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1.
Nat Commun ; 13(1): 2408, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35504910

RESUMO

We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.


Assuntos
Metilação de DNA , Inflamação , Proteína C-Reativa/genética , Ilhas de CpG/genética , Metilação de DNA/genética , Humanos , Inflamação/genética , Motivos de Nucleotídeos
2.
Semin Hematol ; 59(2): 115-119, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35512900

RESUMO

This review paper explores the potential psychiatric and psychological sequelae of vaccine-induced immune thrombotic thrombocytopenia, also called vaccine-induced immune thrombocytopenia, and thrombosis (VITT). In the absence of any literature to date we have extrapolated data from similar conditions, particularly data pertaining to the critical care population. We discuss both the direct and indirect effects of thrombosis, likely psychiatric and psychological challenges during recovery, and ethical issues around vaccination. We have also suggested a comprehensive guide to the psychiatric assessment and management of patients presenting with VITT with the aim of early identification of problems and maximizing rehabilitation potential and quality of life.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombose , Vacinas , Humanos , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Púrpura Trombocitopênica Idiopática/psicologia , Qualidade de Vida , Trombose/induzido quimicamente , Vacinas/efeitos adversos
3.
J Affect Disord ; 305: 206-212, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35283179

RESUMO

BACKGROUND: Alexithymia ("no word for feelings") is a personality feature that is common in patients with psychiatric disorders. However, little is known about biological causes and mechanism behind. Research so far focusses on genetic risk variants primary associated with depression, but analyses on epigenetic mechanisms are still missing. METHODS: In a sample of n = 813 subjects from the "Study of Health in Pomerania" we analyzed the association between alexithymia and plasma circulating micro RNAs (miRNA). Significant miRNAs were compared to associations regarding depression and pathway analyses were performed. RESULTS: Two miRNAs were significantly associated with at least one of the alexithymia scores (hsa-miR-324-3p, hsa-miR-33a-5p) and three miRNAs additionally revealed a strong association pattern to alexithymia (hsa-miR-106b-5p, hsa-miR-484, hsa-miR-25-3p). None of these miRNAs was significantly associated with depressive symptoms in our sample. Literature research showed that all of the miRNAs have been found in association with several neuropsychiatric phenotypes. LIMITATIONS: Main limitations are the lack of a replication sample as well as the limited number of miRNAs analyzed. CONCLUSIONS: This is the first analysis investigating the association between miRNAs and alexithymia. Results indicate that miRNAs are not specific for one psychiatric disorder but may influence biological mechanisms that are involved in various psychiatric conditions which might be relevant for future treatment options and improve the biological understanding of psychiatric conditions.


Assuntos
Sintomas Afetivos , MicroRNAs , Sintomas Afetivos/genética , Humanos
4.
World J Biol Psychiatry ; : 1-12, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35302904

RESUMO

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

5.
J Affect Disord ; 306: 157-166, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35304236

RESUMO

BACKGROUND: Suicidal ideation and behavior constitute important public mental health issues. In this study, we examined whether social integration prevents suicidal ideation over time and whether gender modifies this association. METHODS: Data from the Gutenberg Health Study (population-based representative community sample in midwest Germany) and the Study of Health in Pomerania (population-based cohort study in northeast Germany) were used. Participants reporting low social support were compared to those receiving middle or high social support. Within a longitudinal study design, we calculated multiple logistic regression models including interaction terms and relevant covariates to test whether gender modified the association of social support and suicidal ideation. RESULTS: Suicidal ideation was present in 7.4% (N = 982) of the pooled cohorts' 13,290 participants. More women (8.6%, N = 565) than men (6.2%, N = 417) reported suicidal ideation. Middle or high social support was associated with a lower probability to report suicidal ideation five years later after controlling for sociodemographic factors, living situation, and cohort (OR = 0.42, 95%-CI = 0.34-0.52). Male gender was negatively related to suicidal ideation, but no statistically significant interaction of gender and social support was found (ratio of ORs = 1.00, 95%-CI = 0.73-1.35). LIMITATIONS: The number of people reporting suicidal ideation in the SHIP study was small, especially for men. Suicidal ideation was measured using a single item. CONCLUSIONS: Social support is an important protective factor in preventing suicidal ideation for both women and men. Future research should further clarify gender-specific effects of family variables in suicidal ideation and test similar predictive models of suicidal behavior.


Assuntos
Apoio Social , Ideação Suicida , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco
7.
Artigo em Inglês | MEDLINE | ID: mdl-35217912

RESUMO

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

8.
World J Biol Psychiatry ; : 1-15, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35175181

RESUMO

OBJECTIVES: To describe the cognitive test battery of the German National Cohort (NAKO), a population-based mega cohort of 205,000 randomly selected participants, and to examine associations with demographic variables and selected psychiatric and neurological conditions. METHODS: Initial data from 96,401 participants providing data on the cognitive performance measured by a brief cognitive test battery (12-word list recall task, semantic fluency, Stroop test, digit span backwards) was examined. Test results were summarised in cognitive domain scores using exploratory and confirmatory factor analyses. Associations with sociodemographic and psychiatric factors were analysed using linear regression and generalised additive models. RESULTS: Cognitive test results were best represented by two domain scores reflecting memory and executive functions. Lower cognitive functions were associated with increasing age and male sex. Higher education and absence of childhood trauma were associated with better cognitive function. Moderate to severe levels of anxiety and depression, and a history of stroke, were related to lower cognitive function with a stronger effect on executive function as compared to memory. Some associations with cognition differed by German language proficiency. CONCLUSIONS: The NAKO cognitive test battery and the derived cognitive domain scores for memory and executive function are sensitive measures of cognition.

9.
World J Biol Psychiatry ; : 1-12, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35175174

RESUMO

Objectives. Evaluate the block-adaptive number series task of reasoning, as a time-efficient proxy of general cognitive ability in the Level-2 sample of the German National Cohort (NAKO), a population-based mega cohort. Methods. The number series task consisted of two blocks of three items each, administered as part of the touchscreen-based assessment. Based on performance on the first three items, a second block of appropriate difficulty was automatically administered. Scoring of performance was based on the Rasch model. Relations of performance scores to age, sex, education, study centre, language proficiency, and scores on other cognitive tasks were examined. Results. Except for one very difficult item, the data of the remaining 14 items showed sufficient fit to the Rasch model (Infit: 0.89-1.04; Outfit: 0.80-1.08). The resulting performance scores ( N = 21,056) had a distribution that was truncated at very high levels of ability. The reliability of the performance estimates was satisfactory. Relations to age, sex, education, and the executive function factor of the other cognitive tasks in the NAKO supported the validity. Conclusions. The number series task provides a valid proxy of general cognitive ability for the Level-2 sample of the NAKO, based on a highly time-efficient assessment procedure.

10.
Circulation ; 145(14): 1040-1052, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35050683

RESUMO

BACKGROUND: White matter hyperintensities (WMH), identified on T2-weighted magnetic resonance images of the human brain as areas of enhanced brightness, are a major risk factor of stroke, dementia, and death. There are no large-scale studies testing associations between WMH and circulating metabolites. METHODS: We studied up to 9290 individuals (50.7% female, average age 61 years) from 15 populations of 8 community-based cohorts. WMH volume was quantified from T2-weighted or fluid-attenuated inversion recovery images or as hypointensities on T1-weighted images. Circulating metabolomic measures were assessed with mass spectrometry and nuclear magnetic resonance spectroscopy. Associations between WMH and metabolomic measures were tested by fitting linear regression models in the pooled sample and in sex-stratified and statin treatment-stratified subsamples. Our basic models were adjusted for age, sex, age×sex, and technical covariates, and our fully adjusted models were also adjusted for statin treatment, hypertension, type 2 diabetes, smoking, body mass index, and estimated glomerular filtration rate. Population-specific results were meta-analyzed using the fixed-effect inverse variance-weighted method. Associations with false discovery rate (FDR)-adjusted P values (PFDR)<0.05 were considered significant. RESULTS: In the meta-analysis of results from the basic models, we identified 30 metabolomic measures associated with WMH (PFDR<0.05), 7 of which remained significant in the fully adjusted models. The most significant association was with higher level of hydroxyphenylpyruvate in men (PFDR.full.adj=1.40×10-7) and in both the pooled sample (PFDR.full.adj=1.66×10-4) and statin-untreated (PFDR.full.adj=1.65×10-6) subsample. In men, hydroxyphenylpyruvate explained 3% to 14% of variance in WMH. In men and the pooled sample, WMH were also associated with lower levels of lysophosphatidylcholines and hydroxysphingomyelins and a larger diameter of low-density lipoprotein particles, likely arising from higher triglyceride to total lipids and lower cholesteryl ester to total lipids ratios within these particles. In women, the only significant association was with higher level of glucuronate (PFDR=0.047). CONCLUSIONS: Circulating metabolomic measures, including multiple lipid measures (eg, lysophosphatidylcholines, hydroxysphingomyelins, low-density lipoprotein size and composition) and nonlipid metabolites (eg, hydroxyphenylpyruvate, glucuronate), associate with WMH in a general population of middle-aged and older adults. Some metabolomic measures show marked sex specificities and explain a sizable proportion of WMH variance.


Assuntos
Diabetes Mellitus Tipo 2 , Substância Branca , Idoso , Encéfalo/patologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Metaboloma , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem
11.
World J Biol Psychiatry ; : 1-16, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-34870540

RESUMO

OBJECTIVES: The present study introduces the assessment of depression and depressive symptoms in the German National Cohort (NAKO), a population-based mega cohort. Distribution of core measures, and associations with sociodemographic factors are examined. METHODS: The current analysis includes data from the first 101,667 participants (NAKO data freeze 100,000). Depression and depressive symptoms were assessed using a modified version of the depression section of the Mini-International Neuropsychiatric Interview (MINI), self-reported physician's diagnosis of depression, and the depression scale of the Patient Health Questionnaire (PHQ-9). RESULTS: A lifetime physician's diagnosis of depression was reported by 15.0% of participants. Of those, 47.6% reported having received treatment for depression within the last 12 months. Of the subset of 26,342 participants undergoing the full depression section of the modified MINI, 15.9% were classified by the MINI with a lifetime depressive episode. Based on the PHQ-9, 5.8% of the participants were classified as currently having a major or other depression by the diagnostic algorithm, and 7.8% according to the dimensional assessment (score ≥ 10). Increased frequency of depression measures and higher depression scores were observed in women and participants with lower education level or a family history of depression. CONCLUSIONS: The observed distributions of all depression measures and their associations with sociodemographic variables are consistent with the literature on depression. The NAKO represents a valuable epidemiologic resource to investigate depression, and the range of measures for lifetime and current depression allows users to select the most suitable instrument for their specific research question.

12.
World J Biol Psychiatry ; : 1-16, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-34842503

RESUMO

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

13.
J Magn Reson Imaging ; 55(3): 908-916, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34564904

RESUMO

BACKGROUND: In the medical imaging domain, deep learning-based methods have yet to see widespread clinical adoption, in part due to limited generalization performance across different imaging devices and acquisition protocols. The deviation between estimated brain age and biological age is an established biomarker of brain health and such models may benefit from increased cross-site generalizability. PURPOSE: To develop and evaluate a deep learning-based image harmonization method to improve cross-site generalizability of deep learning age prediction. STUDY TYPE: Retrospective. POPULATION: Eight thousand eight hundred and seventy-six subjects from six sites. Harmonization models were trained using all subjects. Age prediction models were trained using 2739 subjects from a single site and tested using the remaining 6137 subjects from various other sites. FIELD STRENGTH/SEQUENCE: Brain imaging with magnetization prepared rapid acquisition with gradient echo or spoiled gradient echo sequences at 1.5 T and 3 T. ASSESSMENT: StarGAN v2, was used to perform a canonical mapping from diverse datasets to a reference domain to reduce site-based variation while preserving semantic information. Generalization performance of deep learning age prediction was evaluated using harmonized, histogram matched, and unharmonized data. STATISTICAL TESTS: Mean absolute error (MAE) and Pearson correlation between estimated age and biological age quantified the performance of the age prediction model. RESULTS: Our results indicated a substantial improvement in age prediction in out-of-sample data, with the overall MAE improving from 15.81 (±0.21) years to 11.86 (±0.11) with histogram matching to 7.21 (±0.22) years with generative adversarial network (GAN)-based harmonization. In the multisite case, across the 5 out-of-sample sites, MAE improved from 9.78 (±6.69) years to 7.74 (±3.03) years with histogram normalization to 5.32 (±4.07) years with GAN-based harmonization. DATA CONCLUSION: While further research is needed, GAN-based medical image harmonization appears to be a promising tool for improving cross-site deep learning generalization. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.


Assuntos
Aprendizado Profundo , Adolescente , Encéfalo/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Projetos de Pesquisa , Estudos Retrospectivos
14.
Hum Brain Mapp ; 43(1): 341-351, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32198905

RESUMO

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = -0.164 to -0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = -0.173 to -0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.


Assuntos
Tonsila do Cerebelo/patologia , Corpo Estriado/patologia , Transtorno Depressivo Maior/patologia , Hipocampo/patologia , Neuroimagem , Tálamo/patologia , Tonsila do Cerebelo/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Estudos Multicêntricos como Assunto , Tálamo/diagnóstico por imagem
15.
Hum Brain Mapp ; 43(1): 255-277, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32596977

RESUMO

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.


Assuntos
Transtornos de Ansiedade/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Interpretação Estatística de Dados , Metanálise como Assunto , Estudos Multicêntricos como Assunto , Neuroimagem , Humanos , Estudos Multicêntricos como Assunto/métodos , Estudos Multicêntricos como Assunto/normas , Neuroimagem/métodos , Neuroimagem/normas
16.
Hum Brain Mapp ; 43(1): 300-328, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33615640

RESUMO

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.


Assuntos
Encéfalo , Variações do Número de Cópias de DNA , Imageamento por Ressonância Magnética , Transtornos Mentais , Transtornos do Neurodesenvolvimento , Neuroimagem , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Humanos , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/genética , Transtornos Mentais/patologia , Estudos Multicêntricos como Assunto , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/patologia
17.
World J Biol Psychiatry ; : 1-9, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-34906037

RESUMO

OBJECTIVE: Childhood trauma is an important risk factor for the onset and course of psychiatric disorders and particularly major depression. Recently, the renin-angiotensin-aldosterone system, one of the core stress hormone systems, has been demonstrated to be modified by childhood trauma. METHODS: Childhood trauma was obtained using the Childhood Trauma Questionnaire (CTQ) in a community-dwelling sample (N = 2038). Plasma concentrations of renin and aldosterone were measured in subjects with childhood trauma (CT; N = 385) vs. subjects without this experience (NoCT; N = 1653). Multivariable linear regression models were calculated to assess the associations between CTQ, systolic and diastolic blood pressure, renin and aldosterone concentrations, and the ratio of aldosterone and systolic blood pressure (A/SBP). RESULTS: CT subjects demonstrated higher plasma aldosterone (A) concentrations, a lower systolic and diastolic blood pressure, and a higher A/SBP. In addition, both aldosterone concentrations, as well as A/SBP, correlated with the severity of childhood trauma. These findings could not be attributed to differences in concomitant medication. CONCLUSIONS: In conclusion, childhood trauma was associated with neurobiological markers, which may impact the risk for psychiatric disorders, primarily major depression. The altered A/SBP ratio points to a desensitisation of peripheral mineralocorticoid receptor function, which may be a target for therapeutic interventions.

18.
Neurobiol Stress ; 15: 100416, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34786441

RESUMO

BACKGROUND: Basal cortisol concentrations vary between men and women. Likewise, previous findings suggest stress-related cortical thickness alterations. Thus, we aimed at elucidating sex differences in the association between serum cortisol concentrations and cortical thickness. METHODS: Data of 2594 participants (55.55% male; mean age = 53.55 years ± 13.17 years) of the general population were used to investigate sex differences in basal serum cortisol concentrations and associations of serum cortisol concentrations with global and regional cortical thickness. The validity of the results was tested by including sex hormone concentrations as a biological and childhood maltreatment and depressive symptoms as a psychological confounder. RESULTS: Basal serum cortisol concentrations were higher in men than in women (ß = -0.158, t(2575) = -6.852, p = 9.056e-12). Sex differences in serum cortisol concentrations were diminished by including serum concentrations of testosterone, estrone, or estradiol in the models. In men but not in women, serum cortisol concentrations were inversely associated with the global cortical thickness (men: ß = -0.064, t(1412) = -3.010, p = .003; women: ß = -0.016, t(1131) = -0.607, p = .544). Additionally, these effects were observed in eleven cortical regions after adjusting for multiple testing. The associations were independent of childhood maltreatment and depressive symptoms. CONCLUSION: Sex differences in serum cortisol concentrations and the association between serum cortisol concentrations and cortical thickness suggest important sex-specific effects of stress on the brain. Future studies should integrate the interaction between the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis in sex-stratified analyses.

19.
PLoS One ; 16(10): e0258782, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34662349

RESUMO

Victims of childhood trauma report shame and anticipation of stigma, leading to non-disclosure and avoidance of help. Stigma is potentially aggravating the mental health consequences of childhood trauma. So far there is no comprehensive study examining stigma toward adult survivors of various forms of childhood trauma, and it is unclear whether stigma interferes with reaching out to affected individuals. In a vignette study based on a representative sample of the German general population (N = 1320; 47.7% male) we randomly allocated participants to brief case vignettes pertaining to past childhood sexual/physical abuse or accidents, and adult physical abuse. Stigma was elicited by applying the Social Distance Scale, assessing respondents' attitudes/stereotypes toward the persons in the vignette and their reluctance to address the specific trauma in conversation. While one aim was to establish the prevalence of stigma toward persons with CT, we hypothesized that attitudes differ according to type of trauma. Of the respondents, 45% indicated they were unlikely to reach out to a victim of childhood sexual abuse, 38% to a victim of childhood physical abuse, 31% to someone reporting a childhood accident and 25% to someone reporting adult physical abuse. Contrary to our expectations, childhood sexual abuse did not consistently elicit more stigma than childhood physical abuse in Krukall-Wallis tests. Equally, childhood interpersonal trauma did not consistently elicit more stigma than childhood accidental trauma. Structural equation modeling revealed social distance as mediator of the relationship between negative stereotypes and reluctance to address childhood trauma in conversation. Our analyses further revealed an ambiguous role of negative stereotypes in addressing childhood trauma in conversation with trauma victims, which has yet to be examined. There is evidence for stigma associated with having survived childhood trauma, which is interfering with offering help.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Abuso Sexual na Infância/estatística & dados numéricos , Abuso Físico/estatística & dados numéricos , Vergonha , Estigma Social , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Abuso Sexual na Infância/psicologia , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Abuso Físico/psicologia , Distribuição Aleatória , Inquéritos e Questionários , Adulto Jovem
20.
JAMA Netw Open ; 4(10): e2128225, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34609493

RESUMO

Importance: Underlying pathomechanisms of brain white matter hyperintensities (WMHs), commonly observed in older individuals and significantly associated with Alzheimer disease and brain aging, have not yet been fully elucidated. One potential contributing factor to WMH burden is chronic obstructive sleep apnea (OSA), a disorder highly prevalent in the general population with readily available treatment options. Objective: To investigate potential associations between OSA and WMH burden. Design, Setting, and Participants: Analyses were conducted in 529 study participants of the Study of Health in Pomerania-Trend baseline (SHIP-Trend-0) study with complete WMH, OSA, and important clinical data available. SHIP-Trend-0 is a general population-based, cross-sectional, observational study to facilitate the investigation of a large spectrum of common risk factors, subclinical disorders, and clinical diseases and their relationships among each other with patient recruitment from Western Pomerania, Germany, starting on September 1, 2008, with data collected until December 31, 2012. Data analysis was performed from February 1, 2019, to January 31, 2021. Exposures: The apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were assessed during a single-night, laboratory-based polysomnography measurement. Main Outcomes and Measures: The primary outcome was WMH data automatically segmented from 1.5-T magnetic resonance images. Results: Of 529 study participants (mean [SD] age, 52.15 [13.58] years; 282 female [53%]), a total of 209 (40%) or 102 (19%) individuals were diagnosed with OSA according to AHI or ODI criteria (mean [SD] AHI, 7.98 [12.55] events per hour; mean [SD] ODI, 3.75 [8.43] events per hour). Both AHI (ß = 0.024; 95% CI, 0.011-0.037; P <.001) and ODI (ß = 0.033; 95% CI, 0.014-0.051; P <. 001) were significantly associated with brain WMH volumes. These associations remained even in the presence of additional vascular, metabolic, and lifestyle WMH risk factors. Region-specific WMH analyses found the strongest associations between periventricular frontal WMH volumes and both AHI (ß = 0.0275; 95% CI, 0.013-0.042, P < .001) and ODI (ß = 0.0381; 95% CI, 0.016-0.060, P < .001) as well as periventricular dorsal WMH volumes and AHI (ß = 0.0165; 95% CI, 0.004-0.029, P = .008). Conclusions and Relevance: This study found significant associations between OSA and brain WMHs, indicating a novel, potentially treatable WMH pathomechanism.


Assuntos
Apneia Obstrutiva do Sono/complicações , Substância Branca/fisiopatologia , Adulto , Idoso , Envelhecimento/fisiologia , Estudos de Coortes , Estudos Transversais , Feminino , Alemanha/epidemiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/diagnóstico por imagem , Apneia Obstrutiva do Sono/epidemiologia , Substância Branca/anormalidades
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