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Objectives Negative symptom studies frequently use single composite scores as indicators of symptom severity and as primary endpoints in clinical trials. Factor analytic and external validation studies do not support this practice but rather suggest a multidimensional construct. The current study used structural equation modeling (SEM) to compare competing dimensional models of negative symptoms to determine the number of latent dimensions that best capture variance in biological, psychological, and clinical variables known to have associations with negative symptoms. Methods Three independent studies (total n = 632) compared unidimensional, two-factor, five-factor, and hierarchical conceptualizations of negative symptoms in relation to cognition, psychopathology, and community functioning (Study 1); trait emotional experience and defeatist performance beliefs (Study 2); and glutamate and gamma-aminobutyric acid levels in the anterior cingulate cortex quantified using proton magnetic resonance spectroscopy (Study 3). Results SEM favored the five-factor and hierarchical models over the unidimensional and two-factor models regardless of the negative symptom measure or external validator. The five dimensions—anhedonia, asociality, avolition, blunted affect, and alogia—proved vital either as stand-alone domains or as first-order domains influenced by second-order dimensions—motivation and pleasure and emotional expression. The two broader dimensions sometimes masked important associations unique to the five narrower domains. Avolition, anhedonia, and blunted affect showed the most domain-specific associations with external variables across study samples. Conclusions Five domains and a hierarchical model reflect the optimal conceptualization of negative symptoms in relation to external variables. Clinical trials should consider using the two dimensions as primary endpoints and the five domains as secondary endpoints.

Sex differences influence the clinical characteristics and course of illness of bipolar disorder (BD).Therefore, the aim of the present study was to examine the role of sex differences in neurocognitive performance and psychosocial functioning in a large sample of euthymic patients suffering from BD.The sample included 462 individuals, 347 patients with BD (148 males and 199 females) and 115 healthy controls (HC) (45 males and 70 females). Performance on a comprehensive neuropsychological battery assessing six cognitive domains and psychosocial functioning was compared between groups using linear mixed models, with sex and group as main effects, group by sex interactions and center as a random effect.Males performed better than females in working memory (p 0.001), whereas females outperformed males in the verbal learning (p = 0.03) and memory recognition (p = 0.03) tasks. No significant group by sex interactions were detected in cognitive performance. There were no overall sex differences or group by sex interactions in psychosocial functioning.Lack of assessment of visuo-spatial working memory.There were no overall sex differences in neurocognition and psychosocial functioning. However, small sex differences in some measures of working memory and verbal memory were found. Individual differences of each patient, including sex perspective, should be considered in order to perform a tailored intervention plan adjusted to specific needs in the context of personalized treatment.

Resumen Antecedentes Hay pocos estudios que relacionen los habitos alimenticios y nutricionales con la gravedad de la enfermedad y el perfil demografico en pacientes con esquizofrenia. Objetivo Describir los habitos alimenticios y nutricionales y su relacion con la gravedad de la enfermedad en pacientes con esquizofrenia. Metodo Estudio descriptivo transversal. Muestra: 31 pacientes con esquizofrenia (CIE-10) en tratamiento ambulatorio. Criterios de inclusion: edad 18-65 anos, clinicamente estable y consentimiento informado por escrito. Evaluacion: caracteristicas demograficas, clinicas (ICG-G, anos de evolucion de la enfermedad, IMC, perimetro abdominal), cuestionario ad hoc (alimentacion, habito nutricional y actividad fisica). Resultados Edad media 43,13 (DE = 7,85) anos, varones 61,3%. La gravedad media de la enfermedad fue de 3,94 (DE = 1,06), con una media de 18,42 (DE = 8,27) anos evolucion de la enfermedad. El 74,2% comia carne grasa semanalmente y el 64,5% menos de 3-4 porciones de pescado, el 77,4% menos de 3 porciones de fruta por dia y el 51,6% bebia menos de un litro de agua. El 83,9% tomaba cafe diariamente, 2,81 (DE = 2,02) cafes por dia. Los pacientes presentaban niveles mas bajos de vitamina A, D, E, K1, C, acido folico y magnesio. El 93,5% no cumplia con las recomendaciones de la OMS sobre actividad fisica. Solo el retinol (r = -0,602, p = 0,039) y la vitamina K1 (r = -0,693, p = 0,012) en las mujeres se relacionaron con la gravedad de la enfermedad. Conclusiones Los pacientes con esquizofrenia a seguimiento ambulatorio no siguen las recomendaciones de la OMS sobre dietas saludables ni actividad fisica. Tanto la gravedad clinica de la enfermedad como el estado civil y la convivencia se asociaron con malos habitos alimenticios y deficit de nutrientes. Estos datos deben ser tenidos en cuenta por el personal de enfermeria a la hora de implementar cuidados especificos en la practica clinica habitual.

The EUGEI project was supported by the European Community's Seventh Framework Program under grant agreement No. HEALTH-F2-2009-241909 (Project EU-GEI). Dr O'Donovan is supported by MRC programme grant (G08005009) and an MRC Centre grant (MR/L010305/1), Henquet, C., Van Os, J., Pries, L.K., Rauschenberg, C., Delespaul, P., Kenis, G., Luykx, J.J., Lin, B.D., Richards, A.L., Akdede, B., Binbay, T., Altlnyazar, V., Yallnçetin, B., Gümüş-Akay, G., Cihan, B., Soygür, H., Ulaş, H., Cankurtaran, E.S., Kaymak, S.U., Mihaljevic, M.M., Petrovic, S.S., Mirjanic, T., Bernardo, M., Mezquida, G., Amoretti, S., Bobes, J., Saiz, P.A., Garciá-Portilla, M.P., Sanjuan, J., Aguilar, E.J., Santos, J.L., Jiménez-López, E., Arrojo, M., Carracedo, A., López, G., González-Penãs, J., Parellada, M., Maric, N.P., Atbaşoelu, C., Ucok, A., Alptekin, K., Saka, M.C., Arango, C., O'Donovan, M., Rutten, B.P.F., Gülöksüz, S.

Introduction: Coronavirus disease 2019 (COVID-19) forced Spain to implement unprecedented lockdown restriction. In this context, different factors could worsen sleep quality, but the impact of the pandemic and lockdown on sleep is still mostly unknown. In this cross-sectional study, we describe self-reported sleep disturbances in people without mental health disorders from a large Spanish sample (n = 15,070).Methods: During the early phase of the lockdown (19-26 March), an online survey was launched using a snowball sampling method and included sociodemographic and clinical data along with the Depression, Anxiety, and Stress Scale (DASS-21) and the Impact of Event Scale (IES). Two items of the IES were employed to assess sleep characteristics. Descriptive and bivariate analysis and logistic regression models were performed.Results: Difficulty initiating or maintaining sleep were reported by 23.9% of the sample and was associated in the regression model with age (OR = 1.008, p = .003), female sex (OR = 1.344, p 50% (OR = 1.248, p = .037), having one (OR = 1.208, p = .029) and two or more (OR = 1.299, p = .035) elderly dependents, drinking alcohol (OR = 1.129, p = .024), and a higher score on DASS-21 depression (OR = 1.148, p

Government of the Principality of Asturias [PCTI-2021-2023 IDI/2021/111]; CIBERSAM; Fondos Europeos de Desarrollo Regional (FEDER), Ruiz FJ, Sáiz PA, García-Portilla MP, González-Blanco L, García-Álvarez L, Madera PZ, Bobes-Bascarán MT, Treviño LJ, García MV, Cao CM, Fernández AG, Revuelta JR, Lacasa CM, Dal Santo F, Calzón GP, Álvarez MS, Bascarán Fernández MT, Zazo ES, García CI, Pedrero EF, Ruiz RM, Bobes J

BackgroundThere is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.MethodsWe analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.ResultsThe impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).ConclusionsThe results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

Introduction: Negative symptoms can be grouped into five domains: apathy/avolition, anhedonia, asociality, alogia, and affective flattening. There are few validate self-rated measures that assess these five dimensions. Therefore, this study aimed to validate the Self-Evaluation of Negative Symptoms (SNS) in Spanish patients with schizophrenia. Material and methods: Cross-sectional, validation study in 104 outpatients with schizophrenia evaluated using the Spanish version of the following scales: Clinical Assessment Interview for Negative Symptoms (CAINS), Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale for Schizophrenia (CGI-SCH), Personal and Social Performance (PSP), Motivation and Pleasure Scale – Self-Report (MAP-SR), 36-item Short-Form Health Survey (SF-36) and the Self-Evaluation of Negative Symptoms (SNS). Results Reliability: Internal consistency (Cronbach's alpha) was 0.915. Convergent validity: The Pearson correlation coefficient between MAP-SR and SNS Total scores was 0.660 (p < 0.001). For PANSS-N, the correlation was 0.437 (p < 0.005) and with the CAINS-Total was 0.478 (p < 0.005). Divergent validity: The Pearson correlation coefficient between SNS and PSP was r = −0.372 (p ≤ 0.001), and with SF-36 Physical and Mental Summary Component scores were r = −0.213 (p = 0.066) and r = −0.144 (p = 0.219), respectively. Discriminant validity: SNS Total scores were significantly statistically different according to the severity of the negative symptomatology rated by the CGI-SCH negative scale (p < 0.001). Conclusion: The SNS is a reliable and valid instrument to self-rate the five domains of negative symptoms in patients with schizophrenia and seems to be appropriate for use in everyday clinical practice as a complementary measure to the evaluation performed by the clinician.

BackgroundThe aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia.MethodsTwenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects.ResultsThere was a 3-year later age at onset for females (P P P P = .001). No significant effects were found concerning duration of illness.DiscussionOur results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

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 (p0.001), with the exception of the Cued CVLT (worse scores in MDD vs AUD, p0.001). 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.El daño cerebral relacionado con el consumo de alcohol se asocia a alteraciones de las funciones cognitivas, entre las que destacan memoria y aprendizaje verbal. El objetivo principal es evaluar memoria y aprendizaje verbal en una muestra de 111 pacientes con trastorno por consumo de alcohol (TCA) versus 78 con trastorno de depresión mayor (TDM) y 100 controles sanos. La evaluación incluyó variables sociodemográficas y clínicas, la Escala de Hamilton para la Depresión (HDRS) y el Test de Aprendizaje Verbal de California (CVLT). Se utilizó ANOVA de un factor para comparaciones entre los 3 grupos y ANCOVAS bidireccionales incluyendo diferentes covariables. El ANOVA de un factor muestra que los pacientes con TCA y TDM obtienen puntuaciones similares entre sí e inferiores a las del grupo control (p0,001), con excepción del CVLT Guiado (peores puntuaciones en TDM vs TCA, p0,001). Tras incluir como covariables la edad, sexo y los años de estudios completados, persisten las diferencias entre los grupos de TCA y TDM frente al grupo control (p ≤ 0,003) en todos los índices con excepción del CVLT Libre Inmediato y del CVLT Guiado (peor rendimiento en TDM vs TCA, p = 0,022 y p = 0,035, respectivamente). En el segundo ANCOVA, tras controlar por gravedad de la depresión, únicamente se detectan diferencias entre los pacientes con TCA y los controles sanos (p ≤ 0,007). Los pacientes con TCA presentan una importante alteración en aprendizaje y memoria verbal al compararlos con pacientes con TDM y con personas sanas.

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 (50 8%) as stage 3, 37 (20 2%) as stage 4, and 10 (5 5%) 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.

VBM acknowledges the national grant PI16/01770 from the Instituto de Salud Carlos III, ISCIII (The PROBILIFE study). EV thanks the support of the Spanish Ministry of Science and Innovation (PI15/00283, PI18/00805) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM) (...), Cervera-Martínez, J., Atienza-Carbonell, B., Mota, J.C., Bobes-Bascarán, T., Crespo-Facorro, B., Esteban, C., García-Portilla, M.P., Gomes-da-Costa, S., González-Pinto, A., Jaén-Moreno, M.J., Sarramea, F., Vieta, E., Zorrilla, I., Tabarés-Seisdedos, R., Kapczinski, F., De Boni, R.B., Balanzá-Martínez, V.

Few studies have used a multidimensional approach to describe lifestyle changes among undergraduate students during the COVID-19 pandemic or have included controls. This study aimed to evaluate lifestyle behaviors and mental health of undergraduate students and compare them with an age and sex-matched control group. A cross-sectional web survey using snowball sampling was conducted several months after the beginning of COVID-19 pandemic in Spain. A sample of 221 students was recruited. The main outcome was the total SMILE-C score. Students showed a better SMILE-C score than controls (79.8 + 8.1 vs. 77.2 + 8.3, p &lt, 0.001), although these differences disappeared after controlling for covariates. While groups did not differ in the screenings of depression and alcohol abuse, students reported lower rates of anxiety (28.5% vs. 37.1%, p = 0.042). A lower number of cohabitants, poorer self-perceived health and positive screening for depression and anxiety, or for depression only were independently associated (p &lt, 0.05) with unhealthier lifestyles in both groups. History of mental illness and financial difficulties were predictors of unhealthier lifestyles for students, whereas totally/moderate changes in substance abuse and stress management (p &lt, 0.05) were predictors for the members of the control group. Several months after the pandemic, undergraduate students and other young adults had similar lifestyles.

Resumen La estadificacion clinica es una herramienta diagnostica utilizada en otras especialidades de la medicina que surge de la combinacion de un enfoque categorial y dimensional. En las ultimas 2 decadas, se ha planteado su aplicacion en el campo de la psiquiatria, fundamentalmente como herramienta de ayuda diagnostica, de orientacion terapeutica y pronostica. En este trabajo se revisan los modelos de estadificacion clinica que han sido propuestos hasta la fecha para el trastorno bipolar, la depresion y la esquizofrenia. Se realizo una busqueda bibliografica en las bases de datos PubMed y Medline. Se seleccionaron con base en los criterios de inclusion y exclusion un total de 15 estudios. Se describen y comparan las caracteristicas de cada uno de los modelos agrupados segun el tipo de trastorno para el que fueron propuestos (trastorno bipolar: 4; depresion: 5; esquizofrenia: 6). Como conclusion, identificamos la necesidad de validar empiricamente dichos modelos para asi demostrar que son una herramienta util en la practica clinica habitual.

Despite the existence of effective evidence-based treatments for the management of obsessive-compulsive disorder (OCD), the therapeutic approach to this disease remains suboptimal. The availability of a therapeutic pharmacological guideline for OCD could help to improve the management of the disease in our setting and to reduce the burden of disease for the patient. With the sponsorship of the Spanish Society of Psychiatry, a group of experts has developed a guideline for the pharmacological treatment of OCD based on the recommendations of existing guidelines and following the methodology of the ADAPTE Collaboration. This article summarises the process of preparing this guideline and the recommendations adopted by consensus by a guideline panel grouped into five areas of interest: acute treatment, duration of treatment, predictors of response and special symptoms, partial response to lack of response to treatment, and special populations.

Resumen Recientemente se ha planteado que las alteraciones de las capas de la retina podrian ser un biomarcador de determinados trastornos mentales, al derivar esta de la misma capa embrionaria que el cerebro y estar conectada con este a traves del nervio optico. El objeto del presente articulo es ofrecer una revision sistematica de la literatura y una sintesis tematica sobre el estado actual de las alteraciones de las capas de la retina identificadas mediante tomografia de coherencia optica en los pacientes con esquizofrenia, trastorno bipolar y depresion mayor. Para ello se realizo una busqueda sistematica de la literatura, la lectura critica de los articulos seleccionados y la sintesis tematica de los resultados. Los pacientes con esquizofrenia son los que presentan mas alteraciones, seguidos de los pacientes con trastorno bipolar, siendo muy escasos los hallazgos en la depresion. La capa de fibras nerviosas de la retina es la capa retiniana con mas alteraciones en la esquizofrenia y en el trastorno bipolar, mientras que ningun estudio en depresion mayor encontro alteraciones en ella. De los parametros clinicos, la duracion de la enfermedad correlaciona significativa e inversamente con el grosor de las distintas capas en todos los trastornos. A la hora de interpretar estos datos es necesario tener en cuenta las limitaciones y diferencias de los estudios, especialmente el tiempo medio de evolucion de los trastornos. Dado que este era muy diferente entre los 3 trastornos (mas del doble en el caso de la esquizofrenia respecto a la depresion mayor), las diferencias en los resultados encontrados podrian deberse mas al efecto del tiempo de evolucion que al trastorno en si. En conclusion, los hallazgos de la tomografia de coherencia optica son esperanzadores, ya que podrian proporcionar biomarcadores de la neurodegeneracion y/o neuroprogresion tanto de la esquizofrenia como del trastorno bipolar.

Antipsychotics are an essential component in the treatment of schizophrenia. Long-acting injectable formulations (LAI) arose to improve adherence with the associated potential of reducing the risk of relapse. The objective of this article is to analyze the use of LAI antipsychotics in Spain, which is similar to other European countries but with a predominance of the use of second generation LAI, to discuss the possible causes of prescribing differences with respect to other countries (including organizational aspects, attitudes of psychiatrists, patients and family members, and clinical practice guidelines), and to discuss their use in acute psychiatric units, first episode, and in children and adolescents. In our view, while it is necessary to increase existing evidence regarding the advantages of LAI antipsychotics and the differentiation between LAI antipsychotics currently available, their use will likely continue to grow driven by clinical experience.

Resumen A pesar de la existencia de tratamientos efectivos basados en la evidencia para el tratamiento del trastorno obsesivo-compulsivo (TOC), el abordaje de esta enfermedad sigue siendo suboptimo. Disponer de una guia terapeutica farmacologica del TOC puede ayudar a mejorar el manejo de la enfermedad en nuestro entorno y contribuir a reducir la carga de la enfermedad para el paciente. Con el patrocinio de la Sociedad Espanola de Psiquiatria un grupo de expertos ha desarrollado una guia para el tratamiento farmacologico del TOC a partir de algunas guias existentes siguiendo la metodologia de la ADAPTE Collaboration. En este articulo se resume el proceso de elaboracion de esta guia y las recomendaciones adoptadas por consenso por el grupo elaborador de las guias agrupadas en 5 areas de interes: tratamiento agudo, duracion del tratamiento, predictores de respuesta y sintomas especiales, respuesta parcial a falta de respuesta al tratamiento y poblaciones especiales.

Introduction The extent of working memory (WM) and executive function (EF) impairment in mild cognitive impairment (MCI) is not well-characterized. Methods We compared 48 patients with MCI, 124 noncognitively impaired elderly healthy controls, and 57 patients with Alzheimer's disease (AD) on multiple WM/EF measures, frontal lobe integrity indexes, and functioning. Results Patients with MCI demonstrated worse performance on nearly all WM/EF tests. This profile of impairment was refined in a factor analysis that identified three primary WM/EF constructs: WM storage; speed and controlled visual search; and manipulation of information and problem solving. EF impairments were associated with reductions in prefrontal cortical thickness. WM/EF accounted for over 50% of the variance in functional competence. Discussion In MCI, WM/EF impairments are far from rare, based on specific compromises to frontal cortex circuitry, and are associated with loss of everyday functioning. WM/EF impairments, even at this potentially prodromal stage of AD, have clinically deleterious consequences.

Resumen Introduccion Hay evidencias que sugieren la existencia de alteraciones de algunas citocinas en pacientes con esquizofrenia, pero su asociacion con la psicopatologia aun no esta clara. El objetivo de este estudio es determinar si los niveles de citocinas proinflamatorias (factor de necrosis tumoral-α, interleucina [IL]-6, IL-2, IL-1β, IL-1RA) estan aumentados en pacientes ambulatorios clinicamente estables en comparacion con individuos sanos, y analizar si podrian ser biomarcadores especificos de las diferentes dimensiones clinicas de la esquizofrenia. Metodos Se evaluaron 73 pacientes con esquizofrenia en sus primeros 10 anos de evolucion de la enfermedad y 73 controles sanos pareados por edad y sexo. Se realizo una evaluacion precisa de las dimensiones clinicas (positiva, negativa, depresiva y cognitiva) en estos pacientes. Resultados Solo los niveles de IL-6 estan significativamente elevados en los pacientes tras controlar por indice de masa corporal, perimetro abdominal, tabaquismo y tratamiento psicofarmacologico en comparacion con sus controles sanos. Tras ajustar por varios factores de confusion, los modelos de regresion lineal multiple identificaron como las concentraciones de IL-1β predicen los sintomas negativos, psicopatologia general y gravedad global de la Escala del Sindrome Positivo y Negativo, mientras los niveles de IL-2 predicen el dominio motivacion y placer de la Entrevista de Evaluacion Clinica para Sintomas Negativos y la puntuacion global en la Escala de Funcionamiento Personal y Social. Sin embargo, el rendimiento cognitivo, la gravedad de los sintomas depresivos y positivos no correlacionaron con ninguna de las citocinas. Conclusiones Nuestros hallazgos sugieren que las concentraciones de IL-6 permanecen elevadas en pacientes estables con esquizofrenia. Mientras que la IL-2 marca especificamente la gravedad en el dominio motivacion y placer de la sintomatologia negativa, la IL-1β no es especifica para esta dimension, ya que tambien predice la gravedad de la sintomatologia general y global.

Introduction Evidence suggests the existence of cytokine disturbances in patients with schizophrenia but their association with psychopathology is still unclear. The aim of the current study was to determine if pro-inflammatory cytokine levels (tumor necrosis factor-α, interleukin (IL)-6, IL-2, IL-1β, IL-1RA) are increased in stable outpatients compared with healthy subjects, and to analyze if they could be specific biomarkers of clinical dimensions in schizophrenia. Methods We studied 73 stable outpatients with schizophrenia in their first 10 years of illness and 73 age- and sex-matched healthy controls. An accurate assessment of clinical dimensions (positive, negative, depressive, cognitive) was performed in patients. Results Only IL-6 levels were significantly increased in patients after controlling for body mass index, waist circumference, smoking, and psychopharmacological treatment, compared with healthy subjects. After adjusting for several confounders, multiple linear regression models identified that Positive and Negative Syndrome Scale negative symptoms, general psychopathology, and global severity are predicted by IL-1β concentrations, while motivation and pleasure domain of Clinical Assessment Interview for Negative Symptoms and Personal and Social Performance global functioning scores are predicted by IL-2 levels. Cognitive performance, positive, and depressive symptom severity did not correlate with any cytokine. Conclusions Our findings suggested that IL-6 concentrations are elevated in stable patients with schizophrenia. Whereas IL-2 specifically marks severity of the motivation and pleasure domain of negative symptoms, IL-1β is not specific to this dimension as it also predicts severity of general and global symptomatology.

Background: Data on associations between cannabis use and psychopathology, cognition and functional impairment in schizophrenia spectrum disorders (SSD) is controversial. Objectives: To examine the effect of cannabis on psychopathology, cognition and real-world functioning in SSD patients. Method: Naturalistic cross-sectional study, 123 clinically stable SSD outpatients. Assessment: demographic and clinical data, psychometric evaluation: Positive and Negative Syndrome, Hamilton Depression Rating, Clinical Global Impression (CGI), Personal and Social Performance and Screen for Cognitive Impairment in Psychiatry (SCIP) scales. Patients were classified as cannabis user patients (CUP) and non cannabis user patients (NCUP) according to self-report, both lifetime and last year. Statistical analysis: chi-square, Student t test, ANOVA (Duncan post hoc), and general linear model analysis for adjusting for antipsychotic doses. Results: Mean age 40.75, 66.7% male, single (66.7%), prior hospital admissions 2.75, mean length of illness 13.85 years. 53.7% were lifetime cannabis users and 8.9% last year users. Lifetime CUP had more hospitalizations (p = 0.013) at a younger age (p = 0.002), and showed better cognitive functioning globally (CGI-C: p = 0.045) and on working memory and processing speed (SCIP-2: p = 0.039; SCIP-5: p = 0.033) and worse functioning in socially useful activities (p = 0.014) than NCUP. All these differences remained after adjusting for antipsychotic doses. Last year cannabis users had worse mood (Hamilton Depression Rating Scale 9.66 vs. 5.64; p = 0.002), but this difference disappears when adjusting for antipsychotic doses. Conclusions: Lifetime cannabis use is associated with better working memory and processing speed and worse real-world functioning in the area of socially useful activities in patients with schizophrenia-related disorders. Clinicians should, therefore, be aware of it to provide patient-centred care in their daily clinical practice.

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.Hasta la fecha, ningún estudio de seguimiento había evaluado simultáneamente la función ejecutiva, otras funciones no ejecutivas relacionadas con funciones cognitivas y la impulsividad en una muestra suficientemente grande de pacientes con trastorno por uso de alcohol (TUA) entre moderado y grave. Este estudio tuvo como objetivo principal comparar el desempeño neuropsicológico y su relación con el uso de alcohol en pacientes con TUA y en controles sanos, y determinar la evolución del deterioro cognitivo y el uso de alcohol a largo plazo. Con este fin, se diseñó un estudio de seguimiento de seis meses para comparar una muestra de 100 pacientes ambulatorios con TUA (criterios del DSM-5) emparejados con 100 controles sanos. Los pacientes se reclutaron de tres centros sanitarios diferentes de España, Orense, Gijón y Barcelona. La evaluación consistió en una batería sistematizada de pruebas cognitivas para evaluar las siguientes funciones: atención, memoria anterógrada, velocidad de procesamiento, fluidez verbal, función ejecutiva y actitud implícita hacia bebidas alcohólicas. También se compararon variables clínicas asociadas al consumo de alcohol, como el craving y la impulsividad. Después de seis meses, la memoria anterógrada, memoria de trabajo y resistencia a la interferencia mejoraron notablemente en los pacientes con TUA, aunque no llegaron a igualar la población general. Respecto de las variables clínicas, hubo una pequeña pero significativa mejoría cognitiva relacionada con una reducción del consumo de alcohol y de la impulsividad. La disfunción ejecutiva y otras funciones no ejecutivas relacionadas con el deterioro cognitivo pueden considerarse factores pronósticos en pacientes ambulatorios con TUA entre moderado y grave.

Aim To provide a population-based characterization of sociodemographic and clinical risk and protective factors associated with consumption of alcohol, tobacco, or both as a coping strategy in a sample of the Spanish general population during the early phase of the COVID-19 pandemic. Methods Cross-sectional study based on an online snowball recruiting questionnaire. The survey consisted of an ad hoc questionnaire comprising clinical and sociodemographic information and the Spanish versions of the Depression, Anxiety, and Stress Scale (DASS-21) and the Impact of Event Scale (IES). Results The final sample included 21,207 individuals [mean age (SD) = 39.7 (14.0); females: 14,768 (69.6%)]. Up to 2867 (13.5%) of participants reported using alcohol, 2545 (12%) tobacco and 1384 (6.5%) both substances as a strategy to cope with the pandemic. Sex-related factors were associated with alcohol consumption as a coping strategy [female, OR = 0.600, p

European Community's Seventh Framework Program, European Commission [HEALTH-F2-2009-241909]; Scientific and Technological Research Council of Turkey, 2219 International Postdoctoral Research Fellowship Program; Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, and PI19/024)..., Erzin, G., Pries, L.-K., van Os, J., Fusar-Poli, L., Delespaul, P., Kenis, G., Luykx, J.J., Lin, B.D., Richards, A.L., Akdede, B., Binbay, T., Altınyazar, V., Yalınçetin, B., Gümüş-Akay, G., Cihan, B., Soygür, H., Ulaş, H., Cankurtaran, E.Ş., Kaymak, S.U., Mihaljevic, M.M., Andric-Petrovic, S., Mirjanic, T., Bernardo, M., Mezquida, G., Amoretti, S., Bobes, J., Saiz, P.A., García-Portilla, M.P., Sanjuan, J., Aguilar, E.J., Santos, J.L., Jiménez-López, E., Arrojo, M., Carracedo, A., López, G., González-Peñas, J., Parellada, M., Maric, N.P., Atbaşoğlu, C., Ucok, A., Alptekin, K., Saka, M.C., Arango, C., O'Donovan, M.C., Rutten, B.P.F., Guloksuz, S., Genetic Risk and Outcome of Psychosis (GROUP) investigators

Clinical staging is a system of classification for determining the position of an individual within a continuum of severity, taking into account the longitudinal course of the disease. Several studies point to major depressive disorder as a progressive condition that could benefit from a staging approach. Four clinical staging models have been developed for depression, but only one has been empirically tested. Furthermore, five staging models for treatment-resistant depression have been proposed, but there is validity data for only three of those. Staging models could guide the choice of treatment depending on the course of the disease; along this line, some studies have proposed different therapeutic interventions according to clinical stages.

The main objective of the present study is to analyze the presence of cognitive impairment associated with alcohol consumption in patients with moderate or severe alcohol use disorder seeking outpatient treatment for their dependence. To do this, we compared a sample of 111 patients with active alcohol use disorder who initiated ambulatory treatment with 100 healthy controls. We compared sociodemographic and clinical variables associated with alcohol consumption, such as alcohol craving and impulsivity. A systematized battery of cognitive tests was also used in the comparison, which allowed the evaluation of the following functions: Attention, anterograde memory, processing speed, verbal fluency, executive function and implicit attitude towards alcoholic beverages. Compared with healthy controls, patients with moderate or severe alcohol use disorder performed significantly worse in all tests used, and therefore in all cognitive functions evaluated, but for two tests, the Iowa Gambling Test and the Implicit Association Test . The analysis through a correlation matrix of the patient group indicates that patients who report more impulsivity and more chronic alcohol abuse and with more addiction are those who suffer greater deterioration in their cognitive function. Cognitive damage associated with alcohol consumption was distributed heterogeneously among patients. The present study confirms the presence of cognitive deterioration associated with alcohol consumption in patients seeking outpatient treatment.

Introduction: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study. ----- Material and methods: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively. ----- Statistical analysis: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables. ----- Results: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed. ----- Conclusions: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them.

High prevalence of smoking in people with severe mental disorders (SMD) contributes to their medical morbidity and reduced life expectancy. Despite the evidence of gender differences in smoking cessation, few studies have tested those differences among people with SMD. This is a non-randomized, open-label, prospective, 9-month follow-up multicentre trial to examine gender differences in the efficacy, safety and tolerability of a Multi-Component Smoking Cessation Support Programme (McSCSP). The results showed that there were no significant differences in short- (males 44.9% vs females 57.7%, chi-square = 1.112, p = 0.292) or long-term efficacy (week 24: males 40.8%, females 42.3%, chi-square = 0.016, p = 0.901; week 36: males 36.7%, females 38.5%, chi-square = 0.022, p = 0.883) between gender, neither controlled by diagnosis or treatment. Regarding safety and tolerability, there was significant increase in abdominal perimeter in males [from 105.98 (SD 13.28) to 108.52 (SD 14.01), t = -3.436, p = 0.002)], but not in females. However, there were no significant gender differences in adverse events (constipation, abnormal/vivid dreams, nausea/vomiting or skin rash/redness around patch site). In conclusion, we have demonstrated that is effective and safe to help either male or female patients with stabilized SMD to quit smoking. However, it might be a tendency in females to respond better to varenicline treatment in the short-term. Future research with larger samples is required to more clearly determine whether or not the there are differences, in addition to their reliability and robustness.La elevada prevalencia del tabaquismo en personas con trastorno mental grave (TMG) contribuye a su morbilidad médica y reduce su esperanza de vida. A pesar de la existencia de diferencias de género en el cese del tabaquismo, pocos estudios han evaluado esas diferencias en personas con TMG. Este es un ensayo multicéntrico de seguimiento prospectivo, no aleatorizado, abierto de 9 meses para examinar las diferencias de género en la eficacia, seguridad y tolerabilidad de un programa multicomponente de apoyo para el cese del tabaquismo (McSCSP). Los resultados mostraron que no hubo diferencias de género significativas en la eficacia a corto (hombres 44,9% vs mujeres 57,7%, chi cuadrado = 1,112, p = ,292) ni a largo plazo (semana 24: hombres 40,8%, mujeres 42,0.3%, chi cuadrado = 0.016, p = ,901; semana 36: hombres 36,7%, mujeres 38,5%, chi cuadrado = 0,022, p = ,883), incluso controlando por diagnóstico o tratamiento. Con respecto a la seguridad y la tolerabilidad, hubo un aumento significativo en el perímetro abdominal en los hombres [de 105,98 (DT 13,28) a 108,52 (DT 14,01), t = -3,436, p = ,002)], pero no en las mujeres. Sin embargo, no hubo diferencias de género significativas en los eventos adversos (estreñimiento, sueños anormales/vívidos, náuseas/vómitos o erupción cutánea/enrojecimiento alrededor de la zona del parche). En conclusión, hemos demostrado que es efectivo y seguro ayudar a los hombres y mujeres con TMG estabilizados a dejar de fumar. Sin embargo, podría haber una tendencia en las mujeres a responder mejor al tratamiento con vareniclina a corto plazo. Se requiere investigación futura con muestras más amplias para determinar con más claridad la existencia de diferencias, además de la fiabilidad y robustez.

Background: Epidemic outbreaks have significant impact on psychological well-being, increasing psychiatric morbidity among the population. We aimed to describe the early psychological impact of COVID-19 and its contributing factors in a large Spanish sample, globally and according to mental status (never mental disorder NMD, past mental disorder PMD, current mental disorder CMD). Methods: An online questionnaire was conducted between 19 and 26 March, five days after the official declaration of alarm and the lockdown order. Data included sociodemographic and clinical information and the DASS-21 and IES questionnaires. We analysed 21 207 responses using the appropriate descriptive and univariate tests as well as binary logistic regression to identify psychological risk and protective factors. Results: We found a statistically significant gradient in the psychological impact experienced in five domains according to mental status, with the NMD group being the least affected and the CMD group being the most affected. In the three groups, the depressive response was the most prevalent (NMD = 40.9%, PMD = 51.9%, CMD = 74.4%, F = 1011.459, P

This work was partly supported by the Government of the Principality of Asturias PCTI-2018-2022 IDI/2018/235, the CIBERSAM, and Fondos Europeos de Desarrollo Regional (FEDER), and Fundacion para la Investigacion e Innovacion Biosanitaria del Principado de Asturias (FINBA).

HIGHLIGHTS • This study examined the early psychological correlates associated with the COVID-19 pandemic and lockdown in an older adult sample. • Regardless of mental status, depressive and avoidant style were the most prevalent in this older adult sample. • Interventions need to be tailored to alleviate dysfunctional coping strategies and their progression to mental illness., Objective Main aims of the study are to examine the early psychological correlates associated with the COVID-19 pandemic and lockdown on the mental health of a Spanish older adult sample and to analyze the influence of past mental disorder (PMD) and current mental disorder (CMD) on those correlates. Methods Cross-sectional study based on an online snowball recruiting questionnaire. Psychological correlates assessed with the Depression, Anxiety, and Stress Scale (DASS-21) and Impact of Event Scale (IES). Binary and multinomial logistic regression models were used to identify risk and protective factors. Results Final sample included 2,194 individuals aged 60 years or more (mean age [SD]: 65.62 [5.05]; females: 1,198 [54.6%]). There were 342 (15.6%) individuals who reported a PMD and 162 (7.4%) who reported a CMD. Avoidant (32.1%) and depressive (25.6%) styles were the most prevalent, regardless of mental health status. Main risk factors for negative affectivity were female gender and history CMD or PMD. However, job stability and the ability to enjoy free time were generally associated with better outcomes. No differences were found in psychological correlates between those with no lifetime history of mental disorder versus PMD on the DASS-21 or IES. However, CMD was associated with higher anxiety scores on the DASS-21 (odds ratio: 1.838, p < .001). Conclusion Regardless of mental status, avoidant and depressive styles were the most prevalent in this older adult sample. Main protective factor in all subgroups was the ability to enjoy free time, whereas the main risk factors were being female and current or past history of mental disorder.