Artículos (Psiquiatría)
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Artículo Exploratory Analysis of MicroRNA Alterations in a Neurodevelopmental Mouse Model for Autism Spectrum Disorder and Schizophrenia(Mdpi Ag; M, 2024-02-28) García-Cerro, Susana; Gómez-Garrido, Ana; García, Gonzalo; Crespo Facorro, Benedicto; Brites, Dora; Universidad de Sevilla. Departamento de Psiquiatría; Instituto de Salud Carlos III; Junta de Andalucía; Agencia Estatal de Investigación Española; Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalMicroRNAs (miRNAs) play a crucial role in the regulation of gene expression levels and have been implicated in the pathogenesis of autism spectrum disorder (ASD) and schizophrenia (SCZ). In this study, we examined the adult expression profiles of specific miRNAs in the prefrontal cortex (PFC) of a neurodevelopmental mouse model for ASD and SCZ that mimics perinatal pathology, such as NMDA receptor hypofunction, and exhibits behavioral and neurophysiological phenotypes related to these disorders during adulthood. To model the early neuropathogenesis of the disorders, mouse pups were administered subcutaneously with ketamine (30 mg/Kg) at postnatal days 7, 9, and 11. We focused on a set of miRNAs most frequently altered in ASD (miR-451a and miR-486-3p) and in SCZ (miR-132-3p and miR-137-3p) according to human studies. Additionally, we explored miRNAs whose alterations have been identified in both disorders (miR-21-5p, miR-92a-2-5p, miR-144-3p, and miR-146a-5p). We placed particular emphasis on studying the sexual dimorphism in the dynamics of these miRNAs. Our findings revealed significant alterations in the PFC of this ASD- and SCZ-like mouse model. Specifically, we observed upregulated miR-451a and downregulated miR-137-3p. Furthermore, we identified sexual dimorphism in the expression of miR-132-3p, miR-137-3p, and miR-92a-2-5p. From a translational perspective, our results emphasize the potential involvement of miR-92a-2-5p, miR-132-3p, miR-137-3p, and miR-451a in the pathophysiology of ASD and SCZ and strengthen their potential as biomarkers and therapeutic targets of such disorders.Artículo Exercise as a promoter of neurocognitive improvement in people with psychiatric disorders and comorbid obesity: A randomized controlled trial(Elsevier Ireland Ltd, 2024-10-09) Soldevila-Matías, Pau; Sánchez-Ortí, Joan Vicent; Correa-Ghisays, Patricia; Balanzá-Martínez, Vicent; Selva-Vera, Gabriel; Sanchis-Sanchis, Roberto; Crespo Facorro, Benedicto; Tabarés-Seisdedos, Rafael; Universidad de Sevilla. Departamento de Psiquiatría; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Gobierno de España; Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalIntroduction: The psychiatric disorders and obesity comorbidity is related to neurocognitive impairment and inflammation. Exercise is crucial to improve and maintain healthy lifestyles. This randomized controlled trial tested the efficacy of aerobic exercise as promoter of neurocognitive improvement across psychiatric disorders with comorbid obesity (OB). Methods: Patients with major depressive disorder, bipolar disorder and, schizophrenia and with comorbid OB (n =29) received brief healthy lifestyle counseling and were randomized into two groups: guided physical activity group (GPAG) (n =10) which included 12 weeks of guided-exercise of moderate intensity and frequency, and incentive of autonomous physical activity proposals by the specialist. Standard physical activity group (SPAG) (n =19) continue with their usual daily physical activity, without guidance or incentives, over 12 weeks. Peripheral blood biomarkers of inflammation, oxidative stress, vascular mechanisms, and metabolic activity, as well as neurocognitive and functional performance were assessed twice, before and after intervention. Mixed one-way analysis of variance and linear regression analyses were performed. Results: Individuals in GPAG showed better neurocognitive and functional performance than individuals in SPAG after physical activity training (p <0.05; η2p =0.14 to 0.15). A significant improvement in cognition before and after the physical activity training in the GPAG group was found (p < 0.0001; p = 0.29). In all cases, the effect size was from moderate to large. Inflammatory activity (interleukin [IL-6]), oxidative (mitochondrial reactive oxygen species [mROS] and mitochondrial membrane potential [ΔΨm]) and inter cellular adhesion molecule 1 [ICAM1], leukocyte-endothelium adhesion [LEPMN], and p-selectin [PSEL]) levels, and cardio-metabolic (low- density lipoprotein [LDL], systolic blood pressure [SBP], and insulin) processes were significant predicting neurocognitive improve of individuals with psychiatric disorders and comorbid OB. Conclusions: Physical activity programs may have positive impact on neurocognitive and functional performance in individuals with psychiatric disorders and OB. Exercise influences inflammatory, oxidative, vascular, and cardio-metabolic pathways, and modulate cognition. These findings may have a potential translational utility for early intervention in these disorders.Artículo Evaluation and Future Challenges in a Self-Guided Web-Based Intervention With and Without Chat Support for Depression and Anxiety Symptoms During the COVID-19 Pandemic: Randomized Controlled Trial(JMIR Publications, Inc, 2024-09-30) Domínguez-Rodríguez, Alejandro; Sanz Gómez, Sergio; González Ramírez, Leivy Patricia; Herdoiza-Arroyo, Paulina Erika; Trevino García, Lorena Edith; Rosa-Gómez, Anabel de la; González-Cantero, Joel Omar; Macias-Aguinaga, Valeria; Arenas Landgrave, Paulina; Chávez-Valdez, Sarah Margarita; Universidad de Sevilla. Departamento de PsiquiatríaBackground: The COVID-19 pandemic has had an impact on mental health worldwide. Low- and middle-income countries were largely affected by it. Mexico was one of the most affected countries. Extended periods of lockdowns, isolation, and social distancing, among other factors, highlighted the need to introduce web-based psychological interventions to the Mexican population. In this context, Mental Health COVID-19 emerged as a self-guided web-based intervention (SGWI) aimed at adults to improve mental health during the COVID-19 pandemic. Objective: This study aims to assess the efficacy of 2 modalities of a self-guided intervention (with and without chat support) in reducing depression symptoms, generalized anxiety, community posttraumatic stress, widespread fear, anxiety, sleep quality, physiological and affective coping, and suicide ideation. In addition, it aimed to compare the moderating role of coping strategies, acceptance, and satisfaction in participants’ symptom reduction. We hypothesize that the self-guided, chat-supported modality will show higher efficacy than the modality without chat support in achieving clinical change and better performance as a moderator of depression symptoms, generalized anxiety, community posttraumatic stress, widespread fear, anxiety, sleep quality, physiological and affective coping, and suicide ideation, as well as an increase in participants’ satisfaction and acceptability. Methods: A randomized controlled trial was conducted. Data were collected from May 2020 to June 2022. We performed intrasubject measures at 4 evaluation periods: pretest, posttest, and follow-up measurements at 3 and 6 months. Differences between intervention groups were assessed through the Mann-Whitney U test for continuous variables and the chi-square test categorical variables. Changes due to intervention were analyzed using Wilcoxon W test. Moderated regression analysis was performed to test the hypothesized moderating role of coping strategies, usability, and opinion about treatment on clinical change. Results: A total of 36 participants completed the intervention; of these, 5 (14%) were part of the SGWI group, and 31 (86%) were on the SGWI plus chat support (SGWI+C) group, which included a chat service with therapists. The perceived high complexity of the system for the SGWI group had a moderating effect associated with a lack of efficacy of the intervention regarding depression, but not when controlled for sociodemographic variables. A perception of lower helpfulness of the intervention was associated with poorer outcomes. Coping strategies did not show moderating effects. Conclusions: Enhancing the utility of web-based interventions for reducing clinical symptoms by incorporating a support chat to boost treatment adherence seemed to improve the perception of the intervention’s usefulness. Web-based interventions face several challenges, such as eliminating complexities in platform use and increasing the users’perceived utility of the intervention, among other issues identified in the study. Trial Registration: ClinicalTrials.gov NCT04468893; https://clinicaltrials.gov/study/NCT04468893?tab=results International Registered Report Identifier (IRRID): RR2-10.2196/23117Artículo Digital Platform for the Prevention of Suicidal Behaviour and Non-Suicidal Self-Injuries in Adolescents: The SmartCrisis-Teen Study Protocol(Mdpi, 2024-08-25) Abascal-Peiró, Sofía; Peñuelas-Calvo, Inmaculada; Alacreu-Crespo, Adrian; Sáiz, Pilar Alejandra; Torre-Luque, Alejandro de la; Ruiz Veguilla, Miguel; Barrigón, María Luisa; Courtet, Philippe; López-Castroman, Jorge; Baca-García, Enrique; Porras-Segovia, Alejandro; Universidad de Sevilla. Departamento de Psiquiatría; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)Suicidal behavior and Non-Suicidal Self-Injuries (NSSIs) are a major health problem in the adolescent population. New technologies can contribute to the development of innovative interventions in suicide prevention. Here, we present the SmartCrisis-Teen study protocol. The study consists of a randomized clinical trial which aims to evaluate the effectiveness of a digital safety plan to prevent suicidal behavior and NSSIs in adolescents. This is a multicentric study which will be conducted among the adolescent population, both in clinical and student settings, with a target sample of 1080 participants. The intervention group will receive an Ecological Momentary Intervention (EMI) consisting of a digital safety plan on their mobile phone. All participants will receive their Treatment As Usual (TAU). Participants will be followed for six months, with weekly and monthly telephone visits and face-to-face visits at three and six months. Participants will be assessed using traditional questionnaires as well as Ecological Momentary Assessment (EMA) and Implicit Association Tests (IATs). With this intervention, we expect a reduction in NSSIs through the acquisition of coping strategies and a decrease in suicidal behavior over the course of follow-up. This study provides a novel, scalable digital intervention for preventing suicidal behavior and NSSIs in adolescents, which could contribute to improving adolescent mental health outcomes globally.Artículo Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study(Nature Publishing Group; Springernature; Springer Science and Business Media Llc, 2024-02-09) Georgiadis, Foivos; Larivière, Sara; Glahn, David; Hong, L. Elliot; Kochunov, Peter; Mowry, Bryan; Crespo Facorro, Benedicto; Kirschner, Matthias; ENIGMA Schizophrenia Consortium; Universidad de Sevilla. Departamento de Psiquiatría; Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalSchizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n=207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia’s alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.Artículo Clinical predictors and psychosocial risk factors of suicide attempt severity(Elsevier España Slu, 2023-09-29) González-Ortega, Itxaso; López-Peña, Purificación; Andreo-Jover, Jorge; Bobes, Julio; Diaz-Marsa, Marina; Fernández-Sevillano, Jessica; Crespo Facorro, Benedicto; Ruiz Veguilla, Miguel; Pozuelo-Reguera, Pablo; Zorrilla, Iñaki; Universidad de Sevilla. Departamento de Psiquiatría; Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalBackground Suicide attempts are an important predictor of completed suicide and may differ in terms of severity of medical consequences or medical lethality. There is little evidence on serious suicide attempt (SSA) and very few studies have compared SSA with non-SSA. Objective The aim of this multisite, coordinated, cohort study was to analyze the role of clinical variables and the sociodemographic and psychological risk factors of SSA. Method In this multisite, coordinated, cohort study, 684 participants (222 for the mild suicide attempt group, 371 for the moderate suicide attempt group and 91 for the SSA group) were included in the study. Ordinal regression models were performed to analyze the predictor variables of SSA. Results Early physical abuse (OR = 1.231) and impulsivity (OR = 1.036) were predictors of SSA, while depressive symptoms were associated with a lower risk of SSA. Conclusion Environmental and psychological factors as physical abuse and impulsivity are related with severe suicide severity. These findings will help to develop strategies to prevent suicide and may be considered for the treatment and management of suicide.Artículo Aripiprazole as protector against COVID-19 mortality(Nature Publishing Group; Nature Portfolio, 2024-05-29) Loucera-Muñecas, C.; Canal-Rivero, M.; Ruiz Veguilla, Miguel; Carmona, R.; Bostelmann, G.; Garrido-Torres, N.; Dopazo, J.; Crespo Facorro, Benedicto; Universidad de Sevilla. Departamento de Psiquiatría; Gobierno de España; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalThe relation of antipsychotics with severe Coronavirus Disease 19 (COVID‑19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID‑19. A population‑based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18 years old and had a laboratory‑confirmed COVID‑19 infection. Two sub‑cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15 days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate‑adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic‑treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID‑19 [adjusted odds ratio (OR) = 0.86; 95% CI, 0.79–0.93, multiple‑testing adjusted p‑value < 0.05]. Importantly, these findings were consistent for both covariate‑adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID‑19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.Artículo Applied pharmacogenetics to predict response to treatment of first psychotic episode: study protocol(Frontiers Media SA, 2025-01-07) Mas, Sergi; Julià, Laura; Cuesta, Manuel J.; Crespo Facorro, Benedicto; Vázquez-Bourgon, Javier; Spuch, Carlos; González-Pinto, Ana; Ibáñez, Ángela; Usall, Judith; Romero-López-Alberca, Cristina; Catalan, Ana; Mané, Anna; Bernardo, Miquel; Universidad de Sevilla. Departamento de Psiquiatría; Instituto de Salud Carlos III; Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalThe application of personalized medicine in patients with first-episode psychosis (FEP) requires tools for classifying patients according to their response to treatment, considering both treatment efficacy and toxicity. However, several limitations have hindered its translation into clinical practice. Here, we describe the rationale, aims and methodology of Applied Pharmacogenetics to Predict Response to Treatment of First Psychotic Episode (the FarmaPRED-PEP project), which aims to develop and validate predictive algorithms to classify FEP patients according to their response to antipsychotics, thereby allowing the most appropriate treatment strategy to be selected. These predictors will integrate, through machine learning techniques, pharmacogenetic (measured as polygenic risk scores) and epigenetic data together with clinical, sociodemographic, environmental, and neuroanatomical data. To do this, the FarmaPRED-PEP project will use data from two already recruited cohorts: the PEPS cohort from the “Genotype-Phenotype Interaction and Environment. Application to a Predictive Model in First Psychotic Episodes” study (the PEPs study from the Spanish abbreviation) (N=335) and the PAFIP cohort from “Clinical Program on Early Phases of Psychosis” (PAFIP from the Spanish abbreviation) (N = 350). These cohorts will be used to create the predictor, which will then be validated in a new cohort, the FarmaPRED cohort (N = 300). The FarmaPRED-PEP project has been designed to overcome several of the limitations identified in pharmacogenetic studies in psychiatry: (1) the sample size; (2) the phenotype heterogeneity and its definition; (3) the complexity of the phenotype and (4) the gender perspective. The global reach of the FarmaPRED-PEP project is to facilitate the effective deployment of precision medicine in national health systems.Artículo A naturalistic cohort study of first-episode schizophrenia spectrum disorder: A description of the early phase of illness in the PSYSCAN cohort(Elsevier Science Bv; Elsevier, 2024-04) Slot, Margot I.E.; van Hell, Hendrika H.; Winter van Rossum, Inge; Dazzan, Paola; Maat, Arija; Haan, Lieuwe de; Crespo Facorro, Benedicto; Kahn, René S.; Universidad de Sevilla. Departamento de Psiquiatría; Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalBackground: We examined the course of illness over a 12-month period in a large, international multi-center cohort of people with a first-episode schizophrenia spectrum disorder (FES) in a naturalistic, prospective study (PSYSCAN). Method: Patients with a first episode of schizophrenia, schizoaffective disorder (depressive type) or schizophreniform disorder were recruited at 16 institutions in Europe, Israel and Australia. Participants (N = 304) received clinical treatment as usual throughout the study. Results: The mean age of the cohort was 24.3 years (SD = 5.6), and 67 % were male. At baseline, participants presented with a range of intensities of psychotic symptoms, 80 % were taking antipsychotic medication, 68 % were receiving psychological treatment, with 46.5 % in symptomatic remission. The mean duration of untreated psychosis was 6.2 months (SD = 17.0). After one year, 67 % were in symptomatic remission and 61 % were in functional remission, but 31 % had been readmitted to hospital at some time after baseline. In the cohort as a whole, depressive symptoms remained stable over the follow-up period. In patients with a current depressive episode at baseline, depressive symptoms slightly improved. Alcohol, tobacco and cannabis were the most commonly used substances, with daily users of cannabis ranging between 9 and 11 % throughout the follow-up period. Conclusions: This study provides valuable insight into the early course of a broad range of clinical and functional aspects of illness in FES patients in routine clinical practice.Artículo Symptomatic networks in suicide attempt and reattempt: Relevance of psychiatric comorbidity(Elsevier France-Editions Scientifiques Medicales Elsevier; Cambridge Univ Press, 2025-01-10) Pemau, Andrés; Torre-Luque, Alejandro de la; Marín-Martin, Carolina; Diaz-Marsa, M; Andreo-Jover, Jorge; Ayad-Ahmed, Wala; Crespo Facorro, Benedicto; Ruiz Veguilla, Miguel; Pérez, Víctor; Universidad de Sevilla. Departamento de Psiquiatría; Instituto de Salud Carlos III; Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalBackground. One of the most relevant risk factors for suicide is the presence of previous attempts. The symptomatic profile of people who reattempt suicide deserves attention. Network analysis is a promising tool to study this field. Objective. To analyze the symptomatic network of patients who have attempted suicide recently and compare networks of people with several attempts and people with just one at baseline. Methods. 1043 adult participants from the Spanish cohort “SURVIVE” were part of this study. Participants were classified into two groups: single attempt group (n =390) and reattempt group (n=653).Different network analyses were carrie doutto study the relationships between suicidal ideation, behavior, psychiatric symptoms, diagnoses, childhood trauma, and impulsivity. A general network and one for each subgroup were estimated. Results. People with several suicide attempts at baseline scored significantly higher across all clinical scales. The symptomatic networks were equivalent in both groups of patients (p > .05). Although there were no overall differences between the networks, some nodes were more relevant according to group belonging. Conclusions. People with a history of previous attempts have greater psychiatric symptom severity but the relationships between risk factors show the same structure when compared with the single attempt group. All risk factors deserve attention regardless of the number of attempts, but assessments can be adjusted to better monitor theoccurrence of reattempts.Artículo Suicide risk among cannabis, heroin and cocaine users(Springer, 2025-02-19) Pérez Sosa, Miguel Zacarías; Vega Sánchez, Diego de la; Sanz – Gómez, Sergio; Melvin, Glenn; Guija Villa, Julio Antonio; Sánchez – Gómez, Ana; Oquendo, Maria A.; Giner Jiménez, Lucas; Universidad de Sevilla. Departamento de PsiquiatríaIndividuals who use substances such as cocaine, cannabis, heroin, alcohol and nicotine are at increased risk for suicidal behavior. Our objective is to examine the relationship between substance use and suicide. An observational psychological autopsy study design was used to compare substance use in individuals who died by suicide and individuals who died by other manners. Subjects were recruited at the Medical Forensic Institute of Seville between 2006 and 2018. The total sample was 593 decedents including those who had died by suicide (n = 412) and those who died suddenly from non-suicidal causes (n = 181). We determined the association between substance (cannabis, heroin, cocaine, alcohol and nicotine) use and suicide. We also analyzed the behavioral association between the use of any one of these substances (cannabis, heroin, cocaine, alcohol, and nicotine), as well as the use of more than one substance at a time and manner of death (suicide vs not suicide). We established three categories of substance use: never-used, lifetime users (prior use but not in the past month), and past month users (use within the last month). This study found that decedents who died by suicide were more likely to have substance use compared with those who died by other means. Use of cocaine, cannabis, or heroin within the last month prior to death was associated with increased risk of suicide (X2 = 13.050; df = p = 0.001). Of the substances examined, the strongest association was between past month cocaine use and suicide after adjusting for Axis I and Axis II disorders. Our study supports the relationship between the use of illicit substances and suicide. The use of substances, independent of the type, was associated with a greater risk of suicide. Cocaine use had the strongest association with suicide.Artículo Shared molecular signature in Alzheimer's disease and schizophrenia: A systematic review of the reelin signaling pathway(Pergamon Press; Pergamon-Elsevier Science Ltd, 2025-01-31) Valderrama-Mantilla, Ana Isabel; Martín-Cuevas, Celia; Gómez-Garrido, Ana; Morente-Montilla, Cristina; Crespo Facorro, Benedicto; García-Cerro, Susana; Universidad de Sevilla. Departamento de Psiquiatría; Junta de Andalucía; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Instituto de Salud Carlos III; Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalThe Reelin signaling pathway, particularly the RELN-APOER2-DAB1 complex, has emerged as a key contributor to the neuropathology of Alzheimer’s disease (AD) and Schizophrenia (SZ). Despite being distinct clinical conditions, these disorders exhibit similar patterns of cognitive decline, including early disruptions in synaptic function and memory impairments. Notably, individuals with SZ have a 2–4 fold increased risk of developing AD or other dementias, highlighting potential shared molecular mechanisms, and positioning Reelin as a pivotal link between them. This systematic review explores the role of Reelin and its signaling components across these disorders. In AD, Reelin disruption correlates with hallmark features such as Tau hyperphosphorylation, amyloid-beta accumulation, and cognitive deficits. In SZ, alterations in Reelin signaling, including epigenetic modifications affecting RELN expression, are linked to disruptions in neuronal development and synaptic plasticity, particularly in the parietal and prefrontal cortices. Additionally, genomic studies reveal specific RELN variants and allelic imbalances that may influence disease severity and treatment response in SZ, suggesting RELN’s role as a potential biomarker for therapeutic outcomes. Region-specific Reelin alterations in both AD and SZ suggest differing impacts yet underscore a potential common molecular origin. Our findings highlight the Reelin pathway as a molecular convergence point, warranting further investigation as a therapeutic and diagnostic target for AD, SZ, and potentially other neuropsychiatric disorders. The interplay between genetic and epigenetic regulation of RELN may provide novel insights into neurodegeneration, with implications for personalized intervention strategies in AD and SZ.Artículo Reliability and validity of proxy reports of impulsivity and aggression: An evidence-based assessment approach to psychological autopsy methods(Elsevier España Slu, 2023-11-17) Sanz Gómez, Sergio; Alacreu-Crespo, Adrian; Guija Villa, Julio Antonio; Giner Jiménez, Lucas; Universidad de Sevilla. Departamento de PsiquiatríaIntroduction: Psychological autopsy methods often include measures of impulsivity and aggression. The aim is to assess their reliability and validity in a Spanish sample. Methods: Cross-sectional web-based survey was fulfilled by 184 proband and proxy pairs. Data was col lected on sociodemographic characteristics, impulsivity through Barratt Impulsiveness Scale (BIS-11), aggression throughBuss–PerryAggressionQuestionnaire(BPAQ),andhistoryofsuicideideation.Proxies f illed out BIS-11, BPAQ and suicide ideation with the responses they would expect from the probands. Reliability was assessed using intraclass correlation coefficients (ICC) between proband and proxies. Logistic regression analysis was performedtoassessthepredictive validity of proxy reports in predicting probands’ suicide ideation. Results: Bivariate analysis showed differences in BPAQ (Median 68 vs. 62; p=0.001), but not in BIS 11 (p>.050). BIS-11 showed good concordance (ICC=0.754; CI 95% 0.671–0.816) and BPAQ acceptable (ICC=0.592; CI 95%0.442–0.699). In theprobandsregressionmodelBPAQpredictedsuicideideation(OR 1.038; CI 95% 1.016–1.061) but not BIS-11 (OR 0.991; CI 95% 0.958–1.025). In the proxy-report model BPAQalsopredictedprobands’suicideideation(OR1.036;CI95%1.014–1.058)butnotBIS-11(OR0.973; CI 95% 0.942–1.004). Conclusion: Used as proxy-reported assessment tools, BIS-11 showed better reliability than the BPAQ. However, both showed validity in Spanish population and could be included in psychological autopsy protocols.Artículo Efficacy of lurasidone in first episode psychosis: patient phenotypes, dosage, and recommendations from an expert panel(Springer London Ltd, 2025-01-06) Bernardo, Miquel; Díaz Marsá, Marina; González-Pinto, Ana; Martín Carrasco, Manuel; Pérez Sola, Víctor; Sáiz, Pilar Alejandra; Vieta, Eduard; Torrens, Marta; Arango, Celso; Crespo Facorro, Benedicto; Universidad de Sevilla. Departamento de Psiquiatría; Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalIntroduction: For patients with psychosis, early, intensive therapeutic intervention is thought to improve long‑term outcomes. Furthermore, patients with a first‑episode psychosis (FEP) who experience a good early response to antipsychotic medication show a clinical and functional benefit over the longer term if they continue low‑dose antipsychotic treatment. Lurasidone is an atypical antipsychotic agent which is approved in Europe for the treatment of schizophrenia in adults and adolescents (13–17 years). The efficacy and tolerability of lurasidone have been demonstrated in both antipsychoticnaïve and previously treated patients. Areas Covered: This paper provides a review and commentary regarding the use of lurasidone in patients with FEP. Case studies based on the authors’ clinical experiences with lurasidone in real‑world practice are provided Expert Opinion: In our experience, lurasidone has shown efficacy in FEP in different patient profiles, including those with psychoses associated with substance use disorders. Lurasidone provides clinically relevant benefits, especially in patients with affective symptomatology, and has a good tolerability profile.Artículo Determinants of patient satisfaction in clozapine users: results from the Clozapine International Consortium (CLOZIN)(Nature Portfolio, 2025-02-23) Horst, Marte Z. van der; Boer, Nini de; Okhuijsen-Pfeifer, Cynthia; Luykx, Jurjen J.; Crespo Facorro, Benedicto; CLOZIN collaborators; Universidad de Sevilla. Departamento de Psiquiatría; Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalClozapine is highly effective for treatment-resistant schizophrenia but is underutilized due to patient and clinician-related concerns. Little is known about the general level of patient satisfaction with clozapine and determinants thereof. We therefore explored determinants of patient satisfaction with clozapine in individuals diagnosed with schizophrenia spectrum disorders (SSDs). Cross sectional data from 480 clozapine users were used to examine demographic and clinical factors, including symptom severity, treatment response, and adverse drug reactions (ADRs). Patient satisfaction was self-rated on a scale of 1 to 10. Results showed a mean satisfaction score of 7.4 (SD =1.9), with significant associations between satisfaction and treatment response (B =0.42, R² =0.19, p=3.9×10⁻¹⁸), symptom severity (B=0.10, R²=0.05, p=2.06×10-9), occurrence of ADRs (B=−0.16, R²=0.06, p=3.2×10-5), and recreational drug use (B =−1.32, R²=0.05, p=2.09×10-4). Hypersalivation and prolonged sleep duration were the only ADRs linked to lower satisfaction (B =−0.72, R²= 0.06, p=3.5×10-5 and B=−0.57, R²=0.04, p=1.4×10-3, respectively). Despite concerns about ADRs, treatment effectiveness showed a stronger association with patient satisfaction among clozapine users than the occurrence of ADRs. In conclusion, our findings suggest that strategies aimed at bolstering clozapine’s effectiveness may help counter worldwide underprescription rates of clozapine in patients with SSDs.Artículo Clinical outcomes and anti-inflammatory mechanisms predict maximum heart rate improvement after physical activity training in individuals with psychiatric disorders and comorbid obesity(Public Library Science, 2025-01-03) Soldevila-Matías, Pau; Sánchez-Ortí, Joan Vicent; Correa-Ghisays, Patricia; Balanzá-Martínez, Vicent; Selva-Vera, Gabriel; Sanchis-Sanchis, Roberto; Crespo Facorro, Benedicto; Tabarés-Seisdedos, Rafael; Universidad de Sevilla. Departamento de Psiquiatría; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Instituto de Salud Carlos III; Gobierno de España; Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalIntroduction This study aimed to evaluate the predictive validity and discriminatory ability of clinical outcomes, inflammatory activity, oxidative and vascular damage, and metabolic mechanisms for detecting significant improve maximum heart rate after physical activity training in individuals with psychiatric disorders and obesity comorbid using a longitudinal design and transdiagnostic perspective. Methods Patients with major depressive disorder, bipolar disorder and, schizophrenia and with comorbid obesity (n = 29) were assigned to a 12-week structured physical exercise program. Peripheral blood biomarkers of inflammation, oxidative stress, vascular mechanisms, and metabolic activity, as well as neurocognitive and functional performance were assessed twice, before and after intervention. Maximum heart rate was considered a marker of effectiveness of physical activity. Mixed one-way analysis of variance and linear regression analyses were performed. Results Individuals with psychiatric disorders and comorbid obesity exhibited an improvement in cognition, mood symptoms and body mass index, increase anti-inflammatory activity together with enhancement of the oxidative and cardiovascular mechanisms after physical activity training (p<0.05 to 0.0001; d = 0.47 to 1.63). A better clinical outcomes along with regulation of inflammatory, oxidative, and cardiovascular mechanisms were critical for predicting significant maximum heart rate variation over time (χ 2 Conclusions =32.2 to 39.0, p <0.0001). The regulation of the anti-inflammatory mechanisms may be essential for maintained of healthy physical activity across psychiatric disorders and obesity. Likewise, inflammatory activity, oxidative stress, vascular and cardio-metabolic mechanisms may be a useful to identify individuals at greater risk of multi-comorbidity.Artículo Impaired motor cortical plasticity associated with cannabis use disorder in young adults(Wiley, 2020-04-23) Martín Rodríguez, Juan Francisco; Ruiz Veguilla, Miguel; Álvarez de Toledo, Paloma; Aizpurúa Olaizola, Oier; Zarandona, Iratxe; Canal Rivero, Manuel; Rodríguez Baena, Antonio; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Psicología Experimental; Universidad de Sevilla. Departamento de Psiquiatría; Universidad de Sevilla. Departamento de Medicina; Junta de Andalucía; Fundación Alicia Koplowitz; Fundación Mutua Madrileña; Fundación Progreso y Salud; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Sociedad Andaluza de Neurología; Universidad de SevillaMaladaptive cortical plasticity has been described in individuals with heroin and methamphetamine addiction and may mediate other substance abuse disorders. It is unknown whether cannabis dependence in humans alters the capacity for induction of cortical plasticity. The aim of this study was to non-invasively investigate cortical plasticity with transcranial magnetic stimulation in young adults who meet DSM-5 criteria for cannabis use disorder (CUD). Thirty men (ages 20– 30) who used cannabis daily over the previous 6 months (15 diagnosed of CUD) and 15 demographically matched non-users were enrolled in this study. All participants underwent two sessions of theta burst stimulation (TBS) in which either continuous TBS (cTBS; 600 pulses, 80% active motor threshold) or intermittent TBS (iTBS; 2-s train of cTBS repeated every 10 s for a total of 190 s, 600 pulses) was applied over the primary motor cortex. The effects of these protocols were assessed by analysing the contralateral motor evoked potentials (MEPs). The relationships between cortical plasticity and problematic cannabis use, degree of dependence, and nicotine addiction were also investigated. Significant MEP inhibition after cTBS was observed in both cannabis users without CUD and non-users, while this inhibition was not seen in cannabis users with CUD. Strikingly, less motor cortical plasticity was observed in subjects with severe problematic cannabis use. No significant differences between users and non-users were found in the iTBS-induced cortical plasticity measures. Our study provides the first evidence of maladaptive cortical plasticity associated with cannabis use disorder and problematic cannabis use in humans.Artículo Efficacy of clozapine versus standard treatment in adult individuals with intellectual disability and treatment-resistant psychosis (CLOZAID): study protocol of a multicenter randomized clinical trial(Frontiers Media SA, 2024-05-14) Alemany-Navarro, María; Sánchez-Barbero, Bianca; Reguera-Pozuelo, Pablo; Altea-Manzano, Laura; Gómez-Garrido, Ana; Rocha-González, Idalino; Ruiz Veguilla, Miguel; Crespo Facorro, Benedicto; Universidad de Sevilla. Departamento de Psiquiatría; Instituto de Biomedicina de Sevilla (IBIS); Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Universidad de Sevilla. CTS1086: Psiquiatría TraslacionalBackground: Intellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field. Methods: A Phase IIB, open-label, randomized, multicenter clinical trial (NCT04529226) is currently ongoing to assess the efficacy of oral clozapine in individuals diagnosed with ID and suffering from treatment-resistant psychosis. We aim to recruit one-hundred and fourteen individuals (N=114) with ID and resistant psychosis, who will be randomized to TAU(treatmentasusual) and treatment-with clozapine conditions. As secondary outcomes, changes in other clinical scales (PANSS andSANS)andtheimprovementinfunctionality, assessed through changes in the Euro-QoL-5D-5L were assessed. The main outcome variables will be analyzed using generalized linear mixed models (GLMM), assessing the effects of status variable (TAU vs. Clozapine), time, and the interaction between them. Discussion: The treatment of resistant psychosis among ID individuals must be directed by empirically supported research. CLOZAID clinical trial may provide relevant information about clinical guidelines to optimally treat adults with ID and treatment-resistant psychosis and the benefits and risks of an early use of clozapine in this underrepresented population in clinical trials.Artículo La distimia femenina y los fenómenos de amor y desamor(Revista de Neuro-Psiquiatría, 2019-10-01) García Arroyo, José Manuel; Universidad de Sevilla. Departamento de PsiquiatríaAunque el término distimia fue acuñado por Kahlbaum, su significado actual se inició en 1980, cuando aparece en el Manual Diagnóstico de la Asociación Americana de Psiquiatría (DSM) designando una depresión crónica de leve intensidad, distinguible de la depresión mayor. Objetivo: En este trabajo se estudian los casos de dos mujeres con este diagnóstico (según CIE-10) y se examinan los “componentes subjetivos” que sustentan los síntomas depresivos y que habitualmente no se mencionan en las publicaciones. Material y métodos: Se emplea el “Método de Abordaje de la Subjetividad” (MAS), consistente en realizar entrevistas no-directivas y registrar las expresiones verbales de modo fiel, al tiempo que se prescinde de cualquier alusión a teorías, creencias particulares, juicios de valor, etc. Resultados: Se reconoce en estas pacientes una desinserción sentimental respecto al objeto de amor, un convivir desencantado con sus parejas e imposibilidad de separación, al tiempo que aparecen insidiosamente los síntomas depresivos. Este fenómeno tiene como base la caída del “ideal romántico” al que aspiran, que sostiene sus vidas y que funciona como una “agarradera” o “ancla de personalidad”, razones por las que no mejoran su sintomatología. Estas originales apreciaciones cuestionan la noción clásica sobre el duelo. Conclusiones: Para que este tipo de pacientes mejoren sintomáticamente hace falta que hablen y se den cuenta de lo que realmente les está sucediendo. El estudio aquí descrito muestra las coordenadas subjetivas que se requiere conocer para poder conducir una adecuada intervención psicoterapéutica.Article Aspectos subjetivos de la hipocondría(Revista de Neuro-Psiquiatria, 2021-10-13) García Arroyo, José Manuel; Universidad de Sevilla. Departamento de PsiquiatríaObjetivos: Se intenta esclarecer los aspectos subjetivos de la hipocondría (o hipocondriasis), no suficientemente consistentes en las publicaciones sobre el tema, vacío que parece deberse a que actualmente se consideran únicamente las manifestaciones externas (conductuales) del paciente, prescindiendo de aspectos más personales. Material yMétodos: Se incluyen 12 pacientes diagnosticados de hipocondría (CIE-10) que acudieron a consulta en la Asociación de Psicopatología y Psicoanálisis de Sevilla (APPS) y a los que se aplicó el Método de Abordaje de la Subjetividad (MAS). Al expresarse verbalmente en las entrevistas, los pacientes descomponen analíticamente el problema que los aqueja, en distintos elementos; los enunciados así obtenidos se agrupan en categorías que definen los componentes subjetivos buscados. Resultados: Los hallazgos incluyen la exagerada intensidad con que los pacientes experimentan las sensaciones físicas, la anómala dirección de la atención y la atribución de significados erróneos, elementos que, al interactuar, forman un “bucle” o nudo del que les es imposible escapar. La utilización del -cuadrado de Apuleyo- ha contribuido a visualizar cómo los sujetos afectados mantienen el cuerpo por encima de todo, de manera que todos los vectores convergen necesariamente en él; ello explica que no puedan acceder a un encuentro auténtico con los demás, sufriendo entonces cierto deterioro social. Conclusiones: Las claves subjetivas aquí diseñadas puedan orientar adecuadamente a profesionales de la Salud Mental que utilicen enfoques psicoterapéuticos en el tratamiento de pacientes hipocondríacos.