Cibersam Research Center Biomedica En Red Of Salud Mental

Madrid, Spain

Cibersam Research Center Biomedica En Red Of Salud Mental

Madrid, Spain
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Riga M.S.,Institute Dinvestigacions Biomediques Of Barcelona | Riga M.S.,Cibersam Research Center Biomedica En Red Of Salud Mental | Riga M.S.,Institute dInvestigacions Biomediques August Pi i Sunyer IDIBAPS | Teruel-Marti V.,University of Valencia | And 7 more authors.
Neuropharmacology | Year: 2017

Vortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in major depressive patients. Here we compared the effects of 14-day treatments with VOR and escitalopram (ESC, selective serotonin reuptake inhibitor) on neuronal activity in the medial prefrontal cortex (mPFC). Ten groups of rats (5 standard, 5 depleted of 5-HT with p-chlorophenylalanine -pCPA-, used as model of cognitive impairment) were fed with control food or with two doses of VOR-containing food. Four groups were implanted with minipumps delivering vehicle or ESC 10 mg/kg·day s.c. The two VOR doses enable occupation by VOR of SERT+5-HT3-R and all targets, respectively, and correspond to SERT occupancies in patients treated with 5 and 20 VOR mg/day, respectively. Putative pyramidal neurons (n = 985) were recorded extracellularly in the mPFC of anesthetized rats. Sub-chronic VOR administration (but not ESC) significantly increased neuronal discharge in standard and 5-HT-depleted conditions, with a greater effect of the low VOR dose in standard rats. VOR increased neuronal discharge in infralimbic (IL) and prelimbic (PrL) cortices. Hence, oral VOR doses evoking SERT occupancies similar to those in treated patients increase mPFC neuronal discharge. The effect in 5-HT-depleted rats cannot be explained by an antagonist action of VOR at 5-HT3-R and suggests a non-canonical interaction of VOR with 5-HT3-R. These effects may underlie the superior pro-cognitive efficacy of VOR compared with SSRIs in animal models. © 2016 Elsevier Ltd


Moreno-Alcazar A.,FIDMAG Germanes Hospitalaries Research Foundation | Moreno-Alcazar A.,Institute of Neuropsychiatry and Addictions INAD Hospital del Mar | Moreno-Alcazar A.,IMIM Institute Hospital del Mar dInvestigacions Mediques | Moreno-Alcazar A.,Autonomous University of Barcelona | And 33 more authors.
Trials | Year: 2017

Background: Up to 60% of patients with bipolar disorder (BD) have a history of traumatic events, which is associated with greater episode severity, higher risk of comorbidity and higher relapse rates. Trauma-focused treatment strategies for BD are thus necessary but studies are currently scarce. The aim of this study is to examine whether Eye Movement Desensitization and Reprocessing (EMDR) therapy focusing on adherence, insight, de-idealisation of manic symptoms, prodromal symptoms and mood stabilization can reduce episode severity and relapse rates and increase cognitive performance and functioning in patients with BD. Methods/design: This is a single-blind, randomized controlled, multicentre trial in which 82 patients with BD and a history of traumatic events will be recruited and randomly allocated to one of two treatment arms: EMDR therapy or supportive therapy. Patients in both groups will receive 20 psychotherapeutic sessions, 60 min each, during 6 months. The primary outcome is a reduction of affective episodes after 12 and 24 months in favour of the EMDR group. As secondary outcome we postulate a greater reduction in affective symptoms in the EMDR group (as measured by the Bipolar Depression Rating Scale, the Young Mania Rating Scale and the Clinical Global Impression Scale modified for BD), and a better performance in cognitive state, social cognition and functioning (as measured by the Screen for Cognitive Impairment in Psychiatry, The Mayer-Salovey-Caruso Emotional Intelligence Test and the Functioning Assessment Short Test, respectively). Traumatic events will be evaluated by The Holmes-Rahe Life Stress Inventory, the Clinician-administered PTSD Scale and the Impact of Event Scale. Discussion: The results of this study will provide evidence whether a specific EMDR protocol for patients with BD is effective in reducing affective episodes, affective symptoms and functional, cognitive and trauma symptoms. Trial registration: The trial is registered at ClinicalTrials.gov, identifier: NCT02634372. Registered on 3 December 2015. © 2017 The Author(s).


Santamaria-Garcia H.,University Pompeu Fabra | Soriano-Mas C.,University of Barcelona | Soriano-Mas C.,Cibersam Research Center Biomedica En Red Of Salud Mental | Soriano-Mas C.,Autonomous University of Barcelona | And 9 more authors.
Social Neuroscience | Year: 2017

Error monitoring, cognitive control and motor inhibition control are proposed as cognitive alterations disrupted in obsessive-compulsive disorder (OCD). OCD has also been associated with an increased sensitivity to social evaluations. The effect of a social simulation over electrophysiological indices of cognitive alterations in OCD was examined. A case-control cross-sectional study measuring event-related potentials (ERP) for error monitoring (Error-Related Negativity), cognitive control (N2) and motor control (LRP) was conducted. We analyzed twenty OCD patients and twenty control participants. ERP were recorded during a social game consisting of a visual discrimination task, which was performed in the presence of a simulated superior or an inferior player. Significant social effects (different ERP amplitudes in Superior vs. Inferior player conditions) were found for OCD patients, but not for controls, in all ERP components. Performing the task against a simulated inferior player reduced abnormal ERP responses in OCD to levels observed in controls. The hierarchy-induced ERP effects were accompanied effects over reaction times in OCD patients. Social context modulates signatures of abnormal cognitive functioning in OCD, therefore experiencing a social superiority position impacts over cognitive processes in OCD such as error monitoring mechanisms. These results open the door for the research of new therapeutic choices. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Navarro J.A.,University of Regensburg | Llorens J.V.,University of Valencia | Llorens J.V.,Institute Biomedicina | Soriano S.,University of Valencia | And 5 more authors.
PLoS ONE | Year: 2011

Background: Friedreich's ataxia (FA), the most frequent form of inherited ataxias in the Caucasian population, is caused by a reduced expression of frataxin, a highly conserved protein. Model organisms have contributed greatly in the efforts to decipher the function of frataxin; however, the precise function of this protein remains elusive. Overexpression studies are a useful approach to investigate the mechanistic actions of frataxin; however, the existing literature reports contradictory results. To further investigate the effect of frataxin overexpression, we analyzed the consequences of overexpressing human (FXN) and fly (FH) frataxins in Drosophila. Methodology/Principal Findings: We obtained transgenic flies that overexpressed human or fly frataxins in a general pattern and in different tissues using the UAS-GAL4 system. For both frataxins, we observed deleterious effects at the biochemical, histological and behavioral levels. Oxidative stress is a relevant factor in the frataxin overexpression phenotypes. Systemic frataxin overexpression reduces Drosophila viability and impairs the normal embryonic development of muscle and the peripheral nervous system. A reduction in the level of aconitase activity and a decrease in the level of NDUF3 were also observed in the transgenic flies that overexpressed frataxin. Frataxin overexpression in the nervous system reduces life span, impairs locomotor ability and causes brain degeneration. Frataxin aggregation and a misfolding of this protein have been shown not to be the mechanism that is responsible for the phenotypes that have been observed. Nevertheless, the expression of human frataxin rescues the aconitase activity in the fh knockdown mutant. Conclusion/Significance: Our results provide in vivo evidence of a functional equivalence for human and fly frataxins and indicate that the control of frataxin expression is important for treatments that aim to increase frataxin levels. © 2011 Navarro et al.


Lluch-Canut T.,University of Barcelona | Puig-Llobet M.,University of Barcelona | Sanchez-Ortega A.,Catalan Institute for Health | Roldan-Merino J.,University of Barcelona | And 2 more authors.
BMC Public Health | Year: 2013

Background: A holistic perspective on health implies giving careful consideration to the relationship between physical and mental health. In this regard the present study sought to determine the level of Positive Mental Health (PMH) among people with chronic physical health problems, and to examine the relationship between the observed levels of PMH and both physical health status and socio-demographic variables. Methods. The study was based on the Multifactor Model of Positive Mental Health (Lluch, 1999), which comprises six factors: Personal Satisfaction (F1), Prosocial Attitude (F2), Self-control (F3), Autonomy (F4), Problem-solving and Self-actualization (F5), and Interpersonal Relationship Skills (F6). The sample comprised 259 adults with chronic physical health problems who were recruited through a primary care center in the province of Barcelona (Spain). Positive mental health was assessed by means of the Positive Mental Health Questionnaire (Lluch, 1999). Results: Levels of PMH differed, either on the global scale or on specific factors, in relation to the following variables: age: global PMH scores decreased with age (r=-0.129; p=0.038); b) gender: men scored higher on F1 (t=2.203; p=0.028) and F4 (t=3.182; p=0.002), while women scored higher on F2 (t -3.086; p=0.002) and F6 (t=-2.744; p=0.007); c) number of health conditions: the fewer the number of health problems the higher the PMH score on F5 (r=-0.146; p=0.019); d) daily medication: polymedication patients had lower PMH scores, both globally and on various factors; e) use of analgesics: occasional use of painkillers was associated with higher PMH scores on F1 (t=-2.811; p=0.006). There were no significant differences in global PMH scores according to the type of chronic health condition. The only significant difference in the analysis by factors was that patients with hypertension obtained lower PMH scores on the factor Autonomy (t=2.165; p=0.032). Conclusions: Most people with chronic physical health problems have medium or high levels of PMH. The variables that adversely affect PMH are old age, polypharmacy and frequent consumption of analgesics. The type of health problem does not influence the levels of PMH. Much more extensive studies with samples without chronic pathology are now required in order to be able to draw more robust conclusions. © 2013 Lluch-Canut et al.; licensee BioMed Central Ltd.

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