobiological, psychological, and environmental factors. Results: The findings highlight that impulsivity and emotional dysregulation in ADHD contribute to IGD. Gaming is frequently used as a maladaptive coping strategy, with social and family influences modulating risk. Diagnostic complexities arise in distinguishing ADHD-related behaviors from IGD symptoms. Conclusions: Addressing these comorbid conditions requires interdisciplinary collaboration and evidence-based interventions. Future research should focus on understanding ADHD, PIU, or IGD interactions and developing targeted interventions. Longitudinal studies are necessary to establish causal links and assess effective treatment strategies. Full article

Chronic stress significantly contributes to the development of depressive disorders, with the hypothalamic–pituitary–adrenal (HPA) axis playing a central role in mediating stress responses. This review examines the neurobiological alterations in the hippocampus linked to HPA axis dysregulation in chronic stress-associated depressive disorders. The prolonged activation of the HPA axis disrupts cortisol regulation, leading to the decline of both physical and mental health. The chronic stress-induced HPA axis dysfunction interacts with inflammatory pathways and generates oxidative stress, contributing to cellular damage and neuroinflammation that further aggravates depressive symptoms. These processes result in structural and functional alterations in the hippocampus, which is essential for emotional regulation and cognitive function. Comprehending the impact of chronic stress on the HPA axis and associated neurobiological pathways is essential for formulating effective interventions for depressive disorders. This review summarises the existing findings and underscores the necessity for future investigations into intervention strategies to improve physical and psychological wellbeing targeting at HPA axis dysregulation for the betterment of psychological wellbeing and human health. Full article