Same brain, different look? The impact of scanner, sequence and preprocessing on diffusion imaging outcome parameters

In clinical diagnostics and longitudinal studies, the reproducibility of MRI assessments is of high importance in order to detect pathological changes, but developments in MRI hard- and software often outrun extended periods of data acquisition and analysis. This could potentially introduce artefactual changes or mask pathological alterations. However, if and how changes of MRI hardware, scanning protocols or preprocessing software affect complex neuroimaging outcomes from, e.g., diffusion weighted imaging (DWI) remains largely understudied. We therefore compared DWI outcomes and artefact severity of 121 healthy participants (age range 19–54 years) who underwent two matched DWI protocols (Siemens product and Center for Magnetic Resonance Research sequence) at two sites (Siemens 3T Magnetom Verio and Skyrafit). After different preprocessing steps, fractional anisotropy (FA) and mean diffusivity (MD) maps, obtained by tensor fitting, were processed with tract-based spatial statistics (TBSS). Inter-scanner and inter-sequence variability of skeletonised FA values reached up to 5% and differed largely in magnitude and direction across the brain. Skeletonised MD values differed up to 14% between scanners. We here demonstrate that DTI outcome measures strongly depend on imaging site and software, and that these biases vary between brain regions. These regionally inhomogeneous biases may exceed and considerably confound physiological effects such as ageing, highlighting the need to harmonise data acquisition and analysis. Future studies thus need to implement novel strategies to augment neuroimaging data reliability and replicability

Associations between anxiety, body mass index, and sex hormones in women

Background: Several studies have shown a positive association between anxiety and obesity, particularly in women. We aimed to study whether sex hormone alterations related to obesity might play a role in this association. Patients and methods: Data for this study were obtained from a population-based cohort study (the LIFE-Adult-Study). A total of 3,124 adult women (970 premenopausal and 2,154 postmenopausal) were included into the analyses. The anxiety symptomatology was assessed using the GAD-7 questionnaire (cut-off ≥ 10 points). Sex hormones were measured from fasting serum samples. Results: We did not find significant differences in anxiety prevalence in premenopausal obese women compared with normal-weight controls (4.8% vs. 5.5%). Both obesity and anxiety symptomatology were separately associated with the same sex hormone alteration in premenopausal women: higher total testosterone level (0.97 ± 0.50 in obese vs. 0.86 ± 0.49 nmol/L in normal-weight women, p = 0.026 and 1.04 ± 0.59 in women with vs. 0.88 ± 0.49 nmol/L in women without anxiety symptomatology, p = 0.023). However, women with anxiety symptomatology had non-significantly higher estradiol levels than women without anxiety symptomatology (548.0 ± 507.6 vs. 426.2 ± 474.0 pmol/L), whereas obesity was associated with lower estradiol levels compared with those in normal-weight group (332.7 ± 386.5 vs. 470.8 ± 616.0 pmol/L). Women with anxiety symptomatology had also significantly higher testosterone and estradiol composition (p = 0.006). No associations of sex hormone levels and BMI with anxiety symptomatology in postmenopausal women were found. Conclusions: Although both obesity and anxiety symptomatology were separately associated with higher testosterone level, there was an opposite impact of anxiety and obesity on estradiol levels in premenopausal women. We did not find an evidence that the sex hormone alterations related to obesity are playing a significant role in anxiety symptomatology in premenopausal women. This could be the explanation why we did not find an association between obesity and anxiety. In postmenopausal women, other mechanisms seem to work than in the premenopausal group

Social isolation is linked to declining grey matter structure and cognitive functions in the LIFE-Adult panel study

Social isolation has been suggested to increase the risk to develop cognitive decline. However, our knowledge on causality and neurobiological underpinnings is still limited. In this preregistered analysis, we tested the impact of social isolation on central features of brain and cognitive aging using a longitudinal population-based magnetic resonance imaging (MRI) study. Assaying 1335 cognitively healthy participants (50-80 years old, 659 women) at baseline and 895 participants after ∼6 years follow-up, we found baseline social isolation and change in social isolation to be associated with smaller volumes of the hippocampus, reduced cortical thickness and poorer cognitive functions. Combining advanced neuroimaging outcomes with prevalent lifestyle characteristics from a well-characterized population of middle- to older aged adults, we provide evidence that social isolation contributes to human brain atrophy and cognitive decline. Within-subject effects of social isolation were similar to between-subject effects, indicating an opportunity to reduce dementia risk by promoting social networks

What builds resilience? Sociodemographic and social correlates in the population-based LIFE-adult-study

Resilience is closely related to mental health and well-being. Identifying risk groups with lower resilience and the variables associated with resilience informs preventive approaches. Previous research on resilience patterns in the general population is heterogeneous, and comprehensive large-scale studies are needed. The aim of our study is to examine sociodemographic and social correlates of resilience in a large population-based sample. We examined 4795 participants from the LIFE-Adult-Study. Assessments included resilience (RS-11), social support (ESSI), and social network (LSNS), as well as the sociodemographic variables age, gender, marital status, education, and occupation. The association of resilience with sociodemographic and social correlates was examined using linear regression analyses. Higher resilience was associated with female gender, married marital status, high education, and full-time occupation. Social support and social network were positively associated with resilience. Our results implicate that resilience is related to various sociodemographic variables. Social variables seem to be particularly important for resilience. We identified risk groups with lower resilience, which should be given special attention by public health policies, especially in times of crisis. Reducing loneliness and promoting social connectedness may be promising ways to build resilience in the general population

Anxiety and food addiction in men and women: Results from the longitudinal LIFE-adult-study

Background: Anxiety is a widespread phenomenon, and it is connected to disordered eating and obesity. We want to analyze the connection between anxiety and food addiction (FA) over two points in time to better understand the directionality of the association. Since there are gender differences with regard to anxiety and eating, we are also interested in differences between men and women. Methods: We used data from the population-based LIFE-Adult-Study (N = 1,474) at time 1 (baseline) and time 2 (first follow-up) to analyze the connections between anxiety (GAD-7) and FA (YFAS) using a multiple group latent cross-lagged panel model with female and male participants as groups. We controlled for age, marital status, socioeconomic status and social support. Results: Anxiety (women: β = 0.50, p ≤ 0.001; men: β = 0.59, p ≤ 0.001) as well as FA (women: β = 0.37, p ≤ 0.001; men: β = 0.58, p ≤ 0.001) exhibited stability over time for both genders. We found a significant association between anxiety at time 1 and FA at time 2 for women (β = 0.25, p ≤ 0.001) but not for men (β = 0.04, p = 0.10), and significant associations between FA at time 1 and anxiety at time 2 for women (β = 0.23, p ≤ 0.001) as well as men (β = 0.21, p ≤ 0.001). Conclusion: Food addiction longitudinally affects anxiety, independent of gender and other sociodemographic variables. In addition, anxiety affects subsequent FA as well, but only in women. Interventions that address FA could reduce anxiety in men and women, while interventions that mitigate anxiety could help prevent FA in women

Potentiation of the glutamatergic synaptic input to rat locus coeruleus neurons by P2X7 receptors

Locus coeruleus (LC) neurons in a rat brain slice preparation were superfused with a Mg2+-free and bicuculline-containing external medium. Under these conditions, glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) were recorded by means of the whole-cell patch-clamp method. ATP, as well as its structural analogue 2-methylthio ATP (2-MeSATP), both caused transient inward currents, which were outlasted by an increase in the frequency but not the amplitude of the sEPSCs. PPADS, but not suramin or reactive blue 2 counteracted both effects of 2-MeSATP. By contrast, α,β-methylene ATP (α,β-meATP), UTP and BzATP did not cause an inward current response. Of these latter agonists, only BzATP slightly facilitated the sEPSC amplitude and strongly potentiated its frequency. PPADS and Brilliant Blue G, as well as fluorocitric acid and aminoadipic acid prevented the activity of BzATP. Furthermore, BzATP caused a similar facilitation of the miniature (m)EPSC (recorded in the presence of tetrodotoxin) and sEPSC frequencies (recorded in its absence). Eventually, capsaicin augmented the frequency of the sEPSCs in a capsazepine-, but not PPADS-antagonizable, manner. In conclusion, the stimulation of astrocytic P2X7 receptors appears to lead to the outflow of a signalling molecule, which presynaptically increases the spontaneous release of glutamate onto LC neurons from their afferent fibre tracts. It is suggested, that the two algogenic compounds ATP and capsaicin utilise separate receptor systems to potentiate the release of glutamate and in consequence to increase the excitability of LC neurons. © 2010 Springer Science+Business Media B.V

Testosterone imbalance may link depression and increased body weight in premenopausal women

Accumulating evidence supports a link between depression and being overweight in women. Given previously reported sex differences in fat accumulation and depression prevalence, as well as the likely role of sex hormones in both overweight and mood disorders, we hypothesised that the depression-overweight association may be mediated by sex hormones. To this end, we investigated the association of being overweight with depression, and then considered the role of sex hormones in relation to being overweight and depression in a large population-based cohort. We included a total of 3124 women, 970 premenopausal and 2154 postmenopausal from the LIFE-Adult cohort study in our analyses. We evaluated associations between being overweight (BMI >25 kg/m2), sex hormone levels, and depressive symptomatology according to Centre for Epidemiologic Studies Depression (CES-D) scores, and explored mediation of depression in a mediation model. Being overweight was significantly associated with depressive symptoms in premenopausal but not postmenopausal women. Both premenopausal and postmenopausal overweight women had higher free testosterone levels compared with normal weight women. Premenopausal women with depressive symptomatology had higher free testosterone levels compared to women without. We found a significant mediation effect of depressive symptomatology in overweight premenopausal women through free testosterone level. These findings highlight the association between being overweight and depressed, and suggest that high free testosterone levels may play a significant role in depression of overweight premenopausal women. Based on this, pharmacological approaches targeting androgen levels in overweight depressed females, in particular when standard anti-depressive treatments fail, could be of specific clinical relevance

Reading cognition from the eyes: Association of retinal nerve fiber layer thickness with cognitive performance in a population-based study

With the eye as a window to the brain, non-invasive fast screening of retinal nerve fibre layer thickness poses the opportunity for early detection of cognitive decline leading to dementia. Our objective is to determine whether performance in various neurocognitive tests has an association with itemized retinal nerve fibre layer thickness. Detailed investigation of associations factored in sex and eye-side. The large population-based LIFE-Adult study (Leipzig Research Centre for Civilization Diseases) was conducted at Leipzig University, Germany from 2011 to 2014. Randomly selected participants (N = 10 000) were drawn from population registry in an age- and gender-stratified manner, focusing on 40-80 years. Cognitive function was examined with the CERAD-NP Plus test-battery (Consortium to Establish a Registry for Alzheimer's Disease), Stroop-Test, Reading the Mind in the Eyes-Test and Multiple-Choice Vocabulary Intelligence Test. Circumpapillary retinal nerve fibre layer thickness was measured with Optical Coherence Tomography. Subjects with reliable measurements (≥50 B-scan repetitions, signal-to-noise-ratio ≥20 dB, ≤5% missing A-scans) and without clinical eye pathology (sample A) and additional exclusion due to conditions of the central nervous system (sample B) were evaluated. The relationship between cognitive function and retinal nerve fibre layer thickness was investigated for six segments: temporal, temporal-superior, temporal-inferior, nasal, nasal-superior and nasal-inferior. For comparison with other studies, global mean is given. Brain-side projection analysis links results to the corresponding brain hemisphere. We analysed 11 124 eyes of 6471 subjects [55.5 years of age (19.1-79.8 years), 46.9% male]. Low cognitive performance was predominantly associated with thinner retinal nerve fibre layer thickness. Correlation analysis indicated emphasis on global and temporally located effects. Multivariable regression analysis with adjustments (age, sex and scan radius) presented individual results for each test, differentiating between sex and eye-side. For instance, verbal fluency tests and Trail Making Test-B show stronger association in females; Trail Making Test-A shows right-eye dominance. Findings in Trail-Making-Test-A projected to left brain hemisphere, and the ratio incongruent to neutral in the Stroop test projected to right brain-hemisphere. Separate assessment for sex and eye-side is presented for the first time in a population-based study. Location-specific sectorial retinal nerve fibre layer thickness was found to be an indicator for cognitive performance, giving an option for early detection of cognitive decline and the potential of early treatment. The eye as a window to the brain was studied with optical coherence tomography and connected to cognition. Girbardt et al. report that thinner retinal nerve fibre layer thickness was found to be a meaningful index for poorer cognitive performance which presents the potential for prediction of future cognitive decline

TableButler – a Windows based tool for processing large data tables generated with high-throughput methods

<p>Abstract</p> <p>Background</p> <p>High-throughput "omics" based data analysis play emerging roles in life sciences and molecular diagnostics. This emphasizes the urgent need for user-friendly windows-based software interfaces that could process the diversity of large tab-delimited raw data files generated by these methods. Depending on the study, dozens to hundreds of these data tables are generated. Before the actual statistical or cluster analysis, these data tables have to be combined and merged to expression matrices (e.g., in case of gene expression analysis). Gene annotations as well as information concerning the samples analyzed may be appended, renewed or extended. Often additional data values shall be computed or certain features must be filtered out.</p> <p>Results</p> <p>In order to perform these tasks, we have developed a Microsoft Windows based application, "<b><it>TableButler</it></b>", which allows biologists or clinicians without substantial bioinformatics background to perform a plethora of data processing tasks required to analyze the large-scale data.</p> <p>Conclusion</p> <p><b><it>TableButler </it></b>is a monolithic Windows application. It is implemented to handle, join and preprocess large tab delimited ASCII data files. The intuitive user interface enables scientists (e.g. biologists, clinicians or others) to setup workflows for their specific problems by simple drag-and drop like operations.</p> <p>For more details about <b><it>TableButler</it></b>, visit <url>http://www.OncoExpress.org/software/tablebutler</url>.</p

Functional Polymorphism of the CK2α Intronless Gene Plays Oncogenic Roles in Lung Cancer

Protein kinase CK2 is frequently up-regulated in human cancers, although the mechanism of CK2 activation in cancer remains unknown. In this study, we investigated the role of the CK2α intronless gene (CSNK2A1P, a presumed CK2α pseudogene) in the pathogenesis of human cancers. We found evidence of amplification and over-expression of the CSNK2A1P gene in non- small cell lung cancer and leukemia cell lines and 25% of the lung cancer tissues studied. The mRNA expression levels correlated with the copy numbers of the CSNK2A1P gene. We also identified a novel polymorphic variant (398T/C, I133T) of the CSNK2A1P gene and showed that the 398T allele is selectively amplified over the 398C allele in 101 non-small cell lung cancer tissue samples compared to those in 48 normal controls (p = 0.013<0.05). We show for the first time CSNK2A1P protein expression in transfected human embryonic kidney 293T and mouse embryonic fibroblast NIH-3T3 cell lines. Both alleles are transforming in these cell lines, and the 398T allele appears to be more transforming than the 398C allele. Moreover, the 398T allele degrades PML tumor suppressor protein more efficiently than the 398C allele and shows a relatively stronger binding to PML. Knockdown of the CSNK2A1P gene expression with specific siRNA increased the PML protein level in lung cancer cells. We report, for the first time, that the CSNK2A1P gene is a functional proto-oncogene in human cancers and its functional polymorphism appears to degrade PML differentially in cancer cells. These results are consistent with an important role for the 398T allele of the CSNK2A1P in human lung cancer susceptibility