Experimental studies on novel pharmacological strategies in the treatment of schizophrenia

The modified dopamine (DA) hypothesis of schizophrenia suggests a hyperdopaminergic state in subcortical brain regions, which is believed to cause positive symptoms, while cortical regions may show a hypodopaminergic state which is believed to generate negative and cognitive symptoms. Positive symptoms are improved by typical antipsychotic drug (APD) treatment. However, negative and cognitive symptoms remain less affected. Typical APD treatment is often associated with extrapyramidal side effect (EPS) liability due to high DA D2 receptor blockage (≥80%). In comparison with typical APDs, atypical APDs may show better clinical efficacy, e.g. the atypical APD clozapine shows superior efficacy in treatment-resistant schizophrenia in terms of its ability to improve negative symptoms and some aspects of cognitive impairment with an absence of EPS liability, due to its low DA D2 receptor occupancy (about 45%). Contrary to typical APDs, clozapine and other atypicals increase cortical DA release in experimental animals. This effect is thought to be underlying its ability to improve negative and cognitive symptoms. However, clozapine may increase the risk for agranulocytosis and also, similar to some other atypicals, cause weight gain and sedation. Since the severity of cognitive impairment in schizophrenia is a critical determinant of treatment outcome, it is important to find alternative pharmacological strategies with better clinical efficacy and fewer side effects than available APDs. Thus, several drug treatment strategies have been applied clinically in order to achieve this goal. For example, earlier clinical studies have shown that adjunctive low doses of L-dopa to typical APDs improves negative symptoms in schizophrenic patients. Recently, it has been reported that adjunctive treatment with the antiepileptic drug topiramate may improve the effect of APDs, especially against negative symptoms, when used in schizophrenic patients maintained on a stable APD medication. Thus, we here examined experimentally these clinical findings, by investigating the effects of adjunctive treatment with either a low dose of L-dopa or topiramate to low doses of the selective DA D2 receptor antagonist raclopride using the conditioned avoidance response (CAR) paradigm for evaluating antipsychotic activity. EPS liability was assessed by means of the catalepsy test. Using microdialysis, DA output was assessed in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), respectively following these drug combinations. We found that adjunct low dose L-dopa or topiramate markedly augmented the antipsychotic-like effect of a low dose of raclopride in CAR. This augmentation was associated with a significant increase in DA output in the mPFC, but with a smaller increase in DA release in the NAC, and without catalepsy. Our experimental results support previous clinical findings that adjunctive treatment with low doses of L-dopa or topiramate to typical APD treatment may augment therapeutic efficacy in schizophrenia and with lower risk of EPS. These results are in line with our previous finding showing enhanced cortical DA output and antipsychotic-like effect of raclopride by adjunct α2 adrenoceptor blockage and indicate the possibility to augment typical APDs with an absence of severe side effects. Taken together, we conclude that an enhanced prefrontal DA output per se may serve to improve the effect of typical APDs in schizophrenia. Clinical studies have shown that selective serotonin reuptake inhibitors (SSRIs) may, at high doses, induce Parkinsonism in sensitive individuals. However, preclinical studies have revealed that stimulation of 5-HT1A receptors may modulate typical APD-induced catalepsy. Thus, it has been hypothesized that stimulation of 5-HT1A receptors may protect against an inherent potential for parkinsonism of SSRI. Here, we evaluated the possible risk of EPS following the combined treatment with a high dose (40 mg/kg) of the SSRI citalopram and the selective 5-HT1A receptor antagonist WAY 100635 using catalepsy. We observed significant catalepsy following this drug combination, while the drugs were ineffective when given alone, indicating that catalepsy, even without any direct DA D2 receptor blockade, can be induced by SSRIs together with 5-HT1A receptor blockade. This effect may be related to enhanced inhibition of dopaminergic, particularly nigrostriatal, activity and may be mediated via 5-HT receptor subtypes other than the 5-HT1A. Since we showed that a high dose of citalopram/WAY100635 in combination produced significant catalepsy; and because catalepsy and suppression of CAR behavior are thought to be mediated via suppression of dopaminergic neurotransmission, we investigated the potential antipsychotic activity of combined treatment with low doses (10 or 20 mg/kg) of citalopram and WAY100635 in CAR. EPS liability was also evaluated using catalepsy. Combined treatment with citalopram (20 mg/kg) and WAY100635 produced a significant antipsychotic-like effect as revealed by CAR and without producing significant catalepsy. The two drugs were ineffective when given alone. Pretreatment with the selective 5-HT2C receptor antagonist SB242084 completely prevented the citalopram/WAY100635-induced effect on CAR, indicating a specific involvement of the 5-HT2C receptor in the antipsychotic-like effect observed. The effect on CAR by this treatment combination is similar in magnitude to that of a moderate dose of the typical APD haloperidol. Our data suggests a novel treatment option for individuals suffering from e.g. psychotic depression. In conclusion, our studies provide experimental support for previous clinical findings and also suggest novel mechanisms that could be exploited to improve pharmacotherapy of schizophrenia

CLIL for medical universities : How to teach effectively in the glocal classroom

This article offers insights into the knowledge, skills and attitudes medical educators need to teach effectively to culturally diverse cohorts of medical students. "CLIL in Medical Education: Reaching for Tools to Teach Effectively in English in a Multicultural and Multilingual Learning Space" (CLILMED), an Erasmus+ Strategic Partnership, designed a profile to assist medical educators in the process of intentional goal-setting and self-reflection around their pedagogy, language and culture. It is the pluricultural outcomes of education that will be addressed here, since favouring the development of knowledge, attitudes and skills related to otherness, plurality and diversity have a direct impact on the quality of healthcare provision (Bradshaw, 2019; Corbett, 2011; Tiwary et al., 2019). Understanding what competences medical educators need in an intercultural classroom greatly influences their ability to intentionally design, implement and develop their teaching. The CLILMED Glocal Competence Profile for Medical Educators, centred around the intended pluricultural outcomes of Content and Language Integrated Learning (CLIL), is intended to clarify and support lifelong learning for helping medical professionals interact effectively and appropriately with students from other linguistic and cultural backgrounds.Aquest article ofereix una reflexió sobre els coneixements, habilitats i actituds que els educadors mèdics necessiten per a ensenyar eficaçment a cohorts culturalment diverses d'estudiants de medicina. "CLIL in Medical Education: Reaching for Tools to Teach Effectively in English in a Multicultural and Multilingual Learning Space" (CLILMED), una Associació Estratègica Erasmus+, dissenyà un perfil per ajudar els educadors mèdics en el procés de fixació d'objectius educatius i reflexió sobre la pròpia pedagogia, llengua i cultura. En aquest treball s'aborden els resultats pluriculturals de l'educació, donat que afavorir el desenvolupament de coneixements, actituds i habilitats relacionats amb l'alteritat, la pluralitat i la diversitat té un impacte directe en la qualitat de la prestació de l'assistència sanitària (Bradshaw, 2019; Corbett, 2011; Tiwary et al. 2019). Entendre quines competències necessiten els educadors mèdics en una aula intercultural influeix en gran mesura en la seva capacitat per dissenyar, implementar i desenvolupar intencionadament el seu ensenyament. El Perfil de Competència Global CLILMED per a Educadors Mèdics, centrat en els resultats pluriculturals previstos de l'Aprenentatge Integrat de Continguts i Llengües (AICLE), pretén aclarir i promoure l'aprenentatge permanent per ajudar els professionals de la medicina a interactuar de forma eficaç i adequada amb estudiants d'altres orígens lingüístics i culturals.Este artículo ofrece una reflexión sobre los conocimientos, habilidades y actitudes que los educadores médicos necesitan para enseñar eficazmente a cohortes culturalmente diversas de estudiantes de medicina. "AICLE en la educación médica: Reaching for Tools to Teach Effectively in English in a Multicultural and Multilingual Learning Space" (CLILMED), una Asociación Estratégica Erasmus+, diseñó un perfil para ayudar a los educadores médicos en el proceso de fijación de objetivos educativos y autorreflexión en torno a la pedagogía que implementan, su lengua y su cultura. En este trabajo se abordan los resultados pluriculturales de la educación, dado que favorecer el desarrollo de conocimientos, actitudes y habilidades relacionados con la alteridad, la pluralidad y la diversidad tiene un impacto directo en la calidad de la prestación de la asistencia sanitaria (Bradshaw, 2019; Corbett, 2011; Tiwary et al., 2019). Entender qué competencias necesitan los educadores médicos en un aula intercultural influye en gran medida en su capacidad para diseñar, implementar y desarrollar intencionadamente su enseñanza. El Perfil de Competencia Global CLILMED para Educadores Médicos, centrado en los resultados pluriculturales previstos del Aprendizaje Integrado de Contenidos y Lenguas (AICLE), pretende clarificar y promover al aprendizaje permanente para ayudar a los profesionales de la medicina a interactuar de forma eficaz y adecuada con estudiantes de otros orígenes lingüísticos y culturales

Antipsychotic-like effect by combined treatment with citalopram and WAY 100635: involvement ofthe 5-HT2C receptor.

Catalepsy occurs following high dopamine (DA) D2 blockade by typical antipsychotic drugs (APDs). We showed that a combination of a high dose of citalopram, a selective serotonin reuptake inhibitor (SSRI) and the selective 5-HT1A receptor antagonist WAY 100635 produces significant catalepsy in rats, similar to APDs. Here, we investigated the potential antipsychotic activity of lower doses of citalopram+WAY 100635, using the conditioned avoidance response (CAR) test. Cataleptogenic liability of the combination was evaluated with the catalepsy test. Citalopram and WAY 100635 in combination, but not when givenalone, prod uced a significant antipsychotic action in CAR without significant catalepsy, similar to the effect selective 5-HT2C receptor antagonist, SB , completely prevent 242084ed the citalopram/WAY 100635-induced suppression of CAR indicating an involvement of the 5-HT2C receptor. In summary, treatment with an SSRI/5-HT1A antagonist combination might prove beneficial in psychiatric disorders withpsychotic/depressive symptoms.

Antipsychotic-like effect by combined treatment with citalopram and WAY 100635: involvement of the 5-HT 2C receptor

Abstract Catalepsy occurs following high dopamine (DA) D 2 blockade by typical antipsychotic drugs (APDs). We showed that a combination of a high dose of citalopram, a selective serotonin reuptake inhibitor (SSRI) and the selective 5-HT 1A receptor antagonist WAY 100635 produces significant catalepsy in rats, similar to APDs. Here, we investigated the potential antipsychotic activity of lower doses of citalopram+WAY 100635, using the conditioned avoidance response (CAR) test. Cataleptogenic liability of the combination was evaluated with the catalepsy test. Citalopram and WAY 100635 in combination, but not when given alone, produced a significant antipsychotic action in CAR without significant catalepsy, similar to the effect of a low dose of the typical APD haloperidol. Pretreatment with a selective 5-HT 2C receptor antagonist, SB 242084, completely prevented the citalopram/WAY 100635-induced suppression of CAR indicating an involvement of the 5-HT 2C receptor. In summary, treatment with an SSRI/5-HT 1A antagonist combination might prove beneficial in psychiatric disorders with psychotic/depressive symptoms

Community-based doula support for migrant women during labour and birth : study protocol for a randomised controlled trial in Stockholm, Sweden (NCT03461640)

Introduction Migrant women consistently rate their care during labour and birth more negatively than non-migrant women, due to communication difficulties, lack of familiarity with how care is provided, and discrimination and prejudicial staff attitudes. They also report being left alone, feeling fearful, unsafe and unsupported, and have poorer birth outcomes than non-migrant women. Community-based doulas (CBDs) are bilingual women from migrant communities who are trained in childbirth and labour support, and who facilitate communication between woman-partner-staff during childbirth. This study protocol describes the design, rationale and methods of a randomised controlled trial that aims to evaluate the effectiveness of CBD support for improving the intrapartum care experiences and postnatal well-being of migrant women giving birth in Sweden. Methods and analysis A randomised controlled trial. From six antenatal care clinics in Stockholm, Sweden, we aim to recruit 200 pregnant Somali, Arabic, Polish, Russian and Tigrinya-speaking women who cannot communicate fluently in Swedish, are 18 years or older and with no contraindications for vaginal birth. In addition to standard labour support, women are randomised to CBD support (n=100) or no such support during labour (n=100). Trained CBDs meet with women once or twice before the birth, provide emotional, physical and communication support to women throughout labour and birth in hospital, and then meet with women once or twice after the birth. Women's ratings of the intrapartum care experiences and postnatal well-being are assessed at 6-8 weeks after the birth using selected questions from the Migrant Friendly Maternity Care Questionnaire and by the Edinburgh Postnatal Depression Scale. The intervention group will be compared with the control group using intention-to-treat analyses. ORs and 95% CIs will be estimated and adjustments made if key participant characteristics differ between trial arms. Ethics and dissemination The study was approved by the Regional Ethical Review Board in Stockholm (approval number: 2018/12 - 31/2)

Community-based bilingual doula support during labour and birth to improve migrant women's intrapartum care experiences and emotional well-being-Findings from a randomised controlled trial in Stockholm, Sweden

Objectives: To evaluate the effectiveness of community-based bilingual doula (CBD) support for improving the intrapartum care experiences and postnatal wellbeing of migrant women giving birth in Sweden. Design: Randomised controlled trial. Setting: Six antenatal care clinics and five hospitals in Stockholm, Sweden. Participants: 164 pregnant Somali-, Arabic-, Polish-, Russian- and Tigrinya-speaking women who could not communicate fluently in Swedish, were >= 18 years and had no contra-indications for vaginal birth. Intervention: In addition to standard labour support, women were randomised to CBD support (n = 88) or no such support during labour (n = 76). Trained CBDs met with women prior to labour, provided support by telephone after labour had started, then provided emotional, physical and communication support to women throughout labour and birth in hospital, and then met again with women after the birth. Primary outcomes: Women's overall ratings of the intrapartum care experiences (key question from the Migrant Friendly Maternity Care Questionnaire) and postnatal wellbeing (mean value of Edinburgh Postnatal Depression Scale) at 6-8 weeks after birth. Results: In total, 150 women remained to follow-up; 82 women (93.2%) randomised to receive CBD support and 68 women (89.5%) randomised to standard care (SC). Of women allocated CBD support, 60 (73.2%) received support during labour. There were no differences between the groups regarding women's intrapartum care experiences (very happy with care: CBD 80.2% (n = 65) vs SC 79.1% (n = 53); OR 1.07 CI 95% 0.48-2.40) or emotional wellbeing (EPDS mean value: CBD 4.71 (SD 4.96) vs SC 3.38 (SD 3.58); mean difference 1.33; CI 95% - 0.10-2.75). Conclusions: Community-based doula support during labour and birth for migrant women neither increased women's ratings of their care for labour and birth nor their emotional well-being 2 months postpartum compared with receiving standard care only. Further studies on the effectiveness of CBD powered to evaluate obstetric outcomes are needed. Trial registration Trial registration at ClinicalTrial.gov NCT0346164

Coloniality and Whiteness in the Academy: Towards Decolonial Futures (Special Issue of Philosophy and Theory in Higher Education)

This special issue addresses the timely and under-theorised area in higher education, contributing to the knowledge and understanding about the complexities, paradoxes, tensions, and possibilities of designing decolonial futures in higher education. The idea for a special issue emerged during a series of Club Meet conversations within the Philosophy and Theory in Higher Education Society in October 2021. Projecting ‘otherness’ on the non-white and the colonised, (Bhabha, 1994), the western university could be said to maintain and perpetuate colonial power structures, body-politics and geo-politics of knowledge-making. This can further reproduce designs for recolonising people, their Being and Becoming (Welikala, 2021), while suppressing and eradicating the knowledges of the ‘other’ (Bhambra et al., 2018). The recent surge in decolonising curriculum, pedagogy and research in higher education is reinforced by social movements and student activism. Focusing mainly on curriculum, pedagogy and research leaves the structural and systemic coloniality aside, encouraging the practice of embedding decolonisation predominantly within equality, diversity and inclusion (EDI) policies and practices. Subsequently, the notion of decolonisation is often conceptualised as a neutral, apolitical signifier/metaphor that can be used for a wide range of agendas within the neoliberal university, focusing on social justice (Tuck and Yang, 2012). As guest co-editors, we argue that homogenising a wide range of experiences of oppression under the term ‘decolonisation’ can mask decolonisation as philanthropic enterprise initiated by the ‘powerful’ global centres to offer voice to the ‘powerless’, marginalised non-white groups (Cesaire, 2000). This ‘refined’ and comfortable approach to decolonising higher education focuses on limited areas of activity: diversifying the established knowledge/disciplinary cannons by introducing non-white authors; demonstrating interest in the acceptance of ‘alternative’ epistemologies while focusing on the existing epistemic hegemonies; and increasing minority (BME) representation in operationalising EDI work that is led by the majority (white) groups. Rather than effectively addressing coloniality, such activities intensify the centrality of existing knowledge cannons while re-confirming the self-endorsed power of whiteness and the colonial imaginary within the academy (Maldonado-Torres, 2007). The proliferating scholarship on decolonising education in the North, has seldom considered the pioneering, politically-informed perspectives of the global South and its theoretical underpinnings. The more radical decolonial turn pioneered by the scholars in the global South was focused on challenging the implications of modernity/coloniality and dismantling the colonial power hierarchies by transforming epistemic values and improving democracy in education (Mignolo, 2011). The absence of theoretical rigour and the lack of knowledge of the historicity of colonisation and coloniality has led towards a predominantly tokenistic approach to decoloniality in the academy in the global North