Association Between Psychosocial Stress and Brain Aging: Results of the Population-Based Cohort Study of Health in Pomerania (SHIP).

OBJECTIVE: Recent studies suggest that psychosocial factors can have an impact on brain health. Yet, it is unclear whether psychosocial stress affects aging of the brain. The aim of the study was to investigate the association between psychosocial stress and brain aging. METHODS: Data from the German population-based cohort Study of Health in Pomerania (N=991; age range 20-78 years) were used to calculate a total psychosocial stress score by combining subscores from five domains: stress related to the living situation, the occupational situation, the social situation, danger experiences, and emotions. Associations with brain aging, indicated by an MRI-derived score quantifying age-related brain atrophy, were estimated by using regression models adjusted for age, gender, education, diabetes, problematic alcohol consumption, smoking, and hypertension. RESULTS: The relative risk ratio for advanced brain aging was 1.21 (95% CI=1.04-1.41) for stress related to emotions in fully adjusted models. The interactions between stress related to emotions and mental health symptoms were also significantly associated with advanced brain aging. The association between higher total psychosocial stress and brain aging was not statistically significant. CONCLUSIONS: These findings highlight that high stress related to emotions is associated with advanced brain aging. To protect brain health in older age, more research is needed to explore the role of emotional distress.

Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders.

Childhood maltreatment is an important risk factor for adult depression and has been associated with changes in the hypothalamic pituitary adrenal (HPA) axis, including cortisol secretion and methylation of the FKBP5 gene. Furthermore, associations between depression and HPA changes have been reported. This study investigated the associations of whole-blood FKBP5 mRNA levels, serum cortisol levels, childhood maltreatment, and depressive symptoms with the whole-blood methylation status (assessed via target bisulfite sequencing) of 105 CpGs at the FKBP5 locus using data from the general population-based Study of Health in Pomerania (SHIP) (N = 203). Both direct and interaction effects with the rs1360780 single-nucleotide polymorphism were investigated. Nominally significant associations of main effects on methylation of a single CpG site were observed at intron 3, intron 7, and the 3'-end of the gene. Additionally, methylation at two clusters at the 3'-end and intron 7 were nominally associated with childhood maltreatment × rs1360780 and depressive symptoms × rs1360780, respectively. The results add to the understanding of molecular mechanisms underlying the emergence of depression and could aid the development of personalised depression therapy and drug development.

[Life events related to the German reunification and their associations with psychosocial health in a sample of northeast Germany]. / Nach-Wende-Ereignisse und deren Assoziation mit psychosozialer Gesundheit in einer nordostdeutschen Stichprobe.

Objectives: The aim of the present study was to investigate (1) the type and frequency of reported life events of the East German population related to the German reunification and (2) their associations with psychosocial health. Methods: Data of 2247 participants of the Study of Health in Pomerania was used.These qualitative responses were analysed using quantitative content analysis. Their associations with subjective physical and mental health, optimism, social support, depressive symptoms, and chronic stress were examined. Results: Eight life event categories were identified (education, employment-related changes, material changes, new opportunities, personal life events, politics, separations, reunifications). Especially, experiencing new opportunities was associated with a higher level of optimism as well as a lower level of depressive symptoms and chronic stress. Conclusions: In this study, events frequently described in the literature (e.g., employment-related and social changes) were confirmed and systematized.The observed associations of these events with psychosocial factors should be examined further in future studies.

Interaction of childhood abuse and depressive symptoms on cortical thickness: a general population study.

Childhood abuse was inconsistently related to whole-brain cortical thickness in former studies. However, both childhood abuse and cortical thickness have been associated with depressive symptoms. We hypothesised that childhood abuse moderates the association between depressive symptoms and cortical thickness. In 1551 individuals of the general population, associations between whole-brain cortical thickness and the interaction of childhood abuse (emotional, physical, and sexual) and depressive symptoms were analysed using an ANCOVA. Linear regression analyses were used to estimate the same effect on the cortical thickness of 34 separate regions (Desikan-Killiany-atlas). A significant interaction effect of childhood abuse and depressive symptoms was observed for whole-brain cortical thickness (F(2, 1534) = 5.28, p = 0.007). A thinner cortex was associated with depressive symptoms in abused (t value = 2.78, p = 0.025) but not in non-abused participants (t value = - 1.50, p = 0.224). Focussing on non-depressed participants, a thicker whole-brain cortex was found in abused compared to non-abused participants (t value = - 2.79, p = 0.025). Similar interaction effects were observed in 12 out of 34 cortical regions. Our results suggest that childhood abuse is associated with reduced cortical thickness in subjects with depressive symptoms. In abused subjects without depressive symptoms, larger cortical thickness might act compensatory and thus reflect resilience against depressive symptoms.

The interplay between genetic variation and gene expression of the glucocorticoid receptor gene NR3C1 and blood cortisol levels on verbal memory and hippocampal volumes.

The hypothalamus-pituitary-adrenal axis is the main physiological stress response system and regulating the release of cortisol. The two corticoid receptors encoded by the genes NR3C1 and NR3C2 are the main players in regulating the physiological response to cortisol. This biological system has been linked to neurocognitive processes and memory, yet the mechanisms remain largely unclear. In two independent general population studies (SHIP, total sample size > 5500), we aim to diseantangle the effects of genetic variation, gene expression and cortisol on verbal memory and memory associated brain volume. Especially for NR3C1 results exhibited a consistent pattern of direct an interactive effects. All three biological layers, genetic variation (rs56149945), gene expression for NR3C1 and cortisol levels, were directly associated with verbal memory. Interactions between these components showed significant effects on verbal memory as well as hippocampal volume. For NR3C2 such a complex association pattern could not be observed. Our analyses revealed that different components of the stress response system are acting together on different aspects of cognition. Complex phenotypes, such as cognition and memory function are regulated by a complex interplay between different genetic and epigenetic features. We promote the glucocorticoid receptor NR3C1 as a main target to focus in the context of verbal memory and provided a mechanistic concept of the interaction between various biological layers spanning NR3C1 function and its effects on memory. Especially the NR3C1 transcript seemed to be a key element in this complex system.

Childhood Maltreatment and Subclinical Atherosclerosis: Findings From the General Population.

OBJECTIVE: Evidence suggests that childhood maltreatment (CM) is cross-sectionally and prospectively associated with cardiovascular disease. However, its association with proxy markers of atherosclerosis has hardly been investigated. Thus, in this general population study, we examined the association of CM with carotid plaque and intima-media thickness. METHODS: Adults from the general population free of any cardiovascular disease (n = 1909; mean [SD] age = 50.4 (13.6) years, 53.9% women) completed the self-report Childhood Trauma Questionnaire for the assessment of emotional, physical, and sexual abuse as well as emotional and physical neglect; in addition, an ultrasound of the carotid arteries was performed in each participant. RESULTS: At least one type of CM was reported by 25% of the participants. Carotid plaque was significantly more frequent in those with CM compared with those without (odds ratio = 1.47, 95% confidence interval = 1.19-1.81). Accounting for age and sex rendered it nonsignificant (odds ratio = 1.07, 95% confidence interval = 0.81-1.42). Emotional abuse and physical neglect were significantly associated with both carotid intima-media thickness and plaque occurrence, but these associations were fully explained by risk factors. Neither sexual nor physical abuse was related to proxy markers of atherosclerosis. CONCLUSIONS: Our findings suggest that the relationship between CM types and subclinical atherosclerosis as well as its clinical end points is complex and remains inconclusive, suggesting the need for further research.

Interactive impact of childhood maltreatment, depression, and age on cortical brain structure: mega-analytic findings from a large multi-site cohort.

BACKGROUND: Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age. METHODS: Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer. RESULTS: CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions. CONCLUSIONS: Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

Alexithymia Is Associated with Altered Cortical Thickness Networks in the General Population.

BACKGROUND: Alexithymia is a personality trait characterized by difficulties in identifying and describing emotions and associated with various psychiatric disorders. Neuroimaging studies found evidence for morphological and functional brain alterations in alexithymic subjects. However, the neurobiological mechanisms underlying alexithymia remain incompletely understood. METHODS: We study the association of alexithymia with cortical correlation networks in a large community-dwelling sample of the Study of Health in Pomerania. Our analysis includes data of n = 2,199 individuals (49.4% females, age = 52.1 ± 13.6 years) which were divided into a low and high alexithymic group by a median split of the Toronto Alexithymia Scale. Cortical correlation networks were constructed based on the mean thicknesses of 68 regions, and differences in centralities were investigated. RESULTS: We found a significantly increased centrality of the right paracentral lobule in the high alexithymia network after correction for multiple testing. Several other regions with motoric and sensory functions showed altered centrality on a nominally significant level. CONCLUSIONS: Finding increased centrality of the paracentral lobule, a brain area with sensory as well as motoric features and involvement in bowel and bladder voiding, may contribute to explain the association of alexithymia with functional somatic disorders and chronic pain syndromes.

[The application of the BL-38 subjective complaints scale in an epidemiological cohort study (Study of Health in Pomerania)]. / Die Anwendung der Beschwerdeliste-38 zur Erhebung subjektiver Gesundheitsbeschwerden in einer epidemiologischen Kohortenstudie (Study of Health in Pomerania, SHIP).

The application of the BL-38 subjective complaints scale in an epidemiological cohort study (Study of Health in Pomerania) Objective: We provide an overview of the application of the BL-38 complaints scale in the epidemiological Study of Health in Pomerania. We examine the influence of socio-demographic variables on complaint burden and the stability of complaint burden over time. Methods: 16 studies that used the BL-38 in analyses of SHIP-data were examined in terms of how the BL-38 was operationalised and the statistically significant results yielded. We conduct linear regression analyses to assess effects of sociodemographic variables on complaint burden in four SHIP populations and assess test-retest-reliability over a 17-year period. Results: The BL-38 is predominantly used flexibly to depict specific complaints in analyses covering a heterogeneous range of disciplines and study questions. Total, somatic and mental complaint burden have different determinant, predictive and confounding effects. Test-retest-reliability was moderate. Conclusions: The BL-38 allows consideration of (specified) health complaint patterns across many research disciplines. Cross-sectional and longitudinal reproducibility of significant results underlines its validity. The results underscore the importance of subjective health complaints in epidemiological and psychosomatic research.

[Perinatal and postnatal treatment of traumatized parents with mental disorders: impact on parents and their children]. / Peri- und postnatale Therapie traumatisierter, psychisch kranker Eltern: Wirkungen auf Eltern und ihre Kinder.

BACKGROUND: In traumatized parents with mental disorders, pregnancy and related medical examinations can lead to high emotional distress and flashbacks and increase the already tense emotional situation. Besides psychiatric burdens, parental insecurity concerning dealing with and reduced sensitivity for the child often exist. The children themselves have a higher risk of being neglected or abused and to also develop mental disorders. OBJECTIVE: How does interventional research take the special needs of traumatized parents with mental disorders into account? What kind of interventions predominate and what impact do they have on parents and children? MATERIAL AND METHODS: Publications on perinatal and postnatal interventions for traumatized and mentally disordered parents were included in the review if at least one intervention was explicitly described, a parental trauma was discussed and the impact of the intervention on the parents and children was analyzed. RESULTS: A total of 2 reviews and 10 interventional studies were included. Interventions were primarily based on professional educational counseling, psychoeducation, nurse home visits, individual and group therapies and inpatient mother-baby units. The interventions led to reduced psychiatric symptoms, enhanced parental sensitivity for the child's needs, enhanced quality of nurturing and care and an improved mother-child bonding. CONCLUSION: Although only few studies focused on the special needs of traumatized, mentally disordered parents, the described interventions show promising effect sizes, especially in combination with several kinds of interventions. Nevertheless, an adequate integration of fathers into the therapies has so far been neglected.

Assessment of subjective emotional valence and long-lasting impact of life events: development and psychometrics of the Stralsund Life Event List (SEL).

BACKGROUND: Life events (LEs) are associated with future physical and mental health. They are crucial for understanding the pathways to mental disorders as well as the interactions with biological parameters. However, deeper insight is needed into the complex interplay between the type of LE, its subjective evaluation and accompanying factors such as social support. The "Stralsund Life Event List" (SEL) was developed to facilitate this research. METHODS: The SEL is a standardized interview that assesses the time of occurrence and frequency of 81 LEs, their subjective emotional valence, the perceived social support during the LE experience and the impact of past LEs on present life. Data from 2265 subjects from the general population-based cohort study "Study of Health in Pomerania" (SHIP) were analysed. Based on the mean emotional valence ratings of the whole sample, LEs were categorized as "positive" or "negative". For verification, the SEL was related to lifetime major depressive disorder (MDD; Munich Composite International Diagnostic Interview), childhood trauma (Childhood Trauma Questionnaire), resilience (Resilience Scale) and subjective health (SF-12 Health Survey). RESULTS: The report of lifetime MDD was associated with more negative emotional valence ratings of negative LEs (OR = 2.96, p < 0.0001). Negative LEs (b = 0.071, p < 0.0001, ß = 0.25) and more negative emotional valence ratings of positive LEs (b = 3.74, p < 0.0001, ß = 0.11) were positively associated with childhood trauma. In contrast, more positive emotional valence ratings of positive LEs were associated with higher resilience (b = - 7.05, p < 0.0001, ß = 0.13), and a lower present impact of past negative LEs was associated with better subjective health (b = 2.79, p = 0.001, ß = 0.05). The internal consistency of the generated scores varied considerably, but the mean value was acceptable (averaged Cronbach's alpha > 0.75). CONCLUSIONS: The SEL is a valid instrument that enables the analysis of the number and frequency of LEs, their emotional valence, perceived social support and current impact on life on a global score and on an individual item level. Thus, we can recommend its use in research settings that require the assessment and analysis of the relationship between the occurrence and subjective evaluation of LEs as well as the complex balance between distressing and stabilizing life experiences.

Childhood maltreatment and risk of metabolic dysfunction-associated steatotic liver disease - Evidence of sex-specific associations in the general population.

BACKGROUND AND AIMS: Childhood maltreatment (CM) is linked to self-reported liver disease in adulthood. However, specific diagnostic entities, e.g., metabolic dysfunction-associated steatotic liver disease (MASLD) as the most frequent chronic liver disease, and sex-differences have previously not been considered. METHODS: Cross-sectional analyses were conducted in 4188 adults from a population-based cohort in Northeastern Germany after excluding individuals with excessive alcohol consumption, cirrhosis, or chronic viral hepatitis. CM-exposure was assessed using the Childhood Trauma Questionnaire (CTQ). Liver-related outcomes included serologic liver enzymes, fibrosis-4 score (FIB-4) and, in 1863 subjects who underwent magnetic resonance imaging examination, liver fat content. Sex-stratified linear regression and logistic regression models predicting liver-related outcomes and risk for MASLD, respectively, from overall CTQ scores were adjusted for age, school education, alcohol consumption, and waist circumference. Exploratory analyses investigated effects of CTQ-subscales on liver-related outcomes and risk for MASLD. RESULTS: In both sexes, overall CM-exposure was associated with higher levels of serum aspartate aminotransferase and FIB-4 score. In men, effects were mainly driven by physical abuse, and in women by emotional neglect. Only in men, overall CM-exposure (ß = 0.70, 95%-CI 0.26-1.13, p = 0.002) and four CTQ-subscales were associated with greater liver fat content, and physical abuse (aOR = 1.22, 95%-CI 1.02-1.46, p = 0.034) and physical neglect (aOR = 1.25, 95%-CI 1.04-1.49, p = 0.015) were associated with higher risk for MASLD. CONCLUSIONS: These results suggest sex differences in the association between CM and objective serum and imaging markers of MASLD in adulthood. For men especially, a history of CM-exposure may increase risk of developing MASLD in adulthood.

Sex-specific associations of childhood maltreatment with obesity-related traits - The Study of Health in Pomerania (SHIP).

BACKGROUND: Child maltreatment (CM) is linked to obesity in adulthood. However, sex-differences and direct measurements of body fat have previously been insufficiently considered in this context. OBJECTIVE: To assess sex-specific associations of CM with anthropometric markers of overweight/obesity and direct measures of body fat. PARTICIPANTS AND SETTING: Analyses were conducted in 4006 adults from a population-based cohort in Northeastern Germany (SHIP-TREND-0). METHODS: CM was assessed using the Childhood Trauma Questionnaire (CTQ). Obesity-related traits included anthropometric indicators (i.e., height, weight, body mass index [BMI], waist [WC] and hip circumference [HC], waist-to-hip ratio [WHR], waist-to-height ratio [WHtR]), fat mass (FM) and fat-free mass (FFM) derived from bioelectrical impedance analysis (BIA), and subcutaneous (SAT) and visceral adipose tissue (VAT) ascertained using magnetic resonance imaging (MRI). Sex-stratified linear regression models predicting obesity-related traits from total CTQ scores were adjusted for age and education. Exploratory analyses investigated effects of CTQ subscales on obesity-related traits. RESULTS: In men, CM was positively associated with WHtR (ß = 0.04; p = .030) and VAT (ß = 0.02; p = .031) and inversely with body height (ß = -0.05; p = .010). In women, CM-exposure was positively associated with body weight (ß = 0.07; p = .018), BMI (ß = 0.03; p = .013), WC (ß = 0.07; p = .005), HC (ß = 0.05; p = .046), WHR (ß = 0.03; p = .015), WHtR (ß = 0.04; p = .006), FM (ß = 0.04; p = .006), and SAT (ß = 0.06; p = .041). In both sexes, effects were mainly driven by exposure to emotional and physical abuse. CONCLUSIONS: Results suggest that associations between CM-exposure and obesity-related traits in adulthood are primarily present in women. This may have implications for sex-specific obesity-related cardiometabolic risk after CM.

How socio-political change is associated with the number of individually reported negative life events: a population-based study using the German reunification 1989/1990 as an example.

BACKGROUND: Socio-political change often leads to disruptions in employment and social networks, which can exacerbate health issues and increase mortality rates. These consequences are likely observed as an increase in negative life events (NLEs), serving as indicators of the broader social and health impacts. Using the German reunification in 1989/1990 as an example, this study investigates changes in reported numbers of NLEs and differences regarding sociodemographic characteristics. METHODS: We used data from the population-based Study of Health in Pomerania (SHIP-START-0, SHIP-Life-Events and Gene-Environment Interaction in Depression; N=1932). Numbers of NLEs in different categories (work/financial, social/interpersonal, illness (own) and illness/death (others)) were measured retrospectively in 5-year intervals (1980-2004) using a semistructured interview. Pre-reunification and post-reunification changes were modelled using piecewise mixed-effects Poisson regressions with the 1990-1994 interval (reunification) as change point. Interactions with age, sex and education were examined. RESULTS: The number of most NLE categories, except social/interpersonal NLEs, increased at reunification. Whereas work/financial NLEs slightly decreased post-reunification, illness-related NLEs continued to increase. Higher numbers of social/interpersonal NLEs were found with younger age. More illness-related NLEs were reported with older age, lower education (illness (own)) and by women (illness/death (others)). However, the majority reported no NLEs at reunification (68.2%-80.7%, varying by category). CONCLUSION: Our findings suggest that although some individuals experience a marked increase in NLEs due to socio-political changes, many remain unaffected, emphasising the need for a differentiated understanding of these effects. This increase in NLEs may partly account for ongoing health and well-being disparities among countries with differing transformation histories.

Childhood Trauma and Somatic and Mental Illness in Adulthood.

BACKGROUND: Childhood trauma is associated with somatic and mental illness in adulthood. The strength of the association varies as a function of age, sex, and type of trauma. Pertinent studies to date have mainly focused on individual diseases. In this study, we investigate the association between childhood trauma and a multiplicity of somatic and mental illnesses in adulthood. METHODS: Data from 156 807 NAKO Health Study participants were analyzed by means of logistic regressions, with adjustment for age, sex, years of education, and study site. The Childhood Trauma Screener differentiated between no/minor (n = 115 891) and moderate/severe childhood trauma (n = 40 916). The outcome variables were medical diagnoses of five somatic and two mental health conditions as stated in the clinical history. RESULTS: Persons with childhood trauma were more likely to bear a diagnosis of all of the studied conditions: cancer (odds ratio [OR] = 1.10; 95% confidence interval: [1.05; 1.15]), myocardial infarction (OR = 1.13 [1.03; 1.24]), diabetes (OR = 1.16, [1.10; 1.23]), stroke (OR = 1.35 [1.23; 1.48]), chronic obstructive pulmonary disease (OR = 1.45 [1.38; 1.52]), depression (OR = 2.36 [2.29; 2.43]), and anxiety disorders (OR = 2.08 [2.00; 2.17]). All of these associations were stronger in younger persons, regardless of the nature of childhood trauma. Differences between the sexes were observed only for some of these associations. CONCLUSION: Childhood trauma was associated with a higher probability of developing mental as well as somatic illness in adulthood. As childhood trauma is an element of individual history that the victim has little to no control over, and because the illnesses that can arise in adulthood in association with it are a heavy burden on the affected persons and on society, there is a need for research on these associations and for the development of preventive measures.

Association between childhood maltreatment and adult cortisol concentrations mediated through subjective health complaints.

Background: Lower cortisol concentrations in adulthood were repeatedly associated with more severe childhood maltreatment. Additionally, childhood maltreatment was reported to promote health risk behavior, such as smoking or alcohol consumption, and to increase the risk of mental and somatic diseases during adulthood, such as major depressive disorders or obesity. The present study investigated if health risk behavior and disease symptoms in adults mediate the associations between past childhood maltreatment and present basal serum cortisol concentrations. Methods: Data from two independent adult cohorts of the general population-based Study of Health in Pomerania (SHIP-TREND-0: N = 3,517; SHIP-START-2: N = 1,640) was used. Childhood maltreatment was assessed via the Childhood Trauma Questionnaire (CTQ). Cortisol concentrations were measured in single-point serum samples. Health risk behavior and mental and physical symptoms were used as mediators. Mediation analyses were calculated separately for both cohorts; results were integrated via meta-analyses. Results: In mediator-separated analyses, associations between childhood maltreatment and basal serum cortisol concentrations were partly mediated by depressive symptoms (BDI-II: ßindirect effect = -.011, pFDR = .017, 21.0% mediated) and subjective somatic health complaints (somatic complaints: ßindirect effect = -.010, pFDR = .005, 19.4% mediated). In the second step, both mediators were simultaneously integrated into one mediation model. The model replicated the mediation effects of the subjective somatic health complaints (whole model: ßindirect effect = -.014, p = .001, 27.6% mediated; BDI-II: ßindirect effect = -.006, p = .163, 11.4% mediated, somatic complaints: ßindirect effect = -.020, p = .020, 15.5% mediated). Conclusion: The results support the hypothesis that the long-lasting effects of childhood maltreatment on the stress response system are partly mediated through self-perceived disease symptoms. However, no mediation was found for health risk behavior or physically measured mediators. Mediation models with multiple simultaneous mediators pointed to a relevant overlap between the potential mediators. This overlap should be focused on in future studies.

Cortisol and periodontitis: Prospective observational and Mendelian randomization studies.

Purpose: Cortisol has obesogenic, hyperglycemic and immunomodulating effects. Preclinical and observational research suggested that it is associated with periodontitis but the evidence for potential causality in humans is sparse. We triangulated results from prospective observational and Mendelian randomization (MR) analyses to further explore this. Methods: Using pooled data from 3,388 participants of two population cohort studies embedded in the Study of Health in Pomerania (SHIP) project, we associated serum cortisol levels with periodontal outcomes measured after a median follow-up time of 6.9 years, adjusting for confounding and selection bias using propensity score weighting and multiple imputation. We further examined the effect of genetically proxied plasma morning cortisol levels on periodontitis using two-sample MR of 17,353 cases and 28,210 controls. Results: In SHIP, we found that cortisol levels were positively associated with follow-up levels of mean clinical attachment level (CAL), deep interdental CAL and bleeding on probing but were unrelated to mean probing pocket depth and deep periodontal pockets. In MR analysis, cortisol was not associated with periodontitis. Conclusion: The observational study revealed a prospective association of spot cortisol with makers of periodontitis. Contrary to observational studies, genetically instrumented, long-term cortisol was unrelated to periodontitis. Our results find no univocal evidence that cortisol plays a role in periodontitis pathology, casting doubt on cortisol-related pathways.

Pituitary gland volumes and stress: Results of a population-based adult sample.

Early and chronic stress was reported to alter the hypothalamic-pituitary-adrenal axis functioning which regulates the secretion of cortisol. Nevertheless, few studies mainly focused on specific study populations (e.g. adolescents, pregnant women, and psychiatric patients), and researched interactive associations of pituitary volumes and single stress markers. The present study used pituitary volumes of two adult general-population cohorts of the Study of Health in Pomerania (SHIP-START-2: N = 1026, 54% Men, 30-90 years; SHIP-TREND-0: N = 1868, 53% Men, 21-82 years). In linear regression models, main effects of the pituitary volumes as well as interaction effects with childhood abuse and neglect (Childhood Trauma Questionnaire) were estimated using depressive symptoms (Beck Depression Inventory-II), and serum cortisol concentrations as outcome variables. The results of both cohorts were integrated via meta-analyses. No main effect between pituitary volumes and depressive symptoms was observed (START-2: ß = -0.004 [-0.082; 0.075], p = .929; TREND-0: ß = 0.020 [-0.033; 0.073], p = .466; Meta-analysis: ß = 0.012 [-0.031; 0.056], p = .580). However, larger pituitary volumes were associated with more depressive symptoms in participants with more severe childhood neglect (START-2: ß = 0.051 [-0.024; 0.126], p = .183; TREND-0: ß = 0.083 [0.006; 0.159], p = .034; Meta-analysis: ß = 0.066 [0.013; 0.120], p = .015). Further, larger pituitary volumes were associated with lower serum cortisol concentrations in participants with more severe depressive symptoms (START-2: ß = -0.087 [-0.145; -0.030], p = .003; TREND-0: ß = -0.053 [-0.091; -0.015], p = .006; Meta-analysis: ß = -0.063 [-0.095; -0.032], p = 8.39e-05). Summarizing, larger pituitary volumes were associated with more severe psychopathological symptoms, particularly in participants reporting early life stress. This was supported by stronger associations between pituitary volumes and cortisol concentrations in participants with more severe depressive symptoms. Future studies are needed to transfer these results into developmental stages of high hormonal changes and patient samples.

Generalised anxiety and panic symptoms in the German National Cohort (NAKO).

OBJECTIVES: Anxiety disorders (AD) are common in the general population, leading to high emotional distress and disability. The German National Cohort (NAKO) is a population-based mega-cohort study, examining participants in 16 German regions. The present study includes data of the first 101,667 participants and investigates the frequency and severity of generalised anxiety symptoms and panic attacks (PA). METHODS: The Generalised Anxiety Disorder Symptoms Scale (GAD-7) and the first part of the Patient Health Questionnaire Panic Disorder (PHQ-PD) were filled out by NAKO participants (93,002). We examined the correlation of GAD-7 and PHQ-PD with demographic variables, stress (PHQ-Stress), depression (PHQ-9) and childhood trauma (CTS). RESULTS: The total proportion of prior lifetime diagnoses of AD in the NAKO cohort reached 7.8%. Panic attacks were reported by 6.0% and possible/probable current GAD symptoms in 5.2% of the examined participants. Higher anxiety severity was associated with female sex, lower education level, German as a foreign language and younger age as well as high perceived stress and depression. CONCLUSIONS: Clinically relevant GAD symptoms as well as panic attacks are frequent in the NAKO and are associated with sociodemographic factors, and high anxiety symptoms are accompanied by pronounced stress and depression levels.

The assessment of childhood maltreatment and its associations with affective symptoms in adulthood: Results of the German National Cohort (NAKO).

OBJECTIVES: Childhood maltreatment affects 20-30% of the German population and is an important risk factor for physical and mental diseases in adult life. This study reports first results of the distribution of childhood maltreatment in the population-based mega cohort German National Cohort (NAKO) and estimates associations with affective symptoms in adulthood. METHODS: The Childhood Trauma Screener (CTS), a short version of the Childhood Trauma Questionnaire, was used in 83,995 adults (age: 20-72 years; 47.3% men) of NAKO. The five-item CTS assesses the severity of three types of childhood abuse and two types of childhood neglect. RESULTS: Overall, 21,131 participants (27.5%) reported at least one type of childhood maltreatment; 14,017 participants (18.3%) reported exactly one type and 250 participants (0.3%) reported all five types of childhood maltreatment. Small differences regarding age (mean absolute deviation around the mean (MAD)=0.47), sex (MAD = 0.07) and education (MAD = 0.82) were observed. The severity of childhood maltreatment was associated with more severe symptoms of depression (ß = 0.23), anxiety (ß = 0.21) and perceived stress (ß = 0.23) in adulthood, validated particularly for emotional abuse and emotional neglect. CONCLUSIONS: The distribution of childhood maltreatment in NAKO is similar to previous reports. Additionally, our results suggest differential associations with psychopathological symptoms for the five types of childhood maltreatment.