As medical imaging enters its information era and presents rapidly increasing needs for big data analytics, robust pooling and harmonization of imaging data across diverse cohorts with varying ...acquisition protocols have become critical. We describe a comprehensive effort that merges and harmonizes a large-scale dataset of 10,477 structural brain MRI scans from participants without a known neurological or psychiatric disorder from 18 different studies that represent geographic diversity. We use this dataset and multi-atlas-based image processing methods to obtain a hierarchical partition of the brain from larger anatomical regions to individual cortical and deep structures and derive age trends of brain structure through the lifespan (3–96 years old). Critically, we present and validate a methodology for harmonizing this pooled dataset in the presence of nonlinear age trends. We provide a web-based visualization interface to generate and present the resulting age trends, enabling future studies of brain structure to compare their data with this reference of brain development and aging, and to examine deviations from ranges, potentially related to disease.
•Multi-site harmonization method that pools volumetric data from 18 studies, controlling for nonlinear age effects.•Resulting dataset covers ages 3 to 96 and used to derive age trends of brain structure through the lifespan.•Interactive visualization tool provided for exploring age trends and comparing new data.
The number of mentally altered patients a dentist meets in practice is increasing and interaction with them can be very challenging. As a baseline for an interventional study, we want to assess the ...attitude of dental students and identify areas of improvement in patient communication. This work compares the attitude of dental students towards people suffering from dementia to the attitudes of trained medical caregivers and the general population. Our aim is to use the results to assess the need for training in communicating with mentally altered patients.
Fourth-year dental students attended two lectures on dementia given by a psychiatrist as part of the geriatric dentistry lecture and were questioned afterwards using the Dementia Attitude Scale. In 2016 and 2017, 73 students at the University of Greifswald were interviewed. The response rate was 84%. Using a factor analysis, the Dementia Attitude Scale's validated questions were interpreted and compared with data from nursing staff from Switzerland and the USA.
The factor analysis of the data showed the same two-factor loadings as the comparative groups, and that dental students' attitude is more comparable to the general population than to medically trained nursing staff.
Given the results, we conclude that the implementation of a communication module can serve in improving the attitude of dental students towards patients with dementia.
Pregnancy and the postpartum period are times when women are at increased risk for depression and mental problems. This may also negatively affect the foetus. Thus, there is a need for interventions ...with low-threshold access and care. Telemedicine interventions are a promising approach to address these issues. This systematic literature review examined the efficacy of telemedicine interventions for pregnant women and/or new mothers to address mental health-related outcomes. The primary objective was to analyse whether telemedicine interventions can reduce mental health problems in pregnant women and new mothers. The secondary aim was to clarify the impact of type of interventions, their frequency and their targets.
Inclusion criteria: randomized controlled trials, with participants being pregnant women and/or new mothers (with infants up to twelve months), involving telemedicine interventions of any kind (e.g. websites, apps, chats, telephone), and addressing any mental health-related outcomes like depression, postnatal depression, anxiety, stress and others. Search terms were pregnant women, new mothers, telemedicine, RCT (randomised controlled trials), mental stress as well as numerous synonyms including medical subject headings. The literature search was conducted within the databases PubMed, Cochrane Library, Web of Science and PsycINFO. Screening, inclusion of records and data extraction were performed by two researchers according to the PRISMA guidelines, using the online tool CADIMA.
Forty four articles were included. A majority (62%) reported significantly improved mental health-related outcomes for participants receiving telemedicine interventions compared to control. In particular (internet-delivered) Cognitive Behavioural Therapy was successful for depression and stress, and peer support improved outcomes for postnatal depression and anxiety. Interventions with preventive approaches and interventions aimed at symptom reduction were largely successful. For the most part there was no significant improvement in the symptoms of anxiety.
Telemedicine interventions evaluated within RCTs were mostly successful. However, they need to be designed to specifically target a certain mental health issue because there is no one-size-fits-all approach. Further research should focus on which specific interventions are appropriate for which mental health outcomes in terms of intervention delivery modes, content, target approaches, etc. Further investigation is needed, in particular with regard to anxiety.
Nicotine modulates prefrontal processing when tested with functional imaging. Previous studies on changes in regional brain volumes in small samples, reporting different life-time exposure to ...nicotine, identified reduced volume in smokers in prefrontal areas but reported controversial results for other areas. We investigated the association of cigarette smoking and regional gray and white matter volume by using voxel-based morphometry (VBM) for T1-weighted high-resolution magnetic resonance imaging in 315 current-smokers and 659 never-smokers from the representative Study of Health in Pomerania (SHIP). Our study showed that in current-smokers smoking is significantly associated with gray matter volume loss in the prefrontal cortex, the anterior cingulate cortex, the insula, and the olfactory gyrus. White matter volumes were not relevantly reduced in current-smokers. In current-smokers, we found associations of gray matter loss and smoking exposure (pack-years) in the prefrontal cortex, the anterior and middle cingulate cortex, and the superior temporal and angular gyrus, which however did not stand corrections for multiple testing. We confirmed associations between smoking and gray matter differences in the prefrontal cortex, the anterior cingulate cortex and the insula in the general population of Pomerania (Germany). For the first time, we identified differences in brain volumes in the olfactory gyrus. Other cerebral regions did not show significant differences when correcting for multiple comparisons within the whole brain. The regions of structural deficits might be involved in addictive behavior and withdrawal symptoms, whereas further investigations have to show if the observed atrophies were caused by smoking itself or are preexisting differences between smoking and non-smoking individuals.
Minimal phenotyping refers to the reliance on the use of a small number of self-reported items for disease case identification, increasingly used in genome-wide association studies (GWAS). Here we ...report differences in genetic architecture between depression defined by minimal phenotyping and strictly defined major depressive disorder (MDD): the former has a lower genotype-derived heritability that cannot be explained by inclusion of milder cases and a higher proportion of the genome contributing to this shared genetic liability with other conditions than for strictly defined MDD. GWAS based on minimal phenotyping definitions preferentially identifies loci that are not specific to MDD, and, although it generates highly predictive polygenic risk scores, the predictive power can be explained entirely by large sample sizes rather than by specificity for MDD. Our results show that reliance on results from minimal phenotyping may bias views of the genetic architecture of MDD and impede the ability to identify pathways specific to MDD.
Childhood maltreatment and depressive disorders have both been associated with a dysregulation of the hypothalamic-pituitary-adrenal axis. The FKBP5 gene codes for a co-chaperone regulating the ...glucocorticoid-receptor sensitivity. Previous evidence suggests that subjects carrying the TT genotype of the FKBP5 gene single-nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to adverse effects of experimental stress. We therefore tested the hypothesis of an interaction of childhood abuse with rs1360780 in predicting adult depression. In all, 2157 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and Childhood Trauma Questionnaire. The DSM-IV diagnosis of major depressive disorder (MDD) was assessed by interview. Genotypes of rs1360780 were taken from the Affymetrix Human SNP Array 6.0. Significant interaction (p=0.006) of physical abuse with the TT genotype of rs1360780 was found increasing the BDI-II score to 17.4 (95% confidence interval (CI)=12.0-22.9) compared with 10.0 (8.2-11.7) in exposed CC/CT carriers. Likewise, the adjusted odds ratio for MDD in exposed TT carriers was 8.2 (95% CI=1.9-35.0) compared with 1.3 (0.8-2.3) in exposed subjects with CC/CT genotypes. Relative excess risk due to interaction (RERI) analyses confirmed a significant additive interaction effect (RERI=6.8; 95% CI=0.64-33.7; p<0.05). In explorative analyses, the most severe degree of sexual and emotional abuse also yielded significant interaction effects (p<0.05). This study revealed interactions between physical abuse and rs1360780 of the FKBP5 gene, confirming its role in the individual susceptibility to depression. Given the large effect sizes, rs1360780 could be included into prediction models for depression in individuals exposed to childhood abuse.
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 (Aβ) 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.
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.
Caffeine is the most widely consumed psychoactive substance in the world and presents with wide interindividual variation in metabolism. This variation may modify potential adverse or beneficial ...effects of caffeine on health. We conducted a genome-wide association study (GWAS) of plasma caffeine, paraxanthine, theophylline, theobromine and paraxanthine/caffeine ratio among up to 9,876 individuals of European ancestry from six population-based studies. A single SNP at 6p23 (near CD83) and several SNPs at 7p21 (near AHR), 15q24 (near CYP1A2) and 19q13.2 (near CYP2A6) met GW-significance (P < 5 × 10-8) and were associated with one or more metabolites. Variants at 7p21 and 15q24 associated with higher plasma caffeine and lower plasma paraxanthine/caffeine (slow caffeine metabolism) were previously associated with lower coffee and caffeine consumption behavior in GWAS. Variants at 19q13.2 associated with higher plasma paraxanthine/caffeine (slow paraxanthine metabolism) were also associated with lower coffee consumption in the UK Biobank (n = 94 343, P < 1.0 × 10-6). Variants at 2p24 (in GCKR), 4q22 (in ABCG2) and 7q11.23 (near POR) that were previously associated with coffee consumption in GWAS were nominally associated with plasma caffeine or its metabolites. Taken together, we have identified genetic factors contributing to variation in caffeine metabolism and confirm an important modulating role of systemic caffeine levels in dietary caffeine consumption behavior. Moreover, candidate genes identified encode proteins with important clinical functions that extend beyond caffeine metabolism.
The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased ...appetite and/or weight (A/W) during an active episode.
To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index BMI and levels of C-reactive protein CRP and leptin).
This multicenter study assembled genome-wide genotypic and phenotypic measures from 14 data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case-control, cohort, and population-based studies, including 26 628 participants with established psychiatric diagnoses and genome-wide genotype data. Data on BMI were available for 15 237 participants. Data were retrieved and analyzed from September 28, 2015, through May 20, 2017.
Lifetime DSM-IV MDD was diagnosed using structured diagnostic instruments. Patients with MDD were stratified into subgroups according to change in the DSM-IV A/W symptoms as decreased or increased.
Data included 11 837 participants with MDD and 14 791 control individuals, for a total of 26 628 participants (59.1% female and 40.9% male). Among participants with MDD, 5347 (45.2%) were classified in the decreased A/W and 1871 (15.8%) in the increased A/W subgroups. Common genetic variants explained approximately 10% of the heritability in the 2 subgroups. The increased A/W subgroup showed a strong and positive genetic correlation (SE) with BMI (0.53 0.15; P = 6.3 × 10-4), whereas the decreased A/W subgroup showed an inverse correlation (-0.28 0.14; P = .06). Furthermore, the decreased A/W subgroup had a higher polygenic risk for increased BMI (odds ratio OR, 1.18; 95% CI, 1.12-1.25; P = 1.6 × 10-10) and levels of CRP (OR, 1.08; 95% CI, 1.02-1.13; P = 7.3 × 10-3) and leptin (OR, 1.09; 95% CI, 1.06-1.12; P = 1.7 × 10-3).
The phenotypic associations between atypical depressive symptoms and obesity-related traits may arise from shared pathophysiologic mechanisms in patients with MDD. Development of treatments effectively targeting immunometabolic dysregulations may benefit patients with depression and obesity, both syndromes with important disability.
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