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1.
Thyroid ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571530

RESUMO

In numerous studies based predominantly on rodent models, administration of 3,5-diiodo-L-thyronine (3,5-T2), a metabolite of the thyroid hormones (TH) thyroxine (T4) and triiodo-L-thyronine (T3), was reported to cause beneficial health effects including reversal of steatohepatosis and prevention of insulin resistance, in most instances without adverse thyrotoxic side effects. However, the empirical evidence concerning the physiological relevance of endogenously produced 3,5-T2 in humans is comparatively poor. Therefore, to improve the understanding of 3,5-T2 related metabolic processes, we performed a comprehensive metabolomics study relating serum 3,5-T2 concentrations to plasma- and urine metabolite levels within a large general population sample. Serum 3,5-T2 concentrations were determined for 856 participants of the population-based Study of Health in Pomerania-TREND (SHIP-TREND). Plasma and urine metabolome data were generated using mass spectrometry and nuclear magnetic resonance spectroscopy, allowing quantification of 613 and 578 metabolites in plasma and urine, respectively. To detect thyroid function-independent significant 3,5-T2 - metabolite associations, linear regression analyses controlling for major confounders including thyrotropin (TSH) and free T4 were performed. The same analyses were carried out using a sample of 16 male healthy volunteers treated for eight weeks with 250 µg/day levothyroxine to induce thyrotoxicosis. The specific molecular fingerprint of 3,5-T2 comprised 15 and 73 significantly associated metabolites in plasma and urine, respectively. Serum 3,5-T2 concentrations were neither associated with classical thyroid function parameters nor altered during experimental thyrotoxicosis. Strikingly, many metabolites related to coffee metabolism including caffeine and paraxanthine formed the clearest positively associated molecular signature. Importantly, these associations were replicated in the experimental human thyrotoxicosis model. The molecular fingerprint of 3,5-T2 demonstrates a clear and strong positive association of the serum levels of this TH metabolite with plasma levels of compounds indicating coffee consumption, therefore pointing to the liver as an organ the metabolism of which is strongly affected by coffee. Furthermore, 3,5-T2 serum concentrations were found not to be directly TH-dependent. Considering the beneficial health effects of 3,5-T2 administration observed in animal models and those of coffee consumption demonstrated in large epidemiological studies, one might speculate that coffee-stimulated hepatic 3,5-T2 production or accumulation represents an important molecular link in this connection.

2.
Eur J Hum Genet ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31485028

RESUMO

Gallstones Disease (GSD) is one of the most common digestive diseases requiring hospitalization and surgical procedures in the world. GSD has a high prevalence in populations with European or Amerindian ancestry (10-20%) and the influence of genetic factors is broadly acknowledged. However, known genetic variants do not entirely explain the disease heritability suggesting that additional genetic variants remain to be identified. Here, we examined the association of copy number variants (CNVs) with GSD in a sample of 4778 individuals (1929 GSD cases and 2849 controls) including two European cohorts from Germany (n = 3702) and one admixed Latin American cohort from Chile (n = 1076). We detected 2936 large and rare CNVs events (size > 100 kb, frequency < 1%). Case-control burden analysis and generalized linear regression models revealed significant association of CNVs with GSD in men, with the strongest effect observed with CNVs overlapping lipid metabolism genes (p-value = 6.54 × 10-4; OR = 2.76; CI 95% = 1.53-4.89). Our results indicate a clear link between CNVs and GSD in men and provides additional evidence that the genetic components of risk for GSD are complex, can be sex specific and include CNVs affecting genes involved in lipid metabolism.

3.
PLoS One ; 14(9): e0222671, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31539397

RESUMO

BACKGROUND: Little is known about outpatient health services use following critical illness and intensive care. We examined the association of intensive care with outpatient consultations and quality of life in a population-based sample. METHODS: Cross-sectional analysis of data from 6,686 participants of the Study of Health in Pomerania (SHIP), which consists of two independent population-based cohorts. Statistical modeling was done using Poisson regression, negative binomial and generalized linear models for consultations, and a fractional response model for quality of life (EQ-5D-3L index value), with results expressed as prevalence ratios (PR) or percent change (PC). Entropy balancing was used to adjust for observed confounding. RESULTS: ICU treatment in the previous year was reported by 139 of 6,686 (2,1%) participants, and was associated with a higher probability (PR 1.05 [CI:1.03;1.07]), number (PC +58.0% [CI:22.8;103.2]) and costs (PC +64.1% [CI:32.0;103.9]) of annual outpatient consultations, as well as with a higher number of medications (PC +37.8% [CI:17.7;61.5]). Participants with ICU treatment were more likely to visit a specialist (PR 1.13 [CI:1.09; 1.16]), specifically internal medicine (PR 1.67 [CI:1.45;1.92]), surgery (PR 2.42 [CI:1.92;3.05]), psychiatry (PR 2.25 [CI:1.30;3.90]), and orthopedics (PR 1.54 [CI:1.11;2.14]). There was no significant effect regarding general practitioner consultations. ICU treatment was also associated with lower health-related quality of life (EQ-5D index value: PC -13.7% [CI:-27.0;-0.3]). Furthermore, quality of life was inversely associated with outpatient consultations in the previous month, more so for participants with ICU treatment. CONCLUSIONS: Our findings suggest that ICU treatment is associated with an increased utilization of outpatient specialist services, higher medication intake, and impaired quality of life.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31518608

RESUMO

OBJECTIVE: Low levels of vitamin D were found to be associated with different mental disorders. However, the role of vitamin D in the pathogenesis of PTSD is unclear. In this study, we aimed at investigating whether PTSD is linked to reduced vitamin D levels and vitamin D deficiency. Moreover, we sought to investigate the role of the vitamin D-binding protein (also group-specific component or Gc) by testing if two functional polymorphisms (rs4588 and rs7041) were associated with vitamin D levels and PTSD. METHODS: Serum levels of total 25(OH)D were measured in a general-population sample of the Study of Health in Pomerania (SHIP-1). The number of traumatic events and status of PTSD were assessed using the PTSD module of the Structured Clinical Interview for the DSM-IV. Study participants were genotyped for rs4588 and rs7041. Associations of 25(OH)D levels and the genotypes with PTSD were tested in subjects with at least one traumatic event (n = 1653). RESULTS: 25(OH)D levels were inversely (OR: 0.96; p = 0.044) and vitamin D deficiency was positively (OR = 2.02; p = 0.028) associated with PTSD. Both polymorphisms of the Gc were associated with 25(OH)D levels and PTSD: Carriers of the CC-genotype of rs4588 showed significantly higher 25(OH)D levels (ß = 0.179, p < 0.001) and lower odds for PTSD (OR = 0.35; p = 0.023) compared to the AA-genotype. Likewise, carriers of the TT-allele of rs7041 showed lower 25(OH)D levels (-0.122; p < 0.001) and increased odds for PTSD (OR = 2.80; p = 0.015) compared to the GG-genotype. CONCLUSIONS: Our results suggest that an altered vitamin D metabolism may be involved in the pathophysiology of PTSD. Also, genotypes of the Gc and thus Gc serum levels may impact on PTSD development over and above the effects of 25(OH)D. Our findings contribute to explain the associations of PTSD with different mental and physical disorders.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31390012

RESUMO

OBJECTIVE: Impaired glucose tolerance (IGT) is one of the pre-symptomatic states of type 2 diabetes mellitus and requires an oral glucose tolerance test (OGTT) for diagnosis. Our aims were two-fold: 1) characterize signatures of small molecules predicting the OGTT-response and 2) identify metabolic subgroups of participants with IGT. METHODS: Plasma samples from 827 participants of the Study of Health in Pomerania free of diabetes were measured utilizing mass spectrometry and proton-nuclear magnetic resonance spectroscopy. Linear regression analyses were used to screen for metabolites significantly associated with the OGTT-response after two hours adjusting for baseline glucose and insulin levels, as well as important confounders. A signature predictive for IGT was established using regularized logistic regression. All IGT cases (N=159) were selected and subjected to unsupervised clustering using a k-means approach. RESULTS AND CONCLUSION: In total, 99 metabolites and 22 lipoprotein measures were significantly associated with either 2-hour glucose or 2-hour insulin levels. Those comprised variations in baseline concentrations of branched-chain amino keto-acids, acylcarnitines, lysophospholipids or phosphatidylcholines largely confirming previous studies. By the use of these metabolites, IGT-subjects segregated into two distinct groups. Our IGT prediction model combining both clinical and metabolomics traits achieved an AUC of 0.84, slightly improving the prediction based on established clinical measures. The present metabolomics approach revealed molecular signatures associated directly to the response of the OGTT and to IGT in line with previous studies. However, clustering of IGT subjects revealed distinct metabolic signatures of otherwise similar individuals pointing towards the possibility of metabolomics for patient stratification.

6.
Med Sci Monit ; 25: 6383-6390, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31446436

RESUMO

BACKGROUND Age-related macular degeneration (AMD) is the leading cause of visual impairment in developed countries, especially in the older population. The Study of Health in Pomerania (SHIP) is a population-based study designed to investigate risk factors and clinical disorders in the general population. In the present study, we analysed the AMD prevalence and risk factors in the north-eastern German population. MATERIAL AND METHODS From 2008 to 2012, we collected data among participants ages 29-79 years. The study population consisted of 4420 individuals. Non-mydriatic retinal photographs were taken of 3934 participants. AMD stages were graded according to the Rotterdam Classification System and the International Classification System. RESULTS Photographs from 1854 participants were available for grading. The baseline examinations showed small hard drusen (<63 µm, stage 0b and 0c) were present in 10.7% of the participants (stage 0b in 7.5% and stage 0c in 3.2%). Earliest signs of AMD were detected in 28.68% (stage 0b in 7.5% and stage 1b in 21.18%). Late AMD (geographic atrophy and neovascular AMD, stages 4a and 4b) were identified in 0.43% (stage 4a in 0.16% and stage 4b 0.27%). Risk of AMD increased significantly with age and higher body mass index, waist circumference, hip circumference, and weight-waist-ratio. Smoking, sex, systolic and diastolic blood pressure, HbA1c, cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride were not associated with AMD in this study. CONCLUSIONS The prevalence of AMD increases with age and obesity-associated factors. These results must be verified in the follow-up. Data concerning the incidence of AMD will be available after the 5- and 10-year follow-ups.

7.
Thyroid ; 29(9): 1220-1226, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31426720

RESUMO

Background: Untreated overt hypo- and hyperthyroidism can lead to detrimental effects on muscle tissue and physical performance, but it is still unclear whether subclinical hypo- or hyperthyroidism has clinically relevant effects on muscle function and physical performance. The objective of this study was to determine associations of thyrotropin (TSH) with grip strength and physical performance. Methods: A sample of 6196 participants from the Study of Health in Pomerania and the Berlin Aging Study II was included in this cross-sectional analysis. Handgrip strength was measured with a hand-held dynamometer and physical performance was assessed with the timed up and go (TUG) test. Results: Serum TSH levels were significantly inversely associated with handgrip strength (ß -0.11; [95% confidence interval, CI, -0.18 to -0.03]; p < 0.05) in multivariable linear regression. Individuals with high (ß -1.06; [95% CI -1.86 to -0.26]; p < 0.05) or low (ß -0.99; [95% CI -1.70 to -0.28]; p < 0.05) serum TSH levels had a significantly lower handgrip strength than individuals with serum TSH levels within the reference range. There was no association between TSH and the TUG time. Age showed a significant influence on the association of TSH with grip strength and TUG time. Conclusions: Even mild disturbances of thyroid function might lead to a relevant decline in grip strength, particularly in young and middle-aged subjects. Mild subclinical hypothyroidism might not be that unfavorable with regard to physical function in terms of handgrip strength at older age. Further studies are needed to clarify causal relationships.

8.
Endocr Connect ; 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265993

RESUMO

OBJECTIVE: Chemerin and adiponectin are adipokines assumed to be involved in the development of metabolic syndrome-related phenotypes like hepatic steatosis. We aimed to evaluate the associations of circulating chemerin and adiponectin concentrations with liver enzymes, liver fat content, and hepatic steatosis in the general population. METHODS: Data of 3951 subjects from the population-based Study of Health in Pomerania (SHIP-TREND) were used. Hepatic steatosis was assumed when either a hyperechogenic liver (assessed via ultrasound) or a magnetic resonance imaging (MRI)-quantified liver fat content >5% was present. Adjusted sex-specific quantile and logistic regression models were applied to analyse the associations of chemerin and adiponectin with liver enzymes, liver fat content, and hepatic steatosis. RESULTS: The observed associations of chemerin and adiponectin with liver enzymes were very divergent depending on sex, fasting status, and the specific enzyme. More consistent results were seen in the analyses of these adipokines in relation to MRI-quantified liver fat content. Here, we observed inverse associations to adiponectin in both sexes as well as a positive (men) or U-shaped (women) association to chemerin. Similarly, the MRI-based definition of hepatic steatosis revealed strongly consistent results: in both sexes high chemerin concentrations were associated with higher odds of hepatic steatosis whereas high adiponectin concentrations were associated with lower odds. CONCLUSION: Our results suggest a role of these adipokines in the pathogenesis of hepatic steatosis independent of metabolic or inflammatory disorders. However, experimental studies are needed to further clarify the underlying mechanisms and the inter-play between adipokine concentrations and hepatic steatosis.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31284290

RESUMO

Childhood traumatization (CT) is associated with the development of several neuropsychiatric disorders in later life. Experimental data in animals and observational data in humans revealed evidence for biological alterations in response to CT that may contribute to its long-term consequences. This includes epigenetic changes in miRNA levels that contribute to complex alterations of gene expression. We investigated the association between CT and 121 miRNAs in a target sample of N = 150 subjects from the general population and patients from the Department of Psychiatry. We hypothesized that CT exhibits a long-term effect on miRNA plasma levels. We supported our findings using bioinformatics tools and databases. Among the 121 miRNAs 22 were nominally significantly associated with CT and four of them (let-7g-5p, miR-103a-3p, miR-107, and miR-142-3p) also after correction for multiple testing; most of them were previously associated with Alzheimer's disease (AD) or depression. Pathway analyses of target genes identified significant pathways involved in neurodevelopment, inflammation and intracellular transduction signaling. In an independent general population sample (N = 587) three of the four miRNAs were replicated. Extended analyses in the general population sample only (N = 687) showed associations of the four miRNAs with gender, memory, and brain volumes. We gained increasing evidence for a link between CT, depression and AD through miRNA alterations. We hypothesize that depression and AD not only share environmental factors like CT but also biological factors like altered miRNA levels. This miRNA pattern could serve as mediating factor on the biological path from CT to adult neuropsychiatric disorders.

10.
J Periodontol ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31343076

RESUMO

BACKGROUND: Women are generally periodontally healthier than men but they exhibit higher systemic levels of inflammatory markers. Our aim is to evaluate whether this paradox may be explained by different ramifications of adiposity or body shape. METHODS: In 3,268 subjects from the Study of Health in Pomerania, we determined anthropometric and periodontal parameters, C-reactive protein (CRP), and fibrinogen as markers of inflammation. Behavioural and environmental risk factors and hand grip strength were assessed as factors interfering with the outcomes in question. We evaluated sex-specific associations of adiposity characteristics and periodontal variables such as probing depth (PD) with CRP and fibrinogen. RESULTS: After adjusting for age, waist-to-hip ratio (WHR), glycated hemoglobin, smoking, education, and grip strength, the opposite sex role of periodontitis and obesity on CRP levels were confirmed. WHR and body mass index (BMI) were associated with CRP in both men and women (P < 0.001). CRP was associated with PD in men (P = 0.001) but not in women (P = 0.11). When adjusted for BMI this association was attenuated in men by 15% (P = 0.002) but in women by 70% (P = 0.58). PD was related to plaque and bleeding on probing (P < 0.001) in both sexes and also to WHR in women (P = 0.026) and men (P = 0.002). BMI attenuated this association in women but not in men. HbA1c contributed significantly to PD in women (P = 0.013) but not in men (P = 0.76). CONCLUSIONS: Systemic CRP concentrations are affected by periodontitis and obesity in men. In women adiposity is more significant than in men overriding the impact of periodontal measures.

11.
BMJ Open ; 9(7): e029716, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350252

RESUMO

INTRODUCTION: Prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association. METHODS AND ANALYSIS: We will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model. ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal. PROSPERO REGISTRATION NUMBER: CRD42018091627.

12.
J Cell Mol Med ; 23(8): 5144-5153, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31215770

RESUMO

Metabolomics studies now approach large sample sizes and the health characterization of the study population often include complete blood count (CBC) results. Upon careful interpretation the CBC aids diagnosis and provides insight into the health status of the patient within a clinical setting. Uncovering metabolic signatures associated with parameters of the CBC in apparently healthy individuals may facilitate interpretation of metabolomics studies in general and related to diseases. For this purpose 879 subjects from the population-based Study of Health in Pomerania (SHIP)-TREND were included. Using metabolomics data resulting from mass-spectrometry based measurements in plasma samples associations of specific CBC parameters with metabolites were determined by linear regression models. In total, 118 metabolites significantly associated with at least one of the CBC parameters. Strongest associations were observed with metabolites of heme degradation and energy production/consumption. Inverse association seen with mean corpuscular volume and mean corpuscular haemoglobin comprised metabolites potentially related to kidney function. The presently identified metabolic signatures are likely derived from the general function and formation/elimination of blood cells. The wealth of associated metabolites strongly argues to consider CBC in the interpretation of metabolomics studies, in particular if mutual effects on those parameters by the disease of interest are known.

13.
Artigo em Alemão | MEDLINE | ID: mdl-31250039

RESUMO

BACKGROUND: Billing diagnoses are used for quality assurance, estimates of prevalence and resource allocation. Validity studies showed relevant limitations. In Germany, there are no population-based data on the agreement of outpatient billing diagnoses with clinical data of thyroid disorders. OBJECTIVES: The study investigated the agreement of ICD-diagnosed thyroid nodules, goitre, hyperthyroidism, hypothyroidism and thyroiditis with clinical and self-reported data from the population-based cohort study called the Study of Health in Pomerania (SHIP). MATERIALS AND METHODS: Billing data from the Association of Statutory Health Insurance Physicians Mecklenburg-Vorpommern were linked on an individual level for the period from 2002-2016 with data from SHIP. The agreement was evaluated using sensitivity, specificity and positive and negative predictive value (PPW, NPW). Data were weighted to ensure population representativeness. RESULTS: The data of 5746 participants were analysed (46% male, average age 55 years, SD [standard deviation] ± 15, min: 20 years, max: 93 years). Based on clinical data, 63% (3451/5511, missing values n = 235) and based on billing data 25% (1421/5746) of the participants had thyroid disorders. The sensitivity was 12-36%, the specificity was 84-98%, the PPW was highest for thyroid nodules (75%) and hypothyroidism (70%) and the NPW was between 63 and 94%, depending on the investigated thyroid disorder. CONCLUSIONS: Thyroid disorders are common and often undiagnosed. Billing data have a low sensitivity to identify clinically relevant thyroid disorders.


Assuntos
Codificação Clínica , Formulário de Reclamação de Seguro/estatística & dados numéricos , Doenças da Glândula Tireoide/epidemiologia , Glândula Tireoide/anormalidades , Adulto , Idoso , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Atenção Primária à Saúde , Reprodutibilidade dos Testes , Doenças da Glândula Tireoide/diagnóstico
14.
Psychoneuroendocrinology ; 107: 232-240, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31174161

RESUMO

OBJECTIVE: Previous evidence suggested lasting and cumulative effects of traumatization on the renin-angiotensin-aldosterone-system (RAAS). However, it is unclear whether traumas during childhood and those experienced in adulthood differentially impact the RAAS. In this study, we sought to investigate main and putative interactive effects of childhood and adulthood trauma on RAAS functioning. METHODS: Plasma concentrations of renin and aldosterone were measured in a general population sample (n = 2016). Childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ), adulthood trauma was measured using the PTSD module of the Structured Clinical Interview of the DSM-IV. Linear regression models were calculated to assess the relations between childhood or adulthood traumatization with renin and aldosterone concentrations. RESULTS: Exposure to (ß = 0.094; p = 0.01), severity of childhood trauma (ß = 0.004; p = 0.01) were associated with increased aldosterone, but not renin levels. Results were carried by all dimensions of abuse, while childhood neglect was not associated with altered RAAS activity. In contrast, adulthood traumas (ß = 0.113; p < 0.01) were significantly associated with increased renin concentrations. Subjects with PTSD (renin: ß = 0.345; p = 0.01; aldosterone: ß = 0.232; p = 0.04) and those who had been exposed to both childhood and adulthood trauma showed increases in renin (ß = 0.180; p < 0.01) and aldosterone (ß = 0.340; p < 0.01) levels. DISCUSSION: These findings indicate that trauma is associated with differential alterations of the RAAS depending on the time of traumatization. Moreover, exposure to childhood or adulthood trauma may act synergistically on the RAAS, resulting in severe dysregulation of the RAAS. The results contribute to explain associations between trauma and enhanced risk for physical disease.

15.
Cereb Cortex ; 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31240317

RESUMO

Exposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n = 21 251; 4-97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas. In all participants, cortical thickness correlated negatively with the expression of both NR3C1 and NR3C2 across 34 cortical regions. The magnitude of this correlation varied across the lifespan. From childhood through early adulthood, the profile similarity (between NR3C1/NR3C2 expression and thickness) increased with age. Conversely, both profile similarities decreased with age in late life. These variations do not reflect age-related changes in NR3C1 and NR3C2 expression, as observed in 5 databases of gene expression in the human cerebral cortex (502 donors). Based on the co-expression of NR3C1 (and NR3C2) with genes specific to neural cell types, we determine the potential involvement of microglia, astrocytes, and CA1 pyramidal cells in mediating the relationship between corticosteroid exposure and cortical thickness. Therefore, corticosteroids may influence brain structure to a variable degree throughout life.

16.
Am J Psychiatry ; 176(8): 651-660, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31164008

RESUMO

OBJECTIVE: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium. METHODS: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders. RESULTS: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%). CONCLUSIONS: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.

17.
J Clin Periodontol ; 46(7): 713-722, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115952

RESUMO

AIMS: This study aimed to assess 11-year longitudinal effects of powered toothbrush on periodontal health, caries and tooth loss in an adult population. MATERIALS AND METHODS: Participants of Study of Health in Pomerania (SHIP) cohort with dental examinations and interview data at SHIP-1, SHIP-2 or SHIP-3 examinations were included. Mixed-effects linear regression models were constructed between the exposure (manual versus powered toothbrush) and outcome variables (periodontal status using mean probing depth (PD) and mean clinical attachment loss (CAL), caries status using DMFS and DFS scores, and tooth loss), adjusting for potential baseline covariates. RESULTS: Final baseline (SHIP-1) study sample comprised of 2,819 participants. Powered toothbrush users increased from 18.3% (SHIP-1) to 36.9% (SHIP-3); were younger; had significantly less mean PD [ß: -0.09 (95% CI: -0.16; -0.02)] and mean CAL [ß: -0.19 (95% CI: -0.32; -0.07)] progressions; and had 17.7% less DMFS progression and 19.5% more teeth retained than the manual toothbrushers. CONCLUSIONS: In the long-term, powered toothbrush seems to be effective in reducing mean PD and mean CAL progressions, besides increasing the number of teeth retained.

18.
Psychol Med ; : 1-12, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31084657

RESUMO

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.

19.
Invest Radiol ; 54(7): 403-408, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30817380

RESUMO

OBJECTIVES: The aim of this study was to investigate if pancreatic steatosis measured by proton density fat fraction (PDFF) is associated with exocrine pancreatic function defined by fecal elastase concentrations. MATERIALS AND METHODS: A total of 1458 volunteers (777 women; age range, 21-88 years) underwent magnetic resonance imaging of the pancreas, and organ fat content was quantified by using confounder corrected PDFF. Exocrine pancreatic function was categorized by fecal elastase levels using defined cutoffs: greater than 200 µg/g normal function (n = 1319) and 200 µg/g or less impaired function (n = 139). Statistical analysis to correlate pancreatic fat content with fecal elastase included linear regression, and analyses were adjusted for known confounders for pancreatic steatosis, such as age, sex, and body mass index. RESULTS: Overall mean (±standard deviation) of pancreatic fat content was 7.50% ± 3.78%. Pancreatic fat content was significantly higher in subjects with impaired pancreatic exocrine function (9.36% ± 4.95%) compared with subjects with normal function (7.30% ± 3.59%; P < 0.01). Linear regression analyses showed an inverse correlation between pancreatic fat and fecal elastase levels over the whole study population (beta, -7.19 [standard error, 1.39]; P < 0.01) as well as in the subgroup of subjects with normal function (-4.26 [1.32]; P < 0.01). Among subjects with impaired pancreatic exocrine function, a trend toward an inverse relation was detected (-1.28 [0.84]; P < 0.13). CONCLUSIONS: An inverse correlation between PDFF of the pancreas and fecal elastase suggests an association between pancreatic steatosis and impaired pancreatic exocrine function.

20.
PLoS One ; 14(3): e0213658, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870494

RESUMO

BACKGROUND: Platelet count is known to be associated with sex, age and mean platelet volume (MPV). Sex and age were proposed for adjustment of platelet count reference intervals, but MPV is currently not used for further adjustment. We investigated the association of MPV, age and sex with platelet counts and established individualized reference ranges respecting MPV. METHODS: The association of platelet count with age, sex and MPV was assessed in healthy participants (n = 3,033 individuals; 1,542 women) in the cross-sectional population-based cohort Study of Health in Pomerania. Reference intervals respecting age, sex, and MPV were estimated using quantile regressions for the 2.5th and 97.5th percentile. RESULTS: Women had higher platelet counts than men (239 vs. 207 x109/L, p<0.001). Platelet counts correlated with age (p<0.001) and MPV (p<0.001). Quantile regression of lower and upper platelet count limits correlated less with age in female (p = 0.047 for 2.5th percentile; p = 0.906 for 97.5th percentile) and male subjects (p = 0.029 for 2.5th percentile; p = 0.195 for 97.5th percentile) compared to MPV (p<0.001 for upper and lower limit for both sexes). After adjustment for MPV, age did no longer correlate with the 2.5th (p = 0.165) or 97.5th percentile (p = 0.999) of platelet count. In contrast, after adjustment for age, MPV levels still significantly correlated with 2.5th, 50th and 97.5th percentile (p<0.001). CONCLUSION: MPV and sex have a stronger association with platelet count than age. MPV should be considered to adjust platelet count reference intervals and needs to be respected as confounder for platelet counts in epidemiological studies and clinical practice.

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