Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Leadership strategies of mobilisation and demobilisation in Sudan

A Sudanese Revolution overthrew the sitting regime in 2019, and a transitional government is in place. This article explores Sudanese respondents’ take on how the former regime managed to stay in power for so long. The National Congress Party in Sudan held on to power for three decades against all odds after taking over in a coup in 1989. Widely unpopular, the regime relied on repression and coercive tactics to stay in power. Based on interview data from three locations in Sudan 2011 and 2012, respondents’ accounts of the NCP leadership strategies for staying in power are explored in this article. The interview data speaks to two highly intertwined processes. First, to the mobilisation of support from those the government needed in key positions around the country, in the elite, and the security forces. Second, the data speaks to the demobilisation of people in general. Respondents point at five strategies deployed by the NCP to stay in power: Creating a secure repressive base; divide and rule strategies; controlling the media; creating a confusing and closed system and, lastly, not pushing people too far. For each tactic, it seems the regime attempted to demobilise people at large, but also tried to mobilise those it needed. These five strategies are in this study seen in light of leadership, identities and collective action, and the analysis emphasises agency through the concepts of group efficacy and illiberal statebuilding. The study contributes to developing a psychology of demobilisation as it explores the attempted hindering of collective action. Exploring these issues in a non-Western conflict case like Sudan is a particularly important addition to understanding leadership demobilisation in conflict settings. Seeing this in light of the more recent processes of people’s power in Sudan makes it even more relevant

Beyond Conflict and Spoilt Identities: How Rwandan Leaders Justify a Single Recategorization Model for Post-Conflict Reconciliation

Since 1994, the Rwandan government has attempted to remove the division of the population into the ‘ethnic’ identities Hutu, Tutsi and Twa and instead make the shared Rwandan identity salient. This paper explores how leaders justify the single recategorization model, based on nine in-depth semi-structured interviews with Rwandan national leaders (politicians and bureaucrats tasked with leading unity implementation) conducted in Rwanda over three months in 2011/2012. Thematic analysis revealed this was done through a meta-narrative focusing on the shared Rwandan identity. Three frames were found in use to “sell” this narrative where ethnic identities are presented as a) an alien construction; b) which was used to the disadvantage of the people; and c) non-essential social constructs. The material demonstrates the identity entrepreneurship behind the single recategorization approach: the definition of the category boundaries, the category content, and the strategies for controlling and overcoming alternative narratives. Rwandan identity is presented as essential and legitimate, and as offering a potential way for people to escape spoilt subordinate identities. The interviewed leaders insist Rwandans are all one, and that the single recategorization is the right path for Rwanda, but this approach has been criticised for increasing rather than decreasing intergroup conflict due to social identity threat. The Rwandan case offers a rare opportunity to explore leaders’ own narratives and framing of these ‘ethnic’ identities to justify the single recategorization approach

Militæraktivisme brandet som fredsaktivisme? Norges kampanje for en plass i FNs sikkerhetsråd

Hvordan håndterer Norge sin militæraktivisme og sitt NATO-medlemskap når landet vil presentere seg selv som en fredsnasjon? Problemstillingen ble aktuell i det norske utenriksdepartementets nylige kampanje for å få Norge valgt inn i FNs sikkerhetsråd, hvor ideen om Norge som fredsnasjon stod sentralt. I denne artikkelen bruker vi nasjonsbranding som et analytisk rammeverk for å forstå hvordan Norge bygget opp sin kampanje som fredsnasjon og håndterte det konkurrerende narrativet om sin rolle i krig. Som et sekundærfokus ser vi også på hvordan Norges to konkurrenter, Irland og Canada, fremstilte seg på disse to dimensjonene – som er av særinteresse da Irland ikke er NATO-medlem. For å utforske disse spørsmålene analyserer vi taler og tekster fra det norske diplomatiet og regjeringen vedrørende kampanjen, samt ser på kampanjematerialet til de tre landene. Gitt at de tre landenes profil er påfallende lik, fant vi at alle måtte forsøke å finne en måte å brande seg på som uttrykket ens særtrekk og høynet ens relevans i sammenligning med de to andre landene. I analysen av Norge ser vi at militæraktivisme stadig ble hvisket ut i løpet av den norske kampanjen og at andre tematikker ble brukt i brandingen – som for eksempel likestilling og bidrag til internasjonal utvikling. Dette skulle dermed skulle legitimere ideen om fredsnasjonen Norge, et land som alle andre kan stole på

«Gammelt nytt» om militæraktivisme og fredsaktivisme i nye klær

Hvordan Norge håndterer sin militæraktivisme og fredsaktivisme ble aktualisert i kampanjen for et sete i sikkerhetsrådet. Aktivisme forstås her som nasjonens villighet til å ta initiativ på tross av kostnader. I denne replikken svarer vi på Friis sin kommentar som trekker verdien av vårt bidrag i tvil, da han omtaler vår analyse av Norges unnlatelse av å fremme sin militæraktivisme til fordel for «mykere verdier», som «gammelt nytt.» I kampanjen fremmet Norge både militæraktivisme og fredsaktivisme, men i ulikt materiale og forum. Vi hevder dermed at dette som et minimum er gammelt nytt i nye klær. Ved bruk av nasjonsbranding-rammeverket finner vi at Norge ønsket å fremstille seg som en aktør som er villig til å bidra, samtidig med å understreke Norge som en ikke utpreget militæraktør

Intercultural attention in trauma treatment: Western trauma treatment negotiated and modified in Sudan

Western therapeutic methods have increasingly been implemented in non-Western contexts as treatment for traumatic stress reactions. There is a growing awareness of the need for such implementations to incorporate cultural specificity, and discussions are needed on the suitability of Western psychological approaches and theories in different parts of the world. The objective of this paper is to explore the intercultural applicability of trauma treatment through a case study in Sudan. We look at how Western methods are applied and potentially modified in Sudan to fit social-cultural realities – and how specific contexts affects treatments. Such data from a non-Western context is invaluable to the discussion of transcultural aspects of mental health care. This paper presents interview data, where counsellors in a trauma centre in Sudan were asked how they are implementing Western methods, and how these treatments are negotiated and potentially modified to fit the context. The interviewed counsellors emphasise the contextual factors influencing the treatment and the need to modify therapeutic methods to the specific cultural setting. Three themes are discussed: stigma towards mental health and sexual assaults; the negotiation of treatment alongside traditional healers; and the modification of treatments to the cultural context. The findings suggest that although Western methods can be useful in non-Western settings, these need to be carefully modified to the context as well as to each individual client. The study offers valuable insights into such modifications.publishedVersionpublishedVersionacceptedVersio

Making Meaning of Empowerment and Development in Rural Malawi—International Individualism Meets Local Communalism

Empowerment is a prominent concept in psychology, and for decades, it has been a key term in global development policy, theory, and practice. However, in line with similar turns toward individualism in psychology, the prevalent understanding of the concept centers on individual capacity to change circumstances, with less focus on empowerment as a context-dependent or communal approach. In this article, adopting decolonial feminist psychology as a lens, we analyze how rural Malawians make meaning of the overarching empowerment and development approach of non-governmental organizations (NGOs) working in their villages, and how they perceive the approaches as fitting with local contexts. When development implementers largely ignore Malawi’s communal lifestyle, individualized empowerment initiatives can lead to individual and communal disempowerment and distress. Given psychology’s large influence on other arenas, and psychology’s implication with the individualized gender-development-empowerment nexus, we argue that it is imperative to explore the effects and experiences of this empowerment approach in different contexts. A more context-appropriate understanding of empowerment—as with most other psychological concepts—is needed

“Even the NGOs Never Talk About Ufiti [Witchcraft]”: a Decolonial and Feminist Cultural Psychological Analysis of Individualized Development Clashing with Communal Ways of Being.

Conducting a multi-sited psychology study on how Malawian participants perceive Western-oriented non-governmental organizations’ (NGOs) gendered development approaches, it became apparent that perceptions of ufiti (the Malawian term for what loosely translates as witchcraft in English)—and its gendered inclination—was highly relevant. As in many parts of the world, people in Malawi may relate themselves and their social world in connection to spiritual and supernatural dimensions, manifested in practices and discourses often closely linked to communal norms and values. Many international NGOs in Malawi run individualized development initiatives, often particularly focusing on women and girls’ personal empowerment. When local communal ways of experiencing and knowing are not taken account for in the NGOs’ interventions, this indiviualized approach can spur interpersonal resentment, and in worst-case ufiti assaults. This article explores the link between individualized development incentives and perceptions of ufiti. Using decolonial and feminist cultural psychology as a lens, we ask how the individualized focus of the NGOs plays out in Malawi, and what negative and unintended consequences individualized interventions can lead to. Our results indicate the need for contextually grounded and informed development approaches, to avoid that effort to empower individual women and girls lead to their disempowerment, social disruption, and ufiti accusations and assaults. The article speaks to the need for decolonial and feminist cultural psychological approaches that consider subjective intentional worlds