A meta-analysis of genome-wide studies of resilience in the German population.

Resilience is the capacity to adapt to stressful life events. As such, this trait is associated with physical and mental functions and conditions. Here, we aimed to identify the genetic factors contributing to shape resilience. We performed variant- and gene-based meta-analyses of genome-wide association studies from six German cohorts (N = 15822) using the 11-item version of the Resilience Scale (RS-11) as outcome measure. Variant- and gene-level results were combined to explore the biological context using network analysis. In addition, we conducted tests of correlation between RS-11 and the polygenic scores (PGSs) for 12 personality and mental health traits in one of these cohorts (PROCAM-2, N = 3879). The variant-based analysis found no signals associated with resilience at the genome-wide level (p < 5 × 10-8), but suggested five genomic loci (p < 1 × 10-5). The gene-based analysis identified three genes (ROBO1, CIB3 and LYPD4) associated with resilience at genome-wide level (p < 2.48 × 10-6) and 32 potential candidates (p < 1 × 10-4). Network analysis revealed enrichment of biological pathways related to neuronal proliferation and differentiation, synaptic organization, immune responses and vascular homeostasis. We also found significant correlations (FDR < 0.05) between RS-11 and the PGSs for neuroticism and general happiness. Overall, our observations suggest low heritability of resilience. Large, international efforts will be required to uncover the genetic factors that contribute to shape trait resilience. Nevertheless, as the largest investigation of the genetics of resilience in general population to date, our study already offers valuable insights into the biology potentially underlying resilience and resilience's relationship with other personality traits and mental health.

Changes in physical activity and sedentary behavior during the first COVID-19 pandemic- restrictions in Germany: a nationwide survey : Running head: physical activity during the COVID-19 restrictions.

BACKGROUND: The COVID-19 pandemic restrictions posed challenges to maintaining healthy lifestyles and physical well-being. During the first mobility restrictions from March to mid-July 2020, the German population was advised to stay home, except for work, exercise, and essential shopping. Our objective was to comprehensively assess the impact of these restrictions on changes in physical activity and sedentary behavior to identify the most affected groups. METHODS: Between April 30, 2020, and May 12, 2020, we distributed a COVID-19-specific questionnaire to participants of the German National Cohort (NAKO). This questionnaire gathered information about participants' physical activity and sedentary behavior currently compared to the time before the restrictions. We integrated this new data with existing information on anxiety, depressive symptoms, and physical activity. The analyses focused on sociodemographic factors, social relationships, physical health, and working conditions. RESULTS: Out of 152,421 respondents, a significant proportion reported altered physical activity and sedentary behavioral patterns due to COVID-19 restrictions. Over a third of the participants initially meeting the WHO's physical activity recommendation could no longer meet the guidelines during the restrictions. Participants reported substantial declines in sports activities (mean change (M) = -0.38; 95% CI: -.390; -.378; range from -2 to + 2) and reduced active transportation (M = -0.12; 95% CI: -.126; -.117). However, they also increased recreational physical activities (M = 0.12; 95% CI: .117; .126) while engaging in more sedentary behavior (M = 0.24; 95% CI: .240; .247) compared to pre-restriction levels. Multivariable linear and log-binomial regression models indicated that younger adults were more affected by the restrictions than older adults. The shift to remote work, self-rated health, and depressive symptoms were the factors most strongly associated with changes in all physical activity domains, including sedentary behavior, and the likelihood to continue following the physical activity guidelines. CONCLUSIONS: Mobility patterns shifted towards inactivity or low-intensity activities during the nationwide restrictions in the spring of 2020, potentially leading to considerable and lasting health risks.

Grip strength values and cut-off points based on over 200,000 adults of the German National Cohort - a comparison to the EWGSOP2 cut-off points.

BACKGROUND: The European Working Group on Sarcopenia in Older People (EWGSOP) updated in 2018 the cut-off points for low grip strength to assess sarcopenia based on pooled data from 12 British studies. OBJECTIVE: Comparison of the EWGSOP2 cut-off points for low grip strength to those derived from a large German sample. METHODS: We assessed the grip strength distribution across age and derived low grip strength cut-off points for men and women (peak mean -2.5 × SD) based on 200,389 German National Cohort (NAKO) participants aged 19-75 years. In 1,012 Cooperative Health Research in the Region of Augsburg (KORA)-Age participants aged 65-93 years, we calculated the age-standardised prevalence of low grip strength and time-dependent sensitivity and specificity for all-cause mortality. RESULTS: Grip strength increased in the third and fourth decade of life and declined afterwards. Calculated cut-off points for low grip strength were 29 kg for men and 18 kg for women. In KORA-Age, the age-standardised prevalence of low grip strength was 1.5× higher for NAKO-derived (17.7%) compared to EWGSOP2 (11.7%) cut-off points. NAKO-derived cut-off points yielded a higher sensitivity and lower specificity for all-cause mortality. CONCLUSIONS: Cut-off points for low grip strength from German population-based data were 2 kg higher than the EWGSOP2 cut-off points. Higher cut-off points increase the sensitivity, thereby suggesting an intervention for more patients at risk, while other individuals might receive additional diagnostics/treatment without the urgent need. Research on the effectiveness of intervention in patients with low grip strength defined by different cut-off points is needed.

Major depressive disorders increase the susceptibility to self-reported infections in two German cohort studies.

INTRODUCTION: In several claims-based studies, major depressive disorder (MDD) has been associated with increased risk of hospitalization due to acute infections. It remains unclear if this is a causal effect, and if it generalizes to an increased susceptibility to infections. METHODS: We used data of the BiDirect (n = 925) and the HaBIDS (n = 1007) cohort studies to estimate the effect of MDD on self-reported infections, which were assessed with identical infection susceptibility questionnaires in both studies. We used the Center for Epidemiologic Studies Depression Scale (CES-D) to examine if there was a dose-response relationship between depressive symptom severity and self-reported infections. RESULTS: BiDirect participants with MDD diagnosis (48%) had a higher risk of lower respiratory tract infections (incidence rate ratio 1.32, 95% confidence interval [1.00-1.75]), gastrointestinal infections (1.68 [1.30-2.16]) and fever (1.48 [1.11-1.98]) after adjusting for confounders identified by a directed acyclic graph approach. There was a dose-response relationship, i.e. individuals with higher CES-D scores reported more infections. Effect sizes were similar in HaBIDS (4% individuals with MDD). CONCLUSION: We found increased risks of mild infections in patients with MDD diagnosis and a dose-response relationship between depressive symptom severity and infection frequency. While causal immunological pathways remain unclear, the results of our study might contribute to a change in prevention strategies, e.g. by recommending vaccination against influenza and S. pneumoniae to MDD patients because observed effect sizes in our study are similar to those of patients with cardiovascular and metabolic diseases for which the respective vaccinations are recommended.

Associations Between Outcome Resilience and Sociodemographic Factors, Childhood Trauma, Personality Dimensions and Self-Rated Health in Middle-Aged Adults.

BACKGROUND: We examined how sociodemographic factors, childhood trauma, personality dimensions, and self-rated health were associated with outcome resilience and how different stressors influenced depressive symptoms. METHODS: An outcome resilience score for 213 adults was derived by means of a residualization approach. Associations between outcome resilience and sociodemographic and personality factors were evaluated using linear regression. In addition, associations between log-transformed depressive symptoms and the stressors were analyzed using multiple linear regression. A Pearson correlation coefficient between self-rated health and outcome resilience was also computed. RESULTS: Higher neuroticism was negatively and higher conscientiousness was positively associated with outcome resilience. Better self-rated health was associated with higher outcome resilience. Somatic disease events and onset of chronic mental disorders were associated with more depressive symptoms. CONCLUSIONS: Outcome resilience was significantly related to neuroticism, conscientiousness, and self-rated health. Strong associations between depressive symptoms and the stressors somatic disease event, and chronic mental disorder were observed.

A Self-administered Version of the Functioning Assessment Short Test for Use in Population-based Studies: A Pilot Study.

BACKGROUND: The Functioning Assessment Short Test (FAST) is an interviewer-administered scale assessing functional impairment originally developed for psychiatric patients. OBJECTIVES: To adapt the FAST for the general population, we developed a self-administered version of the scale and assessed its properties in a pilot study. METHODS: The original FAST scale was translated into German via forward and backward translation. Afterwards, we adjusted the scale for self-administered application and inquired participants from two ongoing studies in Germany, 'STAAB' (Würzburg) and 'BiDirect' (Münster), both recruiting subjects from the general population across a wide age range (STAAB: 30-79 years, BiDirect: 35-65 years). To assess reliability, agreement of self-assessment with proxy-assessment by partners was measured via intraclass correlation coefficient (ICC) over the FAST score. Construct validity was estimated by conducting correlations with validated scales of depression (PHQ-9), anxiety (GAD-7), and health-related quality of life (SF-12) and regression analyses using these scales besides potentially disabling comorbidities (e.g. Chronic Back Pain (CBP)). RESULTS: Participants (n=54) had a median age of 57.0 years (quartiles: 49.8, 65.3), 46.3% were female. Reliability was moderate: ICC 0.50 (95% CI 0.46-0.54). The FAST score significantly correlated with PHQ-9, GAD-7, and the mental sub-scale of SF-12. In univariable linear regression, all three scales and chronic back pain explained variance of the FAST score. In multivariable analysis, only CBP and the SF-12 remained significant predictors. CONCLUSION: The German self-administered version of the FAST yielded moderate psychometric properties in this pilot study, indicating its applicability to assess functional impairment in the general population.

Establishing the bidirectional relationship between depression and subclinical arteriosclerosis--rationale, design, and characteristics of the BiDirect Study.

BACKGROUND: Depression and cardiovascular diseases due to arteriosclerosis are both frequent and impairing conditions. Depression and (subclinical) arteriosclerosis appear to be related in a bidirectional way, and it is plausible to assume a partly joint causal relationship. However, the biological mechanisms and the behavioral pathways that lead from depression to arteriosclerosis and vice versa remain to be exactly determined. METHODS/DESIGN: This study protocol describes the rationale and design of the prospective BiDirect Study that aims at investigating the mutual relationship between depression and (subclinical) arteriosclerosis. BiDirect is scheduled to follow-up three distinct cohorts of individuals ((i) patients with acute depression (N = 999), (ii) patients after an acute cardiac event (N = 347), and (iii) reference subjects from the general population (N = 912)). Over the course of 12 years, four personal examinations are planned to be conducted. The core examination program, which will remain identical across follow-ups, comprises a personal interview (e.g. medical diagnoses, health care utilization, lifestyle and risk behavior), a battery of self-administered questionnaires (e.g. depressive symptoms, readiness to change health behavior, perceived health-related quality of life), sensory (e.g. olfaction, pain) and neuropsychological (e.g. memory, executive functions, emotional processing, manual dexterity) assessments, anthropometry, body impedance measurement, a clinical work-up regarding the vascular status (e.g. electrocardiogram, blood pressure, intima media thickness), the taking of blood samples (serum and plasma, DNA), and structural and functional resonance imaging of the brain (e.g. diffusion tensor imaging, resting-state, emotional faces processing). The present report includes BiDirect-Baseline, the first data collection wave. DISCUSSION: Due to its prospective character, the integration of three distinct cohorts, the long follow-up time window, the diligent diagnosis of depression taking depression subtypes into account, the consideration of relevant comorbidities and risk factors, the assessment of indicators of (subclinical) arteriosclerosis in different vascular territories, and the structural and functional brain imaging that is performed for a large number of participants, the BiDirect Study represents an innovative approach that combines population-based cohorts with sophisticated clinical work-up methods and that holds the potential to overcome many of the drawbacks characterizing earlier investigations.

Costs associated with insufficient physical activity in Germany: cross-sectional results from the baseline examination of the German national cohort (NAKO).

BACKGROUND: Insufficient physical activity (PA) is a leading risk factor for non-communicable diseases posing a significant economic burden to healthcare systems and societies. The study aimed to examine the differences in healthcare and indirect costs between sufficient and insufficient PA and the cost differences between PA intensity groups. METHODS: The cross-sectional analysis was based on data from 157,648 participants in the baseline examination of the German National Cohort (NAKO) study. Healthcare and indirect costs were calculated based on self-reported information on health-related resource use and productivity losses. PA in the domains leisure, transport, and work was assessed by the Global Physical Activity Questionnaire and categorized into sufficient/insufficient and intensity levels (very low/low/medium/high) based on PA recommendations of the World Health Organization. Two-part models adjusted for relevant covariates were used to estimate mean costs for PA groups. RESULTS AND CONCLUSION: Insufficiently active people had higher average annual healthcare costs (Δ €188, 95% CI [64, 311]) and healthcare plus indirect costs (Δ €482, 95% CI [262, 702]) compared to sufficiently active people. The difference was especially evident in the population aged 60 + years and when considering only leisure PA. An inverse association was observed between leisure PA and costs, whereas a direct association was found between PA at work and costs. Adjusting for the number of comorbidities reduced the differences between activity groups, but the trend persisted. The association between PA and costs differed in direction between PA domains. Future research may provide further insight into the temporal relationship between PA and costs.

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.

Mental health of individuals with pre-existing mental illnesses at the beginning of the COVID-19 pandemic: results of the German National Cohort (NAKO).

Background: The COVID-19 pandemic prompted a range of studies on mental health, with mixed results. While numerous studies reported worsened conditions in individuals with pre-existing mental disorders, others showed resilience and stability in mental health. However, longitudinal data focusing on the German population are sparse, especially regarding effects of age and pre-existing mental disorders during the early stages of the pandemic. Objectives: To assess the interplay between psychiatric history, age, and the timing of the pandemic, with a focus on understanding how these factors relate to the severity of depression and anxiety symptoms. Methods: Exploratory analyses were based on 135,445 individuals aged 20-72 years from the German National Cohort (NAKO). Depressive and anxiety symptoms were assessed before and after the first wave of the pandemic. Inferential statistical analyses and negative binomial regression models were calculated. Results: Persons with a self-reported psychiatric history exhibited comparable levels of depression and anxiety symptom severity after the first wave of the pandemic compared to the time before. In contrast, individuals without a psychiatric history, particularly those in their 20s to 40s, experienced an increase in mental health symptom severity during the first wave of the pandemic. Limitations: Analyses focuses on the first wave of the pandemic, leaving the long-term mental health effects unexplored. Conclusion: Future research should consider age-specific and mental-health-related factors when addressing global health crises. Additionally, it is important to explore factors influencing resilience and adaptation, aiming to develop targeted interventions and informed policies for effective mental health management during pandemics.

Large-scale assessment of physical activity in a population using high-resolution hip-worn accelerometry: the German National Cohort (NAKO).

Large population-based cohort studies utilizing device-based measures of physical activity are crucial to close important research gaps regarding the potential protective effects of physical activity on chronic diseases. The present study details the quality control processes and the derivation of physical activity metrics from 100 Hz accelerometer data collected in the German National Cohort (NAKO). During the 2014 to 2019 baseline assessment, a subsample of NAKO participants wore a triaxial ActiGraph accelerometer on their right hip for seven consecutive days. Auto-calibration, signal feature calculations including Euclidean Norm Minus One (ENMO) and Mean Amplitude Deviation (MAD), identification of non-wear time, and imputation, were conducted using the R package GGIR version 2.10-3. A total of 73,334 participants contributed data for accelerometry analysis, of whom 63,236 provided valid data. The average ENMO was 11.7 ± 3.7 mg (milli gravitational acceleration) and the average MAD was 19.9 ± 6.1 mg. Notably, acceleration summary metrics were higher in men than women and diminished with increasing age. Work generated in the present study will facilitate harmonized analysis, reproducibility, and utilization of NAKO accelerometry data. The NAKO accelerometry dataset represents a valuable asset for physical activity research and will be accessible through a specified application process.

Differential effects of temporal regularity on auditory-evoked response amplitude: a decrease in silence and increase in noise.

BACKGROUND: In daily life, we are continuously exposed to temporally regular and irregular sounds. Previous studies have demonstrated that the temporal regularity of sound sequences influences neural activity. However, it remains unresolved how temporal regularity affects neural activity in noisy environments, when attention of the listener is not focused on the sound input. METHODS: In the present study, using magnetoencephalography we investigated the effects of temporal regularity in sound signal sequencing (regular vs. irregular) in silent versus noisy environments during distracted listening. RESULTS: The results demonstrated that temporal regularity differentially affected the auditory-evoked N1m response depending on the background acoustic environment: the N1m amplitudes elicited by the temporally regular sounds were smaller in silence and larger in noise than those elicited by the temporally irregular sounds. CONCLUSIONS: Our results indicate that the human auditory system is able to involuntarily utilize temporal regularity in sound signals to modulate the neural activity in the auditory cortex in accordance with the surrounding acoustic environment.

The relationship between cortisol awakening response and trait resilience in two patient cohorts and one population-based cohort.

OBJECTIVES: We examined (1) the proportion of cortisol awakening non-responders, (2) the association between cortisol awakening response (CAR) and trait resilience, and (3) the association between CAR increase and trait resilience in two patient cohorts (depression and myocardial infarction [CVD]) and one population-based cohort. METHODS: Eight hundred and eighty study participants delivered CAR scores (response and increase) based on three self-collected saliva samples and a trait resilience score. Descriptive data of CAR non-responders were reported and calculated. Associations between CAR response/increase and trait resilience, sociodemographic and compliance variables were evaluated using multiple logistic and multiple linear regression analyses stratified by cohort. RESULTS: The proportion of CAR non-responders was high in all cohorts (57% depression cohort, 53.4% CVD cohort, 51.6% control cohort). In the depression cohort age was associated with CAR response and increase. In the CVD cohort salivary collection on a weekday was associated with CAR response and awakening time with CAR increase. In the control cohort age was associated with CAR response and sex with CAR increase. CONCLUSIONS: We observed many CAR non-responders and significant associations between CAR response and CAR increase with single sociodemographic and compliance variables. We did not find significant relationships between CAR response or increase and trait resilience.

Periodic limb movements in sleep are linked to decreased hippocampus and amygdala volumes in the population-based BiDirect Study.

STUDY OBJECTIVES: Even though numerous studies indicate that sleep disorders are associated with altered brain morphology, MRI studies focusing on periodic limb movements in sleep (PLMS) are scarce. Our aim was to investigate the association of PLMS with global and regional gray matter volumes as well as white matter hyperintensity (WMH) volume. METHODS: One hundred and eighty-nine subjects (57.0 ± 7.8 years, women: 50.5%) of the population-based BiDirect Study underwent a single-night polysomnography (PSG). Standard criteria of the American Academy of Sleep Medicine were applied to evaluate sleep characteristics and calculate the PLMS index (PLMSI). T1w and FLAIR images were acquired with cerebral MRI at 3 Tesla. Voxel-based morphometry was performed to determine the total gray matter volume as well as the volume of cortical segments and subcortical gray matter areas using SPM12 and CAT12. The WMH volume was quantified with the Brain Intensity AbNormality Classification Algorithm. The independent relationship between MRI markers and PLMSI was analyzed using multivariable linear regression with adjustment for age, sex, body mass index, intracranial volume, PSG scorer, PSG device, sleep apnea, and the use of antidepressants. RESULTS: PLMSI was not significantly related to global gray matter volume and WMH volume. However, significant inverse associations of the PLMSI with the volume of the hippocampus (left and right hemisphere) and left amygdala were observed. CONCLUSIONS: A significant relationship between a higher PLMSI and lower volumes of the hippocampus and amygdala was found among the participants of the BiDirect Study. Since these associations are based on exploratory analyses, further replications are required before drawing firm conclusions.

Seropositivity of Borrelia burgdorferi s.l. in Germany-an analysis across four German National Cohort (NAKO) study sites.

Lyme borreliosis (LB) is caused by the transmission of Borrelia burgdorferi s.l. from ticks to humans. Climate affects tick abundance, and climate change is projected to promote shifts in abundance in Europe, potentially increasing human exposure. We analyzed serum samples collected between the years 2014-2019 from German National Cohort (NAKO) participants at four study sites (Augsburg, Berlin, Hanover, Münster) for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies using an enzyme-linked immunosorbent assay (ELISA) and line blot immunoassay as confirmatory test for positive and equivocal ELISA samples. We reported crude and weighted seropositivity proportions for local estimates. We used mixed model analysis to investigate associated factors, such as age, sex, migration background, or animal contacts. We determined the serostatus of 14,207 participants. The weighted seropositivity proportions were 3.4% (IgG) and 0.4% (IgM) in Augsburg, 4.1% (IgG) and 0.6% (IgM) in northern Berlin, 3.0% (IgG) and 0.9% (IgM) in Hanover, and 2.7% (IgG) and 0.6% (IgM) in Münster. We found higher odds for IgG seropositivity with advancing age (p < 0.001), among males compared to females (p < 0.001) and reduced odds among participants with migration background compared to those without (p = 0.001). We did not find evidence for an association between serostatus and depression, children within the household, or animal contact, respectively. We found low seropositivity proportions and indications of differences across the study locations, although between-group comparisons did not yield significant results. Comparisons to earlier research are subject to important limitations; however, our results indicate no major increases in seropositivity over time. Nevertheless, monitoring of seropositivity remains critical in light of potential climate-related Borrelia exposure.

Effects of age and sex on outcomes of the Q-Motor speeded finger tapping and grasping and lifting tests-findings from the population-based BiDirect Study.

Background: Q-Motor is a suite of motor tests originally designed to assess motor symptoms in Huntington's disease. Among others, Q-Motor encompasses a finger tapping task and a grasping and lifting task. To date, there are no systematic investigations regarding effects of variables which may affect the performance in specific Q-Motor tests per se, and normative Q-Motor data based on a large population-based sample are not yet available. Objective: We investigated effects of age and sex on five selected Q-Motor outcomes representing the two core Q-Motor tasks speeded finger tapping and grasping and lifting in a community sample of middle-aged to elderly adults. Furthermore, we explored effects of the potentially mediating variables educational attainment, alcohol consumption, smoking status, and depressive symptoms. Moreover, we explored inter-examiner variability. Finally, we compared the findings to findings for the Purdue Pegboard test. Methods: Based on a sample of 726 community-dwelling adults and using multiple (Gaussian) regression analysis, we modeled the motor outcomes using age, sex, years in full-time education, depressive symptoms in the past seven days, alcohol consumption in the past seven days, and smoking status as explanatory variables. Results: With regard to the Q-Motor tests, we found that more advanced age was associated with reduced tapping speed, male sex was associated with increased tapping speed and less irregularity, female sex was associated with less involuntary movement, more years of education were associated with increased tapping speed and less involuntary movement, never smoking was associated with less involuntary movement compared to current smoking, and more alcohol consumed was associated with more involuntary movement. Conclusion: The present results show specific effects of age and sex on Q-Motor finger tapping and grasping and lifting performance. In addition, besides effects of education, there also were specific effects of smoking status and alcohol consumption. Importantly, the present study provides normative Q-Motor data based on a large population-based sample. Overall, the results are in favor of the feasibility and validity of Q-Motor finger tapping and grasping and lifting for large observational studies. Due to their low task-complexity and lack of placebo effects, Q-Motor tests may generate additional value in particular with regard to clinical conditions such as Huntington's or Parkinson's disease.

Birth Order, Caesarean Section, or Daycare Attendance in Relation to Child- and Adult-Onset Type 1 Diabetes: Results from the German National Cohort.

(1) Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to "only-children", HRs for second- or later-born individuals were 0.70 (95% CI = 0.50-0.96) and 0.65 (95% CI = 0.45-0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults' T1D risk assessment for early detection.

Childhood trauma and personality explain more variance in depression scores than sociodemographic and lifestyle factors - Results from the BiDirect Study.

OBJECTIVE: Sociodemographic and lifestyle factors, childhood adversities, and personality aspects have been identified as contributing to the onset and course of depression. However, only few studies examined all aspects concomitantly in different populations. This was the objective of the study presented here. METHODS: The BiDirect Study includes three distinct cohorts: Cross-sectional data for 670 patients with depression (DEP), 283 patients with cardiovascular disease (CVD), and 787 population controls (POP) were available for the present analysis. Participants answered interviews and filled in questionnaires assessing depression details, childhood trauma, the Big Five personality traits, trait resilience as well as socioeconomic and lifestyle factors. Descriptive statistics and hierarchical linear regression analyses were employed to identify those factors, which contributed significantly to the explanation of depression severity scores (assessed by the Center for Epidemiologic Studies Depression Scale, CESD). RESULTS: In all three cohorts, the psychological variables explained most variance in depression scores (35-44%), while sociodemographic and lifestyle factors explained only very little variance (1-2%). When all postulated predictors were entered in the same regression model, higher neuroticism and lower resilience scores were associated with higher depression severity levels in all three cohorts, while higher childhood trauma proved significant in the cardiovascular and population cohort. CONCLUSION: Childhood trauma, neuroticism, and low resilience are significantly associated with depression in different populations. Although a considerable part of the variance in depression severity levels was explained by the variables studied here, more research on the impact of lifestyle and social factors on depression is needed.

Sleep characteristics, cognitive performance, and gray matter volume: findings from the BiDirect Study.

STUDY OBJECTIVES: Sleep is essential for restorative metabolic changes and its physiological correlates can be examined using overnight polysomnography. However, the association between physiological sleep characteristics and brain structure is not well understood. We aimed to investigate gray matter volume and cognitive performance related to physiological sleep characteristics. METHODS: Polysomnographic recordings from 190 community-dwelling participants were analyzed with a principal component analysis in order to identify and aggregate shared variance into principal components. The relationship between aggregated sleep components and gray matter volume was then analyzed using voxel-based morphometry. In addition, we explored how cognitive flexibility, selective attention, and semantic fluency were related to aggregated sleep components and gray matter volume. RESULTS: Three principal components were identified from the polysomnographic recordings. The first component, primarily described by apnea events and cortical arousal, was significantly associated with lower gray matter volume in the left frontal pole. This apnea-related component was furthermore associated with lower cognitive flexibility and lower selective attention. CONCLUSIONS: Sleep disrupted by cortical arousal and breathing disturbances is paralleled by lower gray matter volume in the frontal pole, a proposed hub for the integration of cognitive processes. The observed effects provide new insights on the interplay between disrupted sleep, particularly breathing disturbances and arousal, and the brain.

Genetic factors influencing a neurobiological substrate for psychiatric disorders.

A retrospective meta-analysis of magnetic resonance imaging voxel-based morphometry studies proposed that reduced gray matter volumes in the dorsal anterior cingulate and the left and right anterior insular cortex-areas that constitute hub nodes of the salience network-represent a common substrate for major psychiatric disorders. Here, we investigated the hypothesis that the common substrate serves as an intermediate phenotype to detect genetic risk variants relevant for psychiatric disease. To this end, after a data reduction step, we conducted genome-wide association studies of a combined common substrate measure in four population-based cohorts (n = 2271), followed by meta-analysis and replication in a fifth cohort (n = 865). After correction for covariates, the heritability of the common substrate was estimated at 0.50 (standard error 0.18). The top single-nucleotide polymorphism (SNP) rs17076061 was associated with the common substrate at genome-wide significance and replicated, explaining 1.2% of the common substrate variance. This SNP mapped to a locus on chromosome 5q35.2 harboring genes involved in neuronal development and regeneration. In follow-up analyses, rs17076061 was not robustly associated with psychiatric disease, and no overlap was found between the broader genetic architecture of the common substrate and genetic risk for major depressive disorder, bipolar disorder, or schizophrenia. In conclusion, our study identified that common genetic variation indeed influences the common substrate, but that these variants do not directly translate to increased disease risk. Future studies should investigate gene-by-environment interactions and employ functional imaging to understand how salience network structure translates to psychiatric disorder risk.