Quality of life (QoL) in older adults with major psychiatric disorders is affected by various clinical and social factors, yet longitudinal evidence on QoL determinants remains limited. This study tests a comprehensive model of predictors of QoL using structural equation modelling (SEM). We analysed data from the Cohort of individuals with Schizophrenia Aged 55 years or more (CSA) study, a multicenter cohort of older adults diagnosed with schizophrenia, bipolar disorder, or major depressive disorder, recruited from 63 French psychiatric centers. QoL was assessed using the Quality-of-Life Scale (QLS) at baseline and follow-up (median = 3.0 years, SD = 1.44). We examined the simultaneous effects on QLS at follow-up of six predictor groups assessed at baseline, including (1) severity of general psychopathology, (2) severity of depressive symptoms, (3) severity of cognitive impairment, (4) psychotropic medications, (5) general medical conditions, and (6) sociodemographic characteristics. Six predictors showed significant independent longitudinal associations with QoL. Lower QoL was associated with greater depressive symptoms (β=-0.225), greater cognitive impairment (β=-0.117), antipsychotic polypharmacy (β=-0.538) and longer follow-up (β=-0.330) (all p-values<0.05). In contrast, higher baseline QoL (β=0.401) and greater levels of general psychopathology (β=0.291) were positively associated with follow-up QoL. Depression, cognitive impairment and antipsychotic polypharmacy emerged as markers of poorer QoL, independently of baseline QoL and diagnosis, although the association with depression was not robust in sensitivity analyses. The unexpected positive association with psychopathology is compatible with statistical suppression, measurement overlap, survival bias and limited illness awareness rather than a true benefit of symptoms.

Pediatric Tourette syndrome (TS) is heterogeneous, and functional outcomes are associated not only with tic severity but also with comorbid psychopathology and self-regulatory difficulties. We systematically reviewed (i) psychiatric/psychosocial comorbidities and their links to functioning and (ii) executive functioning (EF), explicitly contrasting performance-based and ecological measures. The protocol was preregistered on OSF and reported according to PRISMA. PubMed, PsycINFO, and Web of Science were searched from inception to 30 March 2025. Eligible studies included participants ≤18 years with TS and outcomes on psychiatric/psychosocial features and/or EF. Risk of bias was assessed using the Newcastle-Ottawa Scale. Thirty studies from 12 countries were included; 22 were rated low risk of bias. Given heterogeneity, findings were synthesized narratively. Comorbidity was common and ADHD-related symptoms were the most consistent correlates of externalizing problems, school difficulties, and poorer psychosocial functioning. Anxiety and obsessive-compulsive symptoms were frequent and associated with greater clinical complexity, while depressive symptoms tended to co-occur with broader psychosocial impairment. EF difficulties were more evident in TS with comorbidities, particularly ADHD, but groups with TS-only were not uniformly free of selective or context-dependent vulnerabilities. While performance-based tasks often indicated relatively preserved executive control in groups with TS-only, ecological/parent-report measures more consistently captured everyday difficulties (especially inhibition/behavioral regulation and working memory). A multidimensional view of pediatric TS highlights the importance of assessing tic severity together with psychiatric comorbidities, psychosocial functioning, and both performance-based and ecological EF measures.

Posttraumatic stress disorder (PTSD) is associated with neurocognitive decline and disease but the pathways linking these conditions are unclear. Recent preclinical and clinical research focused on depression and PTSD has suggested that the claudin-5 (CLDN5) protein, which comprises the tight junction proteins that seal the blood brain barrier, may relate to susceptibility to these stress-related conditions and associated neuropathology. We evaluated if we could replicate associations between CLDN5 DNA methylation and PTSD symptom severity in a large cohort of 22,835 Veterans enrolled in the VA Million Veteran Program. In the full cohort, we found evidence of replication for cg17411190 after adjustment for multiple testing (B = 2.76E-05, β = .017, p = .001, p-adj = .026), with cg05460329 replicating at the level of nominal significance (p = .023). In age-stratified analyzes, there was replication at cg17411190 and cg21872764 (ps = .046 and .009, respectively) at the nominally significant level in the age 65+ group. All associations replicated the effect directions seen in prior work. Results highlight the relevance of CLDN5 epigenetics for stress-related psychopathology and suggest that methylation of this gene in blood may be a useful biomarker for symptom severity and could potentially help to explain the association between PTSD and neuropathology.

Personality disorders (PDs) are commonly associated with impairments in social cognition, particularly emotion recognition. However, evidence also suggests deficits in more basic cognitive functions, including face processing (e.g., detection of non-emotional facial features) and indicators of general intelligence (e.g., crystallized intelligence). We addressed two exploratory research questions: first, how emotion recognition, face processing, and crystallized intelligence relate to personality pathology across categorical and dimensional PD models, and second, whether these associations primarily reflect general or specific personality pathology. We further hypothesized that the association between personality functioning and emotion recognition would be attenuated when controlling for face processing or crystallized intelligence. In a clinical sample (n = 219), cognitive abilities were assessed using performance-based measures, and personality pathology was assessed using interviews and self-reports. Structural equation modeling, including correlated factor and bifactor-(S-1) models, was applied to separate general from specific personality pathology variance. General personality pathology showed strong negative associations with emotion recognition and small-to-moderate negative associations with face processing and crystallized intelligence. Associations with specific personality pathology were substantially attenuated when controlling for general personality pathology. The link between personality functioning and emotion recognition was only minimally accounted for by face processing or crystallized intelligence. These findings suggest that cognitive deficits in PD may primarily reflect severity rather than disorder-specific variance, while the association between personality functioning and emotion recognition appears not to be reducible to face processing or crystallized intelligence. Our study suggests that dimensional models provide a more nuanced framework for understanding cognitive impairment in personality pathology.

Bipolar disorder (BD) is associated with cognitive impairment even during remitted states. Evidence suggests that these deficits may be linked to mitochondrial dysfunction and reduced metabolic activity in the prefrontal cortex (PFC), which may manifest as altered cerebral blood flow (CBF). Transcranial infrared laser stimulation (TILS) is a non-invasive photobiomodulation technique that targets the and may enhance mitochondrial activity through stimulation of cytochrome c oxidase, thereby increasing metabolic energy production and tissue oxygenation. However, the effects of TILS on brain perfusion in BD have not been well characterized. This study examined the effects of repeated TILS administration on CBF using arterial spin-labeled (ASL) MRI in individuals with remitted BD. Twenty-nine participants with BD received six weekly TILS sessions targeting bilateral frontopolar regions (Brodmann area 10). MRI scans were conducted at baseline, within 24 hours following the first TILS session, and within 24 hours after the sixth session. Repeated-measures ANOVA assessed CBF changes across time while controlling for bipolar subtype, age, and sex. Results revealed a significant acute increase in CBF following the first TILS session in the left superior frontal gyrus (BA10) and left orbital frontal cortex (BA11), followed by a significant decrease after six weeks of treatment. A decrease in CBF from session one to session six was also observed in the right anterior cingulate gyrus (BA32). These findings suggest a biphasic response to TILS and support further investigation of TILS as a potential intervention for cognitive impairment in BD.

Smooth pursuit eye movements (SPEM) allow the visual tracking of slowly moving objects. SPEM accuracy is adversely influenced by environmental complexity, such as background stimuli, and is impaired in psychiatric conditions including schizophrenia and major depressive disorder (MDD). In the presence of backgrounds, SPEM offer valuable tools to investigate cognitive control processes such as attentional allocation and interference control, thereby enabling the study of these cognitive functions in clinical populations. This preregistered study investigated behavioral and neural correlates of SPEM in individuals with MDD and healthy controls (N = 100). Participants performed a SPEM task during fMRI at 3T comprising blocks with and without a structured background pattern. Behaviorally, the presence of the structured background was associated with decreased pursuit gain, increased root mean square error (RMSE) and higher catch-up saccade rate (CUS), indicating reduced pursuit accuracy irrespective of group. At the neural level, the background condition elicited comparable BOLD response increases in both groups in smooth pursuit-related regions, particularly in occipital, and superior frontal areas. Exploratory functional connectivity analyses revealed increased connectivity in the background condition between key oculomotor and visual regions, including frontal eye fields, lateral geniculate nucleus, posterior parietal cortex, V1, and V5, with occipital fusiform gyri. Group comparisons indicated reduced connectivity within fronto-oculomotor and left fronto-striatal networks, but increased connectivity between visual and right prefrontal regions in MDD. These findings suggest altered and potentially compensatory neural mechanisms underlying SPEM pathways in MDD, despite preserved behavioral performance.

Despite the widespread use of memantine in modulating excitatory/inhibitory balance, the precise changes in the topology of brain networks following memantine administration in preschool children remain clearly undefined. The objective of this study is a quantitative evaluation of brain functional connectivity changes associated with memantine administration in using EEG-based network analysis. In this research, 22 preschool ASD children underwent treatment with memantine for one month. Resting-state electroencephalogram (EEG) signals were recorded before and after the intervention. functional connectivity matrices were extracted using the Phase Locking Value (PLV) index. Individual-level analysis revealed a Neurophysiological heterogeneity pattern, consisting of a 64% Subgroup with increased network integration (n = 14) with increased connectivity and 36% with decreased connectivity. SPN analysis identified distinct spatial components of network reorganization: (1) localized connectivity suppression in the fronto-central (Fz, F3) and left occipital (O1) regions captured by lower-order spatial filters, and (2) reinforcement of long-range functional coupling and enhanced nodal centrality in the right parietal (P4) and left temporal (T3) regions in higher-order filters. These findings suggest spatial network reorganization patterns associated with memantine administration, characterized by a complementary balance between localized phase decoupling and long-range functional integration.

Schizophrenia is characterized by persistent cognitive deficits that are largely refractory to current treatments. The CHRNA7 gene, encoding the α7 nicotinic acetylcholine receptor (α7 nAChR), has been implicated in both cognitive function and Schizophrenia susceptibility; however, its epigenetic regulation remains poorly defined. Here, we quantified DNA methylation (DNAm) at 14 CpG sites within the CHRNA7 promoter in 108 patients with first-episode Schizophrenia (FES) and 60 healthy controls (HCs). Cognitive performance was assessed using the Wisconsin Card Sorting Test (WCST), and clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS). FES patients exhibited promoter-wide hypomethylation, with significant reductions at CpG7/CpG14, and CpG10. CpG-resolved analyses revealed bidirectional associations with executive function: higher methylation at CpG2 and CpG6 correlated with improved performance, whereas hypermethylation at CpG7/CpG14 was associated with impaired cognitive flexibility and concept formation. In addition, CpG-specific methylation patterns were associated with symptom dimensions, including excitement and negative symptoms. Receiver operating characteristic (ROC) analyses showed that CpG3/CpG13, and CpG7/CpG14 discriminated FES patients from controls with moderate accuracy (AUC ≈ 0.791-0.803). Collectively, these findings identify site-specific alterations in CHRNA7 promoter methylation at disease onset and support a model in which CpG-resolved epigenetic variation contributes to cognitive heterogeneity in FES. These loci may represent candidate peripheral biomarkers and potential entry points for targeting cholinergic dysfunction.

The severity of depression and anxiety reflects the intensity of symptoms and their effects on daily functioning. Accurate severity prediction may support timely assessment and intervention. This study presents the Convolutional Kepler Mel Lightweight Equilibrium Fusion Graph (CKMLEG), a multimodal framework that predicts depression and anxiety severity using audiovisual data. The framework integrates the CK-ResNeXt network for visual feature extraction, Mel-frequency audio features, and a Lightweight Equilibrium Bidirectional Long Short-Term Memory model with explainable artificial intelligence (LEBLSTM-XAI). We use fine-grained pruning to reduce computational complexity and the Equilibrium Optimization Algorithm (EOA) to optimize model parameters. A three-layer multimodal architecture combines audio and visual representations for severity estimation. The framework is evaluated using the AVEC 2013 and AVEC 2014 datasets. The reported results include a severity prediction accuracy of 98.99%, a recognition accuracy of 99.87%, a mean absolute error (MAE) of 10%, an R[2] score of 98% and 99%, a mean squared error (MSE) of 40%, and a root mean squared error (RMSE) of 60%. These findings indicate the potential of the proposed framework for audiovisual depression and anxiety severity prediction. Further validation is required to establish its generalizability across different populations and recording conditions.

Prenatal alcohol exposure (PAE) can alter neurodevelopment and cause health and behavioral effects. Mental health challenges disproportionately affect individuals with PAE and are related to brain alterations. Cortical folding (gyrification) is associated with mental health in clinical populations and may help understand mental health difficulties in individuals with PAE. 161 datasets from 125 youth (57 PAE, 59 females) aged 7-21 years were included. T1-weighted magnetic resonance imaging and the caregiver-report Behavior Assessment System for Children were collected at baseline and 2-year follow-up. Images were processed to extract local gyrification index (LGI) from 20 mental health-related regions. Linear mixed-effects models were used to test the effect of PAE on associations between LGI and mental health symptoms. Youth with PAE had more Externalizing Problems (60.7 ± 15.5) than unexposed youth (54.8 ± 11.1; p < 0.001). PAE moderated the relationship between Internalizing Problems and LGI in the left posterior orbital gyrus and the left subcallosal area, and between Externalizing Problems and LGI in the right frontal pole and left subcallosal area. Higher LGI was associated with higher Internalizing and Externalizing Problems in participants with PAE; this association was weaker or absent in unexposed youth. This indicates a potential neurobiological basis for mental health challenges in individuals with PAE.