High rates of comorbid posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) may stem from a shared neurobiological basis; however, research exploring this overlap remains limited. We examined whole-brain structural covariance (SC) across PTSD, AUD, comorbid PTSD & AUD, trauma-exposed controls, and trauma-naïve controls to identify shared and unique SC profiles. Structural brain scans were acquired from individuals across 14 sites (N = 1565), and cortical thickness estimates were extracted to compute SC. Group differences in SC between pairs of cortical regions were examined using the Network-Based statistic and quantified using local and global graph theory (GT) measures. Clinical groups showed consistent alterations in SC compared with trauma-naïve controls, characterised by lower SC involving frontal regions, particularly the inferior frontal gyrus and frontal pole, which also demonstrated high centrality in local GT analyses. In contrast, higher SC was observed in temporal regions, with the fusiform gyrus consistently emerging as a central region. Comparisons involving PTSD & AUD also showed increased SC in occipital regions, suggesting a potentially distinct pattern of structural organization in this group. Global GT analyses demonstrated altered network organization in clinical groups, including increased clustering and path length, and reduced global efficiency relative to trauma-naïve controls. Local efficiency was increased in PTSD and PTSD & AUD, but not AUD alone. Together, these findings indicate that alterations in frontal and temporal regions are implicated across PTSD, AUD, and their comorbidity. However, the PTSD & AUD group also exhibited additional occipital lobe alterations, suggesting a broader distribution of structural covariance alterations in the comorbid group.

Schizophrenia (SZ) is a neurodevelopmental disorder influenced by genetic and environmental factors. The stress-related gene FKBP5 shows genetic, epigenetic, and expression variability associated with SZ. Although FKBP5 methylation has been related to brain structural changes in psychiatric conditions, its role in the cortical thinning and cognitive deficits distinctive of SZ remains unexplored. We examined whether case-control differences in FKBP5 methylation are associated with cortical thickness and cognitive performance. In a case-control study (35 SZ, 35 HC), we assessed FKBP5 methylation (EpiTYPER), cortical thickness (FreeSurfer), and intelligence quotient (IQ). A sparse PLS-DA approach identified a latent component (LC1) capturing methylation differences. We tested the effect of LC1 on cortical thickness (brain clusters showing group differences) and IQ scores, using linear regressions. Next, we examined the relationship among methylation, neuroanatomical, and cognitive changes through a mediation analysis. LC1 was associated with reduced cortical thickness in the right pars opercularis (β = -2.15, p = 0.002). Thickness in this region was positively associated with IQ (β = 35.14, p = 0.011), but there was no direct LC1-IQ association. Mediation analysis revealed a significant indirect effect of methylation on IQ via cortical thickness (ACME = -62.96, p = 0.046; ~40% of the total effect), which was not significant after adjusting for diagnosis. Our results represent the first analysis of the effect of FKBP5 methylation on neuroanatomical and cognitive variability in SZ, highlighting that methylation-related differences associated with the disorder are connected to structural and cognitive alterations.

Resting-state fMRI (RS-fMRI) has been known for decades as a promising method for evaluating cognitive and mental states, both in health and especially in disease, due to its ease of implementation as a short, standard MRI protocol. In clinical settings, a group of patients with a given disorder is typically compared to a group of healthy controls. This poses an inherent challenge of between-group comparison. We propose a new efficient model for characterizing changes to the temporal synchronization of brain activity measured using RS-fMRI between groups, summarized as individual correlation matrices. Our model posits that the between-group differences are the product of single-region effects describing the increase or decay of synchronization with the rest of the brain. This parsimonious model pools the correlation coefficients of each region with all others, and therefore can detect differences between groups even in small samples. Inference for this model accounts for the variability in individual correlation matrices, the within-group differences across individuals, and for the approximation error of the single-region model. This results in per-region estimates and confidence intervals for the parameters governing the difference between groups. In simulations, our model shows increased power to detect model-aligned alternatives compared with competing approaches. To demonstrate feasibility of the method in a clinical application, we use the model to analyze RS-fMRI correlation matrices in patients with transient global amnesia and healthy controls. Our model detects significant decreases in synchronization for the patient population in the amygdala after multiplicity correction as well as borderline decreases in memory-related brain regions that were not detected using mass-univariate tests without prior knowledge, suggesting its usefulness in the application of RS-fMRI in clinical settings.

Since young adults hear sounds up to 20 kHz, the loss of extended high-frequency hearing (EHF; above 8 kHz) is a hallmark of age-related hearing loss, often progressing from early lifetime. However, this deficit frequently goes undetected because routine clinical hearing tests and most hearing aids are currently mostly limited to 8 kHz. EHF hearing has been linked to deficits in speech perception in noise and to self-reported hearing. However, it remains elusive how EHF hearing influences speech intelligibility. Here we recorded neuromagnetic brain responses using magnetoencephalography (MEG) within a frequency-tagging speech paradigm designed to probe hierarchical levels of attention and memory-dependent speech processing and recognition. Auditory evoked cortical magnetic field (AEF) responses were significantly reduced in both left and right brain hemispheres in individuals with impaired EHF hearing compared to those subjects with better EHF hearing. A gradual reinforcement of left-hemispheric AEF seen over age was not observed in young adults (19-29 y) with preserved EHF hearing. This was linked to stronger auditory brainstem responses (ABR), reflecting better neural synchronized auditory responses at stimulus onset. The reinforced left hemispheric dominance in young adults with impaired EHF hearing, in contrast, was linked to lower ABRs. Our findings suggest that through its impact on stimulus-onset synchrony to phase locking of oscillations in the auditory cortex, sound energy above 8 kHz contributes to the intelligibility of speech. Together, the results highlight the need to reconsider EHF hearing in both audiological assessment and hearing-aid design.

Contemporary diagnostic classifications recognise euphoric and irritable mood as core presentations of mania. Whether these predominant affective states reflect distinct clinical profiles or dimensional variations remains unclear, particularly in naturalistic inpatient settings.

We conducted a retrospective observational study of admissions for manic episodes between 2017 and 2025 at a tertiary psychiatric unit in Porto, Portugal. Eligible admissions had an ICD-10 discharge diagnosis within F30 (manic episode) or F31 (bipolar affective disorder). Electronic records were reviewed to classify predominant mood at admission as euphoric or irritable based on the affective tone documented in the admission psychiatric assessment and early inpatient notes. Several reviewers collected data, with each admission assessed by one reviewer. Demographic, clinical and treatment variables were compared between groups, and variables with potential univariate associations were entered into a multivariable GEE logistic regression model accounting for clustering by patient.

A total of 251 inpatient manic episodes were included: 151 (60.2%) predominantly irritable and 100 (39.8%) euphoric. No clear evidence of between-group differences was found in the demographic and clinical characteristics examined, including psychotic symptoms, previous psychiatric admissions and length of stay. No statistically significant differences were observed in the treatment variables examined.

Irritable mood was more frequently documented than euphoric mood in this inpatient sample. No clear evidence of differences was found in the main demographic and clinical characteristics examined; however, the study does not establish equivalence between presentations. Prospective studies using standardised and repeated assessments are needed to determine whether predominant affective tone has independent clinical relevance.

Eating disorders (EDs) frequently emerge during adolescence and are influenced by both individual and contextual factors. Among these, perceived social support has generally been associated with better outcomes, although findings remain inconsistent and may depend on both the source of support and individual differences in responsiveness to environmental inputs. The present study examined the role of Environmental Sensitivity (ES) and perceived social support in adolescent ED symptoms, focusing on different sources of support and their potential interaction within a vantage sensitivity framework. A sample of 466 adolescents (51.61% female; M = 14.80) completed self-report measures of ED symptoms, ES, and perceived social support. At a bivariate level, higher perceived support from family, teachers, friends, and peers was associated with lower ED symptoms. In covariate-adjusted models, only teachers' and family's support remained a significant predictor, while peer-related sources were no longer associated with ED symptoms. ES was consistently and positively associated with ED symptoms. Contrary to hypotheses, ES did not moderate the association between overall perceived social support and ED symptoms. Exploratory analyses suggested a sex-specific pattern, whereby the association between perceived social support and ED symptoms appeared to vary as a function of ES among males, but not females. These findings suggest that the association between social support and adolescent ED symptoms may depend on its source. Moreover, ES was consistently associated with ED symptoms. Exploratory analyses revealed that evidence for differential responsiveness to supportive contexts may vary by ES among males.

Heart rate variability (HRV) and electroencephalography (EEG) are reflective of cardiac autonomic modulation/emotional regulation and cortical brain activity/psychopathology, respectively. This study aimed to determine the key HRV/prefrontal EEG classifiers of healthy controls (HC) versus patients with psychiatric disorders (PT) and to identify the subtypes of these features. A simultaneous 5-min-long acquisition of earlobe photoplethysmography and resting-state prefrontal EEG signals was performed in 147 HC and 123 PT [major depressive disorder (MDD; N = 107) and panic disorder (N = 16)]. A mixed graphical model (MGM) was constructed using the 9 HRV-related features, 11 prefrontal EEG-related features, depressive symptoms and anxiety, and psychiatric diagnosis by licensed psychiatrists. Top 12%-ranked nodes in regards of the betweenness centrality or expected influence were defined as hubs to be employed in the eXtreme Gradient Boosting (XGBoost) classifier model and the latent profile analysis (LPA): 2 HRV-related features [total power (TP), absolute power in low frequency band (LF)], 4 prefrontal EEG-related features [relative powers in frequencies of theta (THETA), low-alpha (L_ALPHA), low-beta (L_BETA), middle-beta (M_BETA)], and anxiety. The XGBoost model had an accuracy of 74.9 ± 5.6%. The SHapley Additive explanation values demonstrated that lower anxiety and M_BETA were indicative of a higher probability of being a HC. A lower LF indicated a greater possibility of being a PT. The LPA identified 3 PT subgroups of (1) hyperarousal [severe depression and moderate anxiety; higher M_BETA and lowered HRV], (2) relatively stable [minimal depressive symptoms and anxiety; no marked frontal EEG deviation and lowered HRV], and (3) frontal EEG slowing [moderate depression and mild anxiety; higher THETA and markedly lowered HRV in TP and LF]. Future studies to determine the results of risk indicators for patients with psychiatric disorders using HRV and prefrontal EEG features derived by the combined use of network-based feature selection, machine learning-based classifiers, and latent class subtyping in diverse populations are warranted. TRIAL REGISTRATION: N/A.

The transition from Judicial Psychiatric Hospitals (OPGs) to the post-OPG system provides a historical context for examining psychiatric residential care in Italy. We described differences in the characteristics of admissions to one high-intensity psychiatric residential facility across two recorded periods surrounding this transition.

This retrospective single-centre study included 117 consecutive patients admitted to SRP1 "Tiziano" in Tuscany (40 in the earlier cohort and 77 in the later cohort). The cohorts were defined by admission before versus on or after 31 March 2015, the statutory OPG-closure deadline; this date serves as a historical reference point rather than an instantaneous intervention. Referral sources, diagnoses and available outcomes were compared descriptively. A post hoc exploratory logistic regression with three covariates was fitted in 116 complete cases; the originally submitted eight-covariate model was retained as sensitivity analysis.

OPG/REMS referrals accounted for 22/40 (55.0%) earlier and 20/77 (26.0%) later admissions; referrals from acute psychiatric wards (SPDCs) accounted for 5/40 (12.5%) and 40/77 (51.9%), respectively (overall referral-source comparison p < 0.001). Multiple psychiatric diagnoses were recorded in 22/40 (55.0%) and 61/77 (79.2%) (p = 0.006); the dedicated personality-disorder indicator was positive in 11/39 (28.2%) and 45/77 (58.4%) (p = 0.002). In the exploratory model, SPDC referral (adjusted odds ratio [aOR] 11.50, 95% CI 3.61-36.67), personality disorder (aOR 5.95, 95% CI 2.20-16.13) and age (aOR 1.05 per year, 95% CI 1.01-1.10) were associated with later-cohort membership. At the 31 December 2025 cut-off, 105 patients had been discharged and 12 later-cohort patients were still admitted. Completed-stay durations were available for all 105 discharged patients, including one duration of 784 days recovered from source clarification; seven discharge destinations were unrecorded or coded as missing.

In this single facility, admission pathways and recorded diagnostic characteristics differed across historical periods surrounding the Italian forensic psychiatric transition. Findings are descriptive and exploratory; they neither establish effects of Law 81/2014 nor support nationwide generalization. At data closure, 12 later-cohort admissions were ongoing and seven of 105 discharged patients had an unavailable destination. Comparisons restricted to completed stays do not estimate overall time to discharge. Multicentre studies with verified dates, standardised outcome coding and appropriately censored follow-up are needed.

Patient safety is a strategic priority for healthcare systems. In Spain, decentralisation of the National Health System (NHS) facilitates the adaptation of policies to regional characteristics, but poses challenges in terms of coordination, standardisation, and evaluation.

To compare regional patient safety strategies, assess their concordance with the 2015-2020 and 2025-2035 NHS strategies, and identify the changes and advances introduced in the new national strategy compared with its predecessor.

A retrospective descriptive study was conducted using documentary analysis of the strategies of Spain's 17 autonomous communities and the autonomous cities of Ceuta and Melilla. Their general characteristics and lines of action were analysed and classified according to their hierarchical level as primary, secondary, or absent. Concordance was assessed by directly comparing regional lines of action with conceptually equivalent lines in the 2015-2020 and 2025-2035 NHS strategies. An evolutionary content analysis was also conducted to identify changes between the two national strategies. Two researchers independently reviewed and coded all documentation, resolving discrepancies by consensus.

Fourteen regional strategies were identified, showing considerable heterogeneity in structure, terminology, content, and evaluation systems. Eleven lines of action were present in all 14 strategies (100%), including organisation and leadership, safety culture and training, patient involvement, risk management, incident reporting, and safe practices related to healthcare-associated infections, surgery, medication, patient identification, and care. Coverage was lower for digital health and safe use of information and communication technologies (28.6%), safe healthcare environments and emergency care (35.7%), and transfusion safety, diagnostic safety, and low-value practices (42.9%). The 2025-2035 NHS strategy broadens the scope of safe clinical practices and incorporates emerging challenges related to digitalisation, continuity of care, and the reduction of low-value practices.

Regional patient safety strategies show broad convergence around core lines of action, together with substantial heterogeneity in structure, terminology, and coverage of less established areas. Areas related to organisation and leadership, safety culture, training, incident management, and several safe clinical practices show greater coverage, whereas diagnostic safety, mental health, support for second and third victims, care transitions, remote care, emergency care, and reduction of low-value practices show more variable presence and hierarchical positioning across regions. The evolution from the 2015-2020 to the 2025-2035 NHS strategy reflects an expansion of strategic priorities, particularly in safe clinical practices, digitalisation, continuity of care, and reduction of low-value practices.

Nutraceuticals and phytoceuticals are increasingly investigated for bipolar disorder (BD). We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs). PubMed/MEDLINE, EMBASE, Scopus, PsycINFO, and ClinicalTrials.gov were searched from inception to July 1, 2025. Co-primary outcomes were changes in depressive or manic symptoms (standardized mean difference [SMD]), treatment response, and acceptability (risk ratio [RR]); tolerability and remission (RR) were secondary outcomes. Heterogeneity, transitivity, inconsistency, small-study effects, risk of bias, and confidence in evidence (CINeMA) were assessed. Twenty-eight RCTs (n=2,222) evaluated 22 treatments. No treatment outperformed placebo for depressive symptoms; placebo outperformed palmitoylethanolamide (SMD=2.69, 95% CI 1.43-3.95), based on one trial, amid substantial heterogeneity (I²=86%) but no global inconsistency. For manic symptoms, palmitoylethanolamide (SMD=-4.58, 95% CI -6.24 to -2.92) and folic acid (SMD=-2.42, 95% CI -4.06 to -0.79) outperformed placebo, with substantial heterogeneity (I²=91.3%) and no global inconsistency. Sensitivity analyses supported palmitoylethanolamide, although the finding relied on one RCT from a region producing larger-than-average SMDs. Meta-regression indicated that larger effects were associated with lower adapted AMSTAR-Plus scores. Free-and-easy-wanderer-plus™ combined with carbamazepine outperformed placebo for response and acceptability. CINeMA ratings varied and were predominantly low or very low, particularly for manic symptoms. Current evidence does not support firm recommendations for any nutraceutical or phytoceutical in acute bipolar depression or mania, and further high-quality research is needed.