Respuesta inmunoinflamatoria sistémica en primeros episodios de psicosis

RESUMEN: En los últimos años ha aumentado la evidencia sobre la participación del sistema inmune en el desarrollo y la evolución de la psicosis. Sin embargo, hasta donde llega nuestro conocimiento, ninguna investigación previa ha comparado el efecto antiinflamatorio entre varios antipsicóticos ni ha estudiado el efecto del sobrepeso sobre la concentración sérica de citocinas/quimiocinas. En esta tesis doctoral hemos estudiado si hay diferencias significativas en las concentraciones séricas de un amplio array de citocinas/quimiocinas entre voluntarios sanos y sujetos con un primer episodio de psicosis (PEP) al inicio de la enfermedad y si las concentraciones séricas se han modificado con el tratamiento antipsicótico. También hemos comparado el efecto antiinflamatorio de la risperidona y del aripiprazol después de los 3 meses de tratamiento. Además, hemos analizado el efecto del IMC en las concentraciones séricas basales de citocinas/quimiocinas entre voluntarios sanos y sujetos con un PEP. Nuestros hallazgos apoyan la hipótesis inmunológica de la esquizofrenia. Hemos encontrado varias citocinas/quimiocinas elevadas en el grupo de sujetos con un PEP, que se normalizaron con el tratamiento antipsicótico. Aunque el efecto antiinflamatorio de la risperidona y del aripiprazol fue similar, el aripiprazol parece tener un mayor tamaño de efecto sobre algunas citocinas/quimiocinas. Además, nuestros resultados también apoyan la hipótesis de que el exceso de peso puede alterar la homeostasis del sistema inmune (first-hit) y por lo tanto, puede tener un efecto proinflamatorio aditivo en sangre periférica sobre el producido por la neuroinflamación asociada a la psicosis (second-hit). La IL-8, quimiocina que ha sido poco estudiada en muestras de PEP, ha sido la quimiocina que ha mostrado las diferencias más significativas y estables en todos los análisis realizados en esta tesis. Podría considerarse como un marcador de estado de la psicosis, ya que sus concentraciones están elevadas al inicio de la enfermedad y se normalizan con el tratamiento antipsicótico.ABSTRACT: In recent years, evidence about the involvement of the immune system in the development and evolution of psychosis has grown. However, as far as we know, no previous researches have compared the anti-inflammatory effect of antipsychotics nor have studied the effect of excess weight on serum cytokine concentrations. In this thesis, we have compared the anti-inflammatory effect of risperidone and aripiprazole on a large array of serum cytokines/chemokines at three months following the onset of treatment. We have also investigated if there is any difference in the serum cytokine/chemokine levels between healthy volunteers and patients at baseline and whether serum concentrations have changed from baseline to 3 months after the initiation of medication. In addition, we have analyzed the effect of BMI on the basal serum cytokine/chemokine levels in first-episode psychosis (FEP) patients and healthy volunteers, separating the total sample into two groups: normal-weight and overweight individuals. Our findings support the immunological hypothesis of schizophrenia. We have found severa! cytokines/chemokines elevated in the FEP group that normalized with antipsychotic treatment. Although the anti-inflammatory effect of risperidone and aripiprazole was similar, aripiprazole seemed to have a greater effect size on sorne cytokines/chemokines. Moreover, our results also support the hypothesis that excess weight can alter the homeostasis of the immune system (first-hit) and therefore may have an additive pro-inflammatory effect on the one produced by neuroinflammation related to psychosis (second-hit) in peripheral blood. IL-8, that has been a chemokine poorly studied in previous researches in FEP samples, was the chemokine that showed the most significant and stable differences in ali of analyses carried out in this thesis. lt might be considered as a state marker of psychosis, as it was increased at baseline and normalized with antipsychotic treatment

Antipsychotic Treatment Effectiveness in First Episode of Psychosis: PAFIP 3-Year Follow-Up Randomized Clinical Trials Comparing Haloperidol, Olanzapine, Risperidone, Aripiprazole, Quetiapine, and Ziprasidone

Background: Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. Method: From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n=55), risperidone (n=63), haloperidol (n=56), aripiprazole (n=78), ziprasidone (n=62), or quetiapine (n=62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. Results: The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine=69.09, risperidone=71.43, aripiprazole=73.08%, ziprasidone=79.03%, haloperidol=89.28%, and quetiapine=95.53%) (x2=79.86; P=.000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank=92.240; P=.000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea. Conclusions: Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis

Aripiprazole vs Risperidone Head-to-Head Effectiveness in First-Episode Non-Affective-Psychosis: A 3-Month Randomized, Flexible-Dose, Open-Label Clinical Trial

Background: Antipsychotic choice for the acute phase of a first episode of psychosis (FEP) is of the utmost importance since it may influence long-term outcome. However, head-to-head comparisons between second-generation antipsychotics remain scarce. The aim of this study was to compare the effectiveness in the short term of aripiprazole and risperidone after FEP outbreak. Methods: From February 2011 to October 2018, a prospective, randomized, open-label study was undertaken. Two hundred-sixty-six first-episode drug-naïve patients were randomly assigned to aripiprazole (n = 136) or risperidone (n = 130) and followed-up for 12 weeks. The primary effectiveness measure was all-cause treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted to assess clinical efficacy. Results: The overall dropout rate at 12 weeks was small (6.39%). Effectiveness measures were similar between treatment arms as treatment discontinuation rates (? 2 = 0,409; P = .522), and mean time to all-cause discontinuation (log rank ? 2 = -1.009; P = .316) showed no statistically significant differences. Despite no statistically significant differences between groups regarding clinical efficacy, aripiprazole required higher chlorpromazine equivalent dosage (? 2 = 2.160; P = .032) and extended mean time (W = 8183.5; P = .008) to reach clinical response. Sex-related adverse events and rigidity were more frequent in the risperidone group, whereas sialorrhea was on the aripiprazole group. Conclusions: No differences regarding effectiveness were found between aripiprazole and risperidone for the short-phase treatment of FEP. Despite the importance of efficacy during this phase, differences in side effect profiles and patient's preferences are essential factors that may lead clinical decisions for these patients

Strategic responses to intimate partner violence against women in Spain: a national study in primary care

Research on women"s responses to intimate partner violence (IPV) has largely been limited to women who have been exposed to severe physical violence with scarce generalisation. This study aimed to analyse how Spanish abused women from different backgrounds and with different IPV characteristics respond to violence

Aripiprazole and Risperidone Present Comparable Long-Term Metabolic Profiles: Data From a Pragmatic Randomized Controlled Trial in Drug-Naïve First-Episode Psychosis

Objective: Aripiprazole and risperidone are 2 of the most used second-generation antipsychotics (SGAs) worldwide. Previous evidence shows a similar effect of these SGAs on weight and metabolic changes in the short term. However, a longer period is necessary for a better assessment of the SGA´s metabolic profile. We aimed to compare the long-term (1-year) metabolic profile of these 2 antipsychotics on a sample of drug-naïve first episode-psychosis (FEP) patients. Methods: A total 188 drug-naïve patients, suffering from a first episode of non-affective psychosis (FEP), were randomly assigned to treatment with either aripiprazole or risperidone. Weight and glycemic/lipid parameters were recorded at baseline and after 1-year follow-up. Results: We observed significant weight increments in both groups (9.2 kg for aripiprazole and 10.5 kg for risperidone) after 1 year of treatment. Despite this, weight and body mass index changes did not significantly differ between treatment groups (P > .05). Similarly, both treatment groups presented similar metabolic clinical impact with a comparable increase in the proportion of participants meeting criteria for metabolic disorders such as obesity or hypercholesterolemia, but not for metabolic syndrome (?9.2% vs ?4.3%) or hypertriglyceridemia (?21.9% vs ?8.0%), where aripiprazole showed worse outcomes than risperidone. Conclusion: This study shows that aripiprazole and risperidone share a similar long-term metabolic profile. After 1 year of antipsychotic treatment, drug-naïve FEP patients in both treatment groups presented a significant increase in weight and metabolic changes, leading to a greater prevalence of metabolic disorders

Características clínicas y psicosociales de personas con fibromialgia. Repercusión del diagnóstico sobre sus actividades

Actualmente se sabe muy poco de las características de las personas diagnosticadas de fibromialgia, su grado de incapacidad y la respuesta del sistema sanitario. Los objetivos de este trabajo son: conocer el perfil sociodemográfico, clínico y psicosocial de las y los pacientes con fibromialgia; describir la respuesta que obtienen del sistema sanitario, y estudiar la repercusión de este síndrome en las actividades habituales de las personas que lo padecen, incluyendo las del ámbito laboral. La fibromialgia fue diagnosticada mayoritariamente en mujeres. Causa una mala percepción del estado de salud y situaciones de incapacidad laboral, afectando negativamente al entorno familiar de la persona que la padece

Pattern of long-Term weight and metabolic changes after a first-episode of psychosis: Results from a 10-years prospective follow-up of the PAFIP cohort

Background: People with psychosis are at higher risk of cardiovascular events, partly explained by a higher predisposition to gain weight. This has been observed in studies on individuals with a first-episode psychosis (FEP) at short and long term (mainly up to 1 year) and transversally at longer term in people with chronic schizophrenia. However, there is scarcity of data regarding longer-term (above 3-year follow-up) weight progression in FEP from longitudinal studies. The aim of this study is to evaluate the longer-term (10 years) progression of weight changes and related metabolic disturbances in people with FEP. Methods: Two hundred and nine people with FEP and 57 healthy participants (controls) were evaluated at study entry and prospectively at 10-year follow-up. Anthropometric, clinical, and sociodemographic data were collected. Results: People with FEP presented a significant and rapid increase in mean body weight during the first year of treatment, followed by less pronounced but sustained weight gain over the study period (?15.2 kg; SD 12.3 kg). This early increment in weight predicted longer-term changes, which were significantly greater than in healthy controls (?2.9 kg; SD 7.3 kg). Weight gain correlated with alterations in lipid and glycemic variables, leading to clinical repercussion such as increments in the rates of obesity and metabolic disturbances. Sex differences were observed, with women presenting higher increments in body mass index than men. Conclusions: This study confirms that the first year after initiating antipsychotic treatment is the critical one for weight gain in psychosis. Besides, it provides evidence that weight gain keep progressing even in the longer term (10 years), causing relevant metabolic disturbances

Creating a Green Chemistry Lab: Towards Sustainable Resource Management and Responsible Purchasing

The main goal of this project was to improve the efficiency and sustainability of the chemistry teaching laboratories of the Faculty of Engineering Vitoria-Gasteiz (University of the Basque Country (UPV/EHU)). With this aim, three different actions were developed. The first two actions aspired to achieve and maintain order and maximize efficiency within the facilities. With this in mind, the first phase involved carrying out an inventory, classifying, and rearranging all the chemical products in the warehouse using a computer storage system. Secondly, 5S lean methodology was implemented in the laboratories. The final phase included the development of a protocol for a joint purchasing strategy of chemical reagents that fostered a more responsible and sustainable acquisition and management of the substances used in various departments of the UPV/EHU. This protocol plays a key role in the transition towards the Circular Economy and its importance lies in the fact that it could be extended to other departments and faculties with similar needs. This project was developed during last two academic years (2017/2019) in the frame of the Campus Bizia Lab Programme, an initiative created to address sustainability challenges within the University.This research was funded by the University of the Basque Country (UPV/EHU) in the frame of Campus Bizia Lab Programme (CBL-17GALL and CBL-18GALL)

Understanding sex differences in long-term outcomes after a first episode of psychosis

While sex differences in schizophrenia have long been reported and discussed, long-term sex differences in outcomes among first episode of psychosis (FEP) patients in terms of the efficacy of Early Intervention Services (EIS) has been an under-explored area. A total of 209 FEP patients (95 females and 114 males) were reassessed after a time window ranging from 8 to 16 years after their first contact with an EIS program (PAFIP) that we will call the 10-year PAFIP cohort. Multiple clinical, cognitive, functioning, premorbid, and sociodemographic variables were explored at 1-year, 3-year and 10-year follow-ups. At first contact, females were older at illness onset, had higher premorbid adjustment and IQ, and were more frequently employed, living independently, and accompanied by a partner and/or children. Existence of a schizophrenia diagnosis, and cannabis and alcohol consumption were more probable among men. During the first 3 years, women showed a significantly better response to minimal antipsychotic dosages and higher rates of recovery than men (50% vs. 30.8%). Ten years later, more females continued living independently and had partners, while schizophrenia diagnoses and cannabis consumption continued to be more frequent among men. Females also presented a lower severity of negative symptoms; however, functionality and recovery differences did not show significant differences (46.7% vs. 34.4%). Between the 3- and 10-year follow-up sessions, an increase in dosage of antipsychotics was observed. These results suggest that the better outcomes seen among women during the first 3 years (while they were treated in an EIS) were in the presence of more favourable premorbid and baseline characteristics. After an average period of 10 years, with the only difference being in negative symptoms course, outcomes for women approximated those of men, drawing particular attention to the increase in dosage of antipsychotic medication once FEP patients were discharged from the EIS program towards community-based services. These findings help to pose the question of whether it is advisable to target sexes and lengthen EIS interventions

VIRTUELE. Desarrollo de la competencia digital y lingüística de docentes y discentes de español como lengua extranjera

Memoria ID-101. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2020-2021