The polygenic basis of relapse after a first episode of schizophrenia.

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.

The RECAPACITA project: Description of the clinical, neuropsychological and functional profile of a sample of people with severe mental disorder and legal capacity modification in Spain.

Severe mental disorder (SMD) includes people with long-term mental disorders, disability and social dysfunction. The mental capacity evaluation of the people has been a key aspect in legislative systems around the world and different proposals have been made. In countries like Spain, until 2021, the mental capacity of individuals was assessed by means of legal proceedings. In the last years, there has been a notable increase in the number of claims for legal incapacity, but no data are available on the total number of persons with CM, neither on the specific pathologies, or clinical and cognitive profiles. In view of the total absence of data on the profile of people with SMD and modification of capacity, the RECAPACITA study was born. This study includes patients with SMD and CM, as well as those without CM, with the aim to describe exhaustively their clinical, neuropsychological and functional profile of people with SMD and CM, as well as obtaining a basic description of the social environment. OBJECTIVES: To describe CM in SMD, to identify clinical diagnoses, clinical severity and neuropsychological deterioration. METHODS: Cross-sectional descriptive study. 77 adult patients with SMD and CM, inpatients from the mental health sector of the Parc Sanitari Sant Joan de Déu (Spain), outpatients linked to the community rehabilitation services (CRS), and penitentiary inmates. CM, sociodemographic, clinical, functional and neuropsychological data are collected. RESULTS: In the sample, 59.5% present total CM. 74.7% are men (mean: 52.5 years). 87,0% have a diagnosis of schizophrenia. The estimated premorbid IQ is 91.4. The Global Assessment of Functioning (GAF) had a mean of 50.5, the "Clinical Global Impression Scale" (CGI) was 4.6 and Scale Unawareness of Mental Disorders (SUMD) was 9.28. The cognitive results shows a profile with slow proceeding speed (mean scale score: 6.6), good working memory (mean SC: 8.3) and adequate verbal comprehension (mean SC: 7.3). In memory, coding is altered (Pz: -1.9), and long-term spontaneous recall (Pz: -2.3). In abstract reasoning, a slight alteration is obtained (Mean SC: 6), as well as in semantic fluency (Mean SC: 6.3), phonological (Mean SC: 5.9), and inhibitory capacity (Mean SC: 5.7). CONCLUSIONS: Most of the sample are men with schizophrenia, with a total MC assumed by a tutelary foundation. They show a moderate alteration in global functioning and clinical global impression, with partial awareness of the disease. They present dysexecutive mild cognitive impairment, with poor memory coding and free retrieval capacity, and a normal IQ, adequate verbal comprehension and working memory. This study is the first to present objective data on the psychiatric, functional and cognitive status of a group of patients with CM. Such research could be a good starting point to address a topic of great interest from the health, social and legal point of view of the CM processes of people with SMD.

Understanding the Subjective Experience of Long-term Remote Measurement Technology Use for Symptom Tracking in People With Depression: Multisite Longitudinal Qualitative Analysis.

BACKGROUND: Remote measurement technologies (RMTs) have the potential to revolutionize major depressive disorder (MDD) disease management by offering the ability to assess, monitor, and predict symptom changes. However, the promise of RMT data depends heavily on sustained user engagement over extended periods. In this paper, we report a longitudinal qualitative study of the subjective experience of people with MDD engaging with RMTs to provide insight into system usability and user experience and to provide the basis for future promotion of RMT use in research and clinical practice. OBJECTIVE: We aimed to understand the subjective experience of long-term engagement with RMTs using qualitative data collected in a longitudinal study of RMTs for monitoring MDD. The objectives were to explore the key themes associated with long-term RMT use and to identify recommendations for future system engagement. METHODS: In this multisite, longitudinal qualitative research study, 124 semistructured interviews were conducted with 99 participants across the United Kingdom, Spain, and the Netherlands at 3-month, 12-month, and 24-month time points during a study exploring RMT use (the Remote Assessment of Disease and Relapse-Major Depressive Disorder study). Data were analyzed using thematic analysis, and interviews were audio recorded, transcribed, and coded in the native language, with the resulting quotes translated into English. RESULTS: There were 5 main themes regarding the subjective experience of long-term RMT use: research-related factors, the utility of RMTs for self-management, technology-related factors, clinical factors, and system amendments and additions. CONCLUSIONS: The subjective experience of long-term RMT use can be considered from 2 main perspectives: experiential factors (how participants construct their experience of engaging with RMTs) and system-related factors (direct engagement with the technologies). A set of recommendations based on these strands are proposed for both future research and the real-world implementation of RMTs into clinical practice. Future exploration of experiential engagement with RMTs will be key to the successful use of RMTs in clinical care.

m-RESIST, a complete m-Health solution for patients with treatmentresistant schizophrenia: a qualitative study of user needs and acceptability in the Barcelona metropolitan area.

BACKGROUND: Despite the theoretical potential of m-health solutions in the treatment of patients with schizophrenia, there remains a lack of technological solutions in daily practice. The aim of this study was to measure the receptivity of patients, informal carers, and clinicians to an integral intervention model focused on patients with persistent positive symptoms: Mobile Therapeutic Attention for Patients with Treatment Resistant Schizophrenia (m-RESIST). METHODS: A qualitative study of the needs and acceptability of outpatients with treatment-resistant schizophrenia was carried out in Parc Sanitari Sant Joan de Déu (Barcelona). We analyzed the opinions of patients, informal carers, and clinicians concerning the services initially thought to be part of the solution. Five focus groups and eight interviews were carried out, using discourse analysis as the analytical approach. RESULTS: A webpage and a virtual forum were perceived as suitable to get reliable information on both the disease and support. Data transmission service, online visits, and instant messages were evaluated as ways to improve contact with clinicians. Alerts were appreciated as reminders of daily tasks and medical appointments. Avoiding stressful situations for outpatients, promoting an active role in the management of the disease, and maintaining human contact with clinicians were the main suggestions for improving the effectiveness of the solution. CONCLUSIONS: Positive acceptance of m-RESIST services is related to its usefulness in meeting user needs, its capacity to empower them, and the possibility of maintaining human contact.

m-RESIST, una solución m-Health integral para personas con Esquizofrenia Resistente: estudio cualitativo de necesidades y aceptabilidad de usuarios en el área de Barcelona / m-RESIST, a complete m-Health solution for patients with treatment-resistant schizophrenia: a qualitative study of user needs and acceptability in the Barcelona metropolitan area

Introducción. A pesar del creciente potencial teórico de las soluciones m-Health en el tratamiento de pacientes con esquizofrenia, siguen faltando soluciones tecnológicas a nivel práctico. El objetivo de este estudio fue medir las necesidades y aceptabilidad de pacientes, familiares y profesionales hacia un modelo m-Health de intervención integral: Salud Móvil para pacientes con esquizofrenia resistente al tratamiento (m-RESIST). Métodos. Se llevó a cabo un estudio cualitativo en el Parc Sanitari Sant Joan de Déu (Barcelona) de las necesidades y aceptabilidad de pacientes con esquizofrenia resistente. Se analizaron sus opiniones, junto con las de familiares y profesionales, relativas a los servicios inicialmente pensados para formar parte del m-RESIST. Se realizaron cinco grupos focales y ocho entrevistas, usando el análisis del discurso como aproximación analítica. Resultados. Se consideró adecuada la creación de una página web y un foro virtual para obtener información fiable sobre la enfermedad y como apoyo entre usuarios. Para mejorar el contacto con los profesionales, se valoró positivamente el servicio de transmisión de datos, visitas "online" y mensajes instantáneos. Las alertas fueron consideradas útiles como recordatorios de tareas diarias y citas médicas. Las principales sugerencias para mejorar la eficacia fueron: evitar el exceso de alertas para no generar estrés, promover un papel activo del paciente en el manejo de la enfermedad y mantener contacto personal con los profesionales. Conclusiones. La buena aceptabilidad hacia el m-RESIST se relaciona con su utilidad para satisfacer las necesidades del usuario, su capacidad para empoderarles y la posibilidad de mantener contacto humano (AU)

Background. Despite the theoretical potential of m-health solutions in the treatment of patients with schizophrenia, there remains a lack of technological solutions in daily practice. The aim of this study was to measure the receptivity of patients, informal carers, and clinicians to an integral intervention model focused on patients with persistent positive symptoms: Mobile Therapeutic Attention for Patients with Treatment Resistant Schizophrenia (m-RESIST). Methods. A qualitative study of the needs and acceptability of outpatients with treatment-resistant schizophrenia was carried out in Parc Sanitari Sant Joan de Déu (Barcelona). We analyzed the opinions of patients, informal carers, and clinicians concerning the services initially thought to be part of the solution. Five focus groups and eight interviews were carried out, using discourse analysis as the analytical approach. Results. A webpage and a virtual forum were perceived as suitable to get reliable information on both the disease and support. Data transmission service, online visits, and instant messages were evaluated as ways to improve contact with clinicians. Alerts were appreciated as reminders of daily tasks and medical appointments. Avoiding stressful situations for outpatients, promoting an active role in the management of the disease, and maintaining human contact with clinicians were the main suggestions for improving the effectiveness of the solution. Conclusions. Positive acceptance of m-RESIST services is related to its usefulness in meeting user needs, its capacity to empower them, and the possibility of maintaining human contact (AU)

Measuring Users' Receptivity Toward an Integral Intervention Model Based on mHealth Solutions for Patients With Treatment-Resistant Schizophrenia (m-RESIST): A Qualitative Study.

BACKGROUND: Despite the theoretical potential of mHealth solutions in the treatment of patients with schizophrenia, there remains a lack of technological tools in clinical practice. OBJECTIVE: The aim of this study was to measure the receptivity of patients, informal carers, and clinicians to a European integral intervention model focused on patients with persistent positive symptoms: Mobile Therapeutic Attention for Patients with Treatment-Resistant Schizophrenia (m-RESIST). METHODS: Before defining the system requirements, a qualitative study of the needs of outpatients with treatment-resistant schizophrenia was carried out in Spain, Israel, and Hungary. We analyzed the opinions of patients, informal carers, and clinicians concerning the services originally intended to be part of the solution. A total of 9 focus groups (72 people) and 35 individual interviews were carried out in the 3 countries, using discourse analysis as the framework. RESULTS: A webpage and an online forum were perceived as suitable to get both reliable information on the disease and support. Data transmission by a smart watch (monitoring), Web-based visits, and instant messages (clinical treatment) were valued as ways to improve contact with clinicians. Alerts were appreciated as reminders of daily tasks and appointments. Avoiding stressful situations for outpatients, promoting an active role in the management of the disease, and maintaining human contact with clinicians were the main suggestions provided for improving the effectiveness of the solution. CONCLUSIONS: Positive receptivity toward m-RESIST services is related to its usefulness in meeting user needs, its capacity to empower them, and the possibility of maintaining human contact.

Pharmacogenetic study of the effects of raloxifene on negative symptoms of postmenopausal women with schizophrenia: A double-blind, randomized, placebo-controlled trial.

Several double-blind clinical trials have reported improvement in positive, negative and cognitive symptoms of schizophrenia with raloxifene, a selective receptor estrogen modulator. However, there are some inconsistencies in replicating findings between studies of different countries. The failure to replicate these findings may result from genetic factors that could explain some of the variability in the treatment response. However, pharmacogenetic studies exploring this topic in women with schizophrenia are lacking. We aimed to conduct an exploratory pharmacogenetic analysis of a double-blind, randomized, parallel, placebo-controlled study of 24 weeks' duration of raloxifene aiming to improve negative symptoms in postmenopausal women with schizophrenia. Four single nucleotide polymorphisms (SNPs) were studied: rs9340799, rs2234693 and rs1801132 in the Estrogen Receptor 1 (ESR1) gene, and rs1042597 in the UDP-glucuronosyltransferase 1A8 (UGT1A8) gene. Sixty-five postmenopausal women with schizophrenia (DSM-IV) were randomized to either 60mg/day adjunctive raloxifene (36 women) or adjunctive placebo (29 women). Psychopathological symptoms were assessed at baseline and at weeks 4, 12, and 24 with the Positive and Negative Syndrome Scale (PANSS). Of the four studied SNPs, the rs1042597 variant in the UGT1A8 gene was associated with a different treatment response in negative symptoms with raloxifene treatment, whereas the rs2234693 variant in the ESR1 gene was associated with a distinct response in general psychopathology. In conclusion, our study suggests that genetic variants in UGT1A8 and ESR1 genes modulate the treatment response to adding raloxifene to antipsychotic treatment in postmenopausal women with schizophrenia.

How Hyperprolactinemia Affects Sexual Function in Patients Under Antipsychotic Treatment.

OBJECTIVE: We aimed to study the relationship between hyperprolactinemia (HPRL) and sexual dysfunction (SED) in a sample of patients being prescribed a dose-stable antipsychotic medication, and to evaluate sex differences in the prevalence of HPRL and SED and their relationship. METHOD: A cross-sectional study was carried out including patients between 18 and 55 years of age with a psychotic spectrum diagnosis who were attending community mental health services or hospitalized in medium and long stay units. Positive and Negative Syndrome scale, Calgary depression scale for schizophrenia, Personal and Social Performance scale, and Changes in Sexual Functioning questionnaire-short form were administered. Not later than 3 months, a determination of prolactin, follicle-stimulating hormone, luteinizing hormone, estrogen (only in women) and testosterone was performed. RESULTS: A final sample of 101 patients (30 women and 71 men) was recruited. Seventy-two patients (71.3%) showed HPRL. Sexual dysfunction was significantly higher in HPRL patients than in non-HPRL patients (79.17% vs 51.72%) (P = 0.006), and mean prolactin values were significantly higher in case of SED (P = 0.020). No sex differences were found in prevalence of HPRL or SED. Low Personal and Social Performance scale scores and HPRL were factors independently associated with SED, whereas alcohol use was an independent protector factor. CONCLUSIONS: In our study, SED was significantly related to HPRL without showing sex differences. Prevalence of HPRL and SED observed was higher than that in previous studies, which should be taken into consideration because these have been associated with higher morbimortality, and noncompliance and relapse, respectively.

Influence of cognition, premorbid adjustment and psychotic symptoms on psycho-social functioning in first-episode psychosis.

OBJECTIVE: The aim of this study is to evaluate the relationship between psycho-social functioning and symptoms, cognitive function, and premorbid adjustment, in patients with a first-episode psychosis. METHOD: Clinical data were obtained from 90 patients, who were assessed with the Disability Assessment Scale (DAS-sv), the Positive and Negative Syndrome Scale (PANSS), the Premorbid Adjustment Scale (PAS-S) and with a battery of cognitive tests including Trail Making Tests A and B (TMTA- B), Continous Performance Test (CPT), some subscales of the Wechler Adult Intelligence Scale (WAIS), and the Verbal Learning Test España-Complutense (TAVEC). RESULTS: The results of the study suggest that psycho-social functioning in first-episode psychosis is significantly related to: positive, negative, excitative, affective and disorganized symptoms, social premorbid adjustment, cognitive flexibility, working memory, short term and long term memory. Of these, those which best explained psycho-social functioning are the positive and excitative symptoms, premorbid adjustment, flexibility and memory. CONCLUSIONS: These findings highlight the importance early intervention on cognitive and clinical variables to help provide a better psycho-social functioning in people with a first-episode of psychosis.

Relationship between menarche and psychosis onset in women with first episode of psychosis.

AIM: The aim of this study was to explore the relationship between age at menarche and age at first episode of psychosis, as well as clinical severity and outcome, in a population of women with first-episode psychosis. METHODS: Clinical and socio-demographical data, age at menarche and at first-episode psychosis, parental history of psychosis and cannabis-use habits were obtained from 42 subjects with a first episode of psychosis. Positive and Negative Syndrome Scale, Clinical Global Impression, Global Assessment Function, Disability Assessment Schedule, Wechsler Adult Intelligence Scale and Wechsler Intelligence Scale for Children, European Quality of Life, and Lewis and Murray Obstetric Complication Scales were administered. Statistical analysis was performed by means of zero-order correlations and Mann-Whitney U and Kruskal-Wallis tests using SPSS version 17.0. RESULTS: We found no significant correlation between age at menarche and age at first-episode psychosis, or with the clinical scores performed. We observed that subjects with earlier age at menarche had more parental history of psychosis. CONCLUSIONS: Our negative results do not support the theory of a possible protective role of oestrogen, which seems to be more complex than previously thought. We would suggest that further research is needed to investigate developmental influences of sex steroids on the onset of psychosis and potentially therapeutic benefits based upon oestrogen.

Hiperprolactinemia y tratamiento antipsicótico. Manifestaciones clínicas y manejo / Hyperprolactinemia and antipsychotic treatment. Clinical manifestations and management

La hiperprolactinemia (HPRL) ha sido considerada hasta hace poco un efecto secundario inevitable e inherente al tratamiento antipsicótico y probablemente por ello sus efectos clínicos sean poco evaluados en la práctica clínica habitual. En esta revisión se evaluará el diferente potencial elevador de prolactina de los fármacos antipsicóticos (AP) y aquellas situaciones clínicas e individuales en las que hay que tener especiales precauciones a la hora de utilizar AP con potencial elevador de prolactina. Las consecuencias clínicas más comunes y conocidas de la HPRL por uso de AP son los síntomas sexuales y reproductivos, con diferentes características según género, pero recientemente se ha presentado mayor evidencia de una afectación también en la densidad mineral ósea, carcinogénesis y sistema cardiovascular. Aunque estos efectos precisan actualmente de mayor evidencia, se han de tener en cuenta a la hora de prescribir fármacos AP especialmente en pacientes susceptibles a desarrollarlos. Se considera de especial interés prevenir y minimizar los efectos de la HPRL por uso de AP así como, una vez instaurada, valorar su gravedad y afectación clínica y poderla manejar, y en su caso tratar, considerando la actuación de otras disciplinas (AU)

Hyperprolactinemia (HPRL) has until recently been considered an unavoidable side effect inherent to antipsychotic treatment, and has probably been the reason why its clinical effects are underestimated in daily clinical practice. In this review we evaluate the different prolactin raising potential of the antipsychotic (AP) drugs, as well as the clinical and individual situations where special precautions must be taken when using these medications. The most common and better known clinical consequences of HPRL-induced by APs are sexual and reproductive symptoms, with different characteristics depending on gender, but recently more evidence has also been provided on an involvement in bone mineral density, carcinogenesis and the cardiovascular system. Though these effects still require more evidence, they are important to be taken into account when prescribing APs drugs in susceptible patients. It is essential to prevent and minimize the effect of HPRL-induced by APs and, once established, to consider its severity and clinical effects, and to provide a proper management, treatment and the involvement of other disciplines (AU)