A house is not a home: a network model perspective on the dynamics between subjective quality of living conditions, social support, and mental health of refugees and asylum seekers

Background: Providing adequate living conditions for forcibly displaced people represents a significant challenge for host countries such as Germany. This study explores refugee mental health’s reciprocal, dynamic relationship with post-migration living conditions and social support. Methods: The study sample included 325 Arabic- or Farsi-speaking asylum seekers and refugees residing in Germany since 2014 and seeking mental health treatment. Associations between reported symptoms of post-traumatic stress and depression and the subjective quality of living conditions and perceived social support were analyzed using a two-level approach including multiple linear regression and network analyses. Results: Post-migration quality of living conditions and perceived social support were significantly associated with negative mental health outcomes on both levels. In the network, both post-migration factors were negatively connected with overlapping symptoms of psychiatric disorders, representing potential target symptoms for psychological treatment. Conclusion: Post-migration quality of living conditions and social support are important factors for refugee mental health and should be targeted by various actors fostering mental well-being and integration

Culturally sensitive stepped care for adolescent refugees: efficacy and cost–utility of a multicentric randomized controlled trial

Adolescent refugees and asylum seekers (ARAS) are highly vulnerable to mental health problems. Stepped care models (SCM) and culturally sensitive therapies offer promising treatment approaches to effectively provide necessary medical and psychological support. To our knowledge, we were the first to investigate whether a culturally sensitive SCM will reduce symptoms of depression and PTSD in ARAS more effectively and efficiently than treatment as usual (TAU). We conducted a multicentric, randomized, controlled and rater-blinded trial across Germany with ARAS between the ages of 14 to 21 years. Participants (N = 158) were stratified by their level of depressive symptom severity and then equally randomized to either SCM or TAU. Depending on their severity level, SCM participants were allocated to tailored interventions. Symptom changes were assessed for depression (PHQ) and PTSD (CATS) at four time points, with the primary end point at post-intervention after 12 weeks. Based on an intention-to-treat sample, we used a linear mixed model approach for the main statistical analyses. Further evaluations included cost–utility analyses, sensitivity analyses, follow-up-analyses, response and remission rates and subgroup analysis. We found a significant reduction of PHQ (d = 0.52) and CATS (d = 0.27) scores in both groups. However, there was no significant difference between SCM and TAU. Cost–utility analyses indicated that SCM generated greater cost–utility when measured as quality-adjusted life years compared to TAU. Subgroup analysis revealed different effects for the SCM interventions depending on the outcome measure. Although culturally sensitive, SCMs did not prove to be more effective in symptom change and represent a more cost-effective treatment alternative for mentally burdened ARAS. Our research contributes to the optimization of clinical productivity and the improvement of therapeutic care for ARAS. Disorder-specific interventions should be further investigated

HLA-DR Alpha 2 Mediates Negative Signalling via Binding to Tirc7 Leading to Anti-Inflammatory and Apoptotic Effects in Lymphocytes In Vitro and In Vivo

Classically, HLA-DR expressed on antigen presenting cells (APC) initiates lymphocyte activation via presentation of peptides to TCR bearing CD4+ T-Cells. Here we demonstrate that HLA-DR alpha 2 domain (sHLA-DRα2) also induces negative signals by engaging TIRC7 on lymphocytes. This interaction inhibits proliferation and induces apoptosis in CD4+ and CD8+ T-cells via activation of the intrinsic pathway. Proliferation inhibition is associated with SHP-1 recruitment by TIRC7, decreased phosphorylation of STAT4, TCR-ζ chain & ZAP70, and inhibition of IFN-γ and FasL expression. HLA-DRα2 and TIRC7 co-localize at the APC-T cell interaction site. Triggering HLA-DR - TIRC7 pathway demonstrates that sHLA-DRα2 treatment inhibits proinflammatory-inflammatory cytokine expression in APC & T cells after lipopolysaccaride (LPS) stimulation in vitro and induces apoptosis in vivo. These results suggest a novel antiproliferative role for HLA-DR mediated via TIRC7, revise the notion of an exclusive stimulatory interaction of HLA-DR with CD4+ T cells and highlights a novel physiologically relevant regulatory pathway

Psychische Belastungen bei Geflüchteten - Prävalenzen, Prädiktoren und Behandlungsansätze

Diese Dissertation verfolgt das übergeordnete Ziel, ein umfassendes wissenschaftliches Bild über psychologische Auffälligkeiten, Behandlungsmethoden und den Hilfebedarf von jungen Geflüchteten zu geben um daraus fundierte Hinweise für die gezielte Entwicklung von Präventionund Interventionsmaßnahmen abzuleiten. Zunächst wurden mittels eines systematischen Reviews und einer Meta-Analyse die Prävalenzraten für PTSD und Depression unter Geflüchteten in Deutschland untersucht (Studie I). Die berechneten Prävalenzraten überstiegen die der Allgemeinbevölkerung um ein Vielfaches. Die hohe Heterogenität der einzelnen Studienergebnisse ließ zudem auf das Vorliegen unterschiedlich stark belasteter Subgruppen schließen. Es wurden deshalb in einer weiteren Studie aktuelle Prävalenzen von Depressivität und allgemeiner psychischer Belastung zwischen unbegleiteten und begleiteten minderjährigen Geflüchteten in Deutschland miteinander verglichen (Studie III). Die Ergebnisse belegen, dass unbegleitete minderjährige Geflüchtete (unaccompanied refugee minors; URM) eine Hochrisikogruppe für die Entwicklung psychischer Erkrankungen darstellen und daher besondere klinische Beachtung erfahren sollten. Um ein fundiertes Bild über die relevanten Prädiktoren mentaler Belastung von URM zu erhalten, wurde ein umfassendes systematisches Review erstellt (Studie II). Hierbei wurden die Faktoren Anzahl erlebter Belastungen, Geschlecht, soziale Unterstützung, Wohnsituation, Familienkontakt und kulturelle Kompetenzen als relevante Prädiktoren identifiziert. Im Anschluss an die systematische Übersichtsarbeit wurde eine weitere Studie zu relevanten Einflussfaktoren psychischer Belastung bei URM auf Basis einer großen Stichprobe in Deutschland durchgeführt (Studie III). Hierfür wurde erstmals ein Screeningfragebogen angewandt, welcher auf den in Studie II identifizierten Prädiktoren basierte. Die Ergebnisse betonen die zentrale Rolle regelmäßigen Familienkontakts, des Schulbesuchs und Spracherwerbs, sowie der raschen Bearbeitung von Asylanträgen hinsichtlich der Prävention psychischer Erkrankungen bei URM. Trotz des hohen therapeutischen Bedarfs erscheint der Zugang zur Gesundheitsversorgung für Geflüchtete erheblich erschwert. In diesem Zusammenhang untersuchten wir ein kultursensibles gestuftes Versorgungsmodel (stepped care model; SCM) im Rahmen einer multizentrischen randomisiert kontrollierten Therapiestudie (Studie IV). Die Ergebnisse weisen auf eine höhere Kosteneffizenz des SCM bei vergleichbarer Effektivität zur Regelversorgung hin. Zudem liefern die Analysen der einzelnen Versorgungsstufen Hinweise zur Optimierung der psychologischen Versorgung, beispielsweise durch den Einsatz niederschwelliger, smartphone-basierter Interventionen

A systematic review of risk and protective factors of mental health in unaccompanied minor refugees

In recent years, there has been a rising interest in the mental health of unaccompanied minor refugees (UMR), who are a high-risk group for mental disorders. Especially the investigation of predictive factors of the mental health of young refugees has received increasing attention. However, there has been no review on this current issue for the specific group of UMR so far. We aimed to summarize and evaluate the existing findings of specific risk and protective factors to identify the most verified influences on the mental health of UMR. Therefore, we conducted a systematic literature search. Study designs were limited to quantitative cross-sectional and longitudinal designs. Eight databases were searched in four different languages and article reference lists of relevant papers were screened. 27 studies were included (N = 4753). Qualitative synthesis revealed the number of stressful life events to be the most evaluated and verified risk factor for mental health of UMR. A stable environment and social support, on the other hand, can protect UMR from developing poor mental health. Besides that, several other influencing factors could be pointed out, such as type of accommodation, family contact, gender and cultural competences. Because of the large heterogeneity of outcome measures, quantitative synthesis was not possible. This review helps to improve our understanding of determinants of UMRs mental health and thus to provide more targeted treatment. Furthermore, it provides information on how to prevent the development of mental health problems by specifying factors that can be modified by different health and immigration sectors in advance. Further research is needed focusing on the interaction between the various predictive factors

Prevalences of mental distress and its associated factors in unaccompanied refugee minors in Germany

Prevalences for mental disorders within minor refugees are comparatively high and heterogeneous. To reduce heterogeneity and identify high-risk subgroups, we compared unaccompanied refugee minors (URM) to accompanied refugee minors (ARM) regarding depressive symptoms and mental distress. Furthermore, we examined associative factors of mental distress in URM on a broad scale. We conducted a survey with a cross-sectional design in four German University hospitals. The sample consisted of n = 172 URM and n = 52 ARM aged 14-21. Depressive symptoms were assessed via the Patient Health Questionnaire (PHQ-9). Mental distress was assessed by the Refugee Health Screener (RHS-15). Mann-Whitney test was used to examine differences between URM and ARM. Associated factors of mental distress were evaluated via a stepwise multiple regression analysis. URM showed significantly higher mean scores for PHQ-9 (p < .001) and RHS-15 (p < .001) compared to ARM indicating medium effect sizes. Furthermore, URM were significantly more likely to surpass the cut-off for depression (61.6% vs. 30.8%) and overall mental distress (81.4% vs. 53.8%) compared to ARM. The factors Number of stressful life events (SLE), Female gender, and Fear of deportation were found to be associated with an increased mental distress in URM, whereas Weekly contact to a family member, School attendance, and German language skills were accompanied with lower distress scores. All six factors accounted for 32% of the variance of mental distress in URM (p < .001). Within minor refugees, URM are a highly vulnerable subgroup, which should receive particular attention and more targeted measures by health authorities. Our results indicate that these measures should comprise a rapid promotion of family contact, school attendance, language acquisition, and the fast processing of asylum applications. However, the cross-sectional design limits the interpretability of the results

HLA-DR alpha 2 domain interacts with TIRC7 protein.

<p>A. Strain AH109 carrying GAL4 activation domain, fused to cDNA containing HLA-DR, was tested for interaction with indicated domains of TIRC7 (N-terminus aa 1-173, large extracellular domain aa 438-512 or C-terminus aa 586-614) as bait. The growth of combined clones on Histidine-negative agar plates indicate a specific interaction between the HLA-DR alpha 2 and TIRC7 extracellular domain whereas no interaction between HLA-DR alpha 2 to the C – terminal or N- terminal domain of TIRC7 was observed. The growth of colonies on Histidine positive agar plates which represents a positive control, is shown in the left panel. B. Lysates were prepared from 1 h allo-activated PBL and Jurkat cells. Lysates were immunoprecipitated (IP) with anti-TIRC7 mAb and immunoblotted (IB) with specific antibody against HLA-DR protein or TIRC7 in denaturing conditions. Co-precipitation of TIRC7 and HLA-DR is observed in PBL whereas only TIRC7 was precipitated in HLA-DR negative Jurkat cells. C. COS7 cells were transiently transfected with a TIRC7-<i>myc</i> fusion protein vector construct, incubated with sHLA-DRα2 and stained with secondary anti-human Fc protein-Cy3 conjugated mAb. Flow cytometry analysis revealed that sHLA-DRα2 solely binds to TIRC7 transfected COS7 cells and fail to bind to non-transfected COS7 control cells. Shown is one experiment out of four. D. COS7 cells transfected with TIRC7-<i>myc</i> fusion protein showed concentration-dependent binding of sHLA-DRα2 (0, 25, 50, 150 µg/ml) using direct immunofluorescence method. No binding of control protein was observed in transfected COS7 cells. Shown is one experiment out of three. E and F. TIRC7 deficient and wild-type mouse splenocytes were isolated and either stimulated with PHA for 48 h or remained unstimulated. Cells were incubated with either human HLA-DR alpha 2 or human control protein prior to flow cytometry (E) or confocal microscopic analysis (F) using anti-human Fc-specific Cy3 as secondary antibody. The results show that HLA-DR alpha 2 solely binds to stimulated WT cells in flow cytometric and microscopic analyses. Shown is one experiment out of three, respectively.</p

Targeting of TIRC7 in lymphocytes induces apoptosis via the mitochondrial intrinsic pathway.

<p>A. PBL were co-incubated 50 µg/ml sHLA-DRα2 or control protein for 5 h, and immunobloting using mAb against caspase 9, caspase 8, caspase 7 and caspase 3 was performed. Activation of caspase 9 and caspase 7 is indicated by the appearance of cleaved fragments with a size of 37 and 20 kDa, respectively. No activation of caspase 8 and 3 was observed. B. Human PBL were isolated, activated with anti-CD3/CD28 antibodies (a) cultured in the presence of 50 µg/ml sHLA-DRα2 (d), and subjected to flow cytometric analysis. In comparison to non-treated controls (b,c) stimulated human T cells incubated with 50 µg/ml sHLA-DRα2 (d) demonstrated a remarkably reduced expression of FasL as detected by FITC labeled anti-FasL mAb. C. Human PBL were recall antigen stimulated for 6 days and incubated with FITC labeled anti-TIRC7 mAb. A monocyte cell line, THP-1, was incubated with anti-HLA-DR mAb and secondary stained with Cy3-conjugate. To increase cell interaction, PBL and THP-1 cells were mixed and incubated at 37°C for 20 min and subjected to confocal microscopic analysis. The data show that HLA-DR (red color) and TIRC7 (green color) co-localize (merge, yellow color) at the physical site of T cell/APC interaction. Shown is one experiment out of three.</p

sHLA-DR α2 binds to TIRC7 expressed in CD4 and CD8 T cells.

<p>CD4+ and CD8+ T cells were separated by magnetic beads, stimulated with anti-CD3/CD28 mAb for 48 h, and incubated with either sHLA-DR α2 or control protein for 30 min prior to confocal microscopic analysis. Using anti-human Fc-Cy3 mAb as secondary antibody, binding of sHLA-DRα2 or control protein to TIRC7 protein was analyzed. The results show a binding in CD4+ and CD8+ human T cells co-incubated with sHLA-DRα2 (upper panel) whereas no binding was observed in various control experiments using either control protein (lower panel) or anti-Fc-Cy3 conjugated secondary mAb only. Shown is one experiment out of three.</p