Search Results (3,021)

Background/Objectives: Borderline personality disorder (BPD) is a psychiatric disorder characterized by emotional instability, impulsive behavior, and impaired interpersonal relationships. It is associated with a high prevalence of childhood trauma and neurobiological changes. This study aimed to compare ophthalmologic parameters, namely, optic nerve sheath diameter, intraocular pressure, and dry eye, in patients with BPD with healthy controls and to investigate the relations between these parameters and childhood trauma. Methods: This study included 51 female patients with BPD between the ages of 18 and 35 years, who were not using psychotropic medication, and 51 healthy controls matched for age and educational level. Optic nerve sheath diameter, intraocular pressure, and tear break-up time were measured, and trauma history was evaluated using the Childhood Trauma Questionnaire-Short Form. Independent t-test and Pearson correlation analysis were used in statistical analyses. Results: Patients with BPD were found to have significantly higher mean optic nerve sheath diameter scores (left: 3.94 ± 0.43, right: 3.97 ± 0.47) compared with healthy controls (left: 3.76 ± 0.44, right: 3.78 ± 0.45) (p < 0.05). The groups showed no significant difference in intraocular pressure and dry eye parameters (p > 0.05). A significant positive correlation was noted between emotional abuse scores and the optic nerve sheath diameter of the left eye in patients with BPD (p < 0.05; r = 0.364). Conclusions: An increased optic nerve sheath diameter may be a potential peripheral biomarker reflecting chronic stress or changes in intracranial physiology in patients with BPD. This increase is particularly associated with a history of emotional abuse. Ophthalmological parameters may contribute to understanding the neurobiological basis of BPD and serve as peripheral biomarkers or indicators of neurobiological changes. Full article

Background: Methamphetamine use, which is disproportionately prevalent among people with HIV, increases risk for cardio- and neurovascular pathology through persistent immune activation and inflammation. Preclinical studies indicate that cannabinoids may reduce markers of pro-inflammatory processes, but data from people with chronic inflammatory conditions are limited. We examined potentially interacting associations of lifetime methamphetamine use disorder (MUD), recent cannabis use, and HIV with four plasma markers of immune and inflammatory functions. Method: Participants with HIV (PWH, n = 86) and without HIV (PWoH, n = 148) provided urine and blood samples and completed neuromedical, psychiatric, and substance use assessments. Generalized linear models examined main and conditional associations of lifetime MUD, past-month cannabis use, and HIV with plasma concentrations of CXCL10/IP-10, CCL2/MCP-1, ICAM-1, and VCAM-1. Results: PWH displayed higher CXCL10/IP-10 than PWoH. Past-month cannabis use was independently associated with lower CXCL10/IP-10 levels and conditionally lower CCL2/MCP-1, ICAM-1, and VCAM-1 levels among people with lifetime MUD, but only PWoH displayed cannabis-associated lower VCAM-1 levels. Conclusions: Human plasma sample evidence suggests that cannabis use is associated with lower levels of immune and inflammatory molecules in the context of MUD or HIV. Cannabinoid pathways may be worthwhile clinical targets for treating sequelae of chronic inflammatory conditions. Full article

Background: Functional Neurological Disorder (FND) encompasses a spectrum of symptoms—including motor, cognitive, and seizure-like manifestations—that are not fully explained by structural neurological disease. Accumulating evidence suggests that comorbid psychiatric and somatic conditions significantly influence the clinical course, diagnostic complexity, and treatment response in FND. Objective: This study systematically explores psychiatric and medical comorbidities across major FND subtypes—Functional Cognitive Disorder (FCD), Functional Movement Disorder (FMD), and Psychogenic Non-Epileptic Seizures (PNES)—with an emphasis on subtype-specific patterns and shared vulnerabilities. Methods: We conducted a narrative review of the published literature, guided by systematic principles for transparency, covering both foundational and contemporary sources to examine comorbid conditions in patients with FCD, FMD, PNES, PPPD and general (mixed) FND populations. Relevant studies were identified through structured research and included based on methodological rigor and detailed reporting of comorbidities (PRISMA). Extracted data were organized by subtype and comorbidity type (psychiatric or medical/somatic). Results: Across all FND subtypes, high rates of psychiatric comorbidities were observed, particularly depression, anxiety, PTSD, and dissociative symptoms. FCD was predominantly associated with internalizing symptoms, affective misattribution, and heightened cognitive self-monitoring. FMD demonstrated strong links with trauma, emotional dysregulation, and personality vulnerabilities. PNES was characterized by the highest burden of psychiatric illness, with complex trauma histories and dissociation frequently reported. Somatic comorbidities—such as fibromyalgia, chronic pain, irritable bowel syndrome, and fatigue—were also prevalent across all subtypes, reflecting overlapping mechanisms involving interoception, central sensitization, and functional symptom migration. Conclusions: Comorbid psychiatric and medical conditions are integral to understanding the presentation and management of FND. Subtype-specific patterns underscore the need for individualized diagnostic and therapeutic approaches, while the shared biopsychosocial mechanisms suggest benefits of integrated care models across the FND spectrum. Full article

Treatment-resistant mental health concerns significantly contribute to society in terms of financial costs and individually by creating emotional and functional costs. An important yet little-recognized cause of treatment-resistant mental health conditions is tetrahydrobiopterin (BH4) deficiency. BH4 is an essential cofactor for producing serotonin, dopamine, norepinephrine, and nitric oxide—molecules critical to mood and focus. The enzyme GTP Cyclohydrolase 1 (GCH1), produced by a gene of the same name, catalyzes the first step in synthesizing BH4. Variants in this gene have been associated with low BH4 levels, as well as depression and ADHD. The case reports presented in this article illustrate that a partial BH4 deficiency, as conveyed by the GCH1 rs841 variant, may contribute to wider issues in mental and neurological health including depression and ADHD but also severe treatment-resistant anxiety, Premenstrual Dysphoric Disorder, insomnia, complex behavioral issues, and autism. The effects of GCH1-mediated BH4 deficiency may be able to be rescued with a low-dose BH4 replacement, as illustrated by these cases, where substantial observational improvements in mental health concerns were reported in all five cases. This paper also demonstrates how a genomics clinical decision support tool can non-invasively flag “low producers” by identifying individuals with the AA genotype for GCH1 rs841, as well as other modifiable genomic contributing factors to mental health concerns. These cases broaden the understanding of BH4′s psychiatric relevance and also serve to further the medical literature by documenting positive responses to low-dose BH4 (ranging from 0.09 to 0.3 mg/kg/day) and other genotype-guided interventions across diverse mental and neurological health presentations, highlighting the potential benefits and importance of a genomically targeted, precision approach to psychiatry. Full article

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

Artemin is a neurotrophic factor that belongs to the four-member family of Glial-derived growth factors. This study aims to investigate changes in artemin correlated with anxiety and depression-like behaviors in a neuroinflammation rodent model. In adult male Wistar rats, neuroinflammation was established through administration of 2 mg/kg LPS. Anxiety-like behaviors and locomotor activity were evaluated by the open field test. The sucrose preference test and the splash test analyzed depression-like behaviors. Tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and artemin levels were measured in the prefrontal cortex, striatum, and serum. In the neuroinflammation group, rearing, total distance traveled, time spent in the central region, and sucrose solution consumption decreased in the open-field test (p < 0.0001). Grooming time and frequency were shortened, and grooming latency was prolonged in the neuroinflammation group (p < 0.0001). TNF-α was significantly increased in the prefrontal cortex (p < 0.05) and striatum (p < 0.01). lL-1β did not change between groups (p > 0.05). Artemin levels decreased in the prefrontal cortex and striatum (p < 0.05). No difference was observed in serum artemin levels; however, artemin levels of brain regions were higher than those in the serum. An increase in anxiety–depression-like behaviors has accompanied decreased levels of artemin in the brain. Artemin may be a target molecule in psychiatric disorders. Further studies are needed to examine the role of artemin in neuropsychiatric disorders. Full article

Background/Objectives: Disruption of AMPAR trafficking at excitatory synapses contributes to impaired synaptic plasticity and memory formation in several neurological and psychiatric disorders. Arc, an immediate early gene product, has been shown to interact with the AMPAR auxiliary subunit TARPγ2, affecting receptor mobility and synaptic stabilization. Methods: To investigate the in vivo functional effects and protein interactions of the Arc-TARPγ2 interfering peptide RIPSYR, we performed in vivo electrophysiology and spatial memory assessments in male rats. as well as proteomic analyses of peptide-protein interactions in synaptosome lysates. We then used in silico docking to evaluate candidate binding partners. Results: In the present study, in vivo electrophysiological measurements revealed that RIPSYR administration altered early-phase long-term potentiation at CA3 synapses of male rats. Subsequent behavioral testing that assessed spatial memory performance revealed depleted memory retrieval after 24 h, indicating that the peptide has a systemic effect on experience-dependent plasticity. Then, we examined the molecular interactome of RIPSYR using magnetic bead-based immunoprecipitation and subsequent LC-MS identification on synaptosome lysates, and identified additional candidate binding partners, suggesting that the peptide may have broader modulatory effects. RIPSYR binding to the other putative binding partners are investigated by in silico methods. Conclusion: Our results raise the question of how the molecular interactions of RIPSYR contribute to its sum effects on electrophysiology and behavior. Full article

In recent years, an increasing amount of research has investigated the impact of chronic inflammation on the development and progression of both neurological and psychiatric disorders, including epilepsy, depression, schizophrenia, and bipolar disorder. Moreover, growing attention is being paid to how inflammatory processes contribute to disease mechanisms, influence symptom severity, and interact with pharmacological treatments in these conditions. Changes in the levels of inflammatory biomarkers, such as cytokines and C-reactive protein, may signal the early stages of neurological disorder development. Furthermore, specific biomarker profiles have been identified for individual diseases, and chronic treatment may affect their blood levels. Over the last two decades, significant progress in the study of inflammatory biomarkers in psychiatric disorders and epilepsy has been achieved, demonstrating an association between biomarkers with symptoms, a potential prognostic role, and possible use in personalising therapy. Furthermore, widely used methods for biomarker evaluation, such as immunoenzymatic assays and flow cytometry, remain essential tools for current research. Despite numerous indications of the importance of inflammation in psychiatry and neurology, the available studies are characterised by considerable heterogeneity in terms of both population selection and methodology. Based on the available data, inflammatory biomarkers represent a promising diagnostic and therapeutic tool for epilepsy and psychiatric disorders. Although existing studies suggest a correlation between inflammation and the symptoms of various disorders, inconsistent results highlight the need for further research to enable wider implementation of these findings in psychiatric and epilepsy practice. Advancing knowledge of inflammatory biomarkers is essential for improving treatment outcomes and promoting the development of targeted interventions. Full article

The complement system is a vital component of innate immunity. Besides its roles in pathogen defense, its significance in neurodevelopment, neurodegeneration, and cancer progression is beginning to be recognized. We performed a comprehensive literature review to summarize the involvement and dysregulation of the complement system in three main CNS-associated conditions: Alzheimer’s disease, schizophrenia, and glioma. In Alzheimer’s disease, activation of the complement system contributes to neuroinflammation, synaptic loss, and neuronal death. In glioblastoma, complement promotes tumor growth, immune evasion, and therapy resistance. In schizophrenia, genetic variations in complement components, particularly C4A, are associated with synaptic pruning abnormalities and disease susceptibility. We conclude that the complement system has a dual role of protector and pathogenic mediator in the central nervous system. While it is critical in neurodegenerative, oncological, and psychiatric disorders, its role is not understood well enough. For therapeutic purposes, targeting the complement system may open new frontiers for therapeutic interventions without disrupting important physiological processes. More research is needed to elucidate the exact roles of the complement and help translate these findings into clinical settings. Full article

Background/Objectives: The extension of euthanasia and physician-assisted suicide to individuals with mental disorders presents a profound ethical, clinical, and legal challenge. While increasingly accepted in some jurisdictions, their application in psychiatric contexts—particularly in cases of depression—raises concerns about diagnostic precision, therapeutic adequacy, and the validity of informed consent. This study examines two controversial Belgian cases to explore the complexities of euthanasia for psychological suffering. Methods: A qualitative case analysis was conducted through a qualitative analysis of publicly available media sources. The cases were examined through clinical, psychoanalytic, and medico-legal lenses to assess diagnostic clarity, treatment history, and ethical considerations. No access to official medical records was available. Case Presentation: The first case involved a young woman whose depressive symptoms were reportedly linked to trauma from a terrorist attack. The second concerned a middle-aged woman convicted of infanticide and later diagnosed with Major Depression. Discussion: In both cases, euthanasia was granted on the grounds of “irreversible psychological suffering.” However, the absence of detailed clinical documentation, potential unresolved trauma, and lack of psychodynamic assessment raised doubts about the robustness of the evaluations and the validity of informed consent. Conclusions: These findings highlight the need for a more rigorous, multidisciplinary, and ethically grounded approach to psychiatric euthanasia. This study underscores the importance of precise diagnostic criteria, comprehensive treatment histories, and deeper exploration of unconscious and existential motivations. Safeguarding clinical integrity and ethical standards is essential in end-of-life decisions involving mental illness. Full article

Hypersomnia may be classified as primary or secondary, with secondary hypersomnia arising from a variety of underlying causes. Thus, according to ICSD3-TR classification, the diagnosis of idiopathic hypersomnia (IH) is established based on (1) excessive daytime sleepiness (EDS); (2) electrophysiological findings including either a mean sleep latency of less than 8 min on the Multiple Sleep Latency Test (MSLT) or increased total sleep (≥11 h) on 24 h polysomnography; and (3) systematic elimination of other potential etiologies, including sleep deprivation, substances, and medical, psychiatric (notably mood disorders), or sleep disorders. Nevertheless, the clinical heterogeneity observed in IH fuels an ongoing debate, reflecting the limited understanding of its underlying pathophysiological mechanisms. This report describes the case of a patient presenting with a clinical and polysomnographic phenotype of IH (MSLT < 8 min). A comprehensive psychopathological evaluation was performed to explore the possibility of secondary hypersomnia, which revealed features consistent with complex post-traumatic stress disorder (c-PTSD). Psychotherapy focused on c-PTSD was administered with positive and objective results in hypersomnolence/EDS. This clinical improvement suggests a potential relationship between psychological trauma and hypersomnia, a connection that is rarely described in the literature and warrants further investigation. This case highlights the need for a comprehensive assessment of secondary factors, particularly complex trauma, even in the presence of a clinical and polysomnographic phenotype consistent with IH. Full article

The early detection of neurological and psychiatric disorders is critical for optimizing patient outcomes and improving the efficacy of healthcare delivery. This study presents a novel multiclass machine learning (ML) framework designed to classify epilepsy, migraine, and schizophrenia simultaneously using electroencephalography (EEG) signals. Unlike conventional approaches that predominantly rely on binary classification (e.g., healthy vs. diseased cohorts), this work addresses a significant gap in the literature by introducing a unified artificial neural network (ANN) architecture capable of discriminating among three distinct neurological and psychiatric conditions. The proposed methodology involves decomposing raw EEG signals into constituent frequency subbands to facilitate robust feature extraction. These discriminative features were subsequently classified using a multilayer ANN, achieving performance metrics of 95% sensitivity, 96% specificity, and a 95% F1-score. To enhance clinical applicability, the model was optimized for potential integration into real-time diagnostic systems, thereby supporting the development of a rapid, reliable, and scalable decision support tool. The results underscore the viability of EEG-based multiclass models as a promising diagnostic aid for neurological and psychiatric disorders. By consolidating the detection of multiple conditions within a single computational framework, this approach offers a scalable and efficient alternative to traditional binary classification paradigms. Full article

Background and Objectives: Borderline personality disorder (BPD) is a complex psychiatric condition characterized by emotional instability, impulsivity, a fluctuating self-image, and persistent difficulties in maintaining close interpersonal relationships. Among university students, these traits may be associated with social adjustment and academic functioning difficulties. The present study aimed to examine the prevalence of borderline traits within a Romanian student population and to investigate the associations between these traits and interpersonal difficulties encountered in family life, romantic relationships, and academic environments. Materials and Methods: This cross-sectional study included a total of 151 undergraduate students enrolled in higher education institutions across Romania. Data were gathered through an online questionnaire available between March and May 2025. The instrument comprised items addressing socio-demographic characteristics, diagnostic criteria for borderline personality traits according to the DSM, as well as self-reported social behaviour patterns. Statistical analysis was performed using GraphPad Prism 9, version 9.3.1 for Windows, employing Fisher’s exact test and the odds ratio (OR), with a significance threshold set at p < 0.05. Results: Most participants reported experiencing affective instability (71.5%) and distorted self-image (58.9%). Fear of abandonment was present in 29.4% of the respondents, while impulsivity was identified in 37.7%. Borderline personality traits were significantly associated with a range of social difficulties, including relational anxiety, outbursts of anger, peer conflicts, social withdrawal, and dissociative symptoms. Individuals who exhibited impulsivity, self-injurious behaviours, or dissociative episodes demonstrated a markedly increased risk of social dysfunction, with odds ratios ranging from 3 to 10 (p < 0.0001). Conclusions: The findings reveal a high prevalence of borderline traits within the analysed sample, along with statistically significant associations with social and emotional difficulties. These results underscore the importance of implementing psychological screening programs in universities, as well as early intervention strategies focused on the mental well-being of young adults. Establishing a supportive academic environment and fostering collaboration between faculty members and mental health professionals may play a key role in preventing symptom escalation and in promoting healthy personal and relational development. Full article

Background: The use of neuromodulation for the treatment of psychiatric disorders has become increasingly common, but this emerging treatment modality comes with ethical concerns. This scoping review aims to synthesize the neuroethical discourse from the past 10 years on the use of neurotechnologies for psychiatric conditions. Methods: A total of 4496 references were imported from PubMed, Embase, and Scopus. The inclusion criteria required a discussion of the neuroethics of neuromodulation and studies published between 2014 and 2024. Results: Of the 77 references, a majority discussed ethical concerns of patient autonomy and informed consent for neuromodulation, with neurotechnologies being increasingly seen as autonomy enablers. Concepts of changes in patient identity and personality, especially after deep brain stimulation, were also discussed extensively. The risks and benefits of neurotechnologies were also compared, with deep brain stimulation being seen as the riskiest but also possessing the highest efficacy. Concerns about equitable access and justice were raised regarding the rise of private transcranial magnetic stimulation clinics and the current experimental status of deep brain stimulation. Conclusions: Neuroethics discourse, particularly for deep brain stimulation, has continued to focus on how post-intervention changes in personality and behavior influence patient identity. Multiple conceptual frameworks have been proposed, though each faces critiques for addressing only parts of this complex phenomenon, prompting calls for pluralistic models. Emerging technologies, especially those involving artificial intelligence through brain computer interfaces, add new dimensions to this debate by raising concerns about neuroprivacy and legal responsibility for actions, further blurring the lines for defining personal identity. Full article

Background/Objectives: Psychotic disorders with childhood or adolescent onset pose major therapeutic challenges due to their complex etiology and variable treatment response. While pharmacogenetics and neuroimaging biomarkers have independently shown potential for guiding therapy, their combined utility remains underexplored. This study aimed to investigate whether integrating CYP2D6 pharmacogenetic profiles with structural neuroimaging findings can enhance personalized treatment and predict clinical outcomes in pediatric psychotic disorders. Methods: This prospective observational study included 63 children and adolescents (10–18 years) with DSM-5 diagnosed psychotic disorders. All patients underwent baseline MRI and standardized clinical assessments (PANSS, CGI, GAF). CYP2D6 genotyping was performed in 31 patients (49.2%), categorizing them as extensive (EMs) or intermediate metabolizers (IMs). Patients were treated with atypical antipsychotics and followed for 18 months. Outcomes included symptom severity, global functioning, and side-effect profiles. Results: EM patients demonstrated superior clinical improvement, as evidenced by a reduction in PANSS scores (from 118 to 40) and a corresponding increase in GAF scores (from 39 to 76), compared to the IM and non-tested groups. IM patients exhibited a higher prevalence of MRI abnormalities and slower response. Significant correlations emerged between CYP2D6 genotype, MRI findings, and treatment outcomes (p < 0.001). Combined biomarker profiles enhanced the prediction of therapeutic response and tolerability. Conclusions: Integrating CYP2D6 pharmacogenetic data with neuroimaging biomarkers provides valuable guidance for personalizing antipsychotic treatment in pediatric psychosis. This approach improves clinical outcomes and reduces adverse effects. Future research should further explore the integration of multimodal biomarkers in larger, longitudinal cohorts to optimize individualized psychiatric care for this vulnerable population. Full article