The VALFASS study evaluated the SPF-10, a new 10-item patient-reported outcome measure developed with direct patient involvement to assess self-perceived functioning in schizophrenia. Covering autonomy, relationships, occupation, independence, and everyday capabilities, the SPF-10 was designed to address limitations of existing instruments, including limited patient input, reduced feasibility for routine use, and incomplete capture of the patient perspective. This cross-sectional, multicenter study included 155 participants: 44 recently exacerbated patients with schizophrenia, 55 clinically stable patients, and 56 healthy controls. The SPF-10 showed excellent feasibility, with a 100% item response rate and a median completion time of 5 min. Exploratory factor analysis supported a two-dimensional structure, Personal and Social Relationships and Self-Care and Capabilities, explaining 57.7% of the variance. The total SPF-10 score discriminated well between patients and controls (AUC = 0.888) and between patients with moderate-to-severe functional impairment and those with mild or no impairment (AUC = 0.851). A cut-off score of ≤32 yielded 80.8% sensitivity, 84.4% specificity, and 82.6% overall correct classification. Correlations with clinician-rated functioning measures were moderate (PSP r = 0.559; GAF r = 0.521), supporting its complementary value, and internal consistency was good in both patients and controls (Cronbach's α = 0.868 and 0.838, respectively). Overall, the SPF-10 showed adequate psychometric performance and high clinical applicability. Its brief format, patient-centered development, and ability to capture aspects of functioning not fully reflected by clinician-rated instruments support its potential value as a complementary tool for person-centered assessment and care planning in schizophrenia.

Functional neurosurgery has evolved from a marginal and controversial intervention into a promising, technically feasible option for carefully selected patients with treatment-resistant psychiatric disorders. Among available techniques, deep brain stimulation has gained increasing clinical acceptance for selected patients with severe obsessive–compulsive disorder and Tourette syndrome, while other psychiatric indications, including treatment-resistant depression, substance use disorders, schizophrenia, anorexia nervosa and pathological aggression, remain largely investigational or restricted to clinical trials and highly specialized programs. However, the absence of harmonized preoperative assessment standards across centers highlights the need for a structured, multidisciplinary framework to guide consistent clinical decision-making and ensure procedural safety. The framework proposed in this review is intended to support structured clinical profiling and outcome monitoring, but should not be interpreted as a substitute for professional consensus recommendations, multidisciplinary clinical judgment, ethics committee review, or applicable regulatory requirements. This narrative review examines the current role of functional psychosurgery in psychiatry, with particular focus on structured preoperative assessment models that optimize patient characterization within specialized clinical settings. We propose a pragmatic, circuit-informed framework integrating diagnostic precision, psychopathological assessment, neuropsychological profiling, functional evaluation, and ethical-regulatory oversight. By synthesizing evidence across psychiatric disorders, neurobiological models, and multidimensional assessment strategies, we outline a practical framework for preoperative characterization and outcome monitoring in psychiatric neurosurgery. When applied within specialized centers and under rigorous clinical, ethical, and regulatory oversight, functional psychosurgery may offer clinically meaningful symptom relief and improved quality of life for carefully selected patients who have exhausted conventional treatments.

INTRODUCTION:Air pollution is a global health threat increasingly linked to mental disorders. Exposure to particulate matter (PM10), nitrogen dioxide (NO2), and ozone (O3) has been linked to higher risk of these conditions. Evidence is strongest for NO2, while findings for PM10 and O3 remain inconsistent, particularly in Southern Europe. METHODS:We conducted a cross-sectional study geolinking 2019 mental health diagnoses from the PADRIS-PRESTO cohort (n=1,415,944) with air pollution data from 30 health districts in Catalonia, Spain. Annual mean concentrations of NO2, O3, and PM10 were estimated. Logistic regression models, adjusted for age, sex, socioeconomic status, and health district, examined associations between pollutant exposure tertiles and the prevalence of major depressive disorder (MDD), anxiety disorder (AD), bipolar disorder, schizophrenia (SCZ), attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). RESULTS:NO2 exposure showed the strongest associations, including a moderate effect for ADHD (OR=2.04, 95%CI: 1.94-2.15) and small positive associations with ASD, SCZ, and AD (OR range: 1.27-1.31). O3 demonstrated a small positive association with ADHD (OR=1.41, 95%CI: 1.36-1.46) but showed no substantive associations with other disorders. PM10 showed mostly null or inverse associations, including a small inverse association with ADHD (OR=0.76, 95%CI: 0.73-0.79). CONCLUSIONS:This large population-based study found consistent associations between NO2 exposure and neurodevelopmental and psychotic disorders, whereas O3 and PM10 showed weaker or inconsistent relationships. These findings highlight the need for longitudinal research to clarify causality.

Employment is a key determinant of recovery in severe mental illness, yet longitudinal evidence from Southern Europe is limited. We aimed to examine national trends in employment status among individuals with schizophrenia and bipolar disorder in Spain between 2018 and 2023. We conducted a register-based trend study using the Spanish Primary Care Clinical Database (BDCAP), including adults aged 20–64 years with schizophrenia (n = 139,594), bipolar disorder (n = 148,968), or other diagnoses (n = 25,953,622). Employment status was classified as employed, unemployed, economically inactive, disability pensions, or other statuses. Trends were analysed with Joinpoint regression, reporting Average Annual Percent Change (AAPC) with 95

BACKGROUND AND HYPOTHESIS:Patients with first-episode psychosis (FEP) frequently experience early metabolic alterations, including antipsychotic-induced weight gain (AIWG) and fasting glucose dysregulation. Birth weight (BW), a marker of the intrauterine environment and development, and its genetic proxy-the polygenic risk score for BW (PRSBW)-may influence these trajectories. This study investigated whether PRSBW and BW are associated with the progression of AIWG and fasting glucose levels over 24 months in individuals with FEP. STUDY DESIGN:A total of 277 FEP patients with genetic, BW and longitudinal metabolic data were included. Linear mixed-effects models assessed associations of BW and the PRSBW with mean AIWG and glucose, as well as interactions with time. BW was analyzed both as a continuous variable and categorically (Lower/Higher vs. Intermediate BW). STUDY RESULTS:BW was significantly associated with mean AIWG across 24 months (p=.009), with higher BW linked to greater AIWG. In contrast, neither BW nor the PRSBW were associated with mean fasting glucose levels. Significant time×BW and time×PRSBW interaction effects emerged for AIWG (p=2.2e-06 and p=4.6e-04, respectively), indicating steeper AIWG trajectories in individuals with higher BW or PRSBW. CONCLUSIONS:Our findings suggest that both BW and PRSBW influence the progression of AIWG in early stages of psychosis, reinforcing the role of early-life, both environmental and genetic, factors in shaping metabolic vulnerability. The consistent association between BW-related markers and AIWG highlights their potential value for early risk stratification and targeted prevention of adverse metabolic outcomes.

Schizophrenia, a chronic psychiatric disorder, has prompted extensive research into its immunological aspects. Studies in genetics, epidemiology, and treatment have revealed immune changes associated with schizophrenia, including shifts in cytokine levels and microglial reactivity within the central nervous system (CNS). However, the term “neuroinflammation” has been used to describe these findings despite inconsistent classical markers, potentially oversimplifying the complex role of immune mediators in neurodevelopment and brain homeostasis. In this paper, we critically examine the limitations of applying “neuroinflammation” to describe immune changes in schizophrenia, focusing on its four classical hallmarks: elevated cytokines, microglial reactivity, peripheral immune cell infiltration, and neurodegeneration. While some alterations in these markers are reported, many findings fall within clinical norms or likely contribute to neurodevelopment, suggesting that the term “neuroinflammation” may misrepresent their role. Instead, we propose using alternative terminology that reflects the broader spectrum of CNS immune responses, both inflammatory and non-inflammatory, and invite the scientific community to join this dialogue to refine terminology. By reframing immune alterations in schizophrenia, we aim to promote accuracy and consistency across medical disciplines, ensuring terminology that accurately represents the underlying biology. This, in turn, will improve communication among researchers and clinicians.

INTRODUCTION:Schizophrenia and autism share neurobiological mechanisms and overlapping clinical features, often resulting in the emergence of autistic traits in early stages of psychosis. The PANSS Autism Severity Score (PAUSS) provides a rapid measure of autistic features within the standard PANSS assessment. We aimed to determine the prevalence of autistic features in first-episode psychosis (FEP), characterise their clinical, cognitive, and functional profile, and examine their impact on 2-year outcomes. METHODS:A total of 328 FEP patients were included from the PEPs multicentre cohort, followed for 2 years. Autistic features were rated using PAUSS (cut-off ≥ 30), yielding autistic (n = 38) and non-autistic (n = 290) groups. Sociodemographic, clinical, cognitive, and functional variables were analysed. Longitudinal analyses examined symptomatic remission rates and trajectories of psychopathology and functioning using logistic regression and mixed-model ANOVA. RESULTS:The autistic group represented 11.6% of the sample. At baseline, they exhibited lower birth weight, greater medication side effects, higher general psychopathology and depressive severity, and poorer global functioning. Cognitively, they showed significant deficits in working memory, social cognition, and cognitive reserve compared to the non-autistic group. Over 2 years, this group was 3.6 times less likely to achieve symptomatic remission and consistently exhibited higher symptom severity and lower functioning across all follow-ups. CONCLUSIONS:Autistic features in FEP identify a subgroup with a possible distinct profile of neurodevelopmental markers, greater cognitive and functional impairments, and poorer clinical outcomes. Early identification may guide more personalised interventions, although further research is needed to refine PAUSS specificity and develop targeted, tailored treatments.

OBJECTIVE:To evaluate the effectiveness, time to discharge, functioning, and tolerability of Risperidone-ISM® in hospitalised patients with schizophrenia relapse. METHODS:Non-interventional, multicentre, prospective study of adults admitted for acute exacerbation of schizophrenia and treated with Risperidone-ISM®. Effectiveness was assessed using the Clinical Global Impression-Severity scale (CGI-S) and 6-item Positive and Negative Syndrome Scale (PANSS-6) at days 8 (FU1), 28 (FU2), and 56 (FV). Functioning was evaluated with the Personal and Social Performance scale (PSP), patient satisfaction with the Medication Satisfaction Questionnaire (MSQ). Admission/discharge data and adverse events were recorded. RESULTS:In 275 patients, significant reductions from baseline in CGI-S and PANSS-6 scores occurred as early as day 8, with continued improvement through day 56 (CGI-S: -1.4 and PANSS-6: -7.6; p < 0.0001), regardless of use of concomitant antipsychotics. Median discharge occurred 8 days after first Risperidone-ISM® injection. PSP improved by 17.6 points at day 28. No new/unexpected safety information was reported; 4% discontinued due to related adverse events. At final visit, 78% reported satisfaction with treatment, and therapeutic alliance improved in 89.4% of participants. CONCLUSIONS:Risperidone-ISM® demonstrated rapid and sustained effectiveness, functional improvement, and favourable tolerability, enabling early stabilisation and discharge. Adding another antipsychotic provided no additional benefits. Results support Risperidone-ISM® for treating acute schizophrenia relapse in real-world settings.

PURPOSE:To examine differences in sociodemographic, clinical, and treatment-related variables between migrant and native patients with schizophrenia admitted to an acute psychiatric unit in Spain. METHODS:We conducted a retrospective cohort study including 689 patients with schizophrenia admitted to the Acute Psychiatric Unit of Santa María University Hospital (Lleida, Spain) between 2010 and 2020. Patients were classified as natives (n = 475) or migrants (n = 214). Group differences were examined using unadjusted comparisons. Multivariable logistic regression analyses were performed for a priori selected outcomes, adjusting for age, sex, and key social factors. Adherence was defined as pharmacological adherence prior to admission and attendance at a scheduled outpatient psychiatric visit one year after discharge. RESULTS:Migrant patients were younger and experienced greater social disadvantage. In adjusted analyses, migrant status remained independently associated with higher odds of hallucinations at admission (OR 1.33, 95% CI 1.12-1.59), lower odds of suicidal ideation (OR 0.78, 95% CI 0.65-0.94), and a higher likelihood of initiation of long-acting injectable antipsychotics during hospitalization (OR 1.30, 95% CI 1.09-1.53). Differences in first-episode presentation, other symptom profiles, and one-year follow-up adherence were attenuated after adjustment. Treatment differences at admission largely converged by discharge, and overall functioning at discharge was comparable between groups. CONCLUSION:Migrant patients with schizophrenia experience social disadvantage and distinct care trajectories. Most differences were largely explained by social and structural factors rather than migrant status itself, although some clinically relevant differences persisted after adjustment, underscoring the importance of addressing social determinants of care.

Understanding how mental health and addictions care is organized and how data are collected is essential for population-based research using administrative records. Catalonia (Spain) has a universal healthcare system and a consolidated mental health and addictions network. This viewpoint provides an overview of service delivery and the real-world data infrastructure supporting health research. We describe the organization of care following a stepped model, including primary care, specialized outpatient and inpatient services, emergency pathways, and support programs. We then map the main population-based registries and digital health platforms, assessing their scope, linkage capabilities, and limitations. Catalonia benefits from universal coverage, integrated policies, and extensive routine data collection across care settings. However, challenges remain, including incomplete interoperability, limited clinical granularity, and unvalidated diagnoses in primary care registries. This viewpoint serves as a reference framework for researchers working with administrative mental health data in Catalonia.

BACKGROUND:Schizophrenia is a chronic psychiatric disorder characterized by acute relapses and significant functional impairment. While antipsychotic medications are effective in managing acute episodes, many patients fail to achieve functional remission. Recent research suggests that immune mechanisms may influence treatment outcomes, yet studies focusing on the relationship between immune biomarkers and functional recovery are limited. OBJECTIVE:This study aims to evaluate whether blood-based immune biomarkers can predict functional response and remission in patients with acute schizophrenia. METHODS:A retrospective cohort study was conducted with 354 inpatients diagnosed with schizophrenia, admitted to an acute psychiatric unit between January 2010 and December 2020. Sociodemographic, clinical, and immune biomarker data were extracted from electronic records. Functional outcomes were measured using Global Assessment of Functioning (GAF) scores at admission and discharge. Immune biomarkers assessed included white blood cell counts, ratios and C-reactive protein. Functional response was defined as a GAF score improvement >40 points, while functional remission was defined as a GAF score ≥70 at discharge. RESULTS:Higher leukocyte counts increased the risk of non-functional response, while a higher platelet-lymphocyte ratio (PLR) was a protective factor. Additionally, Higher lymphocyte and platelet counts were protective against non-functional remission. However, the predictive performance for both functional response and remission was limited, with an AUC ranging from 0.53 to 0.61. CONCLUSION:Immune biomarkers, particularly leukocyte counts, PLR, and lymphocyte counts, show significant associations with functional outcomes in acute schizophrenia. However, their predictive value for clinical practice remains limited.

Assessing clinical symptoms in First Episode Psychosis (FEP) is essential for guiding treatment decisions and predicting outcomes. The Positive and Negative Syndrome Scale (PANSS-30) is widely used for this purpose; however, its length limits feasibility in routine clinical practice. The PANSS-6, a shorter version, represents a promising alternative, though its performance in FEP populations remains underexplored. This study evaluated the predictive abilities of PANSS-30 and PANSS-6 for clinical remission, functional remission, and relapse over a 2-year follow-up in a Spanish cohort of 193 FEP patients. Data were derived from the PEPs Project, with PANSS-30 assessments conducted at baseline and at 2, 6, 12, and 24 months; PANSS-6 scores were calculated from PANSS-30 at the same visits. Clinical remission, functional remission, and relapse were defined using established criteria. Logistic regression and ROC-AUC analyses assessed predictive and discriminatory performance. Agreement between the Remission in Schizophrenia Working Group (RSWG) for PANSS-30 and PANSS-6 remission criteria was near-perfect at 1 and 2 years (κ ≥ 0.98). PANSS-6 demonstrated stronger predictive associations and similar discriminatory performance to PANSS-30 for clinical and functional remission, while its performance for relapse over two years was similar. In conclusion, the PANSS-6 is a reliable and efficient tool for assessing clinical outcomes in FEP, offering similar predictive accuracy to PANSS-30 while being more practical for routine use due to its shorter administration time.

Introduction: Negative symptoms (NS) include asociality, avolition, anhedonia, alogia, and blunted affect and are linked to poor prognosis. It has been suggested that they reflect two different factors: diminished expression (EXP) (blunted affect and alogia) and amotivation/pleasure (MAP) (anhedonia, avolition, asociality). The aim of this article was to examine potential sex differences among first-episode schizophrenia (FES) patients and analyze sex-related predictors of two NS symptoms factors (EXP and MAP) and functional outcome. Material and methods: Two hundred and twenty-three FES (71 females and 152 males) were included and evaluated at baseline, six-months and one-year. Repeated measures ANOVA was used to examine the effects of time and sex on NS and a multiple linear regression backward elimination was performed to predict NS factors (MAP-EXP) and functioning. Results: Females showed fewer NS (p = 0.031; Cohen's d=-0.312), especially those related to EXP (p = 0.024; Cohen's d=-0.326) rather than MAP (p = 0.086), than males. In both male and female group, worse premorbid adjustment and higher depressive symptoms made a significant contribution to the presence of higher deficits in EXP at one-year follow-up, while positive and depressive symptoms predicted alterations in MAP. Finally, in females, lower deficits in MAP and better premorbid adjustment predicted better functioning at one-year follow-up (R-2 = 0.494; p < 0.001), while only higher deficits in MAP predicted worse functioning in males (R-2 =0.088; p = 0.012). Conclusions: Slightly sex differences have been found in this study. Our results lead us to consider that early interventions of NS, especially those focusing on motivation and pleasure symptoms, could improve functional outcomes. (c) 2023 The Authors. Published by Elsevier Espana, S.L.U. on behalf of Sociedad Espanola de Psiquiatr & imath;a y Salud Mental (SEPSM). This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

OBJECTIVE:To analyse the use of antipsychotics for first-episode of psychosis (FEP) and relapsed schizophrenia, and the impact of predominant symptoms on decision making. METHODS:A survey among 150 European psychiatrists was conducted using computer-assisted web interviewing to assess preferred medications, switching, dose adjustments, and maintenance therapy in acute FEP and relapse settings. RESULTS:Negative or affective symptoms were reported as prevalent in 55% of FEP and 59% of relapsed schizophrenia cases, indicating significant unmet treatment needs. Olanzapine and risperidone were the most commonly prescribed antipsychotics for FEP, with treatment choices influenced by symptom profiles. Long-acting injectables (LAIs) were prescribed to 28% of FEP patients, with notable variation across countries (15-43%; p < 0.05). During hospitalisation, 41% of patients required therapy adjustments, while discharge decisions were driven by drug tolerability and symptom severity. For relapsed patients, non-adherence was identified as the primary cause of relapse (71%), and olanzapine, risperidone, and aripiprazole were the most prescribed treatments. Post-discharge adjustments for relapsed patients focused on adherence and long-term treatment goals. CONCLUSION:Despite the prevalence of negative or affective symptoms in FEP and relapsed patients, traditional antipsychotics remain the most prescribed treatments. Non-adherence and variability in LAI usage highlight the need for improved symptom-specific approaches and standardised LAI protocols.

Schizophrenia (SCZ) is a severe, chronic mental disorder of unknown etiology and limited therapeutic options. Bioenergetic deficits in the oxidative phosphorylation system (OXPHOS) during early postnatal brain development may underlie disrupted neuronal metabolism and synaptic signaling, contributing to the neurodevelopmental and behavioral disturbances observed in patients. This narrative review summarizes updated evidence linking mitochondrial-OXPHOS dysfunction to SCZ pathophysiology. The novelty lies in the focus on OXPHOS dysfunction at the enzymatic/functional level, rather than on genetic, transcriptional, or oxidative parameters. While complex I impairment has long been highlighted and proposed as a peripheral marker of the disease, recent studies also report alterations in other OXPHOS complexes and their precursors. These findings suggest that OXPHOS dysfunction is not isolated to a single enzymatic component but affects broader mitochondrial function, alongside oxidative stress, contributing to disease progression through mechanisms involving apoptosis, accelerated aging, and synaptic deterioration. OXPHOS dysfunction in both central and peripheral tissues further supports its relevance to SCZ. Overall, the literature points to mitochondrial OXPHOS abnormalities as a significant biological feature of SCZ. Whether these alterations are causal factors or consequences of disease processes remains unclear. Understanding OXPHOS dysregulation may open new avenues for targeted therapies.

INTRODUCTION:Although psychotic disorders are associated with significant morbidity and mortality, the diagnostic trajectories and mortality risks across the spectrum of these disorders remain poorly understood. This study aimed to characterize diagnostic pathways and compare mortality outcomes across psychotic disorders in Catalonia. METHODS:We conducted a retrospective cohort study using electronic health records of 357,007 adults accessing mental health services in Catalonia from 2015 through 2019. Diagnostic categories included schizophrenia, bipolar disorder, schizoaffective disorder, delusional disorder, other non-organic psychoses, unipolar psychotic depression, and other mental health diagnoses. Cox proportional hazards models assessed mortality risk, adjusting for sociodemographic factors and comorbidities. RESULTS:About one-third of the sample received their first psychotic disorder diagnosis in specialized care. All psychotic disorders showed elevated mortality risk vs other mental health conditions. Schizophrenia had the highest risk (HR, 2.63; 95%CI, 2.46-2.81, p<0.001 followed by schizoaffective (HR, 1.99; 95%CI, 1.77-2.24, p<0.001) and delusional disorders (HR, 1.92; 95%CI, 1.66-2.21, p<0.001). Low socioeconomic status (HR, 3.69; 95%CI, 3.48-3.92, p<0.001) and comorbidities (HR, 1.82 per comorbidity; 95%CI, 1.81-1.83, p<0.001) were significant predictors of mortality across diagnoses. Gradient boosting machine modeling identified comorbidities (56.07%) and diagnostic category (24.51%) as top predictors of mortality risk. CONCLUSIONS:This study demonstrates significantly elevated mortality risk across the spectrum of psychotic disorders in a Southern European context, with socioeconomic factors and medical comorbidities emerging as critical determinants. These findings underscore the need for integrated care approaches addressing both mental and physical health needs in psychotic disorders.

Aim: The use of deep brain stimulation (DBS) has been recently extended for treating resistant psychiatric disorders, but the experience in patients with schizophrenia-related disorders and bipolar disorder (BD) is scarce. Method: We conducted an observational, one-year longitudinal study to evaluate the effects of DBS in four treatment-resistant patients with schizophrenia, schizoaffective, and BD, included in a pilot, last-resource protocol. Patients were digitally monitored for objective assessment of behavioral changes. Results: After one year of its initiation, DBS of the nucleus accumbens (in subjects N2, N3, and N4) and subgenual anterior cingulate cortex (in N1) produced a significant clinical improvement, associated with decreases in the Clinical Global Impression (from 5.25 f 0.5 to 3.5 f 1, p = 0.035) and in the Hamilton Depression Rating Scale (HADRS scores, from 14.5 f 6.56 to 1.5 f 1.29, p = 0.020). We observed a notable, durable therapeutic response in two patients from this cohort (N1 and N3), a clinically relevant relief in a third (N2), and a lack of a significant response in the last one (N4). Maintenance electroconvulsive therapy sessions could be discontinued in the three patients that responded to DBS (N1-3). There were no side effects or relevant changes in cognitive functioning. There were relevant differences between physical activity and sleep time among the four participants. Conclusions: These results suggest initial evidence that DBS may be an effective and safe alternative for treating complex and resistant forms of schizophrenia-related disorders and BD. Digital monitoring may help to capture objective measures of behavioral changes after the intervention. (c) 2023 Sociedad Espanola de Psiquiatria y Salud Mental (SEPSM). Published by Elsevier Espa & ntilde;a, S.L.U. All rights are reserved, including those for text and data mining, AI training, and similar technologies.