Introduction:To investigate the effects of continuous (cTBS) and intermittent (iTBS) theta burst stimulation applied over the lateral cerebellum on corticospinal excitability in healthy individuals. Methods:Twenty right-handed healthy male participants underwent three TBS sessions (cTBS, iTBS, sham) in a randomized crossover design. Motor evoked potentials (MEPs), resting and active motor threshold (RMT and AMT, respectively), and cortical silent period (CSP) were assessed before and after each session using single-pulse transcranial magnetic stimulation over the left primary motor cortex. Transcranial magnetic stimulation was delivered to the right cerebellar hemisphere at 80% of active motor threshold. Results:A significant reduction in MEP amplitude was observed following iTBS (p=0.028), while no significant changes occurred after cTBS or sham stimulation. No significant effects were found in RMT or CSP across any of the protocols. All sessions were well tolerated and considered safe. Mild and transient side effects, such as neck discomfort or headache, were reported in five participants. Conclusion:Intermittent cerebellar TBS was associated with reduced MEP amplitude, suggesting decreased corticospinal excitability, whereas cTBS and sham stimulation did not produce significant effects. Cerebellar TBS was safe and well tolerated in all participants. These findings suggest that cerebellar iTBS may exert modulatory effects on motor cortical excitability and may contribute to a better understanding of cerebellar stimulation effects in healthy individuals.
Introduction:The presence of bipolar disorder (BD) in individuals with ASD exacerbates social and cognitive impairments, complicates diagnosis and treatment. The aim of this study was to compare the serum levels of specific miRNAs between children with ASD with and without BD, and to explore their association with BD comorbidity in ASD. Method:A group of 41 pediatric patients with comorbid ASD + BD and a group of 47 pediatric patients with ASD without BD were included in the study. Serum miRNA levels were measured using quantitative real-time polymerase chain reactions, focusing specifically on miRNAs such as miR-132-5p, miR-134-5p, miR-206, and miR-126-5p. Results:The ASD + BD group exhibited significantly greater ASD severity than the ASD without BD group. Serum levels of miR-134-5p, miR-206, and miR-126-5p were all higher in the ASD + BD group than in the ASD without BD group (p=0.038, p=0.023, and p=0.026, respectively), while miR-132-5p levels were not significantly different (p=0.105). Furthermore, miR-134-5p levels were correlated with the frequency of manic episodes in the ASD + BD group (p=0.007). Conclusion:The study findings suggest that miRNAs may be involved in the pathophysiology of comorbid BD in children with ASD and may potentially represent candidate biomarkers for early diagnosis and intervention, thus contributing to improved clinical outcomes in this population. Further research is now needed to validate these findings and to understand the underlying mechanisms.
Introduction:Repetitive Transcranial Magnetic Stimulation (rTMS) is an FDA-approved, non-invasive neuromodulation technique with clinically supported efficacy in the management of treatment-resistant major depressive disorder (TRD). Although the clinical effectiveness of high-frequency rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) is well established, the molecular mechanisms underlying its long-term therapeutic effects remain incompletely understood. The aim of this brief report is to examine the possible epigenetic modifications (DNA methylation, histone modifications, microRNA) associated with the antidepressant effects of rTMS in light of current literature, and to evaluate the dose-response relationship that may affect treatment response within the framework of homeostatic plasticity. Methods:A summary of current literature from the PubMed, Web of Science, and Google Scholar databases is presented using the keywords "rTMS," "major depression," "epigenetics," "histone modifications," "DNA methylation," "miRNA," and "homeostatic plasticity." Clinical and preclinical studies specifically investigating the molecular effects of rTMS on synaptic plasticity were included. Results:The reviewed studies suggest that rTMS may not merely provide transient electrical stimulation but may also operate through an "epigenetic regulatory" mechanism capable of permanently altering neuronal gene expression. In preclinical studies, changes in histone acetylation (e.g., regulation of CDK5 and PSD-95) and specific microRNAs (e.g., miR-146a-5p) have been observed to modulate synaptic plasticity. Furthermore, it has been proposed that the dose-response relationship of rTMS is non-linear; excessive stimulation may activate "homeostatic plasticity" mechanisms, thereby reducing synaptic sensitivity. Discussion:Current findings indicate that rTMS may exert an antidepressant effect by reorganizing synaptic plasticity through epigenetic modifications. Enhancing treatment efficacy depends on optimizing the dosage by considering homeostatic balances and integrating epigenetic biomarkers capable of predicting treatment response into clinical practice. Future personalized treatment protocols should be designed based on these molecular and neurophysiological insights.
Introduction:Approximately 20-30% of temporal lobe epilepsy (TLE) cases present with no visible abnormalities on conventional magnetic resonance imaging (MRI). When interictal electroencephalography (EEG) recordings are also persistently normal, the diagnosis and lateralization become major clinical challenges. We aimed to investigate whether automated hippocampal subfield volumetry could detect subtle structural alterations in these "electro-clinically silent" MRI-negative cases and to correlate these findings with seizure semiology. Methods:We analyzed 24 patients with clinically diagnosed MRI-negative/EEG-negative TLE and 26 age-matched healthy controls. Despite normal visual inspection on 1.5-T MRI, hippocampal subfield volumes were extracted using an automated segmentation pipeline (volBrain). Seizure semiology was systematically categorized to provide clinical-anatomical correlation. Results:TLE patients exhibited a significant and selective volume reduction in the right CA4-dentate gyrus (CA4-DG) subfield compared to healthy controls (p=0.003), even after adjusting for age, sex, and total intracranial volume (p=0.002). No statistically significant differences were observed in other hippocampal subfields (CA1, CA2/3, or subiculum), indicating a highly localized pattern of structural alteration. Conclusion:These results imply that selective CA4-DG atrophy is a defining characteristic of the MRI-negative TLE phenotype, thereby corroborating the "dentate gate" failure hypothesis. Quantitative volumetry provides a crucial diagnostic tool in settings with limited resources, where advanced techniques like 3-T MRI or invasive monitoring are not accessible. This objective structural marker, when integrated with comprehensive semiological analysis, improves diagnostic accuracy and facilitates early clinical intervention in difficult non-lesional TLE cases.
Interleukin-6 (IL-6) is a multifunctional cytokine that plays a critical role in immune regulation, host defense, and tissue repair. Within the central nervous system (CNS), IL-6 contributes to both neuroprotection and neuroinflammation, depending on the signaling pathway involved; classic signaling, trans-signaling, or trans-presentation. Dysregulation of IL-6, particularly through sustained overexpression, disrupts the blood-brain barrier (BBB) integrity, promotes glial activation, and amplifies chronic inflammation, thereby contributing to the pathophysiology of numerous neurological disorders. This review aims to evaluate the role of IL-6 in neuroinflammatory processes and its clinical implications across a spectrum of neurological diseases. It focuses on the therapeutic potential and safety profile of IL-6 inhibitors, particularly tocilizumab and satralizumab. Key conditions discussed include neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein-associated disease (MOGAD), autoimmune encephalitis (AE), neuro-Behçet's disease (NBD), myasthenia gravis (MG), epilepsy, multiple sclerosis (MS), and Alzheimer's disease (AD). Clinical trials have demonstrated the efficacy of IL-6 receptor blockade in reducing relapse rates in NMOSD, leading to regulatory approvals. Promising off-label results have also been reported in treatment-resistant cases of MOGAD, epilepsy, and autoimmune conditions. However, IL-6 inhibition carries risks such as serious infections and paradoxical inflammatory reactions. Targeting the IL-6 pathway represents a significant advancement in neuroimmunology, offering new therapeutic opportunities for otherwise refractory conditions. Future research should focus on large-scale randomized controlled trials and the development of IL-6 inhibitors capable of crossing the BBB to enhance CNS-specific efficacy. Cost-related accessibility also remains a major challenge for broader clinical application.
Introduction:Perinatal loss is a highly distressing life event that may lead to severe grief reactions. Individual differences in attachment patterns may contribute to variability in perinatal grief severity. In this study, the association between attachment patterns and the severity of perinatal grief was examined, and the roles of psychological and clinical factors were evaluated. Methods:The sample consisted of 140 women with a lifetime history of perinatal loss. Perinatal grief severity was assessed using the Perinatal Grief Scale (PGS). Attachment-related variables were measured with the Parental Bonding Instrument (PBI) and the Experiences in Close Relationships -Revised Scale (ECR-R). Depressive and anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS), and perceived social support using the Multidimensional Scale of Perceived Social Support (MSPSS). Associations were examined using correlation analyses. Separate analyses of covariance were conducted to evaluate the effects of maternal and paternal bonding categories on perinatal grief severity while controlling for depressive symptoms, anxiety symptoms, perceived social support, and the time elapsed since the most recent perinatal loss. Mediation analyses were conducted using PROCESS. Results:Perinatal grief severity was positively correlated with depressive and anxiety symptoms. Maternal and paternal bonding categories were not directly associated with grief severity after adjustment. However, depressive symptoms significantly mediated the associations between maternal neglectful parenting and perinatal grief severity, and between paternal affectionless control and perinatal grief severity. No significant mediation effects were observed via anxiety symptoms. Conclusion:Attachment-related vulnerabilities appear to influence perinatal grief severity primarily through depressive symptoms rather than direct effects, highlighting the importance of assessing and addressing depression following perinatal loss.
Introduction:From the perspective of the developmental correlation between the face and brain, quantitative craniofacial findings such as tooth size may indicate important stages of neurodevelopment in the pathogenesis of schizophrenia. The aim of this study was to evaluate and compare maxillary tooth size and some dental anomalies in patients with schizophrenia in a blinded manner with non-psychiatric controls. Methods:A total of 200 participants (100 patients with schizophrenia and 100 control subjects) aged 18-45 were included in the study. Plaster dental models were prepared from the measurements of the maxillary dental arch. The mesiodistal (MD) and buccolingual (BL) dimensions of the maxillary teeth were measured on dental casts by two observers using digital calipers. In addition to dimensional assessments, dental abnormalities such as tooth rotation, diastema, tooth crowding, and peg-shaped lateral incisors were also recorded. Results:There was no statistically significant difference between the groups in terms of age and sex (p >0.05). Statistical analyses showed that patients with schizophrenia exhibited significantly smaller measurements in both MD (P <0.001) and BL (p <0.001) dimensions across all teeth evaluated. Furthermore, multivariate binomial logistic regression revealed MD size (B=-2.020, p <0.001) and the presence of diastema (Β=1.656, p <0.001) as significant independent predictors of schizophrenia. Conclusion:Reduction in tooth size and increased presence of diastema in patients with schizophrenia may contribute to the hypothesis that there are possible variations that may represent specific markers of embryological dysmorphogenesis underlying schizophrenia.
Introduction:Obesity and lifetime exposure to violence are preventable public health issues. The relationship between exposure to violence and obesity treatment outcomes has not been extensively investigated. The aim of this study was to examine the effect of childhood trauma and violence during adulthood on short -term weight loss success among individuals with obesity. Methods:The study included 89 female patients diagnosed with obesity who had no active psychiatric disorders. Participants were assessed using the Structured Clinical Interview for DSM-5, Clinical Version (SCID-5-CV). Childhood trauma was measured with the Childhood Trauma Questionnaire (CTQ-28). Exposure to physical, emotional, sexual, and economic violence during adulthood was evaluated using a researcher-developed questionnaire. After a three-month follow-up period, participants who achieved at least 5% weight loss, a short-term treatment target recommended for reducing morbidity were compared with those who did not. Results:A substantial proportion of participants (85.4%) reported experiencing at least one type of childhood trauma, and more than half (51.7%) had been exposed to at least one type of violence in adulthood. Participants who failed to achieve ≥5% weight loss had significantly higher CTQ subscale scores for physical abuse, emotional abuse, sexual abuse, physical neglect, and emotional neglect (p <0.05). A significant association was also observed between childhood trauma and subsequent exposure to violence in adulthood (p <0.01). Effective weight loss was less common among individuals exposed to physical, emotional, economic, or sexual violence during adulthood; however, multivariate analyses revealed that only economic violence was a significant risk factor for unsuccessful weight loss (aOR=5.65[2.05-15.55]). Conclusion:This study highlights the high prevalence of exposure to different types of lifetime violence among women with obesity and demonstrates a significant association between trauma history and diminished weight loss outcomes. Integrating trauma-focused approaches into obesity treatment may contribute to improving both treatment and prevention processes.
Introduction: Bipolar disorder is acomplex psychiatric condition marked by recurrent episodes of mania and depression. Despite its prevalence, the underlying pathophysiology remains poorly understood, and there is still a lack of objective biomarkers for diagnosis. Metabolomics is a promising approach for exploring biological alterations associated with specific mood states. This study aimed to investigate differences in the urinary metabolome between patients with bipolar disorder in the manic phase and healthy controls. Methods: Urine samples were collected from 22 manic bipolar disorder patients and 31 healthy controls. Samples were analyzed using Ultra-High Performance Liquid Chromatography Mass Spectrometry. The data were processed using MZmine and TidyMass, and then subjected to statistical and multivariate analyses in MetaboAnalyst 5.0. Metabolites showing significant fold changes were then evaluated using a receiver operating characteristic analysis. Results: The levels of two phosphatidylcholine derivatives, 1.2-dioleoyl-sn-glycero-3-phosphatidylcholine and 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, were significantly higher in the manic group (p<0.05). Receiver Operating Characteristic analysis revealed that these metabolites had limited discriminatory performance when evaluated individually. Conclusion: The findings suggest that the manic phase of bipolar disorder is associated with alterations in urinary lipid-related metabolites. While the identified metabolites exhibited modest diagnostic value individually, they could potentially reflect phase-specific metabolic changes relevant to bipolar disorder. These exploratory results warrant further investigation in larger longitudinal studies that include different mood states.
Introduction:Myeloid-derived suppressor cells (MDSCs) are key regulators of immune responses during chronic inflammation. Their role in early multiple sclerosis (MS) remains incompletely defined. We aimed to evaluate circulating monocytic (M-MDSC) and polymorphonuclear (PMN-MDSC) levels in newly diagnosed, treatment-naïve MS patients and to assess their functional suppressive capacity. Methods:Eighteen newly diagnosed MS patients and ten age- and sex-matched healthy controls were included. Peripheral blood MDSC subsets were quantified by flow cytometry. Clinical characteristics, MRI findings, and cerebrospinal fluid (CSF) parameters were recorded. Proof-of-concept functional validation was performed using T-cell proliferation assays assessed using CFSE fluorescence dilution by flow cytometry. Results:Both M-MDSC and PMN-MDSC percentages were significantly higher in MS patients compared with controls (p<0.001 for both). Myeloid-derived suppressor cell levels did not differ according to sex and showed no correlation with time from symptom onset, MRI activity, or CSF parameters. Functionally, sorted MDSC subsets suppressed activated T-cell proliferation. Conclusion:Newly diagnosed, untreated MS patients exhibit an expansion of circulating MDSCs with preserved suppressive capacity. These findings suggest that early MS may involve a systemic immunoregulatory response that is not fully captured by conventional clinical or radiological measures.
Introduction:Communication between individuals is based on communication in noisy environments. However, audiological tests used for the evaluation of hearing levels or determination of hearing loss are usually applied in a quiet environment. This study aims to evaluate whether depression has an effect on speech-in-noise perception and supra-threshold auditory processing abilities, even in individuals without advanced age or hearing loss. Methods:The study group comprised 29 individuals who did not have hearing loss but were diagnosed with depression. The control group consisted of 29 individuals who did not have hearing loss or a depression diagnosis. All participants underwent the Temporal Fine Structure adaptive frequency (TFS-AF) test to assess supra-threshold auditory processing abilities. The results were then compared between the study and control groups. Results:The study revealed significant differences in TFS sensitivity scores between the study and control groups, with test scores in the depression group being significantly lower than those in the control group (p=0.000). Conclusion:Depression can significantly affect auditory performance. Depression, alongside factors like hearing loss and aging, can impact auditory functions like speech intelligibility. Therefore, a more holistic approach that considers emotional status is essential for comprehensively evaluating listening skills and auditory functions, even in individuals without hearing loss.
Introduction: It has been demonstrated that the circadian rhythm influences the onset of ischemic stroke, however its impact on treatment strategies and clinical outcomes remains uncertain. The aim of this study was to investigate the association between the circadian timing of stroke onset and vascular risk profiles, stroke severity, prognosis, and treatment methods in patients with acute ischemic stroke. Methods: We retrospectively reviewed acute ischemic patients with stroke admitted to our University Hospital Stroke Unit (August 2017-December 2023). Patients were grouped by stroke onset time: Group 1 (wake-up/00:00-awakening), Group 2 (awakening-12:00), Group 3 (12:00-18:00), and Group 4 (18:00-00:00). Demographic and clinical characteristics, and acute stroke treatments, including intravenous thrombolysis (IV tPA) and thrombectomy were recorded. Outcomes were assessed using the modified Rankin Scale (mRS) at the first followup. Following univariate analyses, multivariable binary logistic regression identified independent predictors of IV tPA administration. Results: Among 1047 admissions, 751 patients met the inclusion criteria. There were 212 patients (28.2%) in Group 1, 231 patients (30.8%) in Group 2, 158 patients (21%) in Group 3, and 150 patients (20%) in Group 4. The prevalence of hypertension was significantly lower in Group 3 (p=0.0027). Multivariable analysis identified higher admission National Institutes of Health Stroke Scale scores (OR 1.202, p <0.001) and stroke onset time as independent predictors of IV tPA administration. Group 1 patients were significantly less likely to receive IV tPA (p <0.001), with no significant differences in etiology, mortality, or follow-up mRS scores. Conclusion: This study shows that IV tPA is less frequently administered to patients who experienced ischemic stroke during sleep. This finding highlights the need for tools that can enable earlier detection of stroke occurring during sleep. Despite the differences in IV tPA administration rates, stroke onset time did not significantly impact overall patient prognosis, including mortality and functional outcomes.
