Epilepsy is a chronic neurological disorder characterized by recurrent seizures, with variants in ion channel genes such as SCN1A, SCN1B, and CACNA2D2 implicated in neuronal excitability. This research aims to explore genetic polymorphisms in the SCN1A, SCN1B, and CACNA2D2 genes among Turkish epilepsy patients and assess their impact on responsiveness to antiseizure medications (ASMs). Targeted next-generation sequencing (tNGS) was applied to genomic DNA from 29 patients. Common 15 variants were analyzed in CACNA2D2 (rs2239801, rs56287038), SCN1A (rs2298771, rs3032638, rs11394960, rs67636132, rs566839, rs1461193, rs6432861, rs2020318) and SCN1B (rs72556351, rs2278995, rs557140301, rs67701503, rs55742440). A statistically significant difference in ASM response was observed in the recessive model of SCN1A rs2298771: C>T (TT vs. CC+CT) (p=0.044), with the TT genotype associated with improved response. CACNA2D2 rs56287038:G>T showed significance in the allelic model (p=0.012); the T allele was found only in resistant patients. SCN1A haplotype analysis revealed reduced C allele frequency in responders (p=0.041). The CT (rs2298771+rs2020318), CG (rs2298771+rs1461193), and CC (rs2298771+rs6432861) haplotypes also showed considerable differences among groups (p=0.041, p=0.023, p=0.041, respectively). Moreover, CTG (rs2298771+rs2020318+rs1461193), CCG (rs2298771+rs6432861+rs1461193), and CTCG (rs2298771+rs2020318+rs6432861+rs1461193) haplotypes were significantly associated with treatment response (p=0.023, p=0.023, p=0.022). However, none of these associations remained statistically significant after false discovery rate (FDR) correction, and all findings should therefore be interpreted as exploratory. CACNA2D2 rs56287038:G>T and SCN1A rs2298771:C>T may effect ASM response.

In recent years, growing attention has been given to the role of sleep disturbances in mental health outcomes, assuming a potential link between sleep problems and suicidality. This study applies a network analysis to examine how sleep quality is interconnected with suicidal thoughts and behaviours, as well as with a range of psychopathological symptoms. A total sample of 1674 participants (75.3% female, 24.7% male) from the general population were investigated and completed standardized assessments of sleep quality and psychopathological symptoms. A regularized cross-sectional partial correlation network between sleep quality (PSQI), suicidality (SSEV) and psychopathological symptoms (BSI-18) was estimated using the EBICglasso algorithm. Node centrality, predictability, and bridge centrality were evaluated, and bootstrap methods were employed to test the stability and significance of the network structure. The network was found to be stable, supporting reliable interpretations. Active suicide thoughts, anxiety and subjective sleep quality where found to be the most influential nodes within the investigated psychopathological network. Depression and daytime impairment due to poor sleep quality were observed as nodes with the highest bridge centrality. These findings highlight that depression and, importantly, daytime functioning related to poor sleep quality play a central role in linking suicidality and sleep quality. This emphasizes the need to address not only nighttime sleep problems but also daytime impairments as key clinical targets. Prioritizing interventions that improve sleep and restore daytime functioning may therefore be crucial in suicide prevention and clinical care.

Plain Language SummaryImpairments in facial emotion processing and recognition (FER) may be underpinned by transdiagnostic brain patterns in neuropsychiatric disorders. Identifying them may support shared social cognitive rehabilitation across these disorders. The European Psychiatric Ratings using Intermediate Stratified Markers Project 2 (PRISM2) studies emotional processing across schizophrenia, Alzheimer’s disease (AD), and major depression disorder (MDD) using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). fMRI provides high spatial resolution but limited temporal precision, whereas EEG affords millisecond temporal resolution with low spatial specificity. Magnetoencephalography (MEG) complements both, tracking millisecond-scale activity with better localization than EEG. In this systematic review, we summarized MEG studies of FER in adults with schizophrenia and MDD; no records were found in AD. Participants completed implicit (passive viewing or nonemotional judgment) or explicit (emotion identification/labelling) paradigms. We synthesized outcomes along two dimensions: regional activation and functional connectivity. Across studies, FER deficits were linked to limbic-prefrontal dysfunction in MDD and schizophrenia. Specifically, MEG reveals amygdala hyperactivity and prefrontal hypoactivity in FER tasks, and the temporal cortex shows early hyperactivation during impairments in facial emotion processing. Taken together, these findings outline a rapid spatiotemporal cascade: early amygdala over-response (salience detection), a transient rise in temporal activity during passive viewing (face processing), and later under-recruitment of prefrontal control with disrupted cortico-limbic communication. MEG indicates that social-cognitive impairments reflect a shared imbalance between detecting emotional salience and regulating it. This timing-based signature offers candidate brain targets for future neuromodulation and rehabilitative interventions.

Introduction: Obsessive-compulsive disorder (OCD) and related disorders (OCRDs) represent a group of conditions in which lack of response to first-line treatments, such as serotonin reuptake inhibitors (SRIs), is common. Therefore, exploring alternative strategies is necessary. We conducted a systematic review of the use of lithium in OCRDs. Methods: This systematic review was conducted in accordance with PRISMA guidelines. We included studies evaluating the use of lithium for OCRDs in adults. Eligible designs included case reports, case series, observational studies, and clinical trials. Four databases (PubMed, PsycInfo, Web of Science, and ClinicalTrials.gov) were searched on January 21, 2025. Response to lithium was defined by improvement on validated scales or, when unavailable, based on clinical descriptions. Results: Twenty-nine studies met inclusion criteria, including 25 case reports or case series and four clinical trials. Most studies focused on OCD (n = 20), followed by trichotillomania (n = 5), tic disorders (n = 3), and body dysmorphic disorder (n = 1). Across the full sample (n = 97), 38.1% of the subjects showed “clinical improvement,” although only 54.6% were assessed using validated instruments. Among case reports and case series (n = 37), 89.2% reported “improvement.” However, three crossover RCTs found no consistent benefit of lithium, and the only placebo-controlled trial did not detect significant differences between groups in the final pooled analysis. Analysis of individual data showed response to lithium to be more common among younger individuals (p = 0.02), those with comorbid bipolar disorder (p = 0.005), individuals receiving lithium as monotherapy (p < 0.018), and those without prior exposure to SRIs (p < 0.001). Additionally, responders were less likely to have been assessed using standardized instruments (p < 0.001). Conclusion: This is the first systematic review to evaluate lithium as a treatment strategy for OCRDs. While some reports suggest potential benefits, current evidence – largely based on low-quality studies without standardized assessments – does not support its use. Findings from randomized trials remain inconclusive, and further high-quality research is needed.

Introduction: Depression severely affects the psychosocial functioning and quality of life of patients. Among first-line selective serotonin reuptake inhibitors (SSRIs), the incidence of neuropsychiatric side effects caused by paroxetine is 4–6 times higher than that caused by citalopram. Methods: In this study, a depression model was established using Wistar rats to examine the effects of paroxetine and citalopram on neuronal nitric oxide synthase (nNOS) mRNA expression in the prefrontal cortex and hippocampus and to clarify the possible mechanisms of SSRI-induced neuropsychiatric side effects. Results: In the hippocampus, nNOS expression was significantly higher in the depression group than in the control group. However, in the prefrontal cortex, nNOS expression was significantly lower in the depression group than in the control group. Following the administration of postsynaptic density protein 95 (PSD-95)/nNOS inhibitor ZL006, nNOS levels decreased significantly in the paroxetine group but showed no significant change in the citalopram group. Conclusion: The mechanisms regulating nNOS expression differed between the paroxetine and citalopram groups. Paroxetine-induced nNOS expression may be associated with PSD-95/nNOS.

Introduction: There has been an increasing focus on sex differences in bipolar disorder in recent years, yet much remains to be understood about their impact on clinical characteristics and treatment approaches. The aim of this study was to identify sex differences that could alter diagnosis and treatment strategies, potentially improving patient compliance and outcomes. Methods: This retrospective study analysed data from interviews with 340 participants (171 men, 169 women; ages ranging from 18 to 82 years) from the BIPFAT/BIPLONG study at the specialised outpatient centre for bipolar disorder at the Medical University of Graz, Austria. We examined sex differences in clinical characteristics and drug therapy primarily using logistic and linear regression models, with chi-square tests and Mann-Whitney U tests applied as supplementary analyses for subgroup comparisons. Results: Our findings revealed that the age of onset for bipolar disorder was earlier in women (B = −3.05, 95% confidence interval [CI] = [−5.08, −1.02], p = 0.003), with women reporting their first affective symptoms at an average age of 22.7 (standard deviation [SD] = 9.9) compared to 26.4 (SD = 12.1) in men. Comorbid obsessive-compulsive disorder was significantly more prevalent in women (OR = 2.24, 95% CI = [2.12, 41.33], p = 0.003). In comparison, men were shown to experience manic episodes per year more frequently (B = −0.32, 95% CI = [−0.59, −0.05], p = 0.019). Differences in treatment emerged only within specific age subgroups rather than the overall study sample. Conclusions: Taken together, we found fewer differences than expected, which suggests that factors other than sex play a greater role in the course of bipolar disorder. Our analysis indicates that more women are suffering from obsessive-compulsive disorder (OCD) as comorbidity than men, a topic that has not yet been extensively researched. While previous studies mostly show that men have an earlier onset of symptoms, we found the opposite in our sample. Another notable difference in illness course was that men experienced more manic episodes per year. Further research in this area is needed to verify our findings, ideally focusing specifically on OCD in bipolar men and women, as sex differences in this comorbidity remain underexplored.

Plain Language SummaryAnorexia nervosa (AN) is a serious eating disorder that has become more common since the COVID-19 pandemic, placing a heavy burden on healthcare systems. People with AN often engage in excessive exercise to control their weight, and prolonged fasting can intensify their desire to move, making it harder to manage the disorder. However, treatment approaches rarely address this strong urge to be physically active, even though it plays a key role in maintaining the illness. Our study explored a new method using virtual reality (VR) to help reduce this urge. Three young women with severe AN took part in a 4-week program where they experienced four sessions of virtual jogging. The aim was to reduce the immediate urge to move and improve other symptoms of AN. Before and after the program, we assessed changes in symptoms like body dissatisfaction, emotional regulation, and compulsive exercise habits. The results showed that all participants experienced a noticeable reduction in their urge to move after each VR session. Improvements were also seen in feelings about body image, emotional regulation, and compulsive exercise for some participants. Importantly, the VR experience was well received, with participants suggesting it could be helpful in outpatient care. This study is a promising first step in introducing the use of VR to address physical activity urges in AN treatment, but further research is needed to refine the method and test its efficacy and long-term effectiveness.

Introduction: Major depressive disorder (MDD) is a common, relapse-prone psychiatric disorder with unknown pathogenesis. Previous studies on resting-state functional magnetic resonance imaging of MDD have mostly focused on the spontaneous activity of blood oxygen level-dependent (BOLD) signals; however, a few studies have investigated BOLD signal stability. Methods: We conducted a resting-state functional study in 42 patients with MDD and 42 healthy controls (HC) matched for age and sex. This included the BOLD signal stability, resting-state functional connectivity (RSFC) analysis, correlation analysis, and support vector machine (SVM) analysis. Results: The BOLD signal stability of the left fusiform gyrus, right inferior temporal gyrus, right temporal pole superior temporal gyrus, and left thalamus was significantly lower in the MDD group compared to the HC group. Further RSFC analysis revealed that the connectivity between right inferior temporal gyrus and both left inferior temporal gyrus and left supramarginal gyrus was significantly reduced in the MDD group. Additionally, the RSFC levels of left thalamus and right thalamus were decreased. Combining BOLD signal stability and RSFC, the SVM-based classification model achieved an accuracy of 80.95% (sensitivity: 78.57%; specificity: 83.33%; receiver-operating characteristic area under the curve: 0.8793). Conclusion: The integration of the BOLD signal stability index and RSFC index demonstrates a robust capability to differentiate between individuals with MDD and HC subjects. We tentatively believe that a combination of the BOLD signal stability index and RSFC can be used to diagnose MDD.

Introduction: Light is a key factor in moderating human alertness, both subjective and objective. However, the methodology applies in research on the effects of exposure to light of different wavelengths and intensities on objective and subjective alertness varies greatly and evidence on objective alertness in particular is still inconclusive. Thus, the present, highly standardized within-subject laboratory study on N = 44 healthy males explored how LED light of different intensities (dim vs. bright light) and wavelengths (red vs. blue) affected objective (reaction time/RT) as well as subjective (sleepiness) alertness in the morning after wake-up. Methods: Participants spent two separate nights in the laboratory and were exposed to either one of the two light intensities or colors for 60 min after wake-up. Additionally, they indicated their sleepiness on the Karolinska Sleepiness Scale and participated in an auditory RT task before and after light intervention. It was hypothesized that both bright and blue light would lead to greater subjective and objective alertness when compared to dim and red light, respectively. Results: Results indicated that average RTs were longer for participants in the bright light condition (p = 0.004, f2 = 0.07) and that RTs decreased post-light exposure irrespective of light being dim or bright (p = 0.026, f2 = 0.07). However, dim versus bright light and RT did not interact (p = 0.758, f2 = 0.07). Chronotype was a significant covariate in the interaction of dim versus bright light and subjective sleepiness (p = 0.008, f2 = 0.22). There was no difference in RTs when comparing exposure to red or blue light (p = 0.488, f2 = 0.01). Findings on subjective sleepiness and light of different wavelengths revealed that sleepiness was reduced after light exposure (p = 0.007, f2 = 0.06), although the wavelength of light did not appear to play a role in this effect (p = 0.817, f2 = 0.06). Conclusion: Hence, neither of the hypotheses could be confirmed. However, they indicated that evening types might benefit from exposure to bright light regarding sleepiness, but not morning types.