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Cesar Giron‐Hernandez,1 Joong Hee Han,2 Roberta Alberio,3 Arun Singh,2 Maria Paz García-Portilla,4 Maurizio Pompili,5 R Karl Knight,2 Ute Richarz,6 Srihari Gopal,2,7 José Antunes8 1EMEA Medical Affairs, Janssen-Cilag, Issy-les-Moulineaux, France; 2Janssen Research & Development, LLC, Titusville, NJ, USA; 3Medical Affairs, Janssen-Cilag, Milan, Italy; 4Department of Psychiatry, Universidad de Oviedo, Instituto Sanitario Del Principado de Asturias (ISPA) and CIBERSAM, Oviedo, Spain; 5Department of Neurosciences, Mental Health, and Sensory Organs, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy; 6Janssen Global Services LLC, Cilag Int., Zug, Switzerland; 7Regeneron Pharmaceuticals, Tarrytown, NY, USA; 8EMEA Medical Affairs, Janssen-Cilag, Porto Salvo, PortugalCorrespondence: José Antunes, EMEA Medical Affairs, Janssen-Cilag, Porto Salvo, Portugal, Email jantune1@its.jnj.comPurpose: To examine efficacy and safety of paliperidone palmitate (PP) 6-month (PP6M) vs PP3-month (PP3M) long acting injectable (LAI) in patients with schizophrenia from European sites previously stabilized on PP3M or PP1-month (PP1M).Methods: This post-hoc subgroup analysis used data from a global phase-3 double-blind (DB) randomized non-inferiority study (NCT03345342). Patients were randomized (2:1, respectively) to receive dorsogluteal injections of PP6M (700 mg eq. or 1000 mg eq.) or PP3M (350 mg eq. or 525 mg eq.) in the 12-month DB phase. Primary endpoint was time-to-relapse during the DB phase, using a Kaplan–Meier cumulative survival estimate (non-inferiority margin 95% CI lower bound larger than prespecified as − 10%). Treatment emergent adverse events (TEAEs), physical examinations, and laboratory tests were also evaluated.Results: A total of 384 patients who entered the DB phase were included in European sites (PP6M, n = 260; PP3M, n = 124) with a mean age similar in both groups (mean age [SD] years: PP6M, 40.0 [11.39]; PP3M, 38.8 [10.41]). Baseline characteristics were similar across both groups. The number of patients who experienced a relapse during DB phase were PP6M: 18 (6.9%) vs PP3M: 3 (2.4%) with percentage relapse-free difference of − 4.9% (95% CI: − 9.2%, − 0.5%), thus achieving non-inferiority criteria. Secondary efficacy endpoints indicated comparable improvements. Incidence of TEAEs was similar between PP6M (58.8%) and PP3M (54.8%) groups. Nasopharyngitis, headache, increased weight, and injection-site pain were the most common TEAEs.Conclusion: The efficacy of PP6M was non-inferior to that of PP3M in preventing relapse in the European subgroup previously treated with PP1M or PP3M, which was consistent with the global study. No new safety signals were identified.Keywords: Europe, long-acting injectable, paliperidone palmitate 6-month, relapse-free, schizophrenia

INTRODUCTION: We conducted a follow-up study to evaluate the outcome of a heroin-dependent population 25years after their first enrollment in methadone maintenance treatment (MMT). We assessed mortality in the sample plus actual drug use, treatment, and medical factors associated with drug dependence, focusing on possible gender differences. METHODS: Prospective follow-up study of 214 heroin-dependent patients consecutively admitted for MMT between 1980 and 1984 in the Asturias Public Health Service. The standardized mortality ratio (SMR) and 95% confidence interval (CI) were calculated. An ad-hoc protocol on drug misuse and treatment, drug-related morbidity and Clinical Global Impression (CGI) scores were assessed in the survivors' sample. RESULTS: Information was received on 159 subjects, 106 of whom were deceased. Men accounted for 76.2% of the study cohort. Over the 25-year follow-up period, the SMR was 22.51 (95% CI=22.37-22.64). In the survivors sample, 39.6% were still enrolled in MMT; human immunodeficiency virus (HIV) was diagnosed in 47.2% and hepatitis B/C in 81.1%; current heroin use was reported by 22.6%. There were no gender differences in mortality or HIV and hepatitis B/C status. None of the female survivors were using heroin at the 25-year follow-up compared with 31.1% of males. CONCLUSIONS: This study confirms the high mortality of heroin addicts even after enrollment in MMT. Severity of the addiction in terms of mortality was similar in both genders. Women who survived the 25-year follow-up were more likely to have stopped using heroin than men. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests a potential association between "leaky gut syndrome" and low-grade systemic inflammation in individuals with psychiatric disorders, such as schizophrenia. Gut dysbiosis could increase intestinal permeability, allowing the passage of toxins and bacteria into the systemic circulation, subsequently triggering immune-reactive responses. This study delves into understanding the relationship between plasma markers of intestinal permeability and symptom severity in schizophrenia. Furthermore, the influence of lifestyle habits on these intestinal permeability markers was determined., Methods: Biomarkers of intestinal permeability, namely lipopolysaccharide-binding protein (LBP), lipopolysaccharides (LPS), and intestinal fatty acid binding protein (I-FABP), were analyzed in 242 adult schizophrenia patients enrolled in an observational, cross-sectional, multicenter study from four centers in Spain (PI17/00246). Sociodemographic and clinical data were collected, including psychoactive drug use, lifestyle habits, the Positive and Negative Syndrome Scale to evaluate schizophrenia symptom severity, and the Screen for Cognitive Impairment in Psychiatry to assess cognitive performance., Results: Results revealed elevated levels of LBP and LPS in a significant proportion of patients with schizophrenia (62% and 25.6%, respectively). However, no statistically significant correlation was observed between these biomarkers and the overall clinical severity of psychotic symptoms or cognitive performance, once confounding variables were controlled for. Interestingly, adherence to a Mediterranean diet was negatively correlated with I-FABP levels ( beta  = -0.186, t  = -2.325, p  = 0.021), suggesting a potential positive influence on intestinal barrier function., Conclusions: These findings underscore the importance of addressing dietary habits and promoting a healthy lifestyle in individuals with schizophrenia, with potential implications for both physical and psychopathological aspects of the disorder.

Background: Functional recovery remains a core clinical objective for patients with bipolar disorder (BD). Sociodemographic, clinical, and neurocognitive variables are associated with long-term functional impairment, yet the impact of sex differences is unclear. Functional remediation (FR) is a validated intervention aimed at achieving functional recovery in BD. The present study assessed the effect of sex differences of FR on psychosocial functioning at post-treatment (6-months) and 12-month follow-up (FUP). To the best of our knowledge, this is the first study to explore the role of sex as a factor in the efficacy of FR., Methods: 157 participants with BD were randomly assigned to either FR (N = 77) or treatment as usual group (80). Clinical, sociodemographic, neuropsychological, and functional data were obtained using a comprehensive assessment battery. Sex differences were explored via a general linear model (GLM) for repeated measures to compare the effect of sex on the intervention over time (6 months and FUP)., Results: Results demonstrated that FR benefits both sexes, males (p = 0.001; d' = 0.88) and females (p = 0.04; d' = 0.57), at 6 months suggesting a generalized functional improvement. Conversely, at 12-month FUP sex differences were observed only in males (p = 0.005; d' = 0.68)., Conclusions: FR is a beneficial intervention for males and females after treatment, suggesting that there are no relevant distinct needs. Females may benefit from ongoing psychosocial functioning booster sessions after the intervention to maintain original improvements. Future research exploring sex differences could help to identify strategies to offer personalized FR intervention approaches in individuals with BD., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Recent evidence indicates that the risk of death by suicide in teenagers has increased significantly worldwide. Consequently, different therapeutic interventions have been proposed for suicidal behavior in this particular population. Therefore, the main objective of this study is to provide an updated review of the existing psychological interventions for the treatment of suicide attempts (SA) in adolescents and to analyze the efficacy of such interventions., Methods: A systematic review was conducted following PRISMA guidelines. The studies were identified by searching PubMed, PsychINFO, Web of Science, and Scopus databases from 2016 to 2022. According to the inclusion criteria, a total of 40 studies that tested the efficacy of different psychological interventions were selected., Results: Various psychological interventions for adolescents with suicidal behaviors were identified. Most of those present promising results. However, to summarize results from recent years, dialectical behavior therapy (DBT) was the most common and the only treatment shown to be effective for adolescents at high risk of suicide and SA. In contrast, empirical evidence for other psychological interventions focusing on deliberate self-harm (SH) is inconclusive., Conclusions: Interventions specifically designed to reduce suicidal risk in adolescents have multiplied significantly in recent years. There are a few promising interventions for reducing suicidal behaviors in adolescents evaluated by independent research groups. However, replication and dismantling studies are needed to identify the effects of these interventions and their specific components. An important future challenge is to develop brief and effective interventions to reduce the risk of death by suicide among the adolescent population., (© 2024. The Author(s).)

The role of the oral microbiome in mental health has recently been appreciated within the proposed oral-brain axis. This study examined the structure and composition of the salivary microbiome in a large-scale population-based cohort of individuals reporting mental health symptoms (n = 306) compared to mentally healthy controls (n = 164) using 16S rRNA sequencing. Mental health symptoms were evaluated using validated questionnaires and included depression, anxiety, and posttraumatic stress disorder (PTSD), with accompanying periodontal outcomes. Participants also indicated current or previous diagnoses of anxiety, depression, periodontitis, and gingivitis. Mental and periodontal health variables influenced the overall composition of the oral microbiome. PTSD symptoms correlated with a lower clr-transformed relative abundance of Haemophilus sputorum and a higher clr-transformed relative abundance of Prevotella histicola. The clr-transformed relative abundance of P. histicola was also positively associated with depressive scores and negatively associated with psychological quality of life. Anxiety disorder diagnosis was associated with a lower clr-transformed relative abundance of Neisseria elongate and a higher clr-transformed relative abundance of Oribacterium asaccharolyticum. A higher clr-transformed relative abundance of Shuttleworthia and lower clr-transformed relative abundance of Capnocytophaga were evident in those who reported a clinical periodontitis diagnosis. Higher Eggerthia and lower Haemophilus parainfluenzae clr-transformed relative abundances were associated with reported clinical periodontitis diagnoses and psychotherapeutic efficacy. Functional prediction analysis revealed a potential role for tryptophan metabolism/degradation in the oral-brain axis, which was confirmed by lower plasma serotonin levels across symptomatic groups. This study sheds light on the intricate interplay between oral microbiota, periodontal and mental health outcomes, and a potential role for tryptophan metabolism in the proposed oral-brain axis, emphasizing the need for further exploration to pave the way for novel therapeutic interventions and predicting therapeutic response., (© 2024. The Author(s).)

Introduction: Bipolar disorder (BD) has been reconceptualised as a progressive disorder that develops from mild to severe presentations. An empirical staging model - the Empirically Developed Clinical Staging Model for BD (EmDe-5) - was developed in a previous study. This study aims to further validate that model using a larger and more representative Spanish sample., Material and Methods: 183 BD outpatients were recruited at 11 sites in Spain. Assessment included clinical characteristics of the BD (number of hospitalisations, number of suicide attempts, comorbid personality disorders), physical health (BMI, metabolic syndrome, number of physical illnesses), cognition (SCIP), functioning (permanently disabled due to BD, FAST), and quality of life (SF-36). The CGI-S, VAS-S, and psychopharmacological treatment pattern were used as external validators., Results: Ten patients (51.5%) were classified as stage 1, 33 (18%) as stage 2, 93 (508%) as stage 3, 37 (202%) as stage 4, and 10 (55%) as stage 5. All profilers, other than number of suicide attempts (p=0.311) and comorbid personality disorder (p=0.061), exhibited worse scores from stage 1 to 5. As expected, VAS-S and CGI-S scores were worse in the later stages. Regarding treatment, early stages (1-2) were associated with the use of one to three drugs while late stages (4-5) were associated with four or more drugs (p=0.002)., Conclusions: We confirm the EmDe-5 staging model's construct validity. The ease of obtaining the profilers, together with the operational criteria provided to quantify them, will facilitate the use of the EmDe-5 staging model in daily clinical practice., (Copyright © 2021. Published by Elsevier España S.L.U.)

The Positive and Negative Syndrome Scale (PANSS) is the most widely used rating scale to assess psychotic symptoms in patients with schizophrenia and other primary psychoses. However, a definitive consensus regarding its dimensional structure remains elusive. The present work aims to determine the number of dimensions of the scale through a network analysis approach in a sample of individuals experiencing first-episode schizophrenia spectrum disorder (FE-SSD) with minimal or no prior exposure to antipsychotic treatment. Baseline data of 446 participants (age 25.96 ± 5.99 years, 70% males) enrolled in the OPTiMiSE trial were analysed. Exploratory Graph Analysis (EGA) was conducted to evaluate the dimensionality of the PANSS, and a bootstrap approach (bootEGA) was employed to assess model stability. The analysis was replicated, excluding unstable items with stability values below 0.75, until a stable model was achieved. The analysis of the 30 items of the PANSS revealed inadequate structural consistency, resulting in the exclusion of 9 unstable items. The final model comprised 21 symptoms distributed across four communities (Positive, Cognitive/Disorganised, Excited/Aggressive and Negative) but lacked a depressive domain. In conclusion, we propose a concise version of the PANSS, incorporating 21 items, to better assess the core symptoms of the first episode of SSD. This revised version provides clinicians with a robust psychometric tool with reduced administration time, but the complementary administration of a dedicated instrument for evaluating affective symptoms is advisable., (© 2024. The Author(s).)

Background: Maternal childhood maltreatment (CM) has been repeatedly associated with negative offspring's emotional outcomes. The dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis has emerged as the main underlying physiological mechanism., Objective: To explore the association between maternal CM and newborns' physiological and neurobehavioral stress responses, considering the role of perinatal maternal depression and bonding., Participants and Setting: 150 healthy women were followed throughout pregnancy. 79 mother-infant dyads were included in the final analyses. Maternal CM was evaluated using the Childhood Trauma Questionnaire and depressive symptoms by the Edinburgh Postnatal Depression Scale (EPDS) at each trimester. At 7 weeks postpartum, the EPDS and the Postpartum Bonding Questionnaire were administered. Newborns' behavioral responses were assessed using "States Organization" (SO) and "States Regulation" (SR) subdomains of the Neonatal Behavioral Assessment Scale (NBAS). Newborns' salivary samples were collected before and after the NBAS to study cortisol reactivity., Methods: A cross-lagged panel model was employed., Results: Infants born to mothers with higher CM presented more optimal scores on SO (β (0.635) = 0.216, p 〈001) and SR (ß (0.273) = 0.195, p = .006), and a higher cortisol reactivity after NBAS handling (β(0.019) = 0.217, p = .009). Moreover, newborns of mothers with higher CM and postpartum depressive symptoms exhibited a poorer performance on SR (ß (0.156 = -0.288,p = .002). Analyses revealed non-significant relationships between mother-infant bonding, newborns' cortisol reactivity and SO., Conclusions: Newborns from mothers with greater CM present higher cortisol reactivity and more optimal behavioral responses, which may reflect a prenatal HPA axis sensitization. However, those exposed to maternal postnatal depressive symptoms present poorer stress recovery., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lithium (Li) is the first-line treatment for bipolar disorder (BD) even though only 30 % of BD patients are considered excellent responders. The mechanisms by which Li exerts its action are not clearly understood, but it has been suggested that specific epigenetic mechanisms, such as methylation processes, may play a role. In this regard, DNA methylation patterns can be used to estimate epigenetic age (EpiAge), which is accelerated in BD patients and reversed by Li treatment. Our first aim was to compare the DNA methylation profile in peripheral blood between BD patients categorized as excellent responders to Li (Ex-Rp) and non-responders (N-Rp). Secondly, EpiAge was estimated to detect differential age acceleration between the two groups. A total of 130 differentially methylated positions (DMPs) and 16 differentially methylated regions (DMRs) between Ex-Rp (n = 26) and N-Rp (n = 37) were identified (FDR adjusted p-value < 0.05). We found 122 genes mapping the DMPs and DMRs, nine of which (HOXB6, HOXB3, HOXB-AS3, TENM2, CACNA1B, ANK3, EEF2K, CYP1A1, and SORCS2) had previously been linked to Li response. We found genes related to the GSK3β pathway to be highly represented. Using FUMA, we found enrichment in Gene Ontology Cell Component for the synapse. Gene network analysis highlighted functions related to the cell cycle, nervous system development and function, and gene expression. No significant differences in age acceleration were found between Ex-Rp and N-Rp for any of the epigenetic clocks analysed. Our findings indicate that a specific methylation pattern could determine the response to Li in BD patients. We also found that a significant portion of the differentially methylated genes are closely associated with the GSK3β pathway, reinforcing the role of this system in Li response. Future longitudinal studies with larger samples will help to elucidate the epigenetic mechanisms underlying Li response., Competing Interests: Declaration of competing interest AGP has received CME-related honoraria, or consulting fees unrelated to the present work from Angelini, Janssen-Cilag, Casen Recordati, Rovi, LCN and Lundbeck. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Idorsia, Janssen, Lundbeck, Medincell, Merck, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work. The rest of authors have nothing to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Functioning is a fundamental dimension across all aspects of life, frequently compromised or reduced in individuals with schizophrenia. However, the lack of a commonly agreed definition of functioning in schizophrenia makes it difficult to apply this concept in clinical practice. In this document, we make a detailed analysis of the literature to identify and define functioning and describe how it can be used in clinical practice today. We performed a preliminary literature search in the MEDLINE database (via PubMed) for articles discussing functioning in schizophrenia. The articles retrieved were then read and discussed by a panel of psychiatrists specialising in schizophrenia. The conclusions reached in this meeting formed the basis for a new exhaustive literature search for the purpose of synthesising the evidence published in the past 5 years. In this article, we show the importance a comprehensive, modern, homogeneous definition of functioning in schizophrenia, propose a definition of functioning, and put forward a series of recommendations for assessing functioning in clinical practice. We also review current unmet needs and highlight the need for a standardised tool for evaluating functioning., Competing Interests: Declaration of competing interest IC has received in the last five years fees and honoraria in terms of registrations for congresses, participation in conferences and working groups from Otsuka-Lunbeck, Janssen, Angelini, Casen Recordati and Okedi. DF has been a consultant and/or has received fees from Angelini, Casen-Recordati, Janssen, Lundbeck, and Otsuka, and has received grant support from Instituto de Salud Carlos III (Spanish Ministry of Science and Innovation), Fundación Alicia Koplowitz, and Fundación La Caixa. MPGP has been a consultant to and/or has received honoraria/grants from Alter, Angelini, Cassen-Recordati, Janssen-Cilag, Idorsia, Lundbeck, Otsuka, and SAGE Therapeutics. JMO has received research funding from Instituto de Salud Carlos III (Spanish Ministry of Science and Innovation), ACIS (Agencia del Conocimiento en Salud de Galicia), Xunta de Galicia, Plan Nacional de Drogas (Spanish Ministry of Science and Innovation). He has also received fees as a consultant and/or speaker from: Janssen, Lundbeck, Otsuka, Adamed, Esteve, Oryzon Genomics, Angelini, Casan Recordati, and Rovi. P. Sierra has received fees or funding from Lundbeck, Janssen, Alter, Servier, Angelini and Instituto de Salud Carlos III (Spanish Ministry of Science and Innovation). P. Sánchez has received honoraria as a board advisor from Rovi, Janssen and Lundbeck. He has also been paid by Janssen and Rovi as honoraria for his contributions in medical education., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Child maltreatment is associated with a higher probability of mental disorders and suicidal behavior in adolescence. Therefore, accurate psychometric instruments are essential to assess this., Objective: To validate the Spanish version of the Childhood Trauma Questionnaire-Short Form (CTQ-SF) in adolescents with suicide attempts., Methods: Multisite cohort study of 208 adolescents with suicide attempts using data from the following scales: Mini International Neuropsychiatric Interview (MINI), Columbia Suicide Severity Rating Scale (C-SSRS), Patient Health Questionnaire (PHQ-9), and CTQ-SF. Statistical analysis: CTQ-SF scores analyzed by descriptive statistics. Internal consistency: McDonald's omega and Cronbach's alpha. Concurrent validity with PHQ-9 and C-SSRS scores: Spearman correlation coefficient. Structural validity: Confirmatory factor analysis., Results: Floor and ceiling effects: Physical abuse and neglect as well as sexual abuse demonstrated high floor effects (50.0, 35.1, and 61.1% of adolescents, respectively). No ceiling effects were found. The CTQ-SF had excellent internal consistency (McDonald's omega = 0.94), as did the majority of its subscales (Cronbach's alpha 0.925-0.831) except for physical neglect (0.624). Its concurrent validity was modest, and the emotional neglect subscale had the lowest Spearman correlation coefficients (0.067-0.244). Confirmatory factor analysis: Compared with alternative factor structures, the original CTQ-SF model (correlated 5-factor) exhibited a better fit [S-B χ 2 = 676.653, p < 0; RMSEA (90% CI = 0.076-0.097) = 0.087; SRMR = 0.078; CFI = 0.980; TLI = 0.978]., Conclusion: The Spanish CTQ-SF is a reliable, valid instrument for assessing traumatic experiences in adolescents at high risk of suicide. It appears appropriate for use in routine clinical practice to monitor maltreatment in this group., Competing Interests: IG has received grants and served as consultant, advisor or CME speaker for the following entities: ADAMED, Angelini, Casen Recordati, Esteve, Ferrer, Gedeon Richter, Janssen Cilag, Lundbeck, Lundbeck-Otsuka, Luye, SEI Healthcare, and Viatris outside the submitted work. She also receives royalties from Oxford University Press, Elsevier, and Editorial Médica Panamericana. EV has received grants and served as consultant, advisor, or CME speaker for the following entities: AB-Biotics, AbbVie, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypha Gedeon Richter, GH Research, Glaxo- Smith Kline, Idorsia, Janssen, Lundbeck, Medincell, Novartis, Orion Corporation, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris outside the submitted work. AG-P has received grants and served as consultant, advisor or CME speaker for the following entities: Janssen-Cilag, Lundbeck, Otsuka, Alter, Angelini, Novartis, Rovi, Takeda, the Spanish Ministry of Science and Innovation (CIBERSAM), the Ministry of Science (Carlos III Institute), the Basque Government, and the European Framework Program of Research. IZ has received grants and served as consultant, advisor or CME speaker for the following entities: Janssen-Cilag, Lundbeck, Otsuka, Angelini, Rovi and Takeda. MPG-P has been a consultant to and/or has received honoraria/grants from Alter, Angelini, Cassen-Recordati, Janssen- Cilag, Idorsia, Lundbeck, Otsuka, Rovi, and SAGE Therapeutics. PS has been a consultant to and/or has received honoraria or grants from Adamed, Alter Medica, Angelini Pharma, CIBERSAM, Ethypharm Digital Therapy, European Commission, Government of the Principality of Asturias, Instituto de Salud Carlos III, Johnson & Johnson, Lundbeck, Otsuka, Pfizer, Plan Nacional Sobre Drogas, and Servier. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 García-Fernández, Martínez-Cao, Sánchez-Fernández-Quejo, Bobes-Bascarán, Andreo-Jover, Ayad-Ahmed, Cebriá, Díaz-Marsá, Garrido-Torres, Gómez, González-Pinto, Grande, Iglesias, March, Palao, Pérez-Díez, Roberto, Ruiz-Veguilla, de la Torre-Luque, Zorrilla, Pérez, SURVIVE Group, Sáiz and García-Portilla.)

Introduction: Although there is evidence that higher cognitive reserve (CR) is a protective factor and it has been related to better prognosis, there have been no studies to date that have explored the CR level and its impact in clinical, neurocognitive and lifestyle outcomes according to the stage of the disease: early stage of psychosis (ESP) or chronic schizophrenia (SCZ)., Material and Methods: A total of 60 patients in the ESP and 225 patients with SCZ were enrolled in the study. To test the predictive capacity of CR for each diagnostic group, a logistic regression analysis was conducted. Hierarchical linear regression analyses were performed to explore the associations between CR and different outcomes. The mediation analyses were performed according to the principles of Baron and Kenny., Results: Patients with SCZ showed lower CR than those in the ESP (p<0.001). CR correctly classified 79.6% of the cases (p<0.001; Exp(B)=1.062). In ESP group, CR was related to working memory (p=0.030) and negative symptoms (p=0.027). CR (t=3.925, p<0.001) and cannabis use (t=2.023, p=0.048) explained 26.7% of the variance on functioning (p=0.003). In patients with SCZ, CR predicted all cognitive domains, negative symptoms (R 2 =0.091, p=0.001) and functioning (R 2 =0.074, p=0.005). In both ESP and SCZ groups, higher CR was associated with lower body mass index and circumference. In ESP group, the effect of adherence to Mediterranean diet on functioning (p=0.037) was mediated by CR level (p=0.003)., Conclusions: The implications of CR depend on the stage of the disease (ESP vs. SCZ), with a greater effect on neurocognition and negative symptoms in patients with chronic SCZ., (Copyright © 2024 Sociedad Española de Psiquiatría y Salud Mental (SEPSM). Published by Elsevier España S.L.U. All rights reserved.)

Background: Cognitive impairment is a widespread feature of schizophrenia, affecting nearly 80 % of patients. Prior research has linked the anticholinergic burden of psychiatric medications to these cognitive deficits. However, the impact of the anticholinergic burden from medications for physical morbidity remains underexplored. This study aimed to evaluate the anticholinergic burden of psychiatric and physical medications in patients with schizophrenia and assess its impact on cognitive function., Methods: A total of 178 patients with schizophrenia were recruited. The assessments included an ad hoc questionnaire for collecting demographic and clinical data. Anticholinergic burden was evaluated using the cumulative Drug Burden Index (cDBI) for each participant, and cognitive function was assessed using MATRICS. Psychopathology was measured using the PANSS, CDSS, CAINS, and the CGI-S. Statistical analysis included Student's t -tests, ANOVA, Pearson correlations, and multiple linear regressions., Results: The average cDBI was 1.3 (SD = 0.9). The model developed explained 40.80 % of the variance. The variable with the greatest weight was the cDBI (B = -11.148, p  = 0.010). Negative-expression (B = -2.740, p  = 0.011) and negative-experiential (B = -1.175, p  = 0.030) symptoms were also associated with lower global cognitive score. However, more years of education (B = 5.140, p  < 0.001) and cigarettes per day (B = 1.331, p < 0.001) predicted a better global cognitive score., Conclusion: This study identified specific predictors of global cognition in schizophrenia, with anticholinergic burden emerging as the strongest factor. Our findings underscore the importance of considering the anticholinergic burden of treatments, in addition to negative symptoms, when designing interventions to optimize or maintain cognitive function in patients with schizophrenia., Competing Interests: The authors declare no conflict of interest related to the submitted work., (© 2024 Published by Elsevier Inc.)

Background: The COVID-19 pandemic has brought significant mental health challenges, particularly for vulnerable populations, including non-binary gender individuals. The COMET international study aimed to investigate specific risk factors for clinical depression or distress during the pandemic, also in these special populations., Methods: Chi-square tests were used for initial screening to select only those variables which would show an initial significance. Risk Ratios (RR) were calculated, and a Multiple Backward Stepwise Linear Regression Analysis (MBSLRA) was followed with those variables given significant results at screening and with the presence of distress or depression or the lack of both of them., Results: The most important risk factors for depression were female (RR = 1.59-5.49) and non-binary gender (RR = 1.56-7.41), unemployment (RR = 1.41-6.57), not working during lockdowns (RR = 1.43-5.79), bad general health (RR = 2.74-9.98), chronic somatic disorder (RR = 1.22-5.57), history of mental disorders (depression RR = 2.31-9.47; suicide attempt RR = 2.33-9.75; psychosis RR = 2.14-10.08; Bipolar disorder RR = 2.75-12.86), smoking status (RR = 1.15-5.31) and substance use (RR = 1.77-8.01). The risk factors for distress or depression that survived MBSLRA were younger age, being widowed, living alone, bad general health, being a carer, chronic somatic disorder, not working during lockdowns, being single, self-reported history of depression, bipolar disorder, self-harm, suicide attempts and of other mental disorders, smoking, alcohol, and substance use., Conclusions: Targeted preventive interventions are crucial to safeguard the mental health of vulnerable groups, emphasizing the importance of diverse samples in future research., Limitations: Online data collection may have resulted in the underrepresentation of certain population groups., Competing Interests: Declaration of competing interest None pertaining to the current paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: One of the challenges of psychiatry is the staging of patients, especially those with severe mental disorders. Therefore, we aim to develop an empirical staging model for schizophrenia., Methods: Data were obtained from 212 stable outpatients with schizophrenia: demographic, clinical, psychometric (PANSS, CAINS, CDSS, OSQ, CGI-S, PSP, MATRICS), inflammatory peripheral blood markers (C-reactive protein, interleukins-1RA and 6, and platelet/lymphocyte [PLR], neutrophil/lymphocyte [NLR], and monocyte/lymphocyte [MLR] ratios). We used machine learning techniques to develop the model (genetic algorithms, support vector machines) and applied a fitness function to measure the model's accuracy (% agreement between patient classification of our model and the CGI-S)., Results: Our model includes 12 variables from 5 dimensions: 1) psychopathology: positive, negative, depressive, general psychopathology symptoms; 2) clinical features: number of hospitalizations; 3) cognition: processing speed, visual learning, social cognition; 4) biomarkers: PLR, NLR, MLR; and 5) functioning: PSP total score. Accuracy was 62% (SD = 5.3), and sensitivity values were appropriate for mild, moderate, and marked severity (from 0.62106 to 0.6728)., Discussion: We present a multidimensional, accessible, and easy-to-apply model that goes beyond simply categorizing patients according to CGI-S score. It provides clinicians with a multifaceted patient profile that facilitates the design of personalized intervention plans.

Background: The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders., Methods: The sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions., Results: About 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15-20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome., Conclusions: The finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.

Brain damage related to alcohol consumption is associated with impairments in cognitive functions, among which memory and verbal learning stand out. The main objective is to evaluate memory and verbal learning in a sample of 111 patients with alcohol use disorder (AUD) versus 78 with major depressive disorder (MDD) and 100 healthy controls. The evaluation included sociodemographic and clinical variables, the Hamilton Depression Scale (HDRS) and the California Verbal Learning Test (CVLT). One-way ANOVA was used for comparisons between the 3 groups and two-way ANCOVAS including different covariates. The one-way ANOVA shows that patients with AUD and MDD had scores similar to each other and lower than those of the control group (p < 0.001), with the exception of the Cued CVLT (worse scores in MDD vs AUD, p < 0.001). After including age, sex and years of completed studies as covariates, the differences between the AUD and MDD groups persisted compared to the control group (p ≤ 0.003) in all indices except for the Immediate Free CVLT and the Cued CVLT (worse performance in MDD vs AUD, p = 0.022 and p = 0.035, respectively). In the second ANCOVA, after controlling for depression severity, differences were only detected between AUD patients and healthy controls (p ≤ 0.007). Patients with AUD present a significant impairment in learning and verbal memory when compared with patients with MDD and with healthy people.

Background: Depression during pregnancy is a common complication that can negatively affect fetal health and birth outcomes. Cortisol is believed to be a key mediator of this association. Although pregnancy entails a natural increase in cortisol levels, preclinical depression could alter its circadian rhythm, producing excessively high overall diurnal cortisol levels that might be harmful for the fetus and future offspring development., Objectives: Using a prospective longitudinal design, we aimed to study (i) trimestral cortisol circadian rhythm and its overall levels throughout pregnancy in healthy women, (ii) the extent to which maternal depressive symptoms influence both cortisol rhythmicity and overall levels, and (iii) the possible adverse consequences of elevated maternal cortisol on the offspring's weight and gestational age at birth., Study Design: 112 healthy pregnant women from the general Spanish population were recruited before their first pregnancy. To assess cortisol circadian rhythm, participants provided four saliva samples at each trimester of pregnancy (at awakening, 30 min after awakening, before lunch and before going to bed). Overall cortisol levels were calculated with AUCg approximation. Depressive symptoms were evaluated in each trimester and defined according to EPDS cut-off values (1st trimester, EPDS ≥ 11; 2nd and 3rd trimesters, EPDS ≥ 10). At birth, the risk for low weight, prematurity and weight birth percentile was retrieved for 100 infants. Mixed models and simple effects were employed to study changes of maternal cortisol circadian rhythm and overall levels throughout pregnancy and the possible influence of maternal depressive symptoms. Finally, logistic regressions were performed to assess the associations between maternal overall cortisol levels in each trimester of pregnancy and birth anthropometrics., Results: Although overall diurnal cortisol levels increase throughout pregnancy, cortisol circadian rhythm is preserved in all trimesters [1st (F(3110)= 92.565, p < .001), 2nd (F(3,85)= 46.828, p < .001) and 3rd (F(3,90)= 65.555, p < .001)]. However, women with depressive symptoms showed a flattened cortisol circadian pattern only during the second trimester, characterized by a blunted awakening peak and reduced evening decline (F(3,85)= 4.136, p = .009), but not during the first (F(3,11)= 1.676, p = .176) or the third (F(3,90)= 1.089, p = .358) trimesters. Additionally, they did not show a cortisol increase from second to third trimester (p = .636). Finally, higher maternal cortisol levels in second and third trimesters seemed to be associated with increased risk of prematurity (adjusted OR -0.371, 95% CI 0.490-0.972, p = .034) and low birth weight percentile (adjusted OR -0.612, 95% CI 0.348-0.846, p = .007) respectively., Conclusion: Maternal cortisol levels increased throughout pregnancy, although cortisol circadian rhythm was preserved in all trimesters of pregnancy. However, prenatal depressive symptoms were associated with flattened maternal cortisol circadian rhythm in mid-pregnancy. Therefore, it seems that women with depressive symptoms tended to increase less gradually their cortisol levels from mid to late pregnancy. Finally, higher maternal cortisol levels in mid and late-pregnancy seem to be associated with poorer birth anthropometrics Early detection of depressive symptoms in general population could help to prevent putative obstetrical and birth adverse outcomes., Competing Interests: Declaration of Competing Interest Authors do not have any conflict of interest regarding the publication of this manuscript., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Impaired intestinal permeability has recently been suggested as a possible source of chronic inflammation in schizophrenia, but its association with specific psychopathological features remains uncertain. This study aimed to explore the interaction between intestinal permeability, inflammation, and positive and negative symptoms in schizophrenia using a network analysis approach. The study sample comprised 281 adults with schizophrenia (age 40.29 ± 13.65 years, 63.0 % males), enrolled in a cross-sectional observational study assessing intestinal permeability. We estimated the network with a Gaussian graphical model, incorporating scores from 14 individual items of the Positive and Negative Syndrome Scale (PANSS), along with body mass index (BMI), and plasma C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) levels. We calculated strength centrality and expected influence and used bridge centrality statistics to identify the bridge nodes. Distinct but highly interconnected clusters emerged for positive and negative symptoms. The biological variables were closely associated with each other. LBP was positively linked with CRP and BMI, but only indirectly connected to psychopathology. CRP exhibited direct positive relationships with various PANSS items and bridged LBP and BMI with psychopathology. Bridge nodes included Conceptual Disorganisation (P2), Active Social Avoidance (G16), Suspiciousness/Persecution (P6), and CRP. These findings support the role of gut-derived inflammation as a mechanism underlying greater symptom severity in schizophrenia and emphasise the importance of addressing dietary habits not only to enhance physical health but also to contribute to improving psychotic symptoms., Competing Interests: Declaration of Competing Interest FDS has received grants from the Spanish Foundation of Psychiatry and Mental Health and the European Psychiatric Association. LGB has been a consultant to and/or has received honoraria/grants from the Spanish Foundation of Psychiatry and Mental Health, European Psychiatric Association, Otsuka, Lundbeck, Janssen-Cilag and Pfizer. MPGP has been a consultant to and/or has received honoraria/grants from Angelini, Alianza Otsuka-Lundbeck, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, and Pfizer. MB has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda. GA has received continuing medical education (CME)–related honoraria or consulting fees from Janssen-Cilag, Lundbeck, Lundbeck and Otsuka, and Angelini. SA has been supported by Sara Borrell doctoral programme (CD20/00177) and M-AES mobility fellowship (MV22/00002), from the Instituto de Salud Carlos III (ISCIII), and co-funded by European Social Fund “Investing in your future”. All other authors declare that they have no conflicts of interest related to the current work., (Copyright © 2023. Published by Elsevier B.V.)

Background: The clinical debut of schizophrenia is frequently a first episode of psychosis (FEP). As such, there is considerable interest in identifying associations between biological markers and clinical or cognitive characteristics that help predict the progression and outcome of FEP patients. Previous studies showed that high prolactin, low oxytocin, and high homocysteine are factors associated with FEP 6 months after diagnosis, at which point plasma levels were correlated with some clinical and cognitive characteristics., Methods: We reexamined 75 patients at 12 months after diagnosis to measure the evolution of these molecules and assess their association with clinical features., Results: At follow-up, FEP patients had lower prolactin levels than at baseline, and patients treated with risperidone or paliperidone had higher prolactin levels than patients who received other antipsychotic agents. By contrast, no changes in oxytocin and homocysteine plasma levels were observed between the baseline and follow-up. In terms of clinical features, we found that plasma prolactin and homocysteine levels were correlated with the severity of the psychotic symptoms in male FEP patients, suggesting that they might be factors associated with psychotic symptomatology but only in men. Together with oxytocin, these molecules may also be related to sustained attention, verbal ability, and working memory cognitive domains in FEP patients., Conclusion: This study suggests that focusing on prolactin, oxytocin, and homocysteine at a FEP may help select adequate pharmacological treatments and develop new tools to improve the outcome of these patients, where sex should also be borne in mind., (© The Author(s) 2023. Published by Oxford University Press on behalf of CINP.)

Background: Altered intestinal permeability and low-grade chronic inflammation disrupt the integrity of the blood-brain barrier (microbiota-gut-brain axis), probably playing a role in the pathophysiology of schizophrenia-spectrum disorders. However, studies assessing the microbiota-gut-brain axis are inconsistent. This article describes the rationale, objectives, protocol, and presents descriptive results for a new project., Methods: The sample of this study came from an observational, cross-sectional and multisite study including four centers in Spain (PI17/00246) recruiting adult patients with DSM-5 schizophrenia-spectrum disorders at any stage of the disease. The aims of the project are to assess the interrelation between intestinal permeability and low-grade chronic inflammation in schizophrenia-spectrum disorders and the role of peripheral biomarkers, diet, exercise, metabolic syndrome, disease severity and functioning as well as cognition. Assessments included the following variables: (1) anthropometric, (2) intestinal permeability, diet, and physical exercise, (3) clinical and functional, (4) neuropsychological and cognitive reserve, and (5) peripheral biomarkers from blood., Results: A total of 646 patients were enrolled (257, 39.7% female). Mean age was 43.2±13.6 years, illness duration 15.1±11.5 years. 55.8% consumed tobacco. Positive PANSS score was 13.68±6.55, and 20.38±8.69 in the negative symptoms. CGI was 4.16±2.22 and GAF was 60.00±14.84., Conclusion: The results obtained by this project are expected to contribute toward the understanding of the physiopathology of schizophrenia-spectrum disorders. This will likely aid to personalize treatments in real-world clinical practice, potentially including variables related to intestinal permeability and inflammation., (Copyright © 2023 Sociedad Española de Psiquiatría y Salud Mental (SEPSM). Published by Elsevier España S.L.U. All rights reserved.)

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11-0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse., Competing Interests: Conflict of interest A. Ibáñez has received research support from or served as speaker or advisor for Janssen-Cilag, Lundbeck and Otsuka. A. Gonzalez-Pinto has received grants and served as consultant, advisor or CME speaker for the following entities: Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Sanofi-Aventis, Exeltis, the Spanish Ministry of Science and Innovation (CIBERSAM), the Ministry of Science (Carlos III Institute), and the Basque Government, J. Saiz-Ruiz has been as speaker for and on the advisory boards of Adamed, Lundbeck, Servier, Medtronic, Casen Recordati, Neurofarmagen, Otsuka, Indivior, Lilly, Schwabe, Janssen and Pfizer, outside the submitted work. M. Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda, Pilar A. Saiz has been a consultant to and/or has received honoraria or grants from Adamed, CIBERSAM, European Comission, Government of the Principality of Asturias, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Plan Nacional Sobre Drogas and Servier. R. Rodriguez-Jimenez has been a consultant for, spoken in activities of, or received  grants from: Instituto de Salud Carlos III,  Fondo de Investigación Sanitaria (FIS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid Regional Government (S2010/ BMD-2422 AGES; S2017/BMD-3740), JanssenCilag, Lundbeck, Otsuka, Pfizer, Ferrer, Juste, Takeda, Exeltis, Casen-Recordati, Angelini. The rest of the authors reported no biomedical financial interests or potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Neutrophil/lymphocyte (NLR), monocyte/lymphocyte (MLR), and platelet/lymphocyte (PLR) ratios, and systemic inflammatory index (SII) represent peripheral markers of inflammation associated with different severe mental disorders., Material and Methods: In this study, these parameters were analyzed in a sample of 622 participants [197 patients with major depressive disorder (MDD), 154 with bipolar disorder (BD), 176 with schizophrenia (SCH), and 95 healthy controls (HC)]. Sociodemographic and clinical data of patients were recorded., Results: Differences in age and sex were detected among groups (p<0.001), with SCH patients being younger and MDD patients being older. After stratifying by sex, these ratios were compared using the nonparametric ANCOVA (Quade's test) using age as a covariate. In males, no significant statistical differences were found between groups. However, differences were observed in MLR in the subgroup of females [MDD: 0.23 (SD=0.09); BD: 0.23 (SD=0.11); SCH: 0.24 (SD=0.11); HC: 0.29 (SD=0.13); F=5.376, p=0.001]. Post hoc testing revealed that there are MLR differences between HC versus MDD and between HC versus BD, with higher values in HC versus the other two groups. On the other hand, no differences were found in either males or females for any of the studied ratios, among the three diagnostic groups., Conclusions: MLR is reduced in MDD and BD patients versus HC, but exclusively in the female group. However, based on the analyzed indices, it is not possible to differentiate among the three diagnostic groups of patients. As a limitation of this study, note that the effects of psychopharmacological treatments and smoking have not been controlled for., (Copyright © 2023 The Authors. Published by Elsevier España S.L.U. All rights reserved.)

Background: People with schizophrenia and predominant negative symptoms (PNS) present a different clinical and functional profile from those without such symptomatology. Few studies have examined the risk factors and the incidence of PNS in first-episode schizophrenia patients (FES) and differentiating by sex. This study aims to assess prevalence, demographic and clinical characteristics related to PNS from early stages and to study if there are sex-specific features in terms of developing PNS., Methods: In a sample of 121 FES patients derived from a multicentre and naturalistic study, those who developed PNS at 12-months were identified. Environmental, clinical, functional, and cognitive ratings were examined longitudinally. Binary logistic regressions were applied to detect baseline risk factors for developing PNS at one-year follow-up., Results: In the present FES cohort, 24.8% of the patients (n=30) developed PNS (20% of the women, 27.6% of the men). Compared to non-PNS (75.2%, n=91), at baseline, PNS group had more negative (t=-6.347; p<0.001) and depressive symptoms (t=-5.026; p<0.001), poorer premorbid adjustment (t=-2.791; p=0.006) and functional outcome (t=-2.649; p<0.001), more amotivation (t=-7.333; p<0.001), more expressivity alterations (t=-4.417; p<0.001), worse cognitive reserve (t=2.581; p<0.011), a lower estimated intelligent quotient (t=2.417; p=0.017), worse verbal memory (t=2.608; p=0.011), and worse fluency (t=2.614; p=0.010). Regressions showed that the premorbid adjustment was the main predictor of PNS in females (p=0.007; Exp(B)=1.106) while in males were a worse verbal memory performance (p=0.031; Exp(B)=0.989) and more alterations in the motivation domain (p=0.001; Exp(B)=1.607)., Conclusions: A different baseline clinical profile and notable risk factors differences in the development of PNS between males and females were found. Results suggest that sex may be an important confounder in studies comparing schizophrenia patients with predominant and non-predominant negative symptomatology., (Copyright © 2023 Sociedad Española de Psiquiatría y Salud Mental (SEPSM). Published by Elsevier España S.L.U. All rights reserved.)

Background: Since research in schizophrenia mainly focuses on deficits and risk factors, we need studies searching for high-functioning protective factors. Thus, our objective was to identify protective (PFs) and risk factors (RFs) separately associated with high (HF) and low functioning (LF) in patients with schizophrenia., Methods: We collected information (sociodemographic, clinical, psychopathological, cognitive, and functional) from 212 outpatients with schizophrenia. Patients were classified according to their functional level (PSP) as HF (PSP > 70, n  = 30) and LF (PSP ≤ 50, n  = 95). Statistical analysis consisted of Chi-square test, Student's t -test, and logistic regression., Results: HF model: variance explained: 38.4-68.8%; PF: years of education (OR = 1.227). RFs: receiving a mental disability benefit (OR = 0.062) and scores on positive (OR = 0.719), negative-expression (OR = 0.711), and negative-experiential symptoms (OR = 0.822), and verbal learning (OR = 0.866). LF model: variance explained: 42.0-56.2%; PF: none; RFs: not working (OR = 6.900), number of antipsychotics (OR = 1.910), and scores on depressive (OR = 1.212) and negative-experiential symptoms (OR = 1.167)., Conclusion: We identified specific protective and risk factors for high and low functioning in patients with schizophrenia and confirmed that high functioning factors are not necessarily the opposite of those associated with low functioning. Only negative experiential symptoms are a shared and inverse factor for high and low functioning. Mental health teams must be aware of protective and risk factors and try to enhance or reduce them, respectively, to help their patients improve or maintain their level of functioning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Martínez-Cao, García-Fernández, González-Blanco, Zurrón-Madera, Sáiz, García-Portilla and Bobes.)

Background: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected siblings, and healthy controls., Methods: This cross-sectional sample consisted of 1200 patients, 1371 siblings, and 1564 healthy controls. Neurocognition, social cognition, and perception were assesed using a short version of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the Degraded Facial Affect Recognition Task (DFAR), and the Benton Facial Recognition Test (BFR), respectively. Regression models were used to analyze the association between ES-SCZ and cognitive domains in each group., Results: There were no statistically significant associations between ES-SCZ and cognitive domains in SSD. ES-SCZ was negatively associated with T-score of cognition in siblings (B=-0.40, 95% CI -0.76 to -0.03) and healthy controls (B=-0.63, 95% CI -1.06 to -0.21). Additionally, ES-SCZ was positively associated with DFAR-total in siblings (B=0.83, 95% CI 0.26 to 1.40). Sensitivity analyses excluding cannabis use history from ES-SCZ largely confirmed the main findings., Conclusions: Longitudinal cohorts may elucidate how environmental exposures influence the onset and course of cognitive impairments in trans-syndromic psychosis spectrum., Competing Interests: Declaration of Competing Interest Celso Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. Julio Bobes has received research grants and served as a consultant, advisor, or speaker within the last 5 years for AB-Biotics, Acadia Pharmaceuticals, Alkermes, Allergan, Ambrosetti-Angelini, Biogen, Casen Recordati, D&A Pharma, Exeltis, Gilead, Indivior, GW Pharmaceuticals, Janssen-Cilag, Jazz Pharmaceuticals, Lundbeck, Mundipharma, Newron, Otsuka, Pfizer, Roche, Sage Therapeutics, Servier, Schwabe Farma Ibérica, Shire, and Takeda and has received research funding from the Spanish Ministry of Economy and Competiveness –Centro de Investigación Biomedica en Red area de Salud Mental (CIBERSAM) and Instituto de Salud Carlos III– and the Spanish Ministry of Health. Maria Paz García-Portilla has been a consultant to and/or has received honoraria/grants from Angelini, Otsuka-Lundbeck Alliance, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, and Sage Therapeutics. Pilar A. Sáiz has been a consultant to and/or has received honoraria/research grants from Adamed, Alter Medica, Angelini Pharma, CIBERSAM, Ethypharm Digital Therapy, European Commission, Government of the Principality of Asturias, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Plan Nacional Sobre Drogas, and Servier. Miguel Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda., (Copyright © 2023. Published by Elsevier B.V.)

Background: Deficits in emotional intelligence (EI) were detected in patients with bipolar disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients., Methods: The Emotional Intelligence Quotient (EIQ) was calculated with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model., Results: In total, 184 subjects were included (FEM n = 48, euthymic chronic BD type I n = 75, HC n = 61). BD patients performed significantly worse than HC on the EIQ [mean difference (MD) = 10.09, standard error (s.e.) = 3.14, p = 0.004] and on the understanding emotions branch (MD = 7.46, s.e. = 2.53, p = 0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex ( β = -0.293, p = 0.034) and verbal memory performance ( β = 0.374, p = 0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains., Conclusions: Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness.

Introduction: Experts agree that there is a need for protocols to guide health professionals on how to best manage psychiatric comorbidities in patients with epilepsy (PWE). We aimed to develop practical recommendations for key issues in the management of depression in PWE., Methods: This was a qualitative study conducted in four steps: (1) development of a questionnaire on the management of depression in PWE to be answered; (2) literature review and, if evidence from guidelines/consensus or systematic reviews was available, drafting initial recommendations; (3) a nominal group methodology for reviewing initial recommendations and formulating new recommendations on those issues without available evidence; and (4) drafting and approving the final recommendations. A scientific committee (one neurologist and one psychiatrist) was responsible for the development of the project and its scientific integrity. The scientific committee selected a panel of experts (nine neurologists and nine psychiatrists with experience in this field) to be involved in the nominal group meetings and to formulate final recommendations., Results: Fifteen recommendations were formulated. Four on the screening and diagnosis: screening and diagnosis of depression, evaluation of the risk of suicide, and diagnosis of depression secondary to epilepsy; nine on the management of depression: referral to a psychiatrist, selection of the antiseizure medication, change of antiseizure medication, antidepressant treatment initiation, selection of antidepressant, use of antidepressants during pregnancy, use of psychotherapy, antidepressant treatment duration, and discontinuation of antidepressant treatment; two on the follow-up: duration of the follow-up under usual conditions, and follow-up of patients at risk of suicide., Conclusion: We provide recommendations based on expert opinion consensus to help healthcare professionals assess depression in PWE. The detection and treatment of major depressive disorders are key factors in improving epilepsy outcomes and avoiding suicide risk., (© 2023. The Author(s).)

The early psychological impact of the COVID-19 pandemic and lockdown is greater in people with mental disorders. This study explored the differences in the psychological impact on people with an anxiety disorder by sex in Spain.

Background: The potential impact of the COVID-19 pandemic on suicidal behavior has generated predictions anticipating an increase in suicidal tendencies. The aim of this research is to study its influence on the incidence of hospital-treated suicide attempts throughout the year 2020 in Oviedo, Spain., Methods: Data were collected on all patients admitted to the emergency department of Central University Hospital of Asturias in Oviedo for attempted suicide during 2020. Incidence rates were calculated for three lockdown periods. Suicide attempt trends in 2020 were compared with a non-COVID-19 year (2009) to avoid seasonal variations bias. Chi-square and Fisher's exact tests were performed. The influence of COVID-19 incidence in Oviedo was analyzed using Spearman's correlation coefficient., Results: The cumulative incidence rate of attempted suicide per 100,000 person-years was 136.33 (pre-lockdown), 115.15 (lockdown), and 90.25 (post-lockdown) in adults (over 19 years old), and 43.63 (pre-lockdown), 32.72 (lockdown), and 72.72 (post-lockdown) in adolescents (10-19 years old). No association was found with COVID-19 incidence rates (Spearman's rho -0.222; p  = 0.113). Comparing the years 2020 and 2009, statistically significant differences were observed in adolescents (Fisher's exact test; p  = 0.024), but no differences were observed in adults (chi-square test = 3.0401; p  = 0.218)., Conclusions: Hospital-treated suicide rates attempted during the COVID-19 outbreak in Oviedo, Spain showed a similar trend compared with a non-COVID-19 year. In contrast, the number of adolescents hospital-treated for attempted suicide increased during lockdown, suggesting more vulnerability to COVID-19 restrictions after the initial lockdown period in this age group.

Until now, no follow-up studies had simultaneously evaluated executive functions, other non-executive functions related cognitive functions, and impulsivity in a large enough sample of moderate to severe alcohol use disorder (AUD) patients. The main objective of the present study was to compare neuropsychological performance and its relation to alcohol use in patients with AUD and healthy controls, and to determine the evolution of cognitive impairment and alcohol use over time. For this purpose, a 6-month follow-up study was designed to compare a sample of 100 outpatients with AUD (DSM-5 criteria) with 100 matched healthy controls. The patient group was recruited from three different health centres in Spain located in Orense, Gijón and Barcelona. The assessment consisted of a systematic battery of cognitive tests to evaluate the following functions: attention, anterograde memory, processing speed, verbal fluency, executive function, and implicit attitude toward alcoholic beverages. We also compared clinical variables associated with alcohol use, such as alcohol craving and impulsivity. After 6 months, anterograde memory, working memory, and resistance to interference improved remarkably in AUD patients, although not enough to match the normal population. With regard to clinical variables, there was a small but significant cognitive improvement related to a reduction in alcohol use and impulsivity. Executive dysfunction and other non-executive functions related cognitive functions impairment can be considered prognostic factors in outpatients with moderate to severe AUD.