Association between life events and later depression in the population-based Heinz Nixdorf Recall study-The role of sex and optimism.

BACKGROUND: The association between life event stress and depressive symptoms has not been analyzed in the general population before. METHODS: In the population-based Heinz Nixdorf Recall study, we assessed the association of 1.) the presence of important life events and 2.) life event stress, with the amount of depressive symptoms in univariable linear regressions and in multivariable regressions adjusted for age and sex (model 1) and age, sex and optimism as important determinants of coping with life events (model 2). Presence of life events and life event stress were assessed with the Social Readjustment Rating Scale (SRRS), optimism with the Life Orientation Test-Revised (LOT-R), and depressive symptoms with the 15-item Center for Epidemiological Studies Depression Scale (CES-D). RESULTS: Of the total cohort of 4,814 participants, 1,120 had experienced important life events during the previous 6 months. Presence of important life events was significantly associated with higher CES-D scores (B = 2.6, 95%CI = 2.2 to 3.0, p < .001; model 2) compared to absence of life events. Associations were stronger for women than for men and for pessimists than for optimists. Among the participants with important life events, median (Q1; Q3) stress-score was 45.0 (39.0; 63.0). Stress-scores >Q3 were significantly associated with higher CES-D scores (2.2, 1.1 to 3.3, < .001) with a stronger association in pessimists than in optimists. CONCLUSIONS: Experiencing life-changing events is associated with depression. Women and individuals with pessimistic personality are especially vulnerable which should be considered in prevention strategies.

Facilitating stress prevention in micro and small-sized enterprises: protocol for a mixed method study to evaluate the effectiveness and implementation process of targeted web-based interventions.

BACKGROUND: Workplace-related stress is a major risk factor for mental and physical health problems and related sickness absence and productivity loss. Despite evidence regarding the effectiveness of different workplace-based interventions, the implementation of stress prevention interventions is rare, especially in micro and small-sized enterprises (MSE) with fewer than 50 employees. The joint research project "PragmatiKK"+ aims to identify and address the specific barriers to the implementation of stress prevention interventions in MSE. This study protocol describes a mixed method study design to evaluate the effectiveness of adapted stress prevention interventions and the implementation process via an integrated web-based platform ("System P") specifically targeted at MSE. METHODS: First, we develop a web-based intervention, which accounts for the specific working conditions in MSE and addresses stress prevention at a structural and behavioral level. Second, we use common methods of implementation research to perform an effect and process evaluation. We analyze the effectiveness of the web-based stress prevention interventions by comparing depressive symptoms at baseline and follow-up (after 6 months and 12 months). Indicators for a successful implementation process include acceptability, adoption, feasibility, reach, dose, and fidelity, which we will measure with quantitative web-based questionnaires and qualitative interviews. We will also analyze the accumulated usage data from the web-based platform. DISCUSSION: Collecting data on the implementation process and the effectiveness of a web-based intervention will help to identify and overcome common barriers to stress prevention in MSE. This can improve the mental health of employees in MSE, which constitute more than 90% of all enterprises in Germany. + Full Project Name: "PragmatiKK - Pragmatische Lösungen für die Implementation von Maßnahmen zur Stressprävention in Kleinst- und Kleinbetrieben "(= Pragmatic solutions for the implementation of stress prevention interventions in micro and small-sized enterprises). TRIAL REGISTRATION: German Register of Clinical Studies (DRKS): DRKS00026154 , date of registration: 2021-09-16.

Increase in Mental Disorders During the COVID-19 Pandemic-The Role of Occupational and Financial Strains.

BACKGROUND: Numerous studies have reported an increase in mental disorders during the COVID-19 pandemic, but the exact reasons for this development are not well understood. In this study we investigate whether pandemic-related occupational and financial changes (e.g., reduced working hours, working from home, financial losses) were associated with increased symptoms of depression and anxiety compared with the situation before the pandemic. METHODS: We analyzed data from the German National Cohort (NAKO) Study. Between May and November 2020, 161 849 study participants answered questions on their mental state and social circumstances. Their responses were compared with data from the baseline survey before the pandemic (2014-2019). Linear fixed-effects models were used to determine whether individual changes in the severity of symptoms of depression (PHQ-9) or anxiety (GAD-7) were associated with occupational/ financial changes (controlling for various covariates). RESULTS: The prevalence of moderate or severe symptoms of depression and anxiety increased by 2.4% and 1.5%, respectively, during the COVID-19 pandemic compared with the preceding years. The mean severity of the symptoms rose slightly. A pronounced increase in symptoms was observed among those who became unemployed during the pandemic (+ 1.16 points on the depression scale, 95% confidence interval [0.91; 1.41], range 0-27). Increases were also seen for reduced working hours with no short-time allowance, increased working hours, working from home, insecurity regarding employment, and financial strain. The deterioration in mental health was largely statistically explained by the occupational and financial changes investigated in the model. CONCLUSION: Depressive symptoms and anxiety disorders increased slightly in the study population during the first year of the COVID-19 pandemic. Occupational and financial difficulties were an essential contributory factor. These strains should be taken into account both in the care of individual patients and in the planning of targeted prevention measures.

The Lonely Brain - Associations Between Social Isolation and (Cerebro-) Vascular Disease From the Perspective of Social Neuroscience.

The current COVID-19 pandemic led to a considerable reduction in in-person social contacts all over the world. In most individuals, reduced social contacts lead to the perception of social isolation causing feelings of loneliness, which are experienced as stressful. Experiencing social distress due to actual or perceived social isolation has been associated with negative health outcomes such as depression, (cerebro-) vascular disease and mortality. Concrete mechanisms behind this association are still a matter of debate. A group of researchers around Hugo Critchley with special contributions of Sarah Garfinkel and Lisa Quadt proposes a framework for the underlying brain-body interactions including elements from models of social homeostasis and interoceptive predictive processing that provides important insights and testable pathways. While in a previous publication, we reviewed literature on the observed association between social isolation and stroke and coronary heart disease, we now extent this review by presenting a comprehensive model to explain underlying pathomechanisms from the perspective of social neuroscience. Further, we discuss how neurodivergent people, e.g. autistic individuals or persons with attention deficit disorders, might differ in these pathomechanisms and why they are especially vulnerable to social isolation. Finally, we discuss clinical implications for the prevention and therapy of (cerebro-) vascular diseases.

Comparative effectiveness of guided internet-based stress management training versus established in-person group training in employees - study protocol for a pragmatic, randomized, non-inferiority trial.

BACKGROUND: Occupational stress is a major public health challenge that requires a variety of evidence-based preventative approaches to increase their reach within the working population. Behavioral stress management interventions are considered an established approach for occupational stress prevention. Both in-person group-based stress management training (gSMT) and individual Internet-based training (iSMT) have been shown to be effective at reducing stress in employees. However, there remains a lack of evidence on the comparative efficacy of the newer digital format compared to well-established, in-person, group-based training. This study aims (1) to directly compare an evidence-based iSMT with an established gSMT on stress in employees, (2) to analyze the two conditions from a cost perspective, and (3) to explore moderators of the comparative efficacy. METHODS: In a randomized, controlled, non-inferiority trial employees from the general working population will be allocated to iSMT or gSMT. The primary outcome will be perceived stress, assessed using the Perceived Stress Scale, three months after randomization. The non-inferiority margin for the primary outcome measure will be set at 2 points (Cohen's d = 0.29). This trial will also compare the two interventions from a health economics perspective, and conduct explorative analyses to identify potential effect moderators. DISCUSSION: To reach a larger proportion of the working population, well-established gSMT should be complemented with interventions that fit today's society's increasingly digital lifestyle. The current trial will provide evidence supporting the responsible implementation of Internet-based stress management training if the digital format proves to at least be non-inferior to established group-based training. Additional explorative moderator analyses may guide future practices to aid in matching select programs with select users. TRIAL REGISTRATION: German Register of Clinical Studies (DRKS): DRKS00024892, date of registration: 2021-04-09. Protocol version: 02, 16-10-2021.

Glial Chloride Homeostasis Under Transient Ischemic Stress.

High water permeabilities permit rapid adjustments of glial volume upon changes in external and internal osmolarity, and pathologically altered intracellular chloride concentrations ([Cl-]int) and glial cell swelling are often assumed to represent early events in ischemia, infections, or traumatic brain injury. Experimental data for glial [Cl-]int are lacking for most brain regions, under normal as well as under pathological conditions. We measured [Cl-]int in hippocampal and neocortical astrocytes and in hippocampal radial glia-like (RGL) cells in acute murine brain slices using fluorescence lifetime imaging microscopy with the chloride-sensitive dye MQAE at room temperature. We observed substantial heterogeneity in baseline [Cl-]int, ranging from 14.0 ± 2.0 mM in neocortical astrocytes to 28.4 ± 3.0 mM in dentate gyrus astrocytes. Chloride accumulation by the Na+-K+-2Cl- cotransporter (NKCC1) and chloride outward transport (efflux) through K+-Cl- cotransporters (KCC1 and KCC3) or excitatory amino acid transporter (EAAT) anion channels control [Cl-]int to variable extent in distinct brain regions. In hippocampal astrocytes, blocking NKCC1 decreased [Cl-]int, whereas KCC or EAAT anion channel inhibition had little effect. In contrast, neocortical astrocytic or RGL [Cl-]int was very sensitive to block of chloride outward transport, but not to NKCC1 inhibition. Mathematical modeling demonstrated that higher numbers of NKCC1 and KCC transporters can account for lower [Cl-]int in neocortical than in hippocampal astrocytes. Energy depletion mimicking ischemia for up to 10 min did not result in pronounced changes in [Cl-]int in any of the tested glial cell types. However, [Cl-]int changes occurred under ischemic conditions after blocking selected anion transporters. We conclude that stimulated chloride accumulation and chloride efflux compensate for each other and prevent glial swelling under transient energy deprivation.

Effects of Life Events and Social Isolation on Stroke and Coronary Heart Disease.

The current coronavirus disease 2019 (COVID-19) pandemic represents a severe, life-changing event for people across the world. Life changes may involve job loss, income reduction due to furlough, death of a beloved one, or social stress due to life habit changes. Many people suffer from social isolation due to lockdown or physical distancing, especially those living alone and without family. This article reviews the association of life events and social isolation with cardiovascular disease, assembling the current state of knowledge for stroke and coronary heart disease. Possible mechanisms underlying the links between life events, social isolation, and cardiovascular disease are outlined. Furthermore, groups with increased vulnerability for cardiovascular disease following life events and social isolation are identified, and clinical implications of results are presented.

Multiple social roles in early adulthood and later mental health in different labour market contexts.

Work and family roles entail divergent responsibilities, which can be a source of conflict especially in young adulthood - the so-called "rush-hour" of life. Combining these multiple social roles can result in an accumulation of stress but also be a valuable resource for mental health. The aim of this study is to investigate combined employment, parenthood and partnership trajectories of men and women during early adulthood, and to analyse the relationship of these multiple roles with depressive symptoms at older age. We used harmonised data from the Survey of Health, Ageing and Retirement in Europe (SHARE) and the English Longitudinal Study of Ageing (ELSA) with retrospective information on employment, partnerships and parenthood histories between age 25 and 40 for 18,816 men and 24,686 women (n = 43,502). We applied sequence analysis and clustering to group trajectories into four clusters for women and three clusters for men. We then used multilevel models to analyse the links between combined employment and family roles and later mental health in different historical labour market contexts (indicated by female employment rates). Women and men who did not combine work and family roles between age 25 and 40 report higher levels of depression than those who combined work and family. Results differ by gender and labour market context, with stronger differences between women in countries with higher female employment rates. Overall, combining multiple roles in early adulthood is associated with decreased rather than increased risk for depressive symptoms in older Europeans.

Cellular Physiology and Pathophysiology of EAAT Anion Channels.

Excitatory amino acid transporters (EAATs) optimize the temporal resolution and energy demand of mammalian excitatory synapses by quickly removing glutamate from the synaptic cleft into surrounding neuronal and glial cells and ensuring low resting glutamate concentrations. In addition to secondary active glutamate transport, EAATs also function as anion channels. The channel function of these transporters is conserved in all homologs ranging from archaebacteria to mammals; however, its physiological roles are insufficiently understood. There are five human EAATs, which differ in their glutamate transport rates. Until recently the high-capacity transporters EAAT1, EAAT2, and EAAT3 were believed to conduct only negligible anion currents, with no obvious function in cell physiology. In contrast, the low-capacity glutamate transporters EAAT4 and EAAT5 are thought to regulate neuronal signaling as glutamate-gated channels. In recent years, new experimental approaches and novel animal models, together with the discovery of a human genetic disease caused by gain-of-function mutations in EAAT anion channels have enabled identification of the first physiological and pathophysiological roles of EAAT anion channels.

Interoceptive cardiac signals selectively enhance fear memories.

Fear is coupled to states of physiological arousal. We tested how learning and memory of threat, specifically conditioned fear, is influenced by interoceptive signals. Forty healthy individuals were exposed to two threat (conditioned stimuli [CS+], paired with electrocutaneous shocks) and two safety (CS-) stimuli, time-locked to either cardiac ventricular systole (when arterial baroreceptors signal cardiovascular arousal to brainstem), or diastole (when these afferent signals are quiescent). Threat learning was indexed objectively using skin conductance responses (SCRs). During acquisition of threat contingencies, cardiac effects dominated: Stimuli (both CS+ and CS-) presented at systole evoked greater SCR responses, relative to stimuli (both CS+ and CS-) presented at diastole. This difference was amplified in more anxious individuals. Learning of conditioned fear was established by the end of the acquisition phase, which was followed by an extinction phase when unpaired CSs were presented at either the same or switched cardiac contingencies. One day later, electrocutaneous shocks triggered the reinstatement of fear responses. Subsequent presentation of stimuli previously encoded at systole evoked higher SCRs. Moreover, only those participants for whom stimuli had the same cardiac-contingency over both acquisition and extinction phases retained conditioned fear memory (i.e., CS+ > CS-). Our findings reveal two important cardiac afferent effects on threat learning and memory: 1) Cardiac signals bias processing toward threat; and 2) cardiac signals are a context for fear memory; altering this context can disrupt the memory. These observations suggest how threat reactivity may be reinforced and maintained by both acute and enduring states of cardiac arousal. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Increased glutamate transporter-associated anion currents cause glial apoptosis in episodic ataxia 6.

Episodic ataxia type 6 is an inherited neurological condition characterized by combined ataxia and epilepsy. A severe form of this disease with episodes combining ataxia, epilepsy and hemiplegia was recently associated with a proline to arginine substitution at position 290 of the excitatory amino acid transporter 1 in a heterozygous patient. The excitatory amino acid transporter 1 is the predominant glial glutamate transporter in the cerebellum. However, this glutamate transporter also functions as an anion channel and earlier work in heterologous expression systems demonstrated that the mutation impairs the glutamate transport rate, while increasing channel activity. To understand how these changes cause ataxia, we developed a constitutive transgenic mouse model. Transgenic mice display epilepsy, ataxia and cerebellar atrophy and, thus, closely resemble the human disease. We observed increased glutamate-activated chloride efflux in Bergmann glia that triggers the apoptosis of these cells during infancy. The loss of Bergmann glia results in reduced glutamate uptake and impaired neural network formation in the cerebellar cortex. This study shows how gain-of-function of glutamate transporter-associated anion channels causes ataxia through modifying cerebellar development.

Subgroups with typical courses of depressive symptoms in an elderly population during 13 years of observation: Results from the Heinz Nixdorf Recall Study.

BACKGROUND: Depressive symptoms are volatile over time but empirical studies of intra-individual variations of depressive symptoms over longer periods are sparse. AIMS: We aim to examine fluctuation patterns of depressive symptoms and to investigate the possible influence of age, sex and socioeconomic factors on fluctuation in a population-based sample over a period of 13 years. METHODS: We used data of 4,251 participants (45-75 years; 51.0% women at baseline) of the Heinz Nixdorf Recall Study with at least two of nine possible measurements obtained in the period between 2000 and 2017. Depressive symptoms were assessed via the Center for Epidemiologic Studies Depression Scale (CES-D) short form. Based on the individual mean values and standard deviation from all measurements, we categorized participants as G1 'stable low', G2 'stable high', G3 'stable around cutoff' and G4 'large fluctuations'. RESULTS: Most participants (82.3%) showed stable low depressive symptoms (G1), whereas 2.3% performed stable high values (G2), 6.9% stable around the cutoff (G3) and 8.6% large fluctuations (G4). CONCLUSION: Our longitudinal results reveal that almost 18% (G2, G3 and G4) of the participants have an increased depression score or strong fluctuations at times. According to our classification, a higher proportion of the participants show anomalies with regard to depression compared to a simple classification into depressed and nondepressed, especially if this is based on a single measurement. Thus, longitudinal measurements of depression can prevent misclassification and provide valuable information about the course of depressive symptoms for a better understanding of the changes of depression.

Linked work lives: The interrelation of own and partner's employment history and their relationship with mental health in older European couples.

INTRODUCTION: There is strong evidence for the importance of previous employment for mental health at older age but little is known about the role of partner's employment history in this. Life course theory suggests that individual trajectories are linked and evidence from cross-sectional studies suggest that there are cross-over effects within couples. Therefore, the present study tests the interdependence of own and partner's employment history and their relationship with depressive symptoms. METHODS: Analyses are based on retrospective data from the SHARE survey for 5664 long-term couples aged 50 or older, with employment information for each age between 30 and 50 (full-time, part-time, domestic work or non-employed). We use sequence analysis to group similar employment histories and relate own and partner's employment histories with depressive symptoms (EURO-D) using regression models. RESULTS: Results show that own and partner's employment history are interdependent and mainly follow traditional divisions of paid work, with the majority of men working full-time and women often working part-time or not working. We find increased depressive symptoms after longer episodes of non-employment for men but not for women, regardless of partner's employment situation. CONCLUSION: The study shows that mental health later in life is related to own employment history and that this relationship is not moderated by partner's employment history. The results need to be interpreted against cultural and gender role norms at the time.

Gendered work-family trajectories and depression at older age.

Objectives: The paper identifies types of work-family trajectories of men and women and investigates their links with depression at older age. Method: We use data from the Heinz Nixdorf Recall study, with retrospective information on employment histories and parenthood between age 20 and 50 (1482 men and 1537 women, born between 1925 and 1955). We apply sequence analysis and group trajectories into six clusters for each gender. We test their association with two alternative measures of depression: self-reported depressive symptoms and intake of antidepressant medication. Multivariate models exclude participants with early life depression and adjust for age, marital status, education, and income. Results: We find clear differences of work-family trajectories between men and women, where women's trajectories are generally more diverse, and include family leaves and returns into full or part-time work. For men, work-family trajectories are neither related to depressive symptoms nor to medication intake. In contrast, women who returned into full-time work after family leave show more depression than those who return part-time, both in terms of depressive symptoms and intake of antidepressant medication. Conclusion: Our findings show gender differences in terms of work-family trajectories and their health-related consequences. In particular, findings suggest that mothers who return to full-time work are a vulnerable group for depression at older age and should be the focus of further research attention.

The Gender Lens: Development of a learning aid to introduce gender medicine.

Background and aim: Gender medicine takes into account biological and social differences between men and women in terms of prevalence and course of disease, diagnosis and therapy. Medical students should be made aware of this in the early stages of medical education. However, there is hardly any teaching material currently available. This article presents the adaption and first use of the German "Gender Lens," a tool to introduce gender medicine to medical students. Method: The original Canadian "Gender Lens Tool" was translated into German, tested by (n=5) teachers and adapted based on current scientific concepts. The instrument was applied and evaluated using qualitative methods in a student focus group (n=4). It was then piloted in a cohort of fourth-semester students (n=247) in a seminar addressing gender medicine. These experiences were evaluated using quantitative methods. Results: The German translation of the Gender Lens offers students a framework with which to analyze sex and gender differences in terms of the "prevalence, diagnosis, course, therapy and prevention" of a specific disease. Furthermore, it enables a refined search for causes such as "biological disposition, attitudes and behaviors, family and social networks, occupational and material circumstances and experiences with the health care system." Recommendations were received from the student groups regarding teaching methods. Male and female fourth-semester students agreed that the Gender Lens is useful as an introduction to gender medicine. Discussion: Initial experiences with the Gender Lens adapted for the German curriculum suggest that such a learning aid can contribute to raising awareness of gender medicine in medical students.

Interoceptive dimensions across cardiac and respiratory axes.

Interoception refers to the sensing of signals concerning the internal state of the body. Individual differences in interoceptive sensitivity are proposed to account for differences in affective processing, including the expression of anxiety. The majority of investigations of interoceptive accuracy focus on cardiac signals, typically using heartbeat detection tests and self-report measures. Consequently, little is known about how different organ-specific axes of interoception relate to each other or to symptoms of anxiety. Here, we compare interoception for cardiac and respiratory signals. We demonstrate a dissociation between cardiac and respiratory measures of interoceptive accuracy (i.e. task performance), yet a positive relationship between cardiac and respiratory measures of interoceptive awareness (i.e. metacognitive insight into own interoceptive ability). Neither interoceptive accuracy nor metacognitive awareness for cardiac and respiratory measures was related to touch acuity, an exteroceptive sense. Specific measures of interoception were found to be predictive of anxiety symptoms. Poor respiratory accuracy was associated with heightened anxiety score, while good metacognitive awareness for cardiac interoception was associated with reduced anxiety. These findings highlight that detection accuracies across different sensory modalities are dissociable and future work can better delineate their relationship to affective and cognitive constructs.This article is part of the themed issue 'Interoception beyond homeostasis: affect, cognition and mental health'.

Anger in brain and body: the neural and physiological perturbation of decision-making by emotion.

Emotion and cognition are dynamically coupled to bodily arousal: the induction of anger, even unconsciously, can reprioritise neural and physiological resources toward action states that bias cognitive processes. Here we examine behavioural, neural and bodily effects of covert anger processing and its influence on cognition, indexed by lexical decision-making. While recording beat-to-beat blood pressure, the words ANGER or RELAX were presented subliminally just prior to rapid word/non-word reaction-time judgements of letter-strings. Subliminal ANGER primes delayed the time taken to reach rapid lexical decisions, relative to RELAX primes. However, individuals with high trait anger were speeded up by subliminal anger primes. ANGER primes increased systolic blood pressure and the magnitude of this increase predicted reaction time prolongation. Within the brain, ANGER trials evoked an enhancement of activity within dorsal pons and an attenuation of activity within visual occipitotemporal and attentional parietal cortices. Activity within periaqueductal grey matter, occipital and parietal regions increased linearly with evoked blood pressure changes, indicating neural substrates through which covert anger impairs semantic decisions, putatively through its expression as visceral arousal. The behavioural and physiological impact of anger states compromises the efficiency of cognitive processing through action-ready changes in autonomic response that skew regional neural activity.

Neuroimaging and psychophysiological investigation of the link between anxiety, enhanced affective reactivity and interoception in people with joint hypermobility.

OBJECTIVE: Anxiety is associated with increased physiological reactivity and also increased "interoceptive" sensitivity to such changes in internal bodily arousal. Joint hypermobility, an expression of a common variation in the connective tissue protein collagen, is increasingly recognized as a risk factor to anxiety and related disorders. This study explored the link between anxiety, interoceptive sensitivity and hypermobility in a sub-clinical population using neuroimaging and psychophysiological evaluation. METHODS: Thirty-six healthy volunteers undertook interoceptive sensitivity tests, a clinical examination for hypermobility and completed validated questionnaire measures of state anxiety and body awareness tendency. Nineteen participants also performed an emotional processing paradigm during functional neuroimaging. RESULTS: We confirmed a significant relationship between state anxiety score and joint hypermobility. Interoceptive sensitivity mediated the relationship between state anxiety and hypermobility. Hypermobile, compared to non-hypermobile, participants displayed heightened neural reactivity to sad and angry scenes within brain regions implicated in anxious feeling states, notably insular cortex. CONCLUSIONS: Our findings highlight the dependence of anxiety state on bodily context, and increase our understanding of the mechanisms through which vulnerability to anxiety disorders arises in people bearing a common variant of collagen.