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Abstract There is a lack of knowledge regarding the relationship between proneness to dimensional psychopathological syndromes and the underlying pathogenesis across major psychiatric disorders, i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizoaffective Disorder (SZA), and Schizophrenia (SZ). Lifetime psychopathology was assessed using the OPerational CRITeria (OPCRIT) system in 1,038 patients meeting DSM-IV-TR criteria for MDD, BD, SZ, or SZA. The cohort was split into two samples for exploratory and confirmatory factor analyses. All patients were scanned with 3-T MRI, and data was analyzed with the CAT-12 toolbox in SPM12. Psychopathological factor scores were correlated with gray matter volume (GMV) and cortical thickness (CT). Finally, factor scores were used for exploratory genetic analyses including genome-wide association studies (GWAS) and polygenic risk score (PRS) association analyses. Three factors (paranoid-hallucinatory syndrome, PHS; mania, MA; depression, DEP) were identified and cross-validated. PHS was negatively correlated with four GMV clusters comprising parts of the hippocampus, amygdala, angular, middle occipital, and middle frontal gyri. PHS was also negatively associated with the bilateral superior temporal, left parietal operculum, and right angular gyrus CT. No significant brain correlates were observed for the two other psychopathological factors. We identified genome-wide significant associations for MA and DEP. PRS for MDD and SZ showed a positive effect on PHS, while PRS for BD showed a positive effect on all three factors. This study investigated the relationship of lifetime psychopathological factors and brain morphometric and genetic markers. Results highlight the need for dimensional approaches, overcoming the limitations of the current psychiatric nosology.

Abstract Estuaries play an important role in connecting the global carbon cycle across the land-to-ocean continuum, but little is known about Australia’s contribution to global CO2 emissions. Here we present an Australia-wide assessment, based on CO2 concentrations for 47 estuaries upscaled to 971 assessed Australian estuaries. We estimate total mean (±SE) estuary CO2 emissions of 8.67 ± 0.54 Tg CO2-C yr−1, with tidal systems, lagoons, and small deltas contributing 94.4%, 3.1%, and 2.5%, respectively. Although higher disturbance increased water-air CO2 fluxes, its effect on total Australian estuarine CO2 emissions was small due to the large surface areas of low and moderately disturbed tidal systems. Mean water-air CO2 fluxes from Australian small deltas and tidal systems were higher than from global estuaries because of the dominance of macrotidal subtropical and tropical systems in Australia, which have higher emissions due to lateral inputs. We suggest that global estuarine CO2 emissions should be upscaled based on geomorphology, but should also consider land-use disturbance, and climate.

Light is critical to coral growth through endosymbiont photosynthesis but can also act with elevated temperatures to cause coral bleaching. When more light is absorbed than can be used for photosynthesis, elevated irradiance can damage symbiont photosynthetic machinery. Hence, solar-radiation management through shading has been suggested to alleviate coral bleaching during marine heatwaves. Acropora divaricata and Acropora kenti were tested at two temperatures with 30% shading and an unshaded control to determine the relative impacts of light and temperature on coral bleaching severity. The coral bleaching response was assessed by photochemical (pulse amplitude modulated fluorometry), physiological (symbiont density, chlorophyll a concentration, catalase activity, and lipid peroxidation), and physical (mean intensity of grey or ‘percentage whiteness’) markers. Shading significantly reduced the bleaching response in A. divaricata, whilst for some parameters A. kenti responded negatively to shade. In A. divaricata, shading prevented photochemical collapse up to the experiment’s maximum 4.4 degree-heating weeks (DHW). Biomarkers of coral bleaching stress responded to shade and water temperature at 4.4 DHW; catalase activity was greatest in the shaded and ambient temperature treatment. Shading did not reduce the effects of bleaching in A. kenti; the mean intensity of grey and light saturation coefficient was greatest in the shaded treatment. Shading did, however, reduce lipid peroxidation at 3 DHW. Our results suggest shading during thermal stress may only protect some coral species, highlighting the need to consider species-specific responses when evaluating the potential efficacy of coral bleaching interventions.

AimsImproved long-term survival has widened the treatment goals for adults with congenital heart disease (ACHD) by addressing parameters that impact mental well-being and exercise capacity. Depression, a frequent co-morbidity in ACHD, is linked to both. Whether successful treatment of depression also affects cardiac parameters is a matter of debate.MethodsThis prospective, cross-sectional, longitudinal study included N = 150 ACHD (mean age 35.2 ± 11.3 years, 57% male) at baseline (t0) and N = 114 at follow-up (mean follow-up: 4.8 ± 0.6 years; t1). Patients were interviewed using a structured clinical interview, and severity of depression was assessed using the Montgomery-Asperg Depression Scale (MADRS). Additional testing was performed using self-rating questionnaires concerning depression, anxiety and quality of life (QoL). Exercise capacity (VO2max) was assessed by symptom limited exercise testing.ResultsOf N = 33 patients diagnosed with depression at t0, N = 18 patients remitted and N = 15 were non-remitters. Remitters displayed significantly decreased anxiety (P = 0.013), improved global QoL (P = 0.002), and preserved VO2max (P = 0.958) at t1 compared to t0. This was associated with favourable health behaviour at t1 and stable body-mass-index. Contrarily, non-remitters reported further increased anxiety (P = 0.021) and no significant improvement in QoL (P = 0.405). VO2max declined significantly (P = 0.006) and body-mass-index increased (P = 0.004). Never-depressed patients showed no significant changes in anxiety (P = 0.415) or QoL (P = 0.211). VO2max decreased significantly (P

Ocean alkalinity enhancement (OAE) via the enhanced weathering of alkaline minerals is a promising carbon dioxide removal (CDR) technology. Theoretically, these includes iron and steel slags, although their dissolution kinetics in seawater are unknown. Here, we conducted lab-scale experiments to assess the alkalinity generation potential and dissolution kinetics of various slags in seawater. We show that the alkalinity generated per mass of iron slag was logarithmic, i.e., higher amounts of iron slag added had diminishing alkalinity returns. In contrast, the relatively quick dissolution of steel slags and their linear generation of alkalinity per mass of feedstock dissolved in seawater makes them better OAE candidates. Furthermore, despite the presence of potentially toxic metals in these feedstocks, their low to non-existent presence as dissolution products suggests that harmful concentrations should not be reached, at least for the slag tested here. Finally, if all steel slag produced annually was used for OAE, between 10 and 22 gigatonnes of CO2 could be captured cumulatively by 2,100, highlighting significant CDR potential by slags.

Background: Multivariate data-driven statistical approaches offer the opportunity to study multi-dimensional interdependences between a large set of biological parameters, such as high-dimensional brain imaging data. For gyrification, a putative marker of early neurodevelopment, direct comparisons of patterns among multiple psychiatric disorders and investigations of potential heterogeneity of gyrification within one disorder and a transdiagnostic characterization of neuroanatomical features are lacking. Methods: In this study we used a data-driven, multivariate statistical approach to analyze cortical gyrification in a large cohort of N = 1028 patients with major psychiatric disorders (Major depressive disorder: n = 783, bipolar disorder: n = 129, schizoaffective disorder: n = 44, schizophrenia: n = 72) to identify cluster patterns of gyrification beyond diagnostic categories. Results: Cluster analysis applied on gyrification data of 68 brain regions (DK-40 atlas) identified three clusters showing difference in overall (global) gyrification and minor regional variation (regions). Newly, data-driven subgroups are further discriminative in cognition and transdiagnostic disease risk factors. Conclusions: Results indicate that gyrification is associated with transdiagnostic risk factors rather than diagnostic categories and further imply a more global role of gyrification related to mental health than a disorder specific one. Our findings support previous studies highlighting the importance of association cortices involved in psychopathology. Explorative, data-driven approaches like ours can help to elucidate if the brain imaging data on hand and its a priori applied grouping actually has the potential to find meaningful effects or if previous hypotheses about the phenotype as well as its grouping have to be revisited.

ObjectiveAdult congenital heart disease (ACHD) is a growing disease entity, posing questions concerning psychosocial outcomes across the lifespan. Spousal relationships were shown to benefit cardiovascular and mental health in the general population. We assessed the association of relationship status with anxiety and depression in ACHD patients and determined whether patients considered disease-related concerns potential mediators of relationship problems.MethodsN = 390 ACHD patients were included. Self-report questionnaires were used to assess relationship status, ACHD-related relationship problems, socio-demographic variables, and depression and anxiety scores. Further, clinical parameters concerning the heart condition were determined.ResultsN = 278 (71%) patients were currently in a relationship, while N = 112 (29%) were not in a relationship. Groups did not significantly differ regarding age, sex, and cardiovascular parameters. Two-way MANCOVA with relationship status and sex as independent variables, controlling for age, NYHA class, and NT-proBNP, showed an association of relationship status with depression, while sex was associated with anxiety. N = 97 (25%) patients reported disease-related adverse effects on a current or prior relationship. In detail, worries about body image (N = 57, 61%), own fears (N = 51, 54%), problems arising from wish to have children (N = 33, 35%), fears regarding a joint future (N = 29, 31%), partner’s fears or lack of understanding (N = 28, 30%), and sexual problems (N = 21, 22%) were cited.ConclusionRelationships status was associated with depression, while sex was associated with anxiety in ACHD patients. Relationship status as well as potential relationship problems, and the importance of social support for mental and physical well-being, should be considered when treating ACHD patients.

Ocean artificial upwelling has been suggested to boost primary production and increase harvestable resources such as fish. Yet, for this ecosystem-based approach to work, an effective energy transfer up the food web is required. Here, we studied the trophic role of microzooplankton under artificial upwelling via biomass and community composition as well as grazing rates on phytoplankton. Using mesocosms in the oligotrophic ocean, we supplied nutrient-rich deep water at varying intensities (low to high) and addition modes (a Singular large pulse or smaller Recurring pulses). Deep-water fertilization created a diatom-dominated bloom that scaled with the amount of inorganic nutrients added, but also Synechococcus-like cells, picoeukaryotes and nanophytoplankton increased in abundance with added nutrients. After 30 days, towards the end of the experiment, coccolithophores bloomed under recurring upwelling of high intensity. Across all upwelling scenarios, the microzooplankton community was dominated by ciliates, dinoflagellates (mixo- and heterotrophic) and radiolarians. Under the highest upwelling intensity, the average grazing rates of Synechococcus-like cells, picoeukaryotes and nanophytoplankton by microzooplankton were 0.35 d-1 ± 0.18 (SD), 0.09 d-1 ± 0.12 (SD), and 0.11 d-1 ± 0.13 (SD), respectively. There was little temporal variation in grazing of nanophytoplankton but grazing of Synechococcus-like cells and picoeukaryotes were more variable. There were positive correlations between abundance of these groups and grazing rates, suggesting a response in the microzooplankton community to prey availability. The average phytoplankton to microzooplankton ratio (biovolume) increased with added deep water, and this increase was highest in the Singular treatment, reaching ~30 (m3 m-3), whereas the phytoplankton to total zooplankton biomass ratio (weight) increased from ~1 under low upwelling to ~6 (g g-1) in the highest upwelling but without a difference between the Singular and the Recurring mode. Several smaller, recurring upwelling events increased the importance of microzooplankton compared with one large pulse of deep water. Our results demonstrate that microzooplankton would be an important component for trophic transfer if artificial upwelling would be carried out at scale in the oligotrophic ocean.

BackgroundMany patients with cardiovascular disease also show a high comorbidity of mental disorders, especially such as anxiety and depression. This is, in turn, associated with a decrease in the quality of life. Psychocardiological treatment options are currently limited. Hence, there is a need for novel and accessible psychological help. Recently, we demonstrated that a brief face-to-face metacognitive therapy (MCT) based intervention is promising in treating anxiety and depression. Here, we aim to translate the face-to-face approach into digital application and explore the feasibility of this approach.MethodsWe translated a validated brief psychocardiological intervention into a novel non-blended web app. The data of 18 patients suffering from various cardiac conditions but without diagnosed mental illness were analyzed after using the web app over a two-week period in a feasibility trial. The aim was whether a non-blended web app based MCT approach is feasible in the group of cardiovascular patients with cardiovascular disease.ResultsOverall, patients were able to use the web app and rated it as satisfactory and beneficial. In addition, there was first indication that using the app improved the cardiac patients’ subjectively perceived health and reduced their anxiety. Therefore, the approach seems feasible for a future randomized controlled trial.ConclusionApplying a metacognitive-based brief intervention via a non-blended web app seems to show good acceptance and feasibility in a small target group of patients with CVD. Future studies should further develop, improve and validate digital psychotherapy approaches, especially in patient groups with a lack of access to standard psychotherapeutic care.

Abstract Previous studies have indicated that glabellar botulinum toxin (BTX) injections may lead to a sustained alleviation of depression. This may be accomplished by the disruption of a facial feedback loop, which potentially mitigates the experience of negative emotions. Accordingly, glabellar BTX injection can attenuate amygdala activity in response to emotional stimuli. A prototypic condition with an excess of negative emotionality and impulsivity accompanied by elevated amygdala reactivity to emotional stimuli is borderline personality disorder (BPD). In order to improve the understanding of how glabellar BTX may affect the processing of emotional stimuli and impulsivity, we conducted a functional magnetic resonance imaging (fMRI) study. Our hypotheses were (1) glabellar BTX leads to increased activation in prefrontal areas during inhibition performance and (2) BTX decreases amygdala activity during the processing of emotional stimuli in general. Using an emotional go-/no-go paradigm during fMRI, the interference of emotion processing and impulsivity in a sample of n = 45 women with BPD was assessed. Subjects were randomly assigned to BTX treatment or serial acupuncture (ACU) of the head. After 4 weeks, both treatments led to a reduction in the symptoms of BPD. However, BTX treatment was specifically associated with improved inhibition performance and increased activity in the motor cortex. In addition, the processing of negative emotional faces was accompanied by a reduction in right amygdala activity. This study provides the first evidence that glabellar BTX injections may modify central neurobiological and behavioural aspects of BPD. Since the control treatment produced similar clinical effects, these neurobiological findings may be specific to BTX and not a general correlate of symptomatic improvement.

Abstract Former prospective studies showed that the occurrence of relapse in Major Depressive Disorder (MDD) is associated with volume loss in the insula, hippocampus and dorsolateral prefrontal cortex (DLPFC). However, these studies were confounded by the patient’s lifetime disease history, as the number of previous episodes predict future recurrence. In order to analyze neural correlates of recurrence irrespective of prior disease course, this study prospectively examined changes in brain structure in patients with first-episode depression (FED) over 2 years. N = 63 FED patients and n = 63 healthy controls (HC) underwent structural magnetic resonance imaging at baseline and after 2 years. According to their disease course during the follow-up interval, patients were grouped into n = 21 FED patients with recurrence (FEDrec) during follow-up and n = 42 FED patients with stable remission (FEDrem). Gray matter volume changes were analysed using group by time interaction analyses of covariance for the DLPFC, hippocampus and insula. Significant group by time interactions in the DLPFC and insula emerged. Pairwise comparisons showed that FEDrec had greater volume decline in the DLPFC and insula from baseline to follow-up compared with FEDrem and HC. No group by time interactions in the hippocampus were found. Cross-sectional analyses at baseline and follow-up revealed no differences between groups. This longitudinal study provides evidence for neural alterations in the DLPFC and insula related to a detrimental course in MDD. These effects of recurrence are already detectable at initial stages of MDD and seem to occur without any prior disease history, emphasizing the importance of early interventions preventing depressive recurrence.

IntroductionAdopting an active lifestyle is an important goal, but can be difficult to achieve for people with depressive disorders. Current guidelines recommend the integration of physical activity in the multimodal treatment of depressive disorders. However, the possibilities to provide individual support for physical activities are frequently limited. The aim of our study was to examine how physical activity can be increased in a real-world setting by combining physical training and psychological interventions.Materials and methodsIn this randomized-controlled interventional study, 31 outpatients diagnosed with moderate to severe depression were recruited from the region of Hannover. The intervention group (n = 16) was offered six weekly individual sessions lasting between 60 and 90 min with a sports scientist, including Motivational Interviewing and accompanied exercise activities. The control group (n = 15) received a written booklet with information on steps toward becoming more active. Moderate-to-vigorous physical activity (MVPA) as the primary outcome was analyzed using activity sensors before and after the 6-week intervention, and 3 months subsequently. Secondary outcomes included the Six-Minute Walk Test (6MWT), Sit-to-Stand test (STS), and mental health assessed with self-rating questionnaires.ResultsIn the intervention group, MVPA increased significantly between baseline and the first follow-up and remained at an increased level at the second follow-up in comparison to decreased levels in the control group (difference of 15.5 min/day between groups over time, SE = 6.2 min/day, 95%-CI[2.7, 28.3], p = 0.020). The increased activity level was associated with markers of increased fitness (6MWT and STS) in the intervention group. Both groups showed comparable improvements in depressive symptoms, while the number of patients receiving antidepressants increased in the control group and decreased in the intervention group. Two patients dropped out of the intervention group during the trial.ConclusionThe intervention proved to be a feasible and effective aid to promote a physically active lifestyle for patients diagnosed with depression. Furthermore, the higher level of physical activity was maintained for the follow-up period. Given the success of the approach evaluated in this project, individual support for physical activity should be investigated in larger sample sizes and potentially be considered in the multimodal treatment of depression.Clinical trial registration[https://clinicaltrials.gov/], identifier [DRKS00023257].

Abstract Major depressive disorder (MDD) is frequently associated with poor response to treatment. Common antidepressants target neurotransmission and neuronal plasticity, which require adequate energy supply. As imaging studies indicate disturbances in central energy metabolism, and caloric restriction improves neuroplasticity and impacts mood and cognition, correction of energy status might increase the effectiveness of antidepressant treatments and reduce the psychopathological symptoms of depression. Metabolic parameters, stress hormones, and brain-derived neurotrophic factor (BDNF) levels were assessed in serum of depressed inpatients (MDD, N = 21) and healthy volunteers (Ctrl, N = 28) before and after a 72 h fasting period during which only water was consumed. Depression severity was assessed by Beck’s Depression Inventory (BDI)-2 sum-score and cognitive-affective and somatic sub-scores. Fasting similarly impacted metabolic parameters and stress systems in both groups. Fasting elevated BDI-2 sum-scores and somatic sub-scores in Ctrl. In MDD, fasting increased somatic-, but decreased cognitive-affective symptoms. Sub-group analyses based on BDI-2 sum-scores pre-fasting showed that cognitive-affective symptoms decreased in patients with moderate/severe but not in those with mild symptoms. This was associated with differential changes in BDNF levels. In conclusion, fasting improved cognitive-affective sub-scores in MDD patients with moderate/severe symptoms that had not responded to prior therapy. Interventions that modulate energy metabolism might directly improve cognitive-affective symptoms and/or augment therapeutic efficacy in moderate-to-severely depressed patients.

Abstract Background Hospital physicians have an increased risk for post-traumatic stress caused by work-related trauma. This study examines the frequency of reported traumatic events (TE), post-traumatic stress (PTS) and its possible consequences for the mental state and work ability of physicians at a university hospital. Methods As part of the mandatory psychological risk assessment, n = 145 physicians (n = 56 female; 38.6%) were examined at a university hospital in Germany in a cross sectional study. TE, PTS and symptoms of depression and anxiety were assessed using the self-report questionnaires “Freiburger Screening Fragebogen to identify patients at risk for the development of a post-traumatic stress disorder in the group of severely injured patients” (PTBS-13), the “Patient Health Questionnaire” (PHQ-2) and the “Generalized Anxiety Disorder scale” (GAD-2). Work ability was assessed using a modified version of the questionnaire for workplace analysis (KFZA). The response rate was 52%. Results Traumatic events were experienced by n = 125 physicians (86.2%) throughout their whole career. Of these, 19 physicians (15.2%) reported PTS. PTS is reported by 12 of 56 female physicians (63.2%), compared to 7 of 89 reports of PTS by male physicians (36.8%). Physicians with PTS symptoms had higher depression scores (p = 0.007) compared to physicians without TE or with TE, but without PTS. Physicians with PTS reported significantly reduced work ability caused by constantly interrupted work (p = 0.03). Female gender was the greatest risk factor for the development of PTS. (p = 0.001). Conclusions Physicians – especially females – with PTS may have an increased risk of developing depressive symptoms. Therefore, interventions aimed at reducing trauma-related stress symptoms may be helpful in improving mental health of hospital physicians. Further studies with more physicians from different hospitals are necessary to support the results.

IntroductionThe Attention Training Technique (ATT) developed as part of metacognitive therapy is a psychotherapeutic treatment method used to enhance top-down attentional flexibility and control. This study investigated potential neurocognitive changes due to ATT and its underlying neural mechanisms using pre-to-post functional magnetic resonance imaging (fMRI).Materials and methodsFifty-four healthy participants were subjected to a randomized, sham-controlled attention training and evaluated using a neurocognitive test battery that partly took place in an fMRI environment. Participants received two doses ATT or sham ATT daily for 1 week. On day eight, all subjects completed the neurocognitive test battery again.ResultsAfter the training, the ATT group showed a significant improvement in reaction times regarding attentional disengagement compared to the sham ATT group. fMRI data showed decreased levels of activation in the anterior cingulate cortex (ACC) when comparing the ATT group to the sham ATT group during attentional disengagement post intervention. No ATT > sham ATT effects were found regarding selective auditory attention, working memory performance and inhibitory control.DiscussionThese findings putatively indicate that ATT facilitates faster attention allocation and increased attentional flexibility in healthy subjects. The fMRI results suggest this ATT-dependent improvement is accompanied by reduced ACC activity, indicating a more flexible attentional state.

IntroductionQTc prolongation carries the risk of ventricular tachyarrhythmia (Torsades de Pointes) and sudden cardiac death. Psychotropic drugs can affect ventricular repolarization and thus prolong the QTc interval. The present study sought to investigate the risk factors (pharmacological and non-pharmacological) of severe QTc prolongation in gerontopsychiatric patients.MethodsElectrocardiograms of patients on a gerontopsychiatric ward were screened for QTc prolongation. Medication lists were examined utilizing the AzCERT classification. Potential drug interactions were identified with the electronic drug interaction program mediQ.ResultsThe overall prevalence of QTc prolongation was 13.6%, with 1.9% displaying severe QTc prolongation (≥ 500 ms). No statistically significant differences between patients with moderate and severe QTc prolongation were identified; however, patients with severe QTc prolongation tended to take more drugs (p = 0.063). 92.7% of patients with QTc prolongation took at least one AzCERT-listed drug, most frequently risperidone and pantoprazole. Risperidone and pantoprazole, along with pipamperone, were also most frequently involved in potential drug interactions. All patients displayed additional risk factors for QTc prolongation, particularly cardiac diseases.ConclusionIn addition to the use of potentially QTc-prolonging drugs, other risk factors, especially cardiac diseases, appear to be relevant for the development of QTc prolongation in gerontopsychiatric patients. Pantoprazole was frequently involved in potential drug interactions and should generally not be used for more than 8 weeks in geriatric populations. As clinical consequences of QTc prolongation were rare, potentially QTc-prolonging drugs should not be used overcautiously; their therapeutic benefit should be considered as well. It is paramount to perform diligent benefit–risk analyses prior to the initiation of potentially QTc-prolonging drugs and to closely monitor their clinical (side) effects.

ObjectiveMajor depressive disorder (MDD) constitutes a main risk factor for suicide. Suicide risk in psychiatric patients is primarily determined by often unreliable, self-reported information. We assessed serum levels of three microRNAs (miRNAs), previously demonstrated to be dysregulated in post-mortem brain samples of suicide victims, as potential peripheral biomarkers for suicidality.MethodsAll study participants were diagnosed with MDD according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria. Suicidality, defined as acute suicide risk or suicide attempt within one week prior to study entry, was assessed by clinical interview. Relative serum levels of miR-30a, miR-30e, and miR-200a, normalized to U6, were measured by quantitative real-time PCR in MDD inpatients with (MDD/SI, N = 19) and without (MDD, N = 31) acute suicide risk. Median age and gender distribution were comparable in both groups.ResultsLevels of miR-30a, miR-30e, and miR-200a were significantly elevated in MDD/SI compared to MDD. Subgroup analysis of the MDD/SI group showed that levels of miR-30e and miR-200a were significantly higher and miR-30a was increased by trend in patients admitted following a suicide attempt (N = 7) compared to patients with acute suicide risk but without recent suicide attempt (N = 12). Additionally, use of two databases for in silico transcription factor–miRNA interaction prediction indicated early growth response protein (EGR) 1 as potential transcriptional regulator for all three miRNAs.ConclusionThis study demonstrates suicide risk in MDD patients to be associated with increased levels of miR-30a, miR-30e, and miR-200a. Thus, these miRNAs might constitute potential biomarkers to predict suicidal behavior in MDD patients.

Climate change is expected to alter the intensity and frequency of upwelling in high productive coastal regions, thus impacting nutrient fluxes, primary productivity and consequently carbon cycling. However, it is unknown how these changes will impact the planktonic (phytoplankton and bacteria) community structure, which affects community respiration (CR) and hence the carbon available for sequestration or transfer to upper trophic levels. Here we present results from a 37-day mesocosm experiment where we examined the response of CR to nutrient additions by simulating upwelling events at different intensities (low, medium, high and extreme) and modes (singular and recurring additions). We also analysed the potential contribution of different plankton size classes and functional groups to CR. The trend in accumulated CR with respect to nutrient fertilisation (total nitrogen added during the experiment) was linear in the two modes. Microplankton (mostly diatoms) and nanoplankton (small flagellates) dominated under extreme upwelling intensities and high CR in both singular and recurring upwelling modes, explaining >65% of the observed variability in CR. In contrast, prokaryotic picoplankton (heterotrophic bacteria and autotrophic cyanobacteria) explained

Background and aimAdverse childhood experiences (ACEs) are a major risk factor for unfavorable behavioral, mental and health outcomes later in life. However, the precise pathway via which ACEs convey these risks, in particular regarding health outcomes such as cardiovascular disease, remains unknown. Here, we combined psychiatric and cardiac methods to investigate the pathway via which childhood adversities may lead to adult adverse cardiovascular health, with a focus on epicardial adipose tissue (EAT) as a risk marker.Methods210 adult congenital heart disease outpatients (mean age 35.5 y, 43% female) completed a thorough cardiac and psychiatric evaluation. Psychiatric measurements included an expert interview, the childhood trauma questionnaire (CTQ), Beck's depression inventory II (BDI-II), quality of life and the global scale of functioning, amongst others. All patients completed a full cardiac workup including EAT assessment using echocardiography. We then computed bootstrapping mediation models using ACEs as a predictor, depression and physical activity as mediators and EAT as dependent variable in PROCESS.ResultsCTQ scores had a significant indirect effect on EAT via a serial mediation of BDI and physical activity [a*b2*d = 0.0260, 95% BCa CI [0.0047, 0.0619]].ConclusionUsing mediation analyses, we show that adverse childhood events are linked to increased depressive symptoms, which are linked to decreased physical activity, which in turn are linked to a higher amount of epicardial adipose tissue. While other pathways most certainly exist and replication is needed, this suggests a meaningful pathway via which ACEs lead to adverse cardiovascular health, with several potential targets for health interventions across time.

Introduction: DNA methylation constitutes one important epigenetic mechanism that regulates gene expression in human cells. With regard to obesity, bariatric surgery-induced weight loss has been associated with promoter methylation changes in several genes. Hyperleptinemia is a characteristic feature of obesity. The underlying regulating mechanisms have not yet been completely elucidated. Methods: We investigated the methylation of the promoters of the leptin gene (LEP) and the leptin receptor gene (LEPR) as well as leptin expression in pre- and postbariatric surgery patients using a comparative cross-sectional design. Results: Our results revealed significantly higher LEP promoter methylation patterns in prebariatric surgery patients compared to postoperatively. DNA methylation of the LEPR promoter was significantly higher in the postoperative group. Moreover, we found significantly higher leptin serum levels in patients before the bariatric surgery than afterwards. Discussion: These findings strengthen the suggestion that there is an association between LEP expression and LEP methylation in obesity. We suggest that the epigenetic profile of LEP might be influenced by leptin serum levels in the form of a regulating feedback mechanism.

BackgroundHeart failure (HF) is associated with development of depressive symptoms and reduced quality of life (QoL). Patients with HF and an implantable cardioverter-defibrillator (ICD) were evaluated regarding depressive symptoms and QoL.MethodsThe present study included 446 patients with HF and an ICD. Depressive symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9), QoL was evaluated using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Functional ability and exercise tolerance were assessed at inclusion and after 6 months with help of the 6-min walking test (6MWT).ResultsPatients included in the study had a mean age of 65.8 years and were predominantly male (83.6%), with mostly ischemic (n = 277; 62.1%) or dilated (n = 150; 33.6%) cardiomyopathy. One hundred ninety-three (43.2%) patients had depressive symptoms, of whom 75 patients (16.8%) were classified as moderate to severe depression according to the PHQ-9 at baseline. Depressive symptoms were associated with low QoL independent of NYHA functional class. High NYHA functional class, high PHQ-9 score, age and body mass index (BMI) were associated with a lower 6MWT at enrollment, while depressive symptoms (expressed as higher PHQ-9 score) and age were associated with a lower 6MWT after 6 months. Patients with history of smoking and a higher BMI showed higher PHQ-9 scores after 6 months. Patients under antidepressant medication showed improved PHQ-9 score after 6 months, indicating controlled/treated depression. However, patients with low QoL at inclusion remained with low QoL after 6 months.ConclusionDepressive symptoms correlate with low QoL and lower long-term functional status in patients with HF and an ICD. Depressive symptoms are associated with smoking and obesity, which themselves are risk factors for a poor prognosis in HF. Only a small fraction of patients with HF and ICD showing depressive symptoms receives appropriate treatment. Assessing depressive symptoms and lifestyle factors should be part of a multimodal treatment plan in patients with HF and an ICD.

Earth’s Radiation Budget is partly dictated by the fragile and complex balance between biogenic volatile organic compounds (BVOCs) and greenhouse gases (GHGs), which have the potential to impose cooling or warming once emitted to the atmosphere. Whilst methane (CH4) is strictly associated with global warming due to its solar-radiation absorbing properties, dimethyl sulfide (DMS) is generally considered a cooling gas through the light scattering properties of its atmospheric oxidation products. However, DMS may also partially contribute to the Earth’s warming through a small portion of it being degraded to CH4 in the water column. Coral reefs emit both DMS and CH4 but they have not previously been simultaneously measured. Here, we report DMS and CH4 fluxes as well as aerosol particle counts at Heron Island, southern Great Barrier Reef, during the austral summer of 2016. Sea-to-air DMS and CH4 fluxes were on average 24.9 ± 1.81 and 1.36 ± 0.11 µmol m-2 d-1, whilst intermediate (< 0.5-2.5 um) and large (> 2.5 um) particle number concentrations averaged 5.51 x 106 ± 1.73 x 105 m-3 and 1.15 x 106 ± 4.63 x 104 m-3, respectively. Positive correlations were found between DMS emissions and the abundance of intermediate (R2 = 0.1669, p < 0.001, n = 93) and large (R2 = 0.0869, p = 0.004, n = 93) aerosol particles, suggesting that DMS sea-to-air emissions significantly contribute to the growth of existing particles to the measured size ranges at the Heron Island lagoon. Additionally, a strong positive correlation was found between DMS and CH4 fluxes (R2 = 0.7526, p < 0.00001, n = 93), suggesting that the emission of these volatile compounds from coral reefs is closely linked. The slope of the regression between DMS and CH4 suggests that CH4 emissions at the Heron Island lagoon represent 5% of that of DMS, which is consistent with the average sea-to-air fluxes reported in this study (i.e. 24.9 ± 1.81 µmol m-2 d-1 for DMS and 1.36 ± 0.11 for CH4). These findings provide new insights on the complexity of BVOC and GHG emissions in coral reef systems and their potential role in climate regulation.

Abstract Breast cancer is the most prevalent malignancy amongst women worldwide while ovarian cancer represents the leading cause of death among gynecological malignancies. Women suffering from these cancers displayed heightened rates of major depressive disorder, and antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs) is frequently recommended. Recently, narrative reviews and meta-analyses showed increased recurrence risks and mortality rates in SSRI-treated women with breast and ovarian cancer. We therefore examined whether three commonly prescribed SSRIs, fluoxetine, sertraline and citalopram, affect proliferation or glucose uptake of human breast and ovarian cancer cell lines characterized by different malignancies and metastatic potential. SSRI treatment or serotonin stimulation with therapeutically relevant concentrations over various time periods revealed no consistent dose- or time-dependent effect on proliferation rates. A marginal, but significant increase in glucose uptake was observed in SK-OV-3 ovarian cancer cells upon fluoxetine or sertraline, but not citalopram treatment. In three breast cancer cell lines and in two additional ovarian cancer cell lines no significant effect of SSRIs on glucose uptake was observed. Our data suggest that the observed increase in recurrence- and mortality rates in SSRI-treated cancer patients is unlikely to be linked to antidepressant therapies.

Abstract Aims Peripartum cardiomyopathy (PPCM) is a heart disease affecting women during the last month of pregnancy or in the first months after delivery. The impact of the disease on mental health is largely unknown. Methods and results Major mental disorders were assessed by a structured clinical interview in 40 patients with a confirmed PPCM diagnosis, and the data were compared with published prevalence in postpartum women. Circulating biomarkers associated with mental health, such as kynurenine, serotonin, and microRNA (miR)‐30e, were evaluated in PPCM and compared with matched healthy pregnancy‐matched postpartum controls (PP‐Ctrl). Major mental disorders were diagnosed in 65% (26/40) of the PPCM cohort. The prevalence for major depressive disorders was 4‐fold, for post‐traumatic stress disorder 14‐fold, and for panic disorder 6‐fold higher in PPCM patients compared with postpartum women without a PPCM diagnosis. Compared with PP‐Ctrl, PPCM patients displayed elevated levels of serum kynurenine (P

Abstract Background Several studies have shown the effectiveness of Metacognitive Therapy (MCT) in treating different mental disorders. Most of these studies were performed in English speaking countries using the original English version of the manual. Our study aimed to examine the feasibility of the translated MCT manual in a sample of German patients with major depressive disorder. Methods Twenty outpatients (6 male, 14 female, mean age 42.1y) with major depressive disorder were included. The main outcome was drop-out rate and satisfaction with the treatment; secondary outcomes were changes in metacognitive beliefs assessed with the metacognitive questionnaire 30 (MCQ-30), and symptom reduction measured with the Beck Depression Inventory-2 sum score (BDI-2). Results No drop-outs during the treatment and the follow-up phase were observed. Patients and therapists were highly satisfied with MCT treatment. The MCQ-30 significantly declined over the treatment course, paralleled by a significant reduction of the BDI-2 sum scores (from 29 ± 8.6 at T0 to 8.4 ± 9.6 at the end of treatment). The average treatment duration was 10 ± 4 sessions. Conclusions Applying the German version of the manual for Metacognitive Therapy proved to be feasible in the treatment of depressed patients in an outpatient setting. The treatment was well tolerated by German patients. Outcome in terms of reduction of depressive symptoms was good. Remarkable is the comparably short treatment duration which should be investigated further in future studies. Trial registration German Clinical Trials Register (DRKS): DRKS00023644, 17.11.2020 (retrospectively registered).

The neurobiological and behavioral underpinnings linking mental disorders, in particular, major depressive disorder (MDD), with cardiovascular disorders are a matter of debate. Recent research focuses on visceral (intra-abdominal and epicardial) adipose tissue and inflammation and their impact on the development of cardiometabolic disorders. Intra-abdominal adipose tissue is defined as an endocrine active fat compartment surrounding inner organs and is associated with type 2 diabetes mellitus, a risk factor for the later development of cardiovascular disorders. Epicardial (pericardial) adipose tissue is a fat compartment surrounding the heart with close proximity to the arteries supporting the heart. Visceral adipose tissue (VAT) is an important source of inflammatory mediators that, in concert with other risk factors, plays a leading role in cardiovascular diseases. In conjunction with the behavioral (physical inactivity, sedentary lifestyle), psychological (adherence problems), and hormonal (dysfunction of the hypothalamus–pituitary–adrenal axis with subsequent hypercortisolism) alterations frequently accompanying MDD, an enhanced risk for cardiovascular disorders results.

BackgroundMental disorders are common among patients with severe cardiovascular diseases (CVD). Yet, there is a lack of easily accessible evidence-based treatments. Recent research indicates elevated prevalence of dysfunctional metacognitions in patients with mental disorders following cardiovascular events. As metacognitive therapy (MCT) is an established treatment to modify metacognitions, we tested if a brief metacognitive intervention via videotelephony is effective in this patient group.MethodsA brief MCT treatment was tailored to CVD patients and designed as a face-to-face internet-based intervention. Five patients with CVDs and comorbid mental disorders underwent a psychocardiological examination and diagnostic approach. Each patient participated in eight 50 min sessions via encrypted video messenger service. Metacognitions, depression and anxiety symptoms and quality of life were assessed by self-report measures pre- and post-treatment. Patients rated dysfunctional thought processes, current psychological impairment, and treatment satisfaction after each session. Intended follow-up measures were not reported due to missing data.ResultsFor most patients, the brief metacognitive intervention was associated with a decrease in dysfunctional metacognitions and a reduction of symptoms of anxiety and depression post-treatment. Psychological and physiological quality of life improved. Patients reported high satisfaction with the tailored treatment.ConclusionOur results suggest that a brief internet-based metacognitive treatment may be a promising tool for patients with CVDs and comorbid mental disorders. Feasibility and acceptance of the intervention was rated high by the patients. Further research is necessary to support the preliminary findings and to adapt and evaluate the intervention in a controlled clinical trial setting.

BackgroundThe prevalence of mental disorders, particularly adjustment disorder (AD), major depressive disorder (MDD) and panic disorder (PD) is increased in patients with pulmonary arterial hypertension (PAH). However, it is unclear which pathogenic mechanisms determine their development and could therefore be targeted in prevention or therapeutic interventions. Here, we assessed metacognitions in a sample of PAH patients with and without MDD and PD. Moreover, we reconstructed the course of mental illnesses following the PAH diagnosis.MethodsTwo hundred seventeen PAH patients were included in this cross-sectional study. The prevalence of AD was assessed retrospectively using DSM-V criteria. Current mental disorders were assessed using the structured clinical interview for DSM-V. Additionally, metacognitive beliefs and processes were assessed using established questionnaires (MCQ-30, AnTI).ResultsPatients with an AD consecutive to the PAH diagnosis more frequently developed MDD (37.5 vs. 13.9%, p < 0.001) and PD (26.3 vs. 8.8%, p = 0.001) later on compared to PAH patients without a former AD. Moreover, patients with current MDD/PD displayed more dysfunctional metacognitions than those without current MDD/PD (p < 0.001). Patients with current MDD/PD in the context of former AD had more dysfunctional metacognitive worries and beliefs compared to patients with current MDD/PD without former AD (p = 0.009).ConclusionOur results suggest that in the context of PAH, dysfunctional metacognitions are associated with MDD and PD. Therefore, a metacognitive approach to treat and prevent those mental illnesses seems promising and should be investigated in future studies.

ObjectivePulmonary hypertension (PH) is a chronic and progressive pulmonary vascular disease resulting in symptoms such as shortness of breath and fatigue and leading to death from right heart failure if not adequately treated. Chronic thromboembolic pulmonary hypertension (CTEPH) is a subgroup of PH characterized by obstruction or occlusion of pulmonary arteries by post-embolic fibrotic material. To date, few studies examined symptoms of depression and anxiety in patients with CTEPH, showing depression levels as high as 37.5%. However, none of the former studies used structured expert interviews.MethodsMental disorders were diagnosed using the Structured Clinical Interview for DSM-5 (SCID). The prevalence of mental disorders in patients with CTEPH were compared to the prevalence in patients with pulmonary arterial hypertension (PAH) and the general German population. Quality of life (QoL) was measured with World Health Organization (WHO) Quality of Life questionnaire (short form). Factors associated with QoL were analyzed with linear regression and the diagnostic value of the Hospital Anxiety and Depression Scale (HADS) was evaluated using receiver operating characteristics (ROC) curve analysis.ResultsHundred and seven patients with CTEPH were included. Almost one-third of the patients (31.8%) had current psychological disorders. Panic disorder (8.4%), specific phobia (8.4%), and major depressive disorder (6.5%) were the most prevalent mental illnesses. The prevalence of panic disorders was higher in CTEPH compared to the German population while major depressive disorder was fewer in CTEPH compared to PAH. The presence of mental disorders had a major impact on QoL. Hospital Anxiety and Depression Scale discriminated depression and panic disorder reliably.ConclusionMental disorders are common in patients with CTEPH and associated with an impaired QoL. The HADS may be a useful screening tool for panic and depression disorders in patients with CTEPH. Further research on therapeutic strategies targeting mental disorders in patients with CTEPH is needed.

Patients with mental disorders have an increased risk to develop cardiovascular disease (CVD), and CVD are frequently comorbid with especially adjustment, anxiety and depressive disorders. Therefore, clinicians need to be aware of effective and safe psychological and pharmacological treatment strategies for patients with comorbid CVD and mental disorders. Cognitive behavioral therapy and third-wave of cognitive-behavioral therapy are effective for patients with CVD and mental disorders. Internet-based psychological treatments may also be considered. In more severe cases, psychopharmacological drugs are frequently used. Although generally well tolerated and efficacious, drug- and dose-dependent side effects require consideration. Among antidepressants, selective serotonin reuptake inhibitors, selective serotonin and noradrenalin reuptake inhibitors, and newer antidepressants, such as mirtazapine, bupropion, agomelatine, and vortioxetine, can be considered, while tricyclic antidepressants should be avoided due to their cardiac side effects. Mood stabilizers have been associated with arrhythmias, and some first- and second-generation antipsychotics can increase QTc and metabolic side effects, although substantial differences exist between drugs. Benzodiazepines are generally safe in patients with CVD when administered short-term, and may mitigate symptoms of acute coronary syndrome. Laboratory and ECG monitoring is always recommended in psychopharmacological drug-treated patients with CVD. Presence of a heart disease should not exclude patients from necessary interventions, but may require careful risk-benefit evaluations. Effectively and safely addressing mental disorders in patients with CVD helps to improve both conditions. Since CVD increase the risk for mental disorders and vice versa, care providers need to screen for these common comorbidities to comprehensively address the patients’ needs.

IntroductionIn March 2020, the World Health organization declared COVID-19 a global pandemic. One year later, the direct and indirect burden of the COVID-19 pandemic become more visible. In this context, there is concern about the allocation of medical resources and medical treatment of other diseases than COVID-19. Particularly, patients with chronic diseases need constant medical and pharmacological treatment. Therefore, we evaluated a large cohort of patients with adult congenital heart disease (ACHD) regarding postponed medical appointments and their possibilities to receive medical treatment during the COVID-19 pandemic.MethodsThis cross-sectional study included 559 patients with ACHD (mean age 37.32 ± 11.98; 47% female). Clinical characteristics, answers to questionnaires concerning lifestyle, psychological well-being, addictive behavior and adherence were related to postponed medical appointments and limited access to medical care.ResultsOne hundred and nine patients (19.5%) reported problems getting necessary medical treatment or visiting a physician. Higher anxiety levels (p = 0.004) emerged as the main factor associated with medical undertreatment. The main risk factors for postponement of least one medical appointment (n = 91) were higher depression (p = 0.013) and anxiety (p = 0.05) symptoms as well as female sex (p ≤ 0.0001) and documented arrhythmias (p = 0.007) indicating a particular risk group of cardiovascular complications. In contrast, frequent physical activity identified patients at lower risk.ConclusionIn ACHD anxiety and depressive symptoms handicap patients to receive medical care. Postponement of medical appointments additionally relates to female sex and documented arrhythmias. The latter indicates that patients at high risk of adverse cardiac outcome avoid routine medical care. Our data may lead policy makers to develop strategies for the provision of medical services to particular vulnerable patient groups, and to optimize management of both future pandemics and daily routine.

IntroductionMental disorders are common in patients with pulmonary arterial hypertension (PAH) and contribute to impaired quality of life (QoL). The impact of mental disorders on access to health care, differences in clinical parameters and treatment in patients with PAH is unclear. In this study we sought to assess the impact of mental disorders and other health disparities on health-care-utilization in patients with PAH.MethodsIn a cross-sectional observational study of patients with PAH, mental disorders were characterized using a structed clinical interview. In addition, patients completed a self-administered questionnaire to assess QoL, symptoms of anxiety and depression, lifestyle-factors and educational status. Number of outpatient visits and communication events per year were calculated as a surrogate for health-care-utilization and were compared by the presence of mental disorder. Linear regression analysis was conducted to assess the impact on health-care-utilization.Results117 patients with PAH participated in this study (70% female, median age 59 (interquartile range, 49–70) years). Significant differences between patients with or without mental disorders were found in anxiety, depression and QoL. There were no significant differences in clinical parameters. Patients with mental disorders had higher rates of outpatient visits and communication events than patients without mental disorders. Linear regression revealed a gain of 2.2 communication events per year in the presence of any mental disorders.ConclusionMental disorders in patients with PAH are common and significantly affect health-care-utilization. This higher demand in patients with mental disorder needs to be addressed by physicians, psychiatrists and specialized nurses offering therapeutic strategies.

Background/ObjectiveChild maltreatment is associated with increased risk of psychological consequences, contributes to morbidity and has long lasting effects on mental health and quality of life. Child maltreatment has not been assessed in patients with pulmonary arterial hypertension (PAH). We examined the prevalence of child maltreatment and determined their impact on disease severity in patients with PAH.MethodsA cross-sectional observational multicenter study at two PH centers in Germany was conducted. Patients with a confirmed diagnosis of PAH were given a self-administered questionnaire. Child maltreatment using the Childhood Trauma Questionnaire (CTQ), quality of life (QoL), anxiety, depression, and lifestyle factors were assessed and enhanced by clinical parameters 6-min walk distance (6MWD), WHO functional class (WHO FC), and serum levels of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). Prevalence rates of child maltreatment were compared to the general population and impact of child maltreatment on disease severity was calculated by logistic regression analysis.ResultsTwo-hundred and seventeen patients, 71% female and a median age of 56 years were enrolled in this study. Patients with PAH had higher rates of emotional abuse and lower rates of physical neglect compared to the German population while rates of emotional neglect, physical abuse, and sexual abuse did not differ between patients and German population. Patients with any form of child maltreatment were more likely to be active smokers, had a worse QoL and more anxiety or depression. Moderate associations between child maltreatment, mental health, QoL, lifestyle factors and clinical parameters could be observed. Logistic regression analysis showed a significant impact of CTQ-total score on disease severity with an OR of 1.022 (95%-CI: 1.001–1.042, p = 0.035).ConclusionWe found a higher rate of child maltreatment in patients with PAH in comparison to the German population. Correlations suggest moderate associations between CTQ-scores and mental health as well as QoL. Child maltreatment had significant impact on disease severity. However, effects were moderate. We conclude that child maltreatment has effects on mental health and quality of life in patients with PAH and may have limited effect on disease severity.

IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) is a potentially life-threatening condition associated with high morbidity and mortality. However, advances in medical, surgical and interventional treatment have markedly improved the outcome of patients with CTEPH. Additional factors potentially influencing quality of life (QoL) and outcome in CTEPH are yet to be defined. Child maltreatment is a major risk factor for unfavorable behavioral, mental as well as physical health outcomes and has been associated with decreased QoL. To date, no study assessed the impact of childhood trauma in patients with CTEPH.MethodsPatients with CTEPH were invited to complete the Childhood Trauma Questionnaire (CTQ). Data were compared to prevalence data from the German population. Mental well-being was assessed using the Hospital Anxiety and Depression Scale (HADS) and quality of life was measured using the WHO Quality of Life Questionnaire (WHOQOL). Furthermore, lifestyle factors and physical health parameters were studied.Logistic regression analysis was used to investigate a possible impact of child maltreatment on markers of disease severity.ResultsOne-hundred and seven patients with CTEPH completed the CTQ. These patients reported higher rates of emotional abuse and physical abuse and emotional neglect compared to the German population while rates of physical neglect and sexual abuse did not differ between patients and German population with prevalence of 20.6% for emotional abuse, 20% for physical abuse, 22% for emotional neglect, 46% for physical neglect, and 6% for sexual abuse in patients with CTEPH. Higher CTQ scores were associated with anxiety symptoms as well as negatively associated with QoL. No direct impact of childhood trauma on CTEPH severity was found.ConclusionWe found a higher rate of child maltreatment in patients with CTEPH in comparison to the German population. Correlations suggest moderate associations between CTQ scores and mental health and QoL. Child maltreatment had no significant impact on disease severity. Further investigation on proper interventions to support affected patients is needed.

Objective: Innovative operative and interventional procedures have improved survival in congenital heart disease (CHD), and today more than 90% of these children reach adulthood. Consequently, adherence and psychosocial issues are becoming increasingly important because non-adherence to treatment recommendations worsens morbidity and mortality. This study aimed to identify factors modifying adherence to medication in adult congenital heart disease (ACHD).Methods: This cross-sectional study included 451 outpatients (female 47.9%, average age ± SD: 37.9 ± 12 years) from the ACHD department, who completed a questionnaire assessing medication non-adherence and individual barriers to treatment. Further assessments included psychological well-being (Hospital Anxiety and Depression scale; HADS), childhood traumatization, sociodemographic, and clinical data. Binary logistic regression analysis calculated the impact of these factors on drug adherence.Results: Of the 451 patients 162 participants (35.9%) reported to be non-adherent. In univariate analysis non-adherence to treatment was associated with smoking (P = < 0.001) and internet addiction (P = 0.005). Further factors negatively influencing adherence were the presence of depressive symptoms (P = 0.002), anxiety (P = 0.004), and childhood traumatization (p = 0.002). Factors positively associated with adherence were older age (P = 0.003) and more advanced heart disease as indicated by NYHA class (P = 0.01), elevated NT-proBNP (P = 0.02), device therapy (P = 0.002) and intermittent arrhythmias (P = 0.01). In multivariate analysis especially psychopathological factors such as depression (P = 0.009), anxiety (P = 0.032) and childhood traumatization (P = 0.006) predicted non-adherence.Conclusion: Adherence is a critical issue in the long-term management of ACHD. Identifying modifiable factors that worsen adherence offers the opportunity for targeted interventions. Depressive symptoms, anxiety, and adverse childhood experiences are amenable to psychosocial interventions, as well as cigarette smoking. Our study suggests that a multimodal and interdisciplinary treatment concept for the long-term management of adults with congenital heart disease could be beneficial. Whether it will further improve morbidity and mortality, should be assessed in prospective interventions.

Apart from Alzheimer’s disease (AD), no biomarkers for the differential diagnosis of dementia have been established to date. Inflammatory processes contribute to the pathogenesis of dementia subtypes, e.g., AD or frontotemporal dementia (FTD). In the context of cancer or cardiovascular diseases, white blood cell (WBC) populations and platelet counts, as well as C-reactive protein (CRP), have emerged as biomarkers. Their clinical relevance in dementia, however, is currently only insufficiently investigated. In the present study, hematological and inflammatory parameters were measured in the peripheral blood of 97 patients admitted to the gerontopsychiatric ward of Hannover Medical School, a university hospital in Germany, for dementia assessment. The study population comprised 20 non-demented, depressed patients (control group) and 77 demented patients who were assigned to five different groups based on their underlying dementia etiology: AD, n = 33; vascular dementia, n = 12; mixed dementia, n = 21; FTD, n = 5; and Korsakoff syndrome, n = 6. We observed neither statistically significant differences regarding total WBC populations, platelet counts, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, nor CRP levels between the control group and the five dementia groups. CRP levels tended to be higher in patients with Korsakoff syndrome than in the control group and in AD patients. Thus, CRP could possibly play a role in the differential diagnosis of dementia. This should be investigated further in future prospective studies with larger sample sizes. WBC and platelet counts, by contrast, do not appear to be suitable biomarkers in the differential diagnosis of dementia.

Background: The prevalence of child maltreatment in adults with congenital heart disease (ACHD) has not been assessed so far. Child maltreatment is a major risk factor for unfavorable behavioral, mental, and physical health outcomes and has been associated with decreased quality of life. Given the increased survival time of ACHD, it is essential to assess factors that may worsen the quality of life and interact with classical cardiovascular risk factors and mental well-being.Methods: In a cross-sectional study, 196 ACHD (mean age 35.21 ± 11.24 y, 44,4% female, 55.6% male) completed a thorough psychiatric and cardiac evaluation. Child maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ) and rates were compared to already existing data from the German general population. Further psychological measurements included the WHO Quality of Life Questionnaire, Hospital Anxiety and Depression Scale (HADS) and assessment of lifestyle factors (exercise, smoking, alcohol consumption, body mass index). To identify a relationship between current cardiac function and child maltreatment, we used logistic regression.Results: ACHD reported significantly higher rates of emotional neglect and emotional abuse and sexual abuse and lower rates of physical neglect when compared to the general German population. In addition, total CTQ-scores, emotional abuse, emotional neglect, physical abuse, and sexual abuse correlated with symptoms of depression, anxiety, and negatively correlated with QoL. Furthermore, CTQ scores contributed significantly in predicting higher New York Heart Association (NYHA) scores (p = 0.009).Conclusion: Child maltreatment is more common in ACHD and associated with decreased quality of life and depression and anxiety. Furthermore, we found evidence that self-reported child maltreatment is associated with decreased cardiac function. Given the longer survival time of patients with ACHD, identifying factors that may negatively influence the disease course is essential. The negative consequences of child maltreatment may be the subject of psychosocial interventions that have demonstrated efficacy in treating posttraumatic stress disorders.

Background/Objective: Covid-19 pandemic may affect mental health and quality of life (QoL) in patients with pulmonary arterial hypertension (PAH). We assessed changes in anxiety and depression, quality of life (QoL) and self-described impact of Covid-19 in patients with PAH during the Covid-19 pandemic.Methods: This study included 152 patients with PAH from two German referral centers. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS-A and HADS-D) at two different timepoints before and during the Covid-19 pandemic with a median of 232 days between baseline and follow-up. QoL was assessed using EQ-5D and emPHasis-10. Perceived impact of Covid-19 and related regulations and measures were assessed using a set of specific questions and statements.Results: More than two thirds of patients had an unsuspicious HADS-A and HADS-D. Median scores did not differ from baseline for both HADS-A and HADS-D (p = 0.202; p = 0.621). Overall, no significant changes in HADS-A or HADS-D categories from baseline to follow up were observed (p = 0.07; p = 0.13). QoL did not change between baseline and follow-up. The Covid-19 pandemic had little impact on access to medical care and established PAH therapy. Patients were in agreement with governmental measures and regulations and felt sufficiently safe.Conclusion: First waves of Covid-19 pandemic had little impact on anxiety, depression and QoL in patient with PAH. Established PAH therapy and access to medical care were not affected. Further studies on the impact of prolonged duration of the ongoing Covid-19 pandemic are needed.

Objective: Mental health may affect the quality of life (QoL) in patients with pulmonary arterial hypertension (PAH). However, mental disorders have not been systematically assessed in these patients. We examined the prevalence of mental disorders using structured interviews and determined their impact on QoL in patients with PAH.Methods: This study included 217 patients with PAH from two German referral centers. Psychiatric disorders were assessed using the structured clinical interview for DSM-V. QoL was assessed using the WHO Quality of Life questionnaire (short form). The diagnostic value of the Hospital Anxiety and Depression Scale was evaluated by receiver operating characteristic curve analysis.Results: More than one third of the patients had psychological disorders with current or past adjustment disorder (38.2%), current major depressive disorder (23.0%), and panic disorder (15.2%) being the most prevalent mental illnesses. About half of the patients with a history of adjustment disorder developed at least one other mental illness. The presence of mental disorders had a profound impact on QoL. The Hospital Anxiety and Depression Scale ruled out panic disorder and depression disorder with negative predictive values of almost 90%.Conclusion: Mental disorders, in particular adjustment disorder, major depression, and panic disorder, are common in patients with PAH and contribute to impaired QoL in these patients. The Hospital Anxiety and Depression Scale may be used as a screening tool for the most common mental health disorders. Future studies need to address interventional strategies targeting mental disorders in patients with PAH.

Objectives: To set up a comprehensive health programme for employees, with needs-based allocation to preventive and rehabilitative measures; and to evaluate the effects of the programme on work ability and sick leave. Design: Prospective single-group observational study. Methods: Employees of a university hospital were invited to participate in needs-based interventions of preventive or rehabilitative character. Allocation followed screening questionnaires, anamnesis and clinical examination. The selection of a preventive or rehabilitative measure appropriate to the needs of the patient followed screening questionnaires, anamnesis and clinical examination. Preventive offers can include back training courses, water gymnastics or stress management exercises. Rehabilitative measures can include 3-6 weeks in- or outpatient rehabilitation or one week intensive outpatient rehabilitation. The main outcome parameters were work ability and sick leave duration. Results: At this time of the project included 1,547 participants, who applied voluntarily to enter the programme. The mean age of participants was 44.3 years (standard deviation (SD) 10.3 years), and 72.0% were female. Needs-based allocation to a prevention (n=1,218) or a rehabilitation group (n=329) was effective, and enabled formation of 2 groups with different needs. Overall, more than half of the employees participating in the programme reported sick leave within the last 3 months. Participants in the preventive measures group reported significantly lower duration of sick leave than those in the rehabilitation group. Employees in the rehabilitation group had significantly lower work ability (Work Ability Index (WAI) 30.4 vs 36.6), but higher effects at 6-month follow-up (WAI 33.4 (standardized effect size (SES) 0.51) vs 37.9 (SES 0.17)). In the prevention group mean sick leave reduced significantly from 1.9 to 1.3 weeks (p

Abstract Introduction Depressive disorders are a common illness worldwide. Major depression is known as a significant predictor of the metabolic syndrome. However, the effects of depression on adipose tissue compartments are controversial. This meta‐analysis aimed to evaluate the state of research on the relationship between patients with depression and adipose tissue compartments as compared to nondepressed individuals. Methods The PubMed database was searched for human studies that measured adipose tissue compartments such as visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and/or organ‐specific adipose tissue measurements using dual‐energy X‐ray absorptiometry, magnetic resonance imaging or computed tomography scan and reported the means and a measure of variance separately for depressed individuals and healthy controls. Twelve articles were identified, including a total of 1,141 depressed and 2,545 nondepressed individuals. Results Major depressive disorder and self‐reported depressive symptoms were associated with elevated visceral adipose tissue and elevated subcutaneous adipose tissue. Subanalyses for gender, age, method of adipose tissue measurement, and method of depression assessment showed elevated visceral adipose in depressed individuals. The results could be replicated when focussing on studies controlling for body mass index (BMI). Regarding other adipose tissue compartments, meta‐analysis could not be carried out due to lack of studies. Conclusions Depression is associated with enlarged visceral and subcutaneous adipose tissue. Further, especially longitudinal, research is needed to identify the mechanism through which depressive disorders contribute to visceral adiposity.

An interplay of early environmental and genetic risk factors with recent stressful life events (SLEs) in adulthood increases the risk for adverse mental health outcomes. The interaction of early risk and current SLEs on brain structure has hardly been investigated.Whole brain voxel-based morphometry analysis was performed in N = 786 (64.6% female, mean age = 33.39) healthy subjects to identify correlations of brain clusters with commonplace recent SLEs. Genetic and early environmental risk factors, operationalized as those for severe psychopathology (i.e., polygenic scores for neuroticism, childhood maltreatment, urban upbringing and paternal age) were assessed as modulators of the impact of SLEs on the brain.SLEs were negatively correlated with grey matter volume in the left medial orbitofrontal cortex (mOFC, FWE p = 0.003). This association was present for both, positive and negative, life events. Cognitive-emotional variables, i.e., neuroticism, perceived stress, trait anxiety, intelligence, and current depressive symptoms did not account for the SLE-mOFC association. Further, genetic and environmental risk factors were not correlated with grey matter volume in the left mOFC cluster and did not affect the association between SLEs and left mOFC grey matter volume.The orbitofrontal cortex has been implicated in stress-related psychopathology, particularly major depression in previous studies. We find that SLEs are associated with this area. Important early life risk factors do not interact with current SLEs on brain morphology in healthy subjects.

Introduction Major depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%–60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity.Methods and analysis This is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score

BackgroundMajor depressive disorder and anxiety disorders are associated with less productivity, earlier retirement, and more sick-days at the workplace. These associations also exist for patients with metabolic syndrome. For both, exercise is a generally recommended part of multimodal treatments. However, for individuals with metabolic syndrome, in which depression and anxiety is more prevalent and severe, evidence for the efficacy of exercise interventions is limited.MethodsCompany employees with diagnosed metabolic syndrome (n=314, age: 48 ± 8 yrs) were randomized to a 6-month exercise intervention (150 min per week) or wait-list control. Participants received individual recommendations for exercise activities by personal meetings, telephone, or via a smartphone app. Physical activities were supervised and adapted using activity monitor data transferred to a central database. Work ability (work ability index), depression severity and anxiety severity [hospital anxiety and depression scale (HADS)], and health-related quality of live [short form 36 (SF-36)] were assessed.ResultsWe included 314 subjects from which 287 finished the intervention. Total work ability, depression- and anxiety severity, and the mental component score of the SF-36 improved after 6 months exercise compared to controls. After baseline stratification for normal (HADS scores 0–7) and increased depression- and anxiety scores (HADS scores 8–21) individuals with increased severity scores had similar age, body composition, blood lipids, and cardiorespiratory fitness compared to those with normal scores, but lower total work ability and component sum scores of health-related quality of life. After 6 months total work ability increased in the exercise group compared to controls with the magnitude of the observed increase being significantly greater for subjects with increased depression- and anxiety severity at baseline compared to those with normal severity scores.ConclusionsA 6-month exercise intervention for company employees with metabolic syndrome showed strongest effects on self-perceived work ability in individuals with mild to severe depression- and anxiety severity. This suggests exercise programs offered to workers with metabolic syndrome not only reduces individual disease risk but may also reduce healthcare and employers costs arising from metabolic syndrome and mental disease conditions.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03293264.

ObjectiveMajor depressive disorder (MDD) has a negative impact on individuals ability to work, and is often associated with long phases of sick leave. Consequently, interventions facilitating return to work in patients with MDD gained increased attention during last decades. We here report results of a feasibility study where a “return-to-work” (RTW) module published by Lagerveld and colleagues in the Netherlands was integrated in cognitive behavioral therapy in depressed patients with long-term sick leaves in Germany. Our study aimed to answer the following questions: Is RTW accepted by patients and therapists? Do RTW interventions lead to return-to-work? Do depressive symptoms improve?MethodsTwenty patients with MDD (15 female; mean age, 45 ± 9 years) were included. Patients received cognitive-behavioral therapy with an integrated, standardized return-to-work module (W-CBT). Psychometric measurements included Beck Depression Inventory (BDI-2) and work ability index (WAI). Further, time until return-to-work was measured, and acceptability of W-CBT was assessed using visual analog scales and open questions.ResultsMean sick leave days in depressed patients were 127 ± 97, and 75% of patients were sick leave for more than 6 weeks. After treatment, 11/20 patients had returned to their former occupation (55%), 5/20 were in occupational re-deployment or started a new job (25%), and 3/20 patients were still on sick leave (2/20; 10%) or received a pension (1/20; 5%). One patient dropped out. BDI-2 sum score improved from 23 ± 8 to 8 ± 5 (p < 0.001), and WAI improved from 28 ± 6 to 39 ± 7 (p < 0.001). Acceptability of W-CBT in patients and therapists was high.ConclusionWe here demonstrate feasibility and acceptability of an RTW module integrated in standard cognitive behavioral therapy. W-CBT leads to improvement of work ability, paralleled by improvement of depressive symptoms. Despite the limitations of this uncontrolled study, the results propose that W-CBT may be feasible in the treatment of depressed patients with long sick leaves and justify a controlled trial evaluating the efficacy of W-CBT.

Psychological risk assessment is a legal obligation for companies and part of occupational safety and employment protection in Germany. However, data from psychological risk assessments in nursing staff are scarce, although this population is at increased risk for secondary traumatic stress by patient experienced trauma. Therefore, our study aimed at examining the frequency of reported secondary trauma events, secondary traumatic stress, and its possible consequences for psychological well-being and work ability in nurses. N = 320 nurses (n = 280 female) were assessed at a University Hospital in Germany as part of the psychological risk assessment. Secondary traumatic events, secondary traumatic stress, and symptoms of depression and anxiety were measured using self-report questionnaires (PHQ-2, GAD-2), and work ability was assessed using a modified version of the questionnaire for workplace analysis (KFZA). Of 320 nurses, 292 (91.2%) experienced secondary trauma, and 74 nurses (25.3%) reported secondary traumatic symptoms. Nurses with secondary traumatic symptoms reported higher depression (p < 0.001) and anxiety scores (p < 0.001) compared to nurses without secondary trauma experience, and to nurses with secondary trauma experience but without secondary traumatic stress (both p < 0.001). Further, nurses with secondary traumatic stress reported significantly reduced work ability, social support and control over work, and increased emotional strain and labor time. Nurses with secondary traumatic stress may be at increased risk of developing major depression and anxiety disorders, and particularly need support in overcoming secondary traumatic experiences. Psychological risk assessment is a useful tool to identify groups at risk, and pave the way to implement strategies to improve mental well-being and prevent work ability in high risk groups.

BackgroundAttentional control has been observed to play an important role in affective disorders by impacting information processing, the ability to exert top–down control in response to distracting stimuli, and by affecting emotional regulation. Prior studies demonstrated an association between attentional control and response to psychotherapy, thereby identifying attentional control as an interesting prognostic pre-treatment factor. Improving attentional control and flexibility is a cornerstone in metacognitive therapy (MCT), which is trained by the use of the Attentional Training Technique (ATT). However, as of yet, it remains unclear if pre-treatment attentional control is related to the effect of ATT.MethodsAn aggregated sample of 139 healthy participants [study 1: 85 participants, mean age 23.7 years, previously published (Barth et al., 2019); study 2: 54 participants, mean age 33.7 years, not previously published] performed an attentional performance test battery before and after applying ATT. Before ATT was administered, attentional control was measured using a well-established self-report instrument, i.e., the Attentional Control Scale (ACS; Derryberry and Reed, 2002). ATT was given in 2, 4, or 15 doses and compared to sham ATT. The test battery comprised a selection of established neurocognitive tasks: emotional dot probe, Stroop, 2-back, and dichotic listening.ResultsSham ATT showed no interaction with ACS score on performance outcome in all tests. At four doses of ATT, ACS score was associated with training response, i.e., subjects with high self-reported attentional control before training showed the largest improvements post-training (all P-values