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1.
Front Public Health ; 9: 553071, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33614574

RESUMO

In Germany, large, population-based cohort studies have been implemented in order to identify risk and protective factors for maintaining health across the life span. The purpose of this systematic review is to analyse findings from three large ongoing cohorts and to identify sex-specific prevalence rates, risk and protective factors for mental health. Published studies from the Cooperative Health Research in the Region Augsburg (KORA), the Study of Health in Pomerania (SHIP) and the Gutenberg Health Study (GHS)), representing the southern, north-eastern and middle parts of Germany, were identified through searches of the databases PubMed and Web of Science. A total of 52 articles was identified from the start of each cohort until June 2019. Articles reporting prevalence rates of mental health [N = 22], explanatory factors for mental health [N = 25], or both [N = 5] were identified. Consistent across cohorts, higher prevalence rates of internalizing disorders were found for women and more externalizing disorders for men. Risk and protective factors for mental health included social factors, lifestyle, physical health, body mass index (BMI), diabetes, genetic and biological factors. In all areas, differences and similarities were found between women and men. The most evident were the sex-specific risk profiles for depression with mostly external risk factors for men and internal risk factors for women. Gender was not assessed directly, therefore we examined whether socioeconomic and family-related factors reflecting gender roles or institutionalized gender could be used as a proxy for gender. Overall, this systematic review shows differences and similarities in prevalence rates and determinants of mental health indicators between women and men. They underline the importance of focussing on sex specific approaches in mental health research and in the development of prevention measures. Current research on mental health still lacks focus on gender aspects. Therefore, an increased focus on sex and gender in mental health research is of great importance.

2.
PLoS Comput Biol ; 17(2): e1008735, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33577591

RESUMO

In this work, we introduce an entirely data-driven and automated approach to reveal disease-associated biomarker and risk factor networks from heterogeneous and high-dimensional healthcare data. Our workflow is based on Bayesian networks, which are a popular tool for analyzing the interplay of biomarkers. Usually, data require extensive manual preprocessing and dimension reduction to allow for effective learning of Bayesian networks. For heterogeneous data, this preprocessing is hard to automatize and typically requires domain-specific prior knowledge. We here combine Bayesian network learning with hierarchical variable clustering in order to detect groups of similar features and learn interactions between them entirely automated. We present an optimization algorithm for the adaptive refinement of such group Bayesian networks to account for a specific target variable, like a disease. The combination of Bayesian networks, clustering, and refinement yields low-dimensional but disease-specific interaction networks. These networks provide easily interpretable, yet accurate models of biomarker interdependencies. We test our method extensively on simulated data, as well as on data from the Study of Health in Pomerania (SHIP-TREND), and demonstrate its effectiveness using non-alcoholic fatty liver disease and hypertension as examples. We show that the group network models outperform available biomarker scores, while at the same time, they provide an easily interpretable interaction network.

3.
Hum Brain Mapp ; 2021 Feb 21.
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.

4.
J Psychosom Res ; 143: 110372, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33540301

RESUMO

OBJECTIVE: Alexithymia is associated with various mental as well as physical disorders. Some evidence also suggested high alexithymia to increase mortality risk, but these results are few and based on specific sample compositions. We aimed to investigate the impact of alexithymia on mortality risk in a large population based cohort. In addition, we sought to elucidate the effects of the subfactors of alexithymia and sex differences. METHODS: In a sample of N = 1380 individuals from the Study of Health in Pomerania (SHIP), we investigated the hazard-ratio (HR) of alexithymia as obtained by the Toronto Alexithymia Scale-20 (TAS-20) on all-cause mortality over an average observation time of 10 years. Sex-by-TAS-20-interactions as well as sex-stratified analyses were performed. RESULTS: Alexithymia was significantly associated with enhanced mortality risk (HR = 1.033; 95%-CI = 1.008-1.058); p = 0.009). While sex-by-TAS-20 interactions remained insignificant, sex-stratified analyses showed that this effect was only significant in men (HR = 1.050; 95%-CI = 1.022-1.079; p ≤ 0.001), but not in women (HR: 1.008; 95%-CI = 0.960-1.057; p = 0.76). The effect was validated for the "difficulties identifying feelings" (DIF) and "difficulties describing feelings" (DDF) subfactors of the TAS-20. CONCLUSION: Our study supports and extents previous findings by indicating that mortality risk enhancing effects of alexithymia are specific to male subjects and validated for the DIF and DDF facets. Socioeconomic, clinical and metabolic factors were associated with this relationship. Finding that the impact of alexithymia remains stable in the fully adjusted models suggests that yet unidentified additional factors must be considered.

5.
Psychiatry Res ; 298: 113783, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33567384

RESUMO

Previous studies suggested that childhood trauma and a disturbed serotonergic neurotransmission are involved in the pathogenesis of alexithymia. Specifically, genetic polymorphisms of the serotonin receptors 5-HT1A and 5-HT2A were found to be associated with alexithymia. However, it is unclear whether these factors show main or interaction effects with childhood trauma on alexithymia. Data from two independent general-population cohorts of the Study of Health in Pomerania (SHIP-Trend: N=3,706, Age: range=20-83, 51.6% female, SHIP-LEGEND: N=2,162, Age: range=20-80, 52.5% female) were used. The Toronto Alexithymia Scale-20 (TAS-20) and the Childhood Trauma Questionnaire (CTQ) were applied. Genotypes of rs6295 of 5-HT1A and rs6311 of 5-HT2A were determined. Ordinary least-squared regression models with robust standard errors were applied to investigate associations of the main and interaction effects of childhood maltreatment and the polymorphisms with alexithymia. Childhood trauma, but none of the investigated polymorphisms showed main effects on alexithymia. However, childhood trauma showed significant CTQ sum score x rs6295 interactions in male subjects in both samples such that the presence of the G-allele diminished the CTQ associated increase in the TAS-20 sum scores. Our results support a strong role of early life stress and interactions with rs6295 on alexithymic personality features at least in male subjects.

6.
Sci Rep ; 11(1): 2325, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504924

RESUMO

To identify the most important parameters associated with cerebral white matter hyperintensities (WMH), in consideration of potential collinearity, we used a data-driven machine-learning approach. We analysed two independent cohorts (KORA and SHIP). WMH volumes were derived from cMRI-images (FLAIR). 90 (KORA) and 34 (SHIP) potential determinants of WMH including measures of diabetes, blood-pressure, medication-intake, sociodemographics, life-style factors, somatic/depressive-symptoms and sleep were collected. Elastic net regression was used to identify relevant predictor covariates associated with WMH volume. The ten most frequently selected variables in KORA were subsequently examined for robustness in SHIP. The final KORA sample consisted of 370 participants (58% male; age 55.7 ± 9.1 years), the SHIP sample comprised 854 participants (38% male; age 53.9 ± 9.3 years). The most often selected and highly replicable parameters associated with WMH volume were in descending order age, hypertension, components of the social environment (i.e. widowed, living alone) and prediabetes. A systematic machine-learning based analysis of two independent, population-based cohorts showed, that besides age and hypertension, prediabetes and components of the social environment might play important roles in the development of WMH. Our results enable personal risk assessment for the development of WMH and inform prevention strategies tailored to the individual patient.

7.
Z Psychosom Med Psychother ; 66(4): 337-354, 2020 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-33284068

RESUMO

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

8.
Eur Respir J ; 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33361099

RESUMO

OBJECTIVE: Cumulative evidence indicates that childhood maltreatment (CM) is linked to self-reported asthma and chronic obstructive pulmonary disease. However, the relation between CM and objective measures of lung function as determined by spirometry has not yet been assessed. METHODS: Medical histories and spirometric lung function were taken in 1386 adults from the general population. Participants also completed the Childhood Trauma Questionnaire for the assessment of emotional, physical and sexual abuse as well as emotional and physical neglect. RESULTS: 25.3% of the participants reported at least one type of CM. Among them, use of medication for obstructive airway diseases as well as typical signs and symptoms of airflow limitation were significantly more frequent than in the group without exposure to CM. Although participants with CM had numerically lower values for FEV1, FVC and PEF than those without, these differences were non-significant when accounting for relevant covariates like age, sex, height and smoking. Likewise, there were no differences in the FEV1/FVC ratio nor in the frequency of airflow limitation regardless of its definition. No specific type of CM was related to spirometrically determined parameters of lung function. CONCLUSIONS: Our findings call into question the association of CM with obstructive lung diseases as indicated by prior research relying on self-reported diagnoses. We consider several explanations for these discrepancies.

9.
Addiction ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33155711

RESUMO

BACKGROUND AND AIMS: Existing evidence suggests that text message interventions can help people reduce their alcohol consumption. However, studies with alcohol dependent patients are lacking. In this study a 1-year automatic mobile phone-based short messaging service (SMS) intervention on alcohol consumption in patients after alcohol detoxification in hospital was compared with treatment as usual. DESIGN: Multicenter, randomized, controlled, 2 parallel-group, observer-blinded trial SETTING: Primary and secondary care: 4 hospitals and community (1 million residents, 7600 km2 area in Germany). PARTICIPANTS: A total of 462 patients with alcohol-dependence (ICD-10) were included during inpatient detoxification treatment. Patients were randomly assigned (1:1) to an SMS intervention and treatment as usual (SMS+TAU; n=230; mean age: 45.4 years; 22.6% women) or TAU alone (n=232 mean age: 44.5 years; 22.8% women). INTERVENTIONS: Planned, automated messages were sent to patients over 1 year to record assistance needs. A "Yes" or missing response triggered a phone call from a hospital therapist. Outcome was assessed by an independent survey center. MEASUREMENTS: The primary endpoint was a 3-category alcohol consumption measure covering months 10-12 after discharge: abstinence, non-heavy drinking, heavy drinking (men >60 g/d; women >40 g/d equal to WHO criteria: high risk and very high risk, mean consumption). Secondary endpoints were number of abstinent days over 12 months and frequency of abstinence. FINDINGS: The arms differed primarily in the heavy drinking category (intervention group 22.2%, TAU-only group 32.3%) in months 9 to 12. This is reflected by an odds ratio (OR) 1.68, 95%CI 1.11 to 2.54, p = 0.015 for heavy drinking vs. non-heavy drinking/abstinence. No difference between treatments was found with respect to any drinking vs. abstinence (OR=1.13). These results were confirmed by models adjusting for randomisation strata. CONCLUSIONS: In Germany, a 12 month mobile phone short messaging service-based intervention enhanced the reduction in heavy drinking for 1 year in routine care among adults with alcohol dependence discharged from inpatient alcohol detoxification.

10.
Brain Behav ; : e01884, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33052028

RESUMO

INTRODUCTION: Insufficient vitamin D levels were found to be related to various psychiatric disorders and particularly depression. The functional polymorphisms rs4588 and rs7041 of the vitamin D-binding protein (also group-specific component or Gc) influence vitamin D level and activity. Resilience is considered the individual predisposition to maintain psychological functioning in the face of adversities. We sought to investigate whether associations of vitamin D levels and genotypes of rs4588 and rs7041 were associated with trait resilience and symptoms of depression. METHODS: Serum levels of total 25(OH)D were measured in a general population sample (n = 1,908) of the Study of Health in Pomerania (SHIP-1). The Resilience Scale-25 (RS-25) was applied to assess trait resilience. Lifetime depressive symptoms were assessed using the CID-S, while current depressive symptoms were measured using the Beck Depression Inventory II (BDI-II). Study participants were genotyped for rs4588 and rs7041. RESULTS: Participants with vitamin D insufficiency had lower adjusted mean RS-25 scores as compared to vitamin D replete subjects (p = .002). Linear regression analyses revealed a positive association between 25(OH)D and RS-25 scores (ß = 2.782, p = .002). Additional adjustment for BDI-II scores slightly attenuated this result (ß = 1.830 and p = .026). Symptoms of depression and the lifetime diagnosis of MDD were not significantly associated with vitamin D concentrations. rs4588 and rs7041 showed strong associations with vitamin D concentrations (both p < .001), but not RS-25 scores. CONCLUSIONS: In contrast with previous studies, our findings do not provide evidence for a strong role of vitamin D in the psychopathology of depression. However, considering the role of trait resilience as a common protective factor to different psychiatric disorders, our results support the concept of low vitamin D as a general risk factor to stress-related psychopathologies.

11.
Sleep ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33017007

RESUMO

Advanced brain ageing is commonly regarded as a risk factor for neurodegenerative diseases, e.g. Alzheimer's dementia, and it was suggested that sleep disorders such as obstructive sleep apnoea (OSA) are significantly contributing factors to these neurodegenerative processes. To determine the association between OSA and advanced brain ageing, we investigated the specific effect of two indices quantifying OSA, namely the apnoea-hypopnea index (AHI) and the oxygen desaturation index (ODI), on brain age, a score quantifying age-related brain patterns in 169 brain regions, using magnetic resonance imaging and overnight polysomnography data from 690 participants (48.8% women, mean age 52.5±13.4 years) of the Study of Health in Pomerania. We additionally investigated the mediating effect of subclinical inflammation parameters on these associations via a causal mediation analysis. AHI and ODI were both positively associated with brain age (AHI std. effect [95% CI]: 0.07 [0.03; 0.12], p-value: 0.002; ODI std. effect [95% CI]: 0.09 [0.04; 0.13], p-value: <0.0003). The effects remained stable in the presence of various confounders such as diabetes and were partially mediated by the white blood cell count, indicating a subclinical inflammation process. Our results reveal an association between OSA and brain age, indicating subtle but widespread age-related changes in regional brain structures, in one of the largest general population studies to date, warranting further examination of OSA in the prevention of neurodegenerative diseases.

12.
Alzheimers Dement ; 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32920988

RESUMO

INTRODUCTION: Relationships between brain atrophy patterns of typical aging and Alzheimer's disease (AD), white matter disease, cognition, and AD neuropathology were investigated via machine learning in a large harmonized magnetic resonance imaging database (11 studies; 10,216 subjects). METHODS: Three brain signatures were calculated: Brain-age, AD-like neurodegeneration, and white matter hyperintensities (WMHs). Brain Charts measured and displayed the relationships of these signatures to cognition and molecular biomarkers of AD. RESULTS: WMHs were associated with advanced brain aging, AD-like atrophy, poorer cognition, and AD neuropathology in mild cognitive impairment (MCI)/AD and cognitively normal (CN) subjects. High WMH volume was associated with brain aging and cognitive decline occurring in an ≈10-year period in CN subjects. WMHs were associated with doubling the likelihood of amyloid beta (Aß) positivity after age 65. Brain aging, AD-like atrophy, and WMHs were better predictors of cognition than chronological age in MCI/AD. DISCUSSION: A Brain Chart quantifying brain-aging trajectories was established, enabling the systematic evaluation of individuals' brain-aging patterns relative to this large consortium.

13.
Nutrients ; 12(9)2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32911625

RESUMO

Human donor milk (HDM) provides appropriate nutrition and offers protective functions in preterm infants. The aim of the study is to examine the impact of different storage conditions on the stability of the human breast milk peptidome. HDM was directly frozen at -80 °C or stored at -20 °C (120 h), 4 °C (6 h), or room temperature (RT for 6 or 24 h). The milk peptidome was profiled by mass spectrometry after peptide collection by ultrafiltration. Profiling of the peptidome covered 3587 peptides corresponding to 212 proteins. The variance of the peptidome increased with storage temperature and time and varied for different peptides. The highest impact was observed when samples were stored at RT. Smaller but significant effects were still observed in samples stored at 4 °C, while samples showed highest similarity to those immediately frozen at -80 °C when stored at -20 °C. Peptide structures after storage at RT for 24 h point to the increased activity of thrombin and other proteases cleaving proteins at lysine/arginine. The results point to an ongoing protein degradation/peptide production by milk-derived proteases. They underline the need for immediate freezing of HDM at -20 °C or -80 °C to prevent degradation of peptides and enable reproducible investigation of prospectively collected samples.

14.
Hum Brain Mapp ; 2020 Jun 29.
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.

15.
Brain ; 143(7): 2312-2324, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32591831

RESUMO

Deep learning has emerged as a powerful approach to constructing imaging signatures of normal brain ageing as well as of various neuropathological processes associated with brain diseases. In particular, MRI-derived brain age has been used as a comprehensive biomarker of brain health that can identify both advanced and resilient ageing individuals via deviations from typical brain ageing. Imaging signatures of various brain diseases, including schizophrenia and Alzheimer's disease, have also been identified using machine learning. Prior efforts to derive these indices have been hampered by the need for sophisticated and not easily reproducible processing steps, by insufficiently powered or diversified samples from which typical brain ageing trajectories were derived, and by limited reproducibility across populations and MRI scanners. Herein, we develop and test a sophisticated deep brain network (DeepBrainNet) using a large (n = 11 729) set of MRI scans from a highly diversified cohort spanning different studies, scanners, ages and geographic locations around the world. Tests using both cross-validation and a separate replication cohort of 2739 individuals indicate that DeepBrainNet obtains robust brain-age estimates from these diverse datasets without the need for specialized image data preparation and processing. Furthermore, we show evidence that moderately fit brain ageing models may provide brain age estimates that are most discriminant of individuals with pathologies. This is not unexpected as tightly-fitting brain age models naturally produce brain-age estimates that offer little information beyond age, and loosely fitting models may contain a lot of noise. Our results offer some experimental evidence against commonly pursued tightly-fitting models. We show that the moderately fitting brain age models obtain significantly higher differentiation compared to tightly-fitting models in two of the four disease groups tested. Critically, we demonstrate that leveraging DeepBrainNet, along with transfer learning, allows us to construct more accurate classifiers of several brain diseases, compared to directly training classifiers on patient versus healthy control datasets or using common imaging databases such as ImageNet. We, therefore, derive a domain-specific deep network likely to reduce the need for application-specific adaptation and tuning of generic deep learning networks. We made the DeepBrainNet model freely available to the community for MRI-based evaluation of brain health in the general population and over the lifespan.

16.
J Clin Med ; 9(6)2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32575439

RESUMO

BACKGROUND: agonistic autoantibodies (agAABs) against G protein-coupled receptors (GPCR) have been linked to cardiovascular disease. In dementia patients, GPCR-agAABs against the α1- and ß2-adrenoceptors (α1AR- and ß2AR) were found at a prevalence of 50%. Elimination of agAABs by immunoadsorption (IA) was successfully applied in cardiovascular disease. The IMAD trial (Efficacy of immunoadsorption for treatment of persons with Alzheimer dementia and agonistic autoantibodies against alpha1A-adrenoceptor) investigates whether the removal of α1AR-AABs by a 5-day IA procedure has a positive effect (improvement or non-deterioration) on changes of hemodynamic, cognitive, vascular and metabolic parameters in patients with suspected Alzheimer's clinical syndrome within a one-year follow-up period. METHODS: the IMAD trial is designed as an exploratory monocentric interventional trial corresponding to a proof-of-concept phase-IIa study. If cognition capacity of eligible patients scores 19-26 in the Mini Mental State Examination (MMSE), patients are tested for the presence of agAABs by an enzyme-linked immunosorbent assay (ELISA)-based method, followed by a bioassay-based confirmation test, further screening and treatment with IA and intravenous immunoglobulin G (IgG) replacement. We aim to include 15 patients with IA/IgG and to complete follow-up data from at least 12 patients. The primary outcome parameter of the study is uncorrected mean cerebral perfusion measured in mL/min/100 gr of brain tissue determined by magnetic resonance imaging with arterial spin labeling after 12 months. CONCLUSION: IMAD is an important pilot study that will analyze whether the removal of α1AR-agAABs by immunoadsorption in α1AR-agAAB-positive patients with suspected Alzheimer's clinical syndrome may slow the progression of dementia and/or may improve vascular functional parameters.

17.
Mol Genet Genomic Med ; 8(9): e1345, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32558353

RESUMO

BACKGROUND: The mineralocorticoid receptor (MR) in the brain has a key role in the regulation of the central stress response and is associated with memory performance. We investigated whether the genetic polymorphisms rs5522 and rs2070951 of NR3C2 showed main and interactive effects with childhood trauma on memory decline. METHODS: Declarative memory was longitudinally assessed in 1,318 participants from the community-dwelling Study of Health in Pomerania using the Verbal Learning and Memory Test (VLMT). In a subsample of 377 participants aged 60 and older, the Mini-Mental Status Examination (MMSE) was additionally applied. Mean follow-up time for the VLMT and MMSE were 6.4 and 10.7 years, respectively. RESULTS: Homozygous carriers of the G allele of rs2070951 (p < .01) and of the A allele of rs5522 (p < .001) showed higher immediate recall of words as compared to carriers of C allele (rs2070951) or the G allele (rs5522). The CG haplotype was associated with decreased recall (p < .001). Likewise, in the subsample of older patients, the AA genotype of rs5522 was associated with higher MMSE scores (p < .05). CG haplotypes showed significantly reduced MMSE scores in comparison to the reference haplotype (ß = -0.60; p < .01). CONCLUSIONS: Our results indicate that the GG genotype of rs2070951 as well as the AA genotype of rs5522 are associated with diminished memory decline.

19.
Mol Psychiatry ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424236

RESUMO

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

20.
Mol Psychiatry ; 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32467648

RESUMO

Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = -0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.

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