Journal Articles

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    Sex-dependent metabolic and behavioural alterations in a rat model of forced exertion-induced myopathy
    (BioMed Central Ltd, 2025-12-01) Lubbe C; Harvey BH; Viljoen FP; Meyer L; Wolmarans DW
    Background: Mass boma capture (MBC) of ungulates may trigger a metabolic condition known as capture myopathy (CM), resulting in myoglobinuria and hyperthermia (rhabdomyolysis). Its pathobiology is poorly understood, especially the role of contextual reminders; a preclinical model system could thus be useful. Sixty (60) adult Sprague Dawley rats (30 rats per sex), divided into three experimental series (n = 12—24), were exposed to MBC-like exertion, viz., forced treadmill running (FTR) at 75% of VO2MAX (30 m/min) with and without aversive noise (context) until physical exhaustion. Rectal and surface temperatures were measured before and after reaching exhaustion. Urine myoglobin, plasma lactate dehydrogenase (LDH), lactate, and creatine kinase (CK) were measured immediately and 15 days after MBC. Anxiety was assessed in the light-dark and social interaction tests. Results: Male and female MBC rats presented with significant hyperthermia, with females showing significantly increased urine myoglobin immediately after MBC, although this was not sustained until day 15 post MBC. LDH was significantly elevated in female rats at baseline but not day 15 post-MBC. Contextual re-exposure prior to testing on day 15 resulted in significant sex-dependent differences in myoglobin and CK concentrations, with female rats being significantly more affected. Only female rats trended towards increased anxiety-like behaviour immediately post-MBC exposure, which was not sustained until day 15 post MBC. Conclusions: This work builds on previous research using a rodent model of capture myopathy (CM) that confirmed the running protocol to effectively elicite the necessary muscular response. The MBC protocol emphasizes hyperthermia and increased urine myoglobin, sensitivity to contextual reminder (noise), and a trend towards anxiety, particularly in females, highlighting sex-specific physiological responses. By incorporating behavioural and biochemical assessments, acute versus delayed response and environmental triggers, the study enhances model validity and deepens insights into CM-related responses.
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    Peripherally Restricted Activation of Opioid Receptors Influences Anxiety-Related Behaviour and Alters Brain Gene Expression in a Sex-Specific Manner.
    (MDPI (Basel, Switzerland), 2024-12-07) Parkar N; Young W; Olson T; Hurst C; Janssen P; Spencer NJ; McNabb WC; Dalziel JE; Szumlinski KK; Shiina T
    Although effects of stress-induced anxiety on the gastrointestinal tract and enteric nervous system (ENS) are well studied, how ENS dysfunction impacts behaviour is not well understood. We investigated whether ENS modulation alters anxiety-related behaviour in rats. We used loperamide, a potent μ-opioid receptor agonist that does not cross the blood-brain barrier, to manipulate ENS function and assess changes in behaviour, gut and brain gene expression, and microbiota profile. Sprague Dawley (male/female) rats were acutely dosed with loperamide (subcutaneous) or control solution, and their behavioural phenotype was examined using open field and elevated plus maze tests. Gene expression in the proximal colon, prefrontal cortex, hippocampus, and amygdala was assessed by RNA-seq and caecal microbiota composition determined by shotgun metagenome sequencing. In female rats, loperamide treatment decreased distance moved and frequency of supported rearing, indicating decreased exploratory behaviour and increased anxiety, which was associated with altered hippocampal gene expression. Loperamide altered proximal colon gene expression and microbiome composition in both male and female rats. Our results demonstrate the importance of the ENS for communication between gut and brain for normo-anxious states in female rats and implicate corticotropin-releasing hormone and gamma-aminobutyric acid gene signalling pathways in the hippocampus. This study also sheds light on sexually dimorphic communication between the gut and the brain. Microbiome and colonic gene expression changes likely reflect localised effects of loperamide related to gut dysmotility. These results suggest possible ENS pharmacological targets to alter gut to brain signalling for modulating mood.
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    Depression and anxiety at 1- and 12-months post ischemic stroke: methods for examining individual change over time.
    (CSIRO Publishing on behalf of the Australasian Society for the Study of Brain Impairment, 2024-12-05) Barker-Collo S; Krishnamurthi R; Nair B; Ranta A; Douwes J; Feigin V; Honan C
    Background Depression is commonly studied post stroke, while anxiety is less studied. This study presents prevalence of depression and anxiety at 1- and 12-months post ischemic stroke alongside three methods for examining within-subjects change over time. Methods Participants were ischemic stroke patients of the Auckland Regional Community Stroke Study (ARCOS-V) with Hospital Anxiety and Depression Scale data at 1- (n = 343) and 12-months (n = 307). Change over time was examined using within-subjects repeated measures ANOVA, calculation of the Reliable Change Index, and a Sankey diagram of those meeting cut-off scores (>7) for caseness over time. Results Using repeated measures ANOVA, depression scores didn’t change significantly over time, while anxiety symptoms decreased significantly. When reliable change was calculated, 4.2% of individuals had reliable decreases in anxiety symptoms, while 5.7% had reliable decreases in depression symptoms. Those who had a reliable decrease in one tended to have a reliable decrease in the other. In the Sankey, the proportion of those meeting the cut-off score for anxiety did not change over time (12.8 and 12.7% at 1- and 12-months), while those meeting the cut-off for depression increased slightly (3.7–4.5%) and those meeting cut-offs for both decreased from 10.4 to 8.1%. Conclusion The three methods produced very different findings. Use of cut-off scores is common but has limitations. Calculation of clinically reliable change is recommended. Further work is needed to ensure depression and anxiety are monitored over time post-stroke, and both should be the subject of intervention efforts in both acute and late stages post-stroke.
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    Depression and Anxiety in Old Age during the COVID-19 Pandemic: A Comparative Study of Individuals at Cardiovascular Risk and the General Population.
    (MDPI (Basel, Switzerland), 2023-02-08) Gerhards SK; Luppa M; Röhr S; Pabst A; Bauer A; Frankhänel T; Döhring J; Escales C; Zöllinger IR; Oey A; Brettschneider C; Wiese B; Hoffmann W; Gensichen J; König H-H; Frese T; Thyrian JR; Kaduszkiewicz H; Riedel-Heller SG; Miettunen J
    Our study aims to examine the associations of sociodemographic factors, social support, resilience, and perceptions of the COVID-19 pandemic with late-life depression and anxiety symptoms in a cardiovascular risk group and a matched sample from the German general population during the beginning of the pandemic and draw a comparison regarding psychosocial characteristics. Data of n = 1236 participants (aged 64-81 years) were analyzed, with n = 618 participants showing a cardiovascular risk profile, and n = 618 participants from the general population. The cardiovascular risk sample had slightly higher levels of depressive symptoms and felt more threatened by the virus due to pre-existing conditions. In the cardiovascular risk group, social support was associated with less depressive and anxiety symptoms. In the general population, high social support was associated with less depressive symptoms. Experiencing high levels of worries due to COVID-19 was associated with more anxiety in the general population. Resilience was associated with less depressive and anxiety symptoms in both groups. Compared to the general population, the cardiovascular risk group showed slightly higher levels of depressive symptomatology even at the beginning of the pandemic and may be supported by addressing perceived social support and resilience in prevention programs targeting mental health.
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    Predictors of psychological distress in Syrian refugees with posttraumatic stress in Germany
    (Public Library of Science (PLoS), 2021-08-04) Renner A; Jäckle D; Nagl M; Hoffmann R; Röhr S; Jung F; Grochtdreis T; Dams J; König H-H; Riedel-Heller S; Kersting A
    Syria has been the main country of citizenship of refugees in Germany since 2013. Syrians face numerous human rights violations in their country that can be accompanied by the experience of potentially traumatic events, loss and displacement. Along the migration process, refugees are exposed to various factors that can have an impact on mental health. The aim of this study is to investigate sociodemographic, war- and flight-related as well as post-migration factors as predictors of posttraumatic stress, depression, somatization and anxiety in Syrian refugees with posttraumatic stress symptoms based in Germany. Data were based on the baseline sample of the “Sanadak” randomized-controlled trial. A total of 133 adult Syrian refugees participated in the study. A questionnaire covered sociodemographic and flight-related questions as well as standardized instruments for symptoms of PTSD (PDS-5), depression (PHQ-9), somatization (PHQ-15), anxiety (GAD-7), generalized self-efficacy (GSE), religiousness (Z-Scale), social support (ESSI) and mental health stigma (SSMIS-SF). Linear regression models were executed to predict mental health outcomes. Sociodemographic predictors (i.e., female sex, higher education) and flight-related predicting factors (i.e., variability of traumatic events) have a negative impact on mental health in Syrian refugees with posttraumatic stress symptoms in Germany. Mental health stigma predicts worse mental health outcomes. Post-migration factors have a major impact on mental health, such as low income, lack of social support, low life satisfaction or a strongly felt connection to Syria. Somatization is an important manifestation of mental distress in Syrian refugees with posttraumatic stress symptoms. Our study showed a range of factors predicting the mental health of Syrian refugees with posttraumatic stress symptoms. Measures to foster mental health could be securing financial security, promoting gender equality and tailored psychosocial programs addressing mental health stigma, loss and social support networks.
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    Traumatized Syrian Refugees with Ambiguous Loss: Predictors of Mental Distress
    (MDPI (Basel, Switzerland), 2021-04) Renner A; Jäckle D; Nagl M; Plexnies A; Röhr S; Löbner M; Grochtdreis T; Dams J; König H-H; Riedel-Heller S; Kersting A
    Refugees from war zones often have missing significant others. A loss without confirmation is described as an ambiguous loss. This physical absence with simultaneous mental persistence can be accompanied by economic, social or legal problems, boundary ambiguity (i.e., uncertainty about who belongs to the family system), and can have a negative impact on mental health. The aim of this study was to identify sociodemographic and loss-related predictors for prolonged grief, anxiety, depression, post-traumatic stress disorder (PTSD) and somatization in treatment-seeking Syrian refugees with post-traumatic stress symptoms in Germany experiencing ambiguous loss. For the present study, data were based on the treatment-seeking baseline sample of the “Sanadak” randomized-controlled trial, analyzing a subsample of 47 Syrian refugees with post-traumatic stress symptoms in Germany experiencing ambiguous loss. Sociodemographic and loss-related questions were applied, along with standardized instruments for symptoms of prolonged grief (ICG), anxiety (GAD-7), depression (PHQ-9), PTSD (PDS-5) and somatization (PHQ-15). Linear regression models were used to predict mental health outcomes. Having lost a close family member and higher boundary ambiguity showed a statistically significant association with higher severity in prolonged grief. The overall model for somatization reached statistical significance, while no predictor independently did. Boundary ambiguity showed a statistically significant positive association with depression, while the overall model showed no statistically significant associations. Boundary ambiguity and missing family members seemed to be important predictors for prolonged grief. These findings support the importance of reunification programs and suggest an inclusion of the topic into psychosocial support structures, e.g., including psychoeducational elements on boundary ambiguity in support groups for traumatized individuals and families experiencing ambiguous loss. Further research is needed for a more detailed understanding of the impact of ambiguous loss on refugee populations.
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    Depression, anxiety and quality of life in subjects with atopic eczema in a population-based cross-sectional study in Germany
    (John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology, 2020-04) Treudler R; Zeynalova S; Riedel-Heller SG; Zuelke AE; Roehr S; Hinz A; Glaesmer H; Kage P; Loeffler M; Simon JC
    Background Atopic eczema (AE) may be associated with several mental health problems. In Germany, existing data from selected patient cohorts may lead to misestimation of the problem. Objectives We aimed to cross-sectionally determine associations of AE with depression, anxiety, quality of life (QoL) and social interactions in subjects from the population-based LIFE-Adult-Study. Methods Subjects underwent standardized interviews (medical history) and answered standardized questionnaires [Centre of Epidemiologic studies-Depression scale (CES-D), Generalized Anxiety Disorder (GAD-7), Lubben Social Network Scale (LSNS), Short Form Health Survey (SF-8)]. We compared data from subjects with AE with those from subjects with selected other chronic/disabling diseases (cardiovascular, diabetes, cancer) and adjusted for selected sociodemographic parameters. Multivariate binary logistic regression was used for categorical variables, linear regression for continuous variables. Results Out of 9104 adults included (57% female, median age 54 years), 372 (4.1%) had a history of AE. Compared with controls, subjects with AE showed higher scores for depressive symptoms (9.3% vs. 6.3%; P < 0.001) and anxiety (8.4% vs. 5.6%, P < 0.001). Odds ratio (OR) was 1.5 [CI 1.0; 2.3] (P = 0.031) for depression, which was comparable to OR in patients with a history of cancer (OR 1.6 [1–2.3], P = 0.001. OR for anxiety in AE was 1.5 [1.0; 2.2], P < 0.049, which was slightly higher than in diabetes mellitus (OR 1.2) and stroke (OR 1.4). Other than in diabetes and/or stroke, we did not find a significant association between AE and social isolation. QoL scores were lower in AE than in controls (mean 46.9 vs. 48.0, P < 0.001 for physical and 50.6 vs. 52.5, P < 0.001 for mental components). Conclusions Subjects with AE showed higher values for depression and anxiety as well as lower QoL scores compared to controls. With regard to depression, odds in AE and cancer were hardly different. Medical care of AE patients should therefore include mental health evaluation and treatment if indicated.
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    Social isolation, mental health, and use of digital interventions in youth during the COVID-19 pandemic: A nationally representative survey
    (Cambridge University Press on behalf of the European Psychiatric Association, 2021) Rauschenberg C; Schick A; Goetzl C; Roehr S; Riedel-Heller SG; Koppe G; Durstewitz D; Krumm S; Reininghaus U
    Background Public health measures to curb SARS-CoV-2 transmission rates may have negative psychosocial consequences in youth. Digital interventions may help to mitigate these effects. We investigated the associations between social isolation, COVID-19-related cognitive preoccupation, worries, and anxiety, objective social risk indicators, and psychological distress, as well as use of, and attitude toward, mobile health (mHealth) interventions in youth. Methods Data were collected as part of the “Mental Health And Innovation During COVID-19 Survey”—a cross-sectional panel study including a representative sample of individuals aged 16–25 years (N = 666; Mage = 21.3; assessment period: May 5, 2020 to May 16, 2020). Results Overall, 38% of youth met criteria for moderate or severe psychological distress. Social isolation worries and anxiety, and objective risk indicators were associated with psychological distress, with evidence of dose–response relationships for some of these associations. For instance, psychological distress was progressively more likely to occur as levels of social isolation increased (reporting “never” as reference group: “occasionally”: adjusted odds ratio [aOR] 9.1, 95% confidence interval [CI] 4.3–19.1, p < 0.001; “often”: aOR 22.2, CI 9.8–50.2, p < 0.001; “very often”: aOR 42.3, CI 14.1–126.8, p < 0.001). There was evidence that psychological distress, worries, and anxiety were associated with a positive attitude toward using mHealth interventions, whereas psychological distress, worries, and anxiety were associated with actual use. Conclusions Public health measures during pandemics may be associated with poor mental health outcomes in youth. Evidence-based digital interventions may help mitigate the negative psychosocial impact without risk of viral infection given there is an objective need and subjective demand.