Maternal socioeconomic and lifestyle factors and life dissatisfaction associated with a small for gestational age infant. The Survey of Neonates in Pomerania (SNiP).

PURPOSE: The aim is to investigate the associations of the mother's socioeconomic and lifestyle factors and life satisfaction with the delivery of a small for gestational age (SGA) infant. METHODS: Data from 4598 participants of the population-based birth cohort study Survey of Neonates in Pomerania (SniP) including comprehensive information on pregnancies, mothers, and their offspring in Western Pomerania, Germany were used in this study. The associations were analyzed using linear and logistic regression models. RESULTS: After logistic regression analysis adjusted for height of the mother, women who delivered SGA infants, had lower education (p < 0.01) and smoked more frequently during pregnancy (p < 0.01) compared with mothers of adequate for gestational age (AGA) neonates. A mother with less than 10 years of education and one who continued smoking during pregnancy had an odds ratio (OR) of 2.23 [95% confidence interval (CI) = 1.44 to 3.46] and 2.68 (95% CI = 2.06-3.49) of having an SGA infant, respectively. There was no association between the employment of the mother (p = 0.28), the monthly income (p = 0.09), the family status (p = 0.80), the number of friendships outside the household that the mother would not wish to relinquish (p = 0.47), the number of people that she could rely on in case of an emergency (p = 0.75), or alcohol consumption prior to (p = 0.14) or during the pregnancy (p = 0.99) with SGA. Finally, women who delivered SGA infants were more frequently dissatisfied with their employment (p = 0.03) and financial status (p < 0.01). CONCLUSIONS: Women who delivered SGA infants had more associated socioeconomic and lifestyle risk factors and were more frequently dissatisfied with their life conditions than mothers of AGA neonates.

Genome-wide interaction study with major depression identifies novel variants associated with cognitive function.

Major Depressive Disorder (MDD) often is associated with significant cognitive dysfunction. We conducted a meta-analysis of genome-wide interaction of MDD and cognitive function using data from four large European cohorts in a total of 3510 MDD cases and 6057 controls. In addition, we conducted analyses using polygenic risk scores (PRS) based on data from the Psychiatric Genomics Consortium (PGC) on the traits of MDD, Bipolar disorder (BD), Schizophrenia (SCZ), and mood instability (MIN). Functional exploration contained gene expression analyses and Ingenuity Pathway Analysis (IPA®). We identified a set of significantly interacting single nucleotide polymorphisms (SNPs) between MDD and the genome-wide association study (GWAS) of cognitive domains of executive function, processing speed, and global cognition. Several of these SNPs are located in genes expressed in brain, with important roles such as neuronal development (REST), oligodendrocyte maturation (TNFRSF21), and myelination (ARFGEF1). IPA® identified a set of core genes from our dataset that mapped to a wide range of canonical pathways and biological functions (MPO, FOXO1, PDE3A, TSLP, NLRP9, ADAMTS5, ROBO1, REST). Furthermore, IPA® identified upstream regulator molecules and causal networks impacting on the expression of dataset genes, providing a genetic basis for further clinical exploration (vitamin D receptor, beta-estradiol, tadalafil). PRS of MIN and meta-PRS of MDD, MIN and SCZ were significantly associated with all cognitive domains. Our results suggest several genes involved in physiological processes for the development and maintenance of cognition in MDD, as well as potential novel therapeutic agents that could be explored in patients with MDD associated cognitive dysfunction.

Cardiorespiratory Fitness and Gray Matter Volume in the Temporal, Frontal, and Cerebellar Regions in the General Population.

OBJECTIVE: To analyze the association between cardiorespiratory fitness (CRF) and global and local brain volumes. PARTICIPANTS AND METHODS: We studied 2103 adults (21-84 years old) from 2 independent population-based cohorts (Study of Health in Pomerania, examinations from June 25, 2008, through September 30, 2012). Cardiorespiratory fitness was measured using peak oxygen uptake (VO2peak), oxygen uptake at the anaerobic threshold (VO2@AT), and maximal power output from cardiopulmonary exercise testing on a bicycle ergometer. Magnetic resonance imaging brain data were analyzed by voxel-based morphometry using regression models with adjustment for age, sex, education, smoking, body weight, systolic blood pressure, glycated hemoglobin level, and intracranial volume. RESULTS: Volumetric analyses revealed associations of CRF with gray matter (GM) volume and total brain volume. After multivariable adjustment, a 1-standard deviation increase in VO2peak was related to a 5.31 cm³ (95% CI, 3.27 to 7.35 cm³) higher GM volume. Whole-brain voxel-based morphometry analyses revealed significant positive relations between CRF and local GM volumes. The VO2peak was strongly associated with GM volume of the left middle temporal gyrus (228 voxels), the right hippocampal gyrus (146 voxels), the left orbitofrontal cortex (348 voxels), and the bilateral cingulate cortex (68 and 43 voxels). CONCLUSION: Cardiorespiratory fitness was positively associated with GM volume, total brain volume, and specific GM and white matter clusters in brain areas not primarily involved in movement processing. These results, from a representative population sample, suggest that CRF might contribute to improved brain health and might, therefore, decelerate pathology-specific GM decrease.

Inflammatory markers and imaging patterns of advanced brain aging in the general population.

Inflammaging describes the complexity between low-grade chronic inflammation with the pathogenesis of brain aging and Alzheimer´s disease (AD). We aimed to find associations of inflammatory markers: i) white blood cell count (WBC), ii) high-sensitivity C-reactive protein (hs-CRP), and iii) fibrinogen with brain structures, sensitive neuroimaging markers of advanced brain aging and AD-like atrophy, and cognitive aging scores. We analyzed magnetic resonance imaging (MRI) scans of 2204 participants from the Study of Health in Pomerania-2 (SHIP-2) and SHIP-Trend (55.6% women, mean age 52.4±13.7 years). Associations of the inflammatory markers with specific brain signatures of brain aging (SPARE-BA), AD-like brain atrophy (SPARE-AD) and white matter disease (white matter hyperintensities volume (WMHV)) were investigated. Furthermore we explored their association with general brain structures including total brain volume (TBV), gray matter volume (GMV), and white matter volume (WMV), as well as cognitive scores (Nurnberger Age Inventory (NAI); Verbal Learning and Memory Test (VLMT). We adjusted for multiple vascular risk factors (VRF; e.g. smoking and blood pressure) and corresponding medication use to take their brain aging effects into account and corrected for false-discovery rate (FDR). Results:WBC was inversely associated with SPARE-BA (FDR-adjusted p=0.003), TBV (FDR-adjusted p=0.019) and GMV (FDR-adjusted p= 0.017). GMV was also inversely associated with hs-CRP (FDR-adjusted p=0.039) and fibrinogen (FDR-adjusted p=0.039). None of the inflammatory markers was associated with WMHV. Regression analysis also revealed a trend-level interaction between intake of antiinflammatory medication and hs-CRP with brain aging (SPARE-BA; FDR-adjusted p=0.062). Inflammatatory markers are associated with neuroimaging markers, with elevated WBC leading to significant acceleration in brain aging patterns but not with AD-like imaging structural changes. Given the overlap between accelerated brain aging and AD-like atrophy, increased WBC might be associated with global dementia symptoms due to this overlap in atrophy patterns. Elevated WBC may be not causal to preclinical AD dementia, but an accessory symptom of inflammaging. At population level, our results support the relevant roles of inflammatory markers on brain aging related atrophy.

Brain-derived neurotrophic factor is related with adverse cardiac remodeling and high NTproBNP.

The brain-derived neurotrophic factor (BDNF) is a neuronal growth factor essential for normal cardiac contraction and relaxation. Alterations in BDNF signaling are related to the development of cardiovascular disease. Whether BDNF is related to subclinical cardiac remodeling is unclear. We related BDNF with echocardiographic parameters and NTproBNP in a large population-based cohort (n = 2,976, median age 48 years; 45% male). Transthoracic echocardiography was performed on all subjects and BDNF was measured by ELISA. Study participants with severe kidney dysfunction, previous myocardial infarction, and LV ejection fraction <40% were excluded. Linear regression models were adjusted for age, sex, lean mass, fat mass, current smoking, systolic blood pressure and depression. Low BDNF was associated with high NTproBNP. A 10,000 pg/ml lower BDNF was related with a 2.5 g higher (95%-confidence interval [CI]: 0.2 to 4.9; p = 0.036) LV mass, 0.01 cm posterior wall thickness (0.003 to 0.022; p = 0.007) and 0.02 E/A ratio (0.003 to 0.042, p = 0.026). Here we show that low BDNF levels are related with adverse cardiac remodeling and higher levels of NTproBNP. Further research is warranted to assess if BDNF may be used to monitor neuronal-cardiac damage during CVD progression.

Sex-Specific Associations of Brain-Derived Neurotrophic Factor and Cardiorespiratory Fitness in the General Population.

The brain-derived neurotrophic factor (BDNF) was initially considered to be neuron-specific. Meanwhile, this neurotrophin is peripherally also secreted by skeletal muscle cells and increases due to exercise. Whether BDNF is related to cardiorespiratory fitness (CRF) is currently unclear. We analyzed the association of serum BDNF levels with CRF in the general population (Study of Health in Pomerania (SHIP-TREND) from Northeast Germany; n = 1607, 51% female; median age 48 years). Sex-stratified linear regression models adjusted for age, height, smoking, body fat, lean mass, physical activity, and depression analyzed the association between BDNF and maximal oxygen consumption (VO2peak), maximal oxygen consumption normalized for body weight (VO2peak/kg), and oxygen consumption at the anaerobic threshold (VO2@AT). In women, 1 mL/min higher VO2peak, VO2peak/kg, and VO2@AT were associated with a 2.43 pg/mL (95% confidence interval [CI]: 1.16 to 3.69 pg/mL; p = 0.0002), 150.66 pg/mL (95% CI: 63.42 to 237.90 pg/mL; p = 0.0007), and 2.68 pg/mL (95% CI: 0.5 to 4.8 pg/mL; p = 0.01) higher BDNF serum concentration, respectively. No significant associations were found in men. Further research is needed to understand the sex-specific association between CRF and BDNF.

Prospective associations of androgens and sex hormone-binding globulin with 12-month, lifetime and incident anxiety and depressive disorders in men and women from the general population.

BACKGROUND: Findings on associations of androgens and sex hormone-binding globulin (SHBG) with anxiety and depressive disorders in the general population remain inconclusive. METHODS: We used data of n = 993 men and n = 980 women from the Study of Health in Pomerania (SHIP, a prospective-longitudinal general population study from northeastern Germany). Immunoassay-measured serum concentrations of total testosterone, androstenedione and SHBG were assessed when participants were aged 20-80. 12-month, lifetime and incident DSM-IV anxiety and depressive disorders were assessed with the DIA-X/M-CIDI at 10-year follow-up, when participants were aged 29-89. Logistic regressions were adjusted for age, smoking, alcohol consumption, physical activity, waist circumference, hypertension and oral contraceptive use (women only) at baseline and follow-up interval. RESULTS: In men and women, androgens and SHBG were not associated significantly with incident anxiety and depressive disorders. In men, higher total testosterone predicted any 12-month (OR = 1.46) and lifetime (OR = 1.34) anxiety disorder, lifetime social phobia (OR = 2.15), and 12-month (OR = 1.48) and lifetime (OR = 1.39) specific phobia, but neither 12-month nor lifetime depression. Moreover, androstenedione in men interacted with age in predicting lifetime anxiety disorders (OR = 0.98): Higher androstenedione more strongly predicted lifetime anxiety in younger vs. older men. These findings, however, did not survive correction for multiple testing. In women, androgens and SHBG were not associated significantly with 12-month and lifetime anxiety and depressive disorders. LIMITATIONS: The follow-up period was relatively long and other factors might have affected the examined associations. CONCLUSIONS: Higher serum total testosterone in men and androstenedione in younger men may relate to an increased risk of anxiety disorders.

Alcohol consumption and cardiorespiratory fitness in five population-based studies.

Background Poor cardiorespiratory fitness is a risk factor for cardiovascular morbidity. Alcohol consumption contributes substantially to the burden of disease, but its association with cardiorespiratory fitness is not well described. We examined associations between average alcohol consumption, heavy episodic drinking and cardiorespiratory fitness. Design The design of this study was as a cross-sectional population-based random sample. Methods We analysed data from five independent population-based studies (Study of Health in Pomerania (2008-2012); German Health Interview and Examination Survey (2008-2011); US National Health and Nutrition Examination Survey (NHANES) 1999-2000; NHANES 2001-2002; NHANES 2003-2004) including 7358 men and women aged 20-85 years, free of lung disease or asthma. Cardiorespiratory fitness, quantified by peak oxygen uptake, was assessed using exercise testing. Information regarding average alcohol consumption (ethanol in grams per day (g/d)) and heavy episodic drinking (5+ or 6+ drinks/occasion) was obtained from self-reports. Fractional polynomial regression models were used to determine the best-fitting dose-response relationship. Results Average alcohol consumption displayed an inverted U-type relation with peak oxygen uptake ( p-value<0.0001), after adjustment for age, sex, education, smoking and physical activity. Compared to individuals consuming 10 g/d (moderate consumption), current abstainers and individuals consuming 50 and 60 g/d had significantly lower peak oxygen uptake values (ml/kg/min) (ß coefficients = -1.90, ß = -0.06, ß = -0.31, respectively). Heavy episodic drinking was not associated with peak oxygen uptake. Conclusions Across multiple adult population-based samples, moderate drinkers displayed better fitness than current abstainers and individuals with higher average alcohol consumption.

Microglia ablation alleviates myelin-associated catatonic signs in mice.

The underlying cellular mechanisms of catatonia, an executive "psychomotor" syndrome that is observed across neuropsychiatric diseases, have remained obscure. In humans and mice, reduced expression of the structural myelin protein CNP is associated with catatonic signs in an age-dependent manner, pointing to the involvement of myelin-producing oligodendrocytes. Here, we showed that the underlying cause of catatonic signs is the low-grade inflammation of white matter tracts, which marks a final common pathway in Cnp-deficient and other mutant mice with minor myelin abnormalities. The inhibitor of CSF1 receptor kinase signaling PLX5622 depleted microglia and alleviated the catatonic symptoms of Cnp mutants. Thus, microglia and low-grade inflammation of myelinated tracts emerged as the trigger of a previously unexplained mental condition. We observed a very high (25%) prevalence of individuals with catatonic signs in a deeply phenotyped schizophrenia sample (n = 1095). Additionally, we found the loss-of-function allele of a myelin-specific gene (CNP rs2070106-AA) associated with catatonia in 2 independent schizophrenia cohorts and also associated with white matter hyperintensities in a general population sample. Since the catatonic syndrome is likely a surrogate marker for other executive function defects, we suggest that microglia-directed therapies may be considered in psychiatric disorders associated with myelin abnormalities.

Integrating evolutionary and regulatory information with a multispecies approach implicates genes and pathways in obsessive-compulsive disorder.

Obsessive-compulsive disorder is a severe psychiatric disorder linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding and regulatory elements for 608 genes potentially involved in obsessive-compulsive disorder in human, dog, and mouse. Using a new method that prioritizes likely functional variants, we compared 592 cases to 560 controls and found four strongly associated genes, validated in a larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains. CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants, of which at least six (35%) alter transcription factor-DNA binding in neuroblastoma cells. NRXN1 achieves genome-wide significance (p = 6.37 × 10-11) when we include 33,370 population-matched controls. Our findings suggest synaptic adhesion as a key component in compulsive behaviors, and show that targeted sequencing plus functional annotation can identify potentially causative variants, even when genomic data are limited.Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with symptoms including intrusive thoughts and time-consuming repetitive behaviors. Here Noh and colleagues identify genes enriched for functional variants associated with increased risk of OCD.

Associations of androgens with depressive symptoms and cognitive status in the general population.

OBJECTIVES: Associations between androgens and depressive symptoms were mostly reported from cross-sectional and patient-based studies. STUDY DESIGN/MAIN OUTCOME MEASURES: Longitudinal data from 4,110 participants of the Study of Health in Pomerania were used to assess sex-specific associations of baseline total and free testosterone, androstenedione and sex hormone-binding globulin with incident depressive symptoms and cognitive status at 5- and 10-year follow-up. RESULTS: Despite sex-specific differences in depressive symptoms prevalence at baseline (women: 17.4%, men: 8.1%), cross-sectional analyses showed no associations between sex hormones and depressive symptoms. In age-adjusted longitudinal analyses, total testosterone was associated with incident depressive symptoms (relative risk at 5-year follow-up: 0.73, 95% confidence interval: 0.58-0.92). Similarly, age-adjusted analyses showed a positive association between sex hormone-binding globulin and cognitive status in men (ß-coefficient per standard deviation: 0.44, 95% confidence interval: 0.13-0.74). In women, age-adjusted associations of androstenedione with baseline depressive symptoms (relative risk: 0.88, 95% confidence interval: 0.77-0.99) were found. None of the observed associations remained after multivariable adjustment. CONCLUSIONS: The present population-based, longitudinal study revealed inverse associations between sex hormones and depressive symptoms. However, the null finding after multivariable adjustment suggests, that the observed associations were not independent of relevant confounders including body mass index, smoking and physical inactivity. Furthermore, the low number of incident endpoints in our non-clinical population-based sample limited the statistical power and reduced the chance to detect a statistically significant effect.

Mortality is associated with inflammation, anemia, specific diseases and treatments, and molecular markers.

Lifespan is a complex trait, and longitudinal data for humans are naturally scarce. We report the results of Cox regression and Pearson correlation analyses using data of the Study of Health in Pomerania (SHIP), with mortality data of 1518 participants (113 of which died), over a time span of more than 10 years. We found that in the Cox regression model based on the Bayesian information criterion, apart from chronological age of the participant, six baseline variables were considerably associated with higher mortality rates: smoking, mean attachment loss (i.e. loss of tooth supporting tissue), fibrinogen concentration, albumin/creatinine ratio, treated gastritis, and medication during the last 7 days. Except for smoking, the causative contribution of these variables to mortality was deemed inconclusive. In turn, four variables were found to be associated with decreased mortality rates: treatment of benign prostatic hypertrophy, treatment of dyslipidemia, IGF-1 and being female. Here, being female was an undisputed causative variable, the causal role of IFG-1 was deemed inconclusive, and the treatment effects were deemed protective to the degree that treated subjects feature better survival than respective controls. Using Cox modeling based on the Akaike information criterion, diabetes, mean corpuscular hemoglobin concentration, red blood cell count and serum calcium were also associated with mortality. The latter two, together with albumin and fibrinogen, aligned with an"integrated albunemia" model of aging proposed recently.

Associations of Leisure-Time and Occupational Physical Activity and Cardiorespiratory Fitness With Incident and Recurrent Major Depressive Disorder, Depressive Symptoms, and Incident Anxiety in a General Population.

OBJECTIVE: Physical activity and cardiorespiratory fitness may help prevent depression and anxiety. Previous studies have been limited by error-prone measurements. We examined whether self-reported physical activity domains and peak exercise capacity (peakVO2) are associated with incident and recurrent major depressive disorder (MDD), depressive symptoms, and anxiety disorders. METHODS: This was a prospective population-based study of 1,080 adult men and women (25-83 years) with a median follow-up of 4.5 years and measures of physical activity during leisure time, sports, and work (Baecke questionnaire); a measure of depressive symptoms (Beck Depression Inventory II); symptom-limited cycle ergometer testing (peakVO2, oxygen uptake at anaerobic threshold [VO2@AT], maximum power output at peak exertion); and a structured psychiatric interview (Munich Composite International Diagnostic Interview). Baseline data were collected between 2002 and 2006, and follow-up data, between 2007 and 2010. RESULTS: After adjustment for age, sex, education, smoking, alcohol consumption, and waist circumference, the relative risks for incident MDD per standard deviation (SD) increase in leisure-time physical activity, physical activity during sport, physical activity at work, peakVO2, VO2@AT, and maximum power output were 1.002 (95% confidence interval, 0.90 to 1.12), 1.02 (0.90 to 1.15), 0.94 (0.80 to 1.10), 0.71 (0.52 to 0.98), 0.83 (0.66 to 1.04), and 0.71 (0.52 to 0.96), respectively. PeakVO2, VO2@AT, and maximum power output were associated with recurrent MDD, depressive symptoms, and anxiety. PeakVO2 was more strongly related to the co-occurrence of MDD and anxiety (adjusted odds ratio [OR] = 0.45 [0.24 to 0.84]) than depression or anxiety alone (OR = 0.71 [0.53 to 0.94]). CONCLUSIONS: Greater cardiorespiratory fitness but not domain-specific physical activity was associated with a lower incidence of MDD and clinical anxiety.

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype.

BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. RESULTS: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10-9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10-9). CONCLUSIONS: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.

Measuring Biological Age via Metabonomics: The Metabolic Age Score.

Chronological age is one of the most important risk factors for adverse clinical outcome. Still, two individuals at the same chronological age could have different biological aging states, leading to different individual risk profiles. Capturing this individual variance could constitute an even more powerful predictor enhancing prediction in age-related morbidity. Applying a nonlinear regression technique, we constructed a metabonomic measurement for biological age, the metabolic age score, based on urine data measured via (1)H NMR spectroscopy. We validated the score in two large independent population-based samples by revealing its significant associations with chronological age and age-related clinical phenotypes as well as its independent predictive value for survival over approximately 13 years of follow-up. Furthermore, the metabolic age score was prognostic for weight loss in a sample of individuals who underwent bariatric surgery. We conclude that the metabolic age score is an informative measurement of biological age with possible applications in personalized medicine.

Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10(-8)) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68-2.81, P = 8.1×10(-8)), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26-1.82, P = 2.9×10(-6)), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66-0.89, P = 6.5×10(-4)). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22-1.54, P = 1.2×10(-7) and OR: 1.25, 95% CI 1.12-1.39, P = 6.2×10(-5)). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18-2.10, P = 1.9×10(-3)). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction.

[The childhood trauma screener (CTS) - development and validation of cut-off-scores for classificatory diagnostics]. / Der Childhood Trauma Screener (CTS) - Entwicklung und Validierung von Schwellenwerten zur Klassifikation.

OBJECTIVES: Childhood abuse and neglect are associated with worse physical and mental health outcomes. There is some evidence, that the CTS is a brief and valid screening tool. To support the application of the CTS for categorical diagnostics cut-offs will be identified and validated. METHODS: Based on two large-scale population studies suitable cut-off-scores for the different dimensions of childhood abuse and neglect were identified due to comparable case identification rates in the CTS compared with the Childhood Trauma Questionnaire. The cut-off-scores were validated with respect to depression as an external criterion. RESULTS: Suitable cut-off-scores were identified for all subscales in both samples. The cases and non-cases according to the cut-off-scores differed significantly regarding the severity of depressive symptoms and the prevalence of depression. Good to very good sensitivity and specificity of the CTS-items and the related subscales of the CTQ are shown, except for the dimension "physical neglect". CONCLUSION: With the help of the cut-off-scores it is possible to use the CTS for categorical diagnostics, especially in large-scale studies with two-step diagnostic approaches.

[The lifetime prevalence of mental disorders in north-eastern Germany. What is the influence of earlier mental morbidity on survey participation and prevalence estimates? Results from the SHIP-study]. / Die Lebenszeitprävalenz psychischer Störungen in Vorpommern. Welchen Einfluss haben frühere psychische Auffälligkeiten auf die Survey-Teilnahme und Prävalenzschätzungen? Ergebnisse der SHIP-Studie.

OBJECTIVE: This work addresses the life-time-prevalence of mental disorders in the adult general population in a German region (Vorpommern). We address effects of attrition on prevalence estimates. METHODS: Analyses are based on a general population cohort study (29 - 89 years, Study of Health in Pomerania, N = 2400), using the M-CIDI to obtain life-time diagnoses of mental disorders according to ICD-10. Statistical weights were used to assess the effects of selective non-response on prevalence estimates related to baseline physical and psychological morbidity and sociodemographic variables, measured 10 years before. RESULTS: In total 44.6 % of the male and 55.2 % of the female participants fulfilled criteria for at least one ICD mental disorder including specific phobias and tobacco dependence. Physical but not psychological baseline morbidity showed relevant associations to participation in the psychological examination ten years later. Weighted and unweighted prevalence estimates for mental disorders were very similar. CONCLUSION: Our results illustrate the high burden due to mental disorders. Most prevalence estimates seem robust to prior mental comorbidities.

Impact of depressive symptoms on prosthetic status--results of the study of health in Pomerania (SHIP).

OBJECTIVES: Previous investigations have confirmed that every fifth dental patient suffers from clinically significant depressive symptoms. However, the putative impact of depressive symptoms on the prosthetic status has not been addressed in these studies. The objective of this study was to investigate the association between depressive symptoms and prosthetic status based on data from the Study of Health in Pomerania (SHIP-0). METHODS: Data from 2,135 participants aged 30 to 59 years were analyzed. A classification (six classes regarding the number and position of missing teeth per jaw) was used to identify the degree of prosthetic status (no/suboptimal/optimal tooth replacement). The presence of depressive symptoms was assessed with a modified version of von Zerssen's complaints scale. Screening for lifetime diagnoses of mental disorders was performed with the Composite International Diagnostic-Screener (CID-S). Multivariable logistic regressions including several confounders were calculated. RESULTS: A significant protective dose-response effect of depressive symptoms on prosthetic status was found only in men for the lower jaw [0-1 depressive symptoms: odds ratio (OR) = 3.84, 95 % confidence interval (CI, 1.65-8.92), p < 0.01; 2-3: OR = 2.87 (CI, 1.22-6.74), p < 0.05; reference, ≥8; adjusted for age, school education, smoking status, household income, marital status, living without a partner, risky alcohol consumption, obesity, diabetes, and physical activity]. There was no such association in women or for the upper jaw. The analyses using the CID-S confirmed these results. CONCLUSIONS: In the lower jaw, men with depressive symptoms had a better prosthetic status than men without depressive symptoms suggesting a higher level of concern regarding their personal health. CLINICAL RELEVANCE: If dentists might have an opportunity to identify men with depressive symptoms they can provide a wide range of treatment options that may enhance patients' self-esteem and contribute to the patient' well-being. Furthermore, depressive symptoms could indicate a discrepancy between self-perception of the dental health and the actual status which influence the dentists' treatment decision making.

[A brief instrument for the assessment of childhood abuse and neglect: the childhood trauma screener (CTS)]. / Ein Screeninginstrument für Missbrauch und Vernachlässigung in der Kindheit: der Childhood Trauma Screener (CTS).

OBJECTIVE: There is a lack of a psychometrically sound screening questionnaire that assesses important dimensions of traumatic experiences during childhood and adolescence in a time-efficient way. Based on the German version of the "Childhood Trauma Questionnaire" (CTQ, 28 items) we developed a five-item self-report childhood trauma screener (CTS) that covers sexual, emotional and physical abuse and emotional and physical neglect. METHOD: The data set of the SHIP-LEGEND study (n = 1668) was used to extract five items of the CTQ that optimally covered the five dimensions and showed a high correlation with the total score. In two validation samples (clinical sample [n = 211] and subjects from the BiDirect study [n = 288]) the psychometric properties of the CTS were evaluated. RESULTS: The correlations between the five CTS Items and the corresponding dimensions from the CTQ were r = 0.55 to 0.87 (p < 0.0001) within the clinical sample. Furthermore, we found high correlations (r = 0.88; p < 0.0001) with the total CTQ score. The internal consistency was 0.757 (Cronbachs α). CONCLUSION: The CTS is a reliable, valid and economic screener for the retrospective assessment of adverse childhood experiences especially in large epidemiological studies.