Vascular risk factors, white matter microstructure, and depressive symptoms: a longitudinal analysis in the UK Biobank.

BACKGROUND: Cumulative burden from vascular risk factors (VRFs) has been associated with an increased risk of depressive symptoms in mid- and later life. It has been hypothesised that this association arises because VRFs disconnect fronto-subcortical white matter tracts involved in mood regulation, which puts older adults at higher risk of developing depressive symptoms. However, evidence for the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms from longitudinal studies is scarce. METHODS: This preregistered study analysed longitudinal data from 6,964 middle-aged and older adults from the UK Biobank who participated in consecutive assessments of VRFs, brain imaging, and depressive symptoms. Using mediation modelling, we directly tested to what extend white matter microstructure mediates the longitudinal association between VRF burden and depressive symptoms. RESULTS: VRF burden showed a small association with depressive symptoms at follow-up. However, there was no evidence that fractional anisotropy (FA) of white matter tracts mediated this association. Additional analyses also yielded no mediating effects using alternative operationalisations of VRF burden, mean diffusivity (MD) of single tracts, or overall average of tract-based white matter microstructure (global FA, global MD, white matter hyperintensity volume). CONCLUSIONS: Our results lend no support to the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms, while highlighting the relevance of using longitudinal data to directly test pathways linking vascular and mental health.

Postdoctoral researchers' perspectives on working conditions and equal opportunities in German academia.

Postdoctoral researchers (postdocs) are an essential component of the scientific workforce in German universities and research institutions and play a vital role in advancing knowledge and innovation. However, the experiences of postdocs and other early career researchers (ECRs) indicate that working conditions pose a significant challenge to the pursuit of a long-term research career in Germany-particularly for international scientists and those from marginalized groups. We examine how unstable working conditions as well as insufficient structural support for equal opportunities and diversity are significant obstacles for the career development of ECRs in German academia. We discuss these issues with the aid of an extensive survey recently conducted and published by PostdocNet, a target-group network representing the interests of postdocs across Germany's Max Planck Society. The survey drew responses from 659 postdoctoral researchers working at the Max Planck Society and represents one of the few datasets of postdoctoral researchers' perspectives in Germany. Building on these findings, we suggest actions at governmental, institutional, and individual levels to improve the working conditions of postdoctoral researchers in Germany.

Mediation of the Association Between Vascular Risk Factors and Depressive Symptoms by C-Reactive Protein.

Background: This study examined whether C-reactive protein (CRP), a marker of low-grade systemic inflammation, mediates the association between vascular risk factor (VRF) burden and depressive symptoms. Methods: We drew on the prospective design of the UK Biobank to include participants with longitudinal data on VRF burden, CRP, and depressive symptoms. Total, direct, and indirect effects were estimated using regression-based mediation models while controlling for confounding by sociodemographic factors, baseline CRP, and baseline depression. Sensitivity analyses probed the robustness of results to unmeasured confounding. Results: We analyzed data from 10,470 participants from the UK Biobank (mean age = 56.75 years at baseline). Net of covariates, VRFs at baseline were associated with higher depressive symptoms at follow-up (total effect = 0.099; 95% CI, 0.002-0.163). CRP mediated this association (indirect effect = 0.010; 95% CI, 0.004-0.017), accounting for 10.0% (95% CI, 0.3%-30.0%) of the total effect of VRF burden on depressive symptoms. Exploratory analyses suggested that the total and indirect effects pertained to somatic depressive symptoms (tiredness and appetite). Conclusions: These results suggest that inflammation-promoting effects of VRFs may contribute to depressive symptoms in mid- and later life. However, the mediating pathway via CRP explains only a small part of the association between VRFs and depression after accounting for important covariates and may pertain to specific depressive symptoms. Future studies leveraging similar longitudinal designs are needed to further disentangle the time-varying effects between VRFs, inflammation, and certain depressive symptoms while addressing important confounders.

Associations between mental health, blood pressure and the development of hypertension.

Multiple studies have reported a link between mental health and high blood pressure with mixed or even contradictory findings. Here, we resolve those contradictions and further dissect the cross-sectional and longitudinal relationship between mental health, systolic blood pressure, and hypertension using extensive psychological, medical and neuroimaging data from the UK Biobank. We show that higher systolic blood pressure is associated with fewer depressive symptoms, greater well-being, and lower emotion-related brain activity. Interestingly, impending hypertension is associated with poorer mental health years before HTN is diagnosed. In addition, a stronger baseline association between systolic blood pressure and better mental health was observed in individuals who develop hypertension until follow-up. Overall, our findings offer insights on the complex relationship between mental health, blood pressure, and hypertension, suggesting that-via baroreceptor mechanisms and reinforcement learning-the association of higher blood pressure with better mental health may ultimately contribute to the development of hypertension.

Rapid volumetric brain changes after acute psychosocial stress.

Stress is an important trigger for brain plasticity: Acute stress can rapidly affect brain activity and functional connectivity, and chronic or pathological stress has been associated with structural brain changes. Measures of structural magnetic resonance imaging (MRI) can be modified by short-term motor learning or visual stimulation, suggesting that they also capture rapid brain changes. Here, we investigated volumetric brain changes (together with changes in T1 relaxation rate and cerebral blood flow) after acute stress in humans as well as their relation to psychophysiological stress measures. Sixty-seven healthy men (25.8±2.7 years) completed a standardized psychosocial laboratory stressor (Trier Social Stress Test) or a control version while blood, saliva, heart rate, and psychometrics were sampled. Structural MRI (T1 mapping / MP2RAGE sequence) at 3T was acquired 45 min before and 90 min after intervention onset. Grey matter volume (GMV) changes were analysed using voxel-based morphometry. Associations with endocrine, autonomic, and subjective stress measures were tested with linear models. We found significant group-by-time interactions in several brain clusters including anterior/mid-cingulate cortices and bilateral insula: GMV was increased in the stress group relative to the control group, in which several clusters showed a GMV decrease. We found a significant group-by-time interaction for cerebral blood flow, and a main effect of time for T1 values (longitudinal relaxation time). In addition, GMV changes were significantly associated with state anxiety and heart rate variability changes. Such rapid GMV changes assessed with VBM may be induced by local tissue adaptations to changes in energy demand following neural activity. Our findings suggest that endogenous brain changes are counteracted by acute psychosocial stress, which emphasizes the importance of considering homeodynamic processes and generally highlights the influence of stress on the brain.

Heritability of hippocampal functional and microstructural organisation.

The hippocampus is a uniquely infolded allocortical structure in the medial temporal lobe that consists of the microstructurally and functionally distinct subregions: subiculum, cornu ammonis, and dentate gyrus. The hippocampus is a remarkably plastic region that is implicated in learning and memory. At the same time it has been shown that hippocampal subregion volumes are heritable, and that genetic expression varies along a posterior to anterior axis. Here, we studied how a heritable, stable, hippocampal organisation may support its flexible function in healthy adults. Leveraging the twin set-up of the Human Connectome Project with multimodal neuroimaging, we observed that the functional connectivity between hippocampus and cortex was heritable and that microstructure of the hippocampus genetically correlated with cortical microstructure. Moreover, both functional and microstructural organisation could be consistently captured by anterior-to-posterior and medial-to-lateral axes across individuals. However, heritability of functional, relative to microstructural, organisation was found reduced, suggesting individual variation in functional organisation may be explained by experience-driven factors. Last, we demonstrate that structure and function couple along an inherited macroscale organisation, suggesting an interplay of stability and plasticity within the hippocampus. Our study provides new insights on the heritability of the hippocampal of the structure and function within the hippocampal organisation.

Heritability and cross-species comparisons of human cortical functional organization asymmetry.

The human cerebral cortex is symmetrically organized along large-scale axes but also presents inter-hemispheric differences in structure and function. The quantified contralateral homologous difference, that is asymmetry, is a key feature of the human brain left-right axis supporting functional processes, such as language. Here, we assessed whether the asymmetry of cortical functional organization is heritable and phylogenetically conserved between humans and macaques. Our findings indicate asymmetric organization along an axis describing a functional trajectory from perceptual/action to abstract cognition. Whereas language network showed leftward asymmetric organization, frontoparietal network showed rightward asymmetric organization in humans. These asymmetries were heritable in humans and showed a similar spatial distribution with macaques, in the case of intra-hemispheric asymmetry of functional hierarchy. This suggests (phylo)genetic conservation. However, both language and frontoparietal networks showed a qualitatively larger asymmetry in humans relative to macaques. Overall, our findings suggest a genetic basis for asymmetry in intrinsic functional organization, linked to higher order cognitive functions uniquely developed in humans.

The Age-Dependent Association Between Vascular Risk Factors and Depressed Mood.

OBJECTIVES: Cumulative burden of vascular risk factors (VRFs) has been linked to an increased risk of depressed mood. However, the role of age in this association is still unclear. Here, we investigated whether VRF burden is associated with levels and changes in depressed mood and whether these associations become stronger or weaker from mid- to later life. METHOD: We used longitudinal data from 5,689 participants (52-89 years) of the English Longitudinal Study of Ageing. A composite score incorporated the presence of 5 VRFs: hypertension, diabetes, smoking, obesity, and hypercholesterolemia. Second-order latent growth models were used to test whether levels and changes of depressed mood differed as a function of baseline VRF burden, and whether these associations were moderated by age. RESULTS: Baseline VRF burden showed a small association with higher levels of depressed mood (estimate = 0.081; 95% CI: 0.024, 0.138, p = .005). This association varied with age, such that it was stronger in midlife compared to later life (estimate = -0.007; 95% CI: -0.013, -0.002, p = .017). There was no evidence that VRF burden was associated with changes in depressed mood. DISCUSSION: Our findings suggest that VRF burden in midlife, but less so in later life, predicts individual differences in depressed mood. These findings are consistent with reports on the importance of midlife VRFs and support the idea that promotion of vascular health in this age group or earlier in life may be critical to maintain mental health across adulthood.

Anger regulation choice-The role of age and habitual reappraisal.

The ability to choose emotion regulation strategies in accordance to contextual demands, known as emotion regulation flexibility, is key to healthy adaptation. While recent investigations on spontaneous emotion regulation choice tested the effects of emotional intensity and age using standardized negative pictures with no particular emotional quality, we elicited the discrete emotion of anger with personally relevant autobiographical memories in a sample of 52 younger and 41 older adults. In addition, we included habitual reappraisal as a predictor of emotion regulation choice. Our main hypothesis was that, compared with younger adults, older adults prefer less resource-demanding emotion regulation strategies (i.e., distraction) over more resource-demanding strategies (i.e., reappraisal), particularly if older adults' habitual reappraisal is low and the to-be-regulated anger is of high intensity. Surprisingly, our findings suggest that only older adults' emotion regulation choices depend on the emotional intensity of the autobiographical memory and habitual reappraisal. Only older adults with high habitual reappraisal preferred to reappraise their anger in situations of low anger intensity but switched to the less demanding strategy of distraction in high anger memories, indicating emotion regulation flexibility. This study extends previous research by testing emotion regulation choices in natural contexts and considering regulation habits. Although we replicate previous findings of emotion regulation flexibility according to emotional intensity in anger memories for older adults with high habitual reappraisal only, our findings illustrate the relevance of reappraisal habits to emotion regulation choice in age-comparative research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Behavioral, Anatomical and Heritable Convergence of Affect and Cognition in Superior Frontal Cortex.

Cognitive abilities and affective experience are key human traits that are interrelated in behavior and brain. Individual variation of cognitive and affective traits, as well as brain structure, has been shown to partly underlie genetic effects. However, to what extent affect and cognition have a shared genetic relationship with local brain structure is incompletely understood. Here we studied phenotypic and genetic correlations of cognitive and affective traits in behavior and brain structure (cortical thickness, surface area and subcortical volumes) in the pedigree-based Human Connectome Project sample (N = 1091). Both cognitive and affective trait scores were highly heritable and showed significant phenotypic correlation on the behavioral level. Cortical thickness in the left superior frontal cortex showed a phenotypic association with both affect and cognition. Decomposing the phenotypic correlations into genetic and environmental components showed that the associations were accounted for by shared genetic effects between the traits. Quantitative functional decoding of the left superior frontal cortex further indicated that this region is associated with cognitive and emotional functioning. This study provides a multi-level approach to study the association between affect and cognition and suggests a convergence of both in superior frontal cortical thickness.

Acute psychosocial stress alters thalamic network centrality.

Acute stress triggers a broad psychophysiological response that is adaptive if rapidly activated and terminated. While the brain controls the stress response, it is strongly affected by it. Previous research of stress effects on brain activation and connectivity has mainly focused on pre-defined brain regions or networks, potentially missing changes in the rest of the brain. We here investigated how both stress reactivity and stress recovery are reflected in whole-brain network topology and how changes in functional connectivity relate to other stress measures. Healthy young males (n = 67) completed the Trier Social Stress Test or a control task. From 60 min before until 105 min after stress onset, blocks of resting-state fMRI were acquired. Subjective, autonomic, and endocrine measures of the stress response were assessed throughout the experiment. Whole-brain network topology was quantified using Eigenvector centrality (EC) mapping, which detects central hubs of a network. Stress influenced subjective affect, autonomic activity, and endocrine measures. EC differences between groups as well as before and after stress exposure were found in the thalamus, due to widespread connectivity changes in the brain. Stress-driven EC increases in the thalamus were significantly correlated with subjective stress ratings and showed non-significant trends for a correlation with heart rate variability and saliva cortisol. Furthermore, increases in thalamic EC and in saliva cortisol persisted until 105 min after stress onset. We conclude that thalamic areas are central for information processing after stress exposure and may provide an interface for the stress response in the rest of the body and in the mind.

A functional connectome phenotyping dataset including cognitive state and personality measures.

The dataset enables exploration of higher-order cognitive faculties, self-generated mental experience, and personality features in relation to the intrinsic functional architecture of the brain. We provide multimodal magnetic resonance imaging (MRI) data and a broad set of state and trait phenotypic assessments: mind-wandering, personality traits, and cognitive abilities. Specifically, 194 healthy participants (between 20 and 75 years of age) filled out 31 questionnaires, performed 7 tasks, and reported 4 probes of in-scanner mind-wandering. The scanning session included four 15.5-min resting-state functional MRI runs using a multiband EPI sequence and a hig h-resolution structural scan using a 3D MP2RAGE sequence. This dataset constitutes one part of the MPI-Leipzig Mind-Brain-Body database.

A mind-brain-body dataset of MRI, EEG, cognition, emotion, and peripheral physiology in young and old adults.

We present a publicly available dataset of 227 healthy participants comprising a young (N=153, 25.1±3.1 years, range 20-35 years, 45 female) and an elderly group (N=74, 67.6±4.7 years, range 59-77 years, 37 female) acquired cross-sectionally in Leipzig, Germany, between 2013 and 2015 to study mind-body-emotion interactions. During a two-day assessment, participants completed MRI at 3 Tesla (resting-state fMRI, quantitative T1 (MP2RAGE), T2-weighted, FLAIR, SWI/QSM, DWI) and a 62-channel EEG experiment at rest. During task-free resting-state fMRI, cardiovascular measures (blood pressure, heart rate, pulse, respiration) were continuously acquired. Anthropometrics, blood samples, and urine drug tests were obtained. Psychiatric symptoms were identified with Standardized Clinical Interview for DSM IV (SCID-I), Hamilton Depression Scale, and Borderline Symptoms List. Psychological assessment comprised 6 cognitive tests as well as 21 questionnaires related to emotional behavior, personality traits and tendencies, eating behavior, and addictive behavior. We provide information on study design, methods, and details of the data. This dataset is part of the larger MPI Leipzig Mind-Brain-Body database.

Association of peripheral blood pressure with gray matter volume in 19- to 40-year-old adults.

OBJECTIVE: To test whether elevated blood pressure (BP) relates to gray matter (GM) volume (GMV) changes in young adults who had not previously been diagnosed with hypertension (systolic BP [SBP]/diastolic BP [DBP] ≥140/90 mm Hg). METHODS: We associated BP with GMV from structural 3T T1-weighted MRI of 423 healthy adults between 19 and 40 years of age (mean age 27.7 ± 5.3 years, 177 women, SBP/DBP 123.2/73.4 ± 12.2/8.5 mm Hg). Data originated from 4 previously unpublished cross-sectional studies conducted in Leipzig, Germany. We performed voxel-based morphometry on each study separately and combined results in image-based meta-analyses (IBMA) to assess cumulative effects across studies. Resting BP was assigned to 1 of 4 categories: (1) SBP <120 and DBP <80 mm Hg, (2) SBP 120-129 or DBP 80-84 mm Hg, (3) SBP 130-139 or DBP 85-89 mm Hg, (4) SBP ≥140 or DBP ≥90 mm Hg. RESULTS: IBMA yielded the following results: (1) lower regional GMV was correlated with higher peripheral BP; (2) lower GMV was found with higher BP when comparing individuals in subhypertensive categories 3 and 2, respectively, to those in category 1; (3) lower BP-related GMV was found in regions including hippocampus, amygdala, thalamus, frontal, and parietal structures (e.g., precuneus). CONCLUSION: BP ≥120/80 mm Hg was associated with lower GMV in regions that have previously been related to GM decline in older individuals with manifest hypertension. Our study shows that BP-associated GM alterations emerge continuously across the range of BP and earlier in adulthood than previously assumed. This suggests that treating hypertension or maintaining lower BP in early adulthood might be essential for preventing the pathophysiologic cascade of asymptomatic cerebrovascular disease to symptomatic end-organ damage, such as stroke or dementia.