Neurogenetics of Dynamic Connectivity Patterns Associated With Obsessive-Compulsive Symptoms in Healthy Children

Obsessive-compulsive symptoms (OCSs) during childhood predispose to obsessive-compulsive disorder and have been associated with changes in brain circuits altered in obsessive-compulsive disorder samples. OCSs may arise from disturbed glutamatergic neurotransmission, impairing cognitive oscillations and promoting overstable functional states. A total of 227 healthy children completed the Obsessive Compulsive Inventory-Child Version and underwent a resting-state functional magnetic resonance imaging examination. Genome-wide data were obtained from 149 of them. We used a graph theory-based approach and characterized associations between OCSs and dynamic functional connectivity (dFC). dFC evaluates fluctuations over time in FC between brain regions, which allows characterizing regions with stable connectivity patterns (attractors). We then compared the spatial similarity between OCS-dFC correlation maps and mappings of genetic expression across brain regions to identify genes potentially associated with connectivity changes. In post hoc analyses, we investigated which specific single nucleotide polymorphisms of these genes moderated the association between OCSs and patterns of dFC. OCSs correlated with decreased attractor properties in the left ventral putamen and increased attractor properties in (pre)motor areas and the left hippocampus. At the specific symptom level, increased attractor properties in the right superior parietal cortex correlated with ordering symptoms. In the hippocampus, we identified two single nucleotide polymorphisms in glutamatergic neurotransmission genes (GRM7, GNAQ) that moderated the association between OCSs and attractor features. We provide evidence that in healthy children, the association between dFC changes and OCSs may be mapped onto brain circuits predicted by prevailing neurobiological models of obsessive-compulsive disorder. Moreover, our findings support the involvement of glutamatergic neurotransmission in such brain network changes

ReseArch with Patient and Public invOlvement: a RealisT evaluation - the RAPPORT study

Background Patient and public involvement (PPI) is a prerequisite for many funding bodies and NHS research ethics approval. PPI in research is defined as research carried out with or by the public rather than to, about or for them. While the benefits of PPI have been widely discussed, there is a lack of evidence on the impact and outcomes of PPI in research. Objectives To determine the types of PPI in funded research, describe key processes, analyse the contextual and temporal dynamics of PPI and explore the experience of PPI in research for all those involved. Mechanisms contributing to the routine incorporation of PPI in the research process were assessed, the impact of PPI on research processes and outcomes evaluated, and barriers and enablers to effective PPI identified. Design A three-staged realist evaluation drawing on Normalisation Process Theory to understand how far PPI was embedded within health-care research in six areas: diabetes mellitus, arthritis, cystic fibrosis, dementia, public health and learning disabilities. The first two stages comprised a scoping exercise and online survey to chief investigators to assess current PPI activity. The third stage consisted of case studies tracked over 18 months through interviews and document analysis. The research was conducted in four regions of England. Participants Non-commercial studies currently running or completed within the previous 2 years eligible for adoption on the UK Clinical Research Network portfolio. A total of 129 case study participants included researchers and PPI representatives from 22 research studies, and representatives from funding bodies and PPI networks

Additional file 2: of Music therapy versus treatment as usual for refugees diagnosed with posttraumatic stress disorder (PTSD): study protocol for a randomized controlled trial

Informed consent (English version). (DOCX 167 kb

Music therapy versus treatment as usual for refugees diagnosed with posttraumatic stress disorder (PTSD): study protocol for a randomized controlled trial

Abstract Background Meta-analyses of studies on psychological treatment of refugees describe highly varying outcomes, and research on multi-facetted and personalized treatment of refugees with post-traumatic stress disorder (PTSD) is needed. Music therapy has been found to affect arousal regulation and emotional processing, and a pilot study on the music therapy method Trauma-focused Music and Imagery (TMI) with traumatized refugees resulted in significant changes of trauma symptoms, well-being and sleep quality. The aim of the trial is to test the efficacy of TMI compared to verbal psychotherapy. Methods A randomized controlled study with a non-inferiority design is carried out in three locations of a regional outpatient psychiatric clinic for refugees. Seventy Arabic-, English- or Danish-speaking adult refugees (aged 18–67 years) diagnosed with PTSD are randomized to 16 sessions of either music therapy or verbal therapy (standard treatment). All participants are offered medical treatment, psychoeducation by nurses, physiotherapy or body therapy and social counseling as needed. Outcome measures are performed at baseline, post therapy and at 6 months’ follow-up. A blind assessor measures outcomes post treatment and at follow-up. Questionnaires measuring trauma symptoms (HTQ), quality of life (WHO-5), dissociative symptoms (SDQ-20, DSS-20) and adult attachment (RAAS) are applied, as well as physiological measures (salivary oxytocin, beta-endorphin and substance P) and participant evaluation of each session. Discussion The effect of music therapy can be explained by theories on affect regulation and social engagement, and the impact of music on brain regions affected by PTSD. The study will shed light on the role of therapy for the attainment of a safe attachment style, which recently has been shown to be impaired in traumatized refugees. The inclusion of music and imagery in the treatment of traumatized refugees hopefully will inform the choice of treatment method and expand the possibilities for improving refugee health and integration. Trial registration ClinicalTrials.gov ID number NCT03574228, registered retrospectively on 28 June 2016

Music therapy versus treatment as usual for refugees diagnosed with posttraumatic stress disorder (PTSD): study protocol for a randomized controlled trial

Abstract Background Meta-analyses of studies on psychological treatment of refugees describe highly varying outcomes, and research on multi-facetted and personalized treatment of refugees with post-traumatic stress disorder (PTSD) is needed. Music therapy has been found to affect arousal regulation and emotional processing, and a pilot study on the music therapy method Trauma-focused Music and Imagery (TMI) with traumatized refugees resulted in significant changes of trauma symptoms, well-being and sleep quality. The aim of the trial is to test the efficacy of TMI compared to verbal psychotherapy. Methods A randomized controlled study with a non-inferiority design is carried out in three locations of a regional outpatient psychiatric clinic for refugees. Seventy Arabic-, English- or Danish-speaking adult refugees (aged 18–67 years) diagnosed with PTSD are randomized to 16 sessions of either music therapy or verbal therapy (standard treatment). All participants are offered medical treatment, psychoeducation by nurses, physiotherapy or body therapy and social counseling as needed. Outcome measures are performed at baseline, post therapy and at 6 months’ follow-up. A blind assessor measures outcomes post treatment and at follow-up. Questionnaires measuring trauma symptoms (HTQ), quality of life (WHO-5), dissociative symptoms (SDQ-20, DSS-20) and adult attachment (RAAS) are applied, as well as physiological measures (salivary oxytocin, beta-endorphin and substance P) and participant evaluation of each session. Discussion The effect of music therapy can be explained by theories on affect regulation and social engagement, and the impact of music on brain regions affected by PTSD. The study will shed light on the role of therapy for the attainment of a safe attachment style, which recently has been shown to be impaired in traumatized refugees. The inclusion of music and imagery in the treatment of traumatized refugees hopefully will inform the choice of treatment method and expand the possibilities for improving refugee health and integration. Trial registration ClinicalTrials.gov ID number NCT03574228, registered retrospectively on 28 June 2016

Additional file 1: of Music therapy versus treatment as usual for refugees diagnosed with posttraumatic stress disorder (PTSD): study protocol for a randomized controlled trial

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Checklist: recommended items to address in a clinical trial protocol and related documents*. (DOCX 45 kb

International Social Survey Programme: Citizenship II - ISSP 2014

Citizen and state. Topics: Qualities of a good citizen; attitude towards the right of public meetings for religious extremists, people who want to overthrow the government by force, or people prejudiced against any racial or ethnic group; social and political participation; frequency of media use to get political news or information; number of people the respondent has contact with in a typical week day; active and passive memberships in different kinds of groups or associations (a political party, a trade union, business, or professional association, a church or other religious organization, a sports, leisure or cultural group); importance of different people´s rights in democracy (scale); suggestibility of the political system and personal level of information about politics; estimation of political influence possibilities (political efficacy): likeliness of counter-action against an unjust law and expected chance of serious attention to people´s demand; interest in politics; left-right self-placement; trust in politicians and people in government; estimation of people’s fairness; frequency of political discussions with friends; opinion leadership in politics; political parties encourage people to become active in politics; real policy choice between parties; attitude towards a referendum as a good way to decide important political questions; level of honesty and fairness in the last national election; commitment to serve people in public service; corruption in the public service; functioning of democracy in the country at present, in the past and in the future.Optional: frequencies of media use (read the political content of a newspaper, watch political news on television, listen to political news on the radio, use the Internet to get political news or information). Demography: Sex; age; year of birth; years in school; education (country specific); highest completed degree; work status; hours worked weekly; employment relationship; number of employees; supervision of employees; number of supervised employees; type of organization: for-profit vs. non profit and public vs. private; occupation (ISCO-08); main employment status; living in steady partnership; union membership; religious affiliation or denomination (country specific); groups of religious denominations; attendance of religious services; top-bottom self-placement; vote in last general election; country specific party voted in last general election; party voted (left-right); self-assessed affiliation of ethnic group 1 and 2 (country specific); number of children; number of toddlers; size of household; earnings of respondent (country specific); family income (country specific); father´s and mother´s country of birth; marital status; place of living: urban – rural; region (country specific). Information about spouse/partner on: Work status; hours worked weekly; employment relationship; supervises other employees; occupation (ISCO-08); main employment status. Additionally encoded: Date of interview; case substitution flag; weight; mode of data collection; group (participation in data collection mixed mode experiment)

International Social Survey Programme: Work Orientations IV - ISSP 2015

Attitude towards work. Work orientation. Conflict and social exclusion. Subjective experience of job. Work satisfaction. Non-standard employment. Work life balance. Job and working flexibility. Human capital. Outcome of work. Employability, new job. Topics: work centrality (a job is just a way of earning money vs. would enjoy having a paid job even if the money is not needed); importance of selected demands of a job like job security, high income, etc. (work values); work life balance: willingness to give up good job opportunities for the benefit of the family; willingness to remain in a job that is not satisfying for the benefit of the family; conflict and social exclusion: experience of discrimination with regard to work, for instance when applying for a job; main reason for the discrimination; experience of harassment at the workplace by superiors or co-workers (for example bullying, physical or psychological abuse); solidarity and conflict with regard to trade unions (workers need strong trade unions to protect their interests vs. strong trade unions are bad for the country´s economy); preferred employment arrangements (full-time, part-time, less than 10 hours a week, no paid job at all); currently working for pay (employment status); preference for more work (and money) or for reduction in working hours (work longer hours and earn more money, work the same number of hours and earn the same money, or work fewer hours and earn less money); characteristics (social dimension) of own job; subjective experience of job: frequency of hard physical work and stressful work; non-standard employment: frequency of working at home during the usual working hours and working on weekends; job and working flexibility concerning starting and finishing times; non-standard employment: usual working schedule in the main job; job and working flexibility: organisation of daily work (free decision, decision within certain limits, no free decision); work life balance: difficult to take an hour off during working hours to take care of personal or family matters; demands of the job interfere with the family life and the demands of family life interfere with the job; human capital: usefulness of the abilities learned from past work experience for the present job; job training over the past twelve months to improve job skills; judgement on the relations between management and employees and the relations between workmates/ colleagues (working atmosphere); outcome of work: work satisfaction in the main job; identification with firm or organisation; occupational commitment (would change the present type of work for something different, proud of the present type of work); employability/ new job: expected difficulties in finding a new job at least as good as the current one; likeliness of job search in the next twelve months; worried about the possibility of losing own job; job and working flexibility: accepted concessions to avoid unemployment (acceptance of a job that requires new skills, acceptance of a lower paid position, acceptance of temporary employment, longer travel to reach the place of work, movement within the country, movement to a different country); existence of a side job in addition to the main job; earning from the additional job(s) in total compared with the main job. Respondents who are not currently employed were asked: ever worked for pay for one year or more; month and year the last paid job ended; work satisfaction in the last job; main reason for the end of last employment; interest in finding a paid job; expected difficulties in finding a new job; worried about the possibility of not finding a job; accepted concessions in order to get a job (acceptance of a job that requires new skills, acceptance of a lower paid position, acceptance of temporary employment, longer travel to reach the place of work, movement within the country, movement to a different country); job seeking activities in the past twelve months and training to improve own job skills; currently looking for a job; main source of economic support; worried about the possibility of losing this main economic support. Optional items: recent work histories: ever worked for pay over the past five years; experience of selected changes in working life (unemployment for a period longer than three months, change of the employer, change of the occupation, started own business/ became self-employed, took up an additional job); self-assessment of current financial situation; change of current financial situation compared to five years ago; expected financial situation in five years; attitude towards senior citizens´ work (good for the country´s economy, employed people aged 60 and over take jobs away from younger people). Optional background variable: self-assessment of physical and mental health. Additional compulsory background variable: age of the youngest child in the household. Demography: sex; age; year of birth; years in school; education (country specific); highest completed degree; work status; hours worked weekly; employment relationship; number of employees; supervision of employees; number of supervised employees; type of organisation: for-profit vs. non profit and public vs. private; occupation (ISCO-08); main employment status; living in steady partnership; union membership; religious affiliation or denomination (country specific); groups of religious denominations; attendance of religious services; top-bottom self-placement; vote in last general election; country specific party voted in last general election; party voted (left-right); self-assessed affiliation of ethnic group 1 and 2 (country specific); number of children; number of toddlers; size of household; earnings of respondent (country specific); family income (country specific); father´s and mother´s country of birth; marital status; place of living: urban – rural; region (country specific). Information about spouse/ partner on: work status; hours worked weekly; employment relationship; supervises other employees; occupation (ISCO-08); main employment status. Additionally encoded: respondent-ID number; date of interview (year, month, day); case substitution flag; mode of data collection; weight