Mediation of the association between vascular risk factors and depressive symptoms by c-reactive protein: Longitudinal evidence from the UK Biobank

People with vascular risk factors (VRFs) are at higher risk for depressive symptoms. Given recent findings implicating low-grade systemic inflammation in both vascular and mental health, this study examined the extent to which the VRF–depressive symptom association might be mediated by low-grade systemic inflammation. To this end, we analysed longitudinal data of 9,034 participants from the UK Biobank (mean age = 56.54 years), who took part in three consecutive assessments over the course of about 8 years. Cumulative VRF burden at baseline was defined as the presence of 5 VRFs (hypertension, obesity, hypercholesterolemia, diabetes, and smoking). Low-grade systemic inflammation was assessed using serum-derived C-reactive protein (CRP) and depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9). We performed mediation models using longitudinal data and a path analytic framework, while controlling for age, gender, racial-ethnic background, socioeconomic status, and baseline mood. VRFs at baseline showed a small association with higher depressive symptoms at follow-up (total effect = 0.014, 95% CI [0.007; 0.021]). CRP mediated this association (indirect effect = 0.003, 95% CI [0.001; 0.005]) and accounted for 20.10% of the total effect of VRF burden on depressive symptoms. Exploratory analyses taking a symptom-based approach revealed that mediating pathways pertained to specific depressive symptoms: tiredness and changes in appetite. These results suggest that the small association between VRF burden and depressive symptoms may be partly explained by the inflammation-promoting effects of VRFs, which might promote a specific symptom-profile of depression

Positivity in younger and in older age: Associations with future time perspective and socioemotional functioning

Aging has been associated with a motivational shift to positive over negative information (i.e., positivity effect), which is often explained by a limited future time perspective (FTP) within the framework of socioemotional selectivity theory (SST). However, whether a limited FTP functions similarly in younger and older adults, and whether inter-individual differences in socioemotional functioning are similarly associated with preference for positive information (i.e., positivity) is still not clear. We investigated younger (20–35 years, N = 73) and older (60–75 years, N = 56) adults’ gaze preferences on pairs of happy, angry, sad, and neutral faces using an eye-tracking system. We additionally assessed several parameters potentially underlying inter-individual differences in emotion processing such as FTP, stress, cognitive functioning, social support, emotion regulation, and well-being. While we found no age-related differences in positivity when the entire trial duration was considered, older adults showed longer fixations on the more positive face in later stages of processing (i.e., positivity shifts). This allocation of resources toward more positive stimuli might serve an emotion regulatory purpose and seems consistent with the SST. However, our findings suggest that age moderates the relationship between FTP and positivity shifts, such that the relationship between FTP and positivity preferences was negative in older, and positive in younger adults, potentially stemming from an age-related differential meaning of the FTP construct across age. Furthermore, our exploratory analyses showed that along with the age and FTP interaction, lower levels of worry also played a significant role in positivity shifts. We conclude that positivity effects cannot be solely explained by aging, or the associated reduced FTP per se, but is rather determined by a complex interplay of psychosocial and emotional features

Mental health, blood pressure and the development of hypertension

Hypertension (HTN) has been associated with a greater risk of affective disorders. Paradoxically, several studies have shown the opposite effect in which high blood pressure relates to less depressive symptoms and greater well-being. Here we dissolve this paradox and clarify the relationship between mental health, blood pressure and the development of HTN using the UK Biobank. In adjusted multiple linear regression models, we found that the presence of a HTN diagnosis was associated with impaired mental health (i.e. more depressive symptoms (N = 303,771; β = 0.043; 95% CI [0.039, 0.047]; p<0.001) and lower well-being scores (N = 129,876; β = -0.057; 95% CI [-0.064, - 0.050]; p<0.001)) at baseline, whereas higher systolic blood pressure (SBP) was associated with fewer depressive symptoms (N = 303,771; β = -0.063; 95% CI [-0.067, -0.060]; p<0.001) and higher well-being scores (N = 129,876; β = 0.057; 95% CI [0.051, 0.063]; p<0.001). These effects persisted until follow-up (∼10 years later). To explore a potential link between the mental health-blood pressure association and the development of HTN, we compared participants who were normotensive at baseline and developed HTN until follow-up with those who stayed normotensive. Notably, the adjusted model showed impaired mental health already at baseline in HTN developers (i.e., before HTN diagnosis; depressive symptoms: β = 0.060; 95% CI [0.045, 0.076]; p<0.001; well-being: β = -0.043; 95% CI [-0.068, -0.017]; p<0.001), indicating that people who develop HTN might require higher blood pressure levels for the same mental health outcomes as normotensives. In addition, the negative association between SBP and depressive symptoms at baseline was moderated by HTN development (β = -0.014; 95% CI [-0.026, -0.003]; p=0.015), suggesting that the negative relationship between mental health and blood pressure was accentuated in people developing HTN several years before receiving their HTN diagnosis. We further observed that higher SBP was associated with lower emotion-related brain activity from functional magnetic resonance imaging (fMRI; β = -0.032 95% CI [-0.045, -0.019]; p<0.001). This effect was also moderated by HTN diagnosis, suggesting an impact of SBP and HTN on the central nervous processing of emotions. Possible mechanisms are discussed, including regulatory baroreceptor circuits linking arterial blood pressure to neural processing of emotions. Overall, our results show an interrelation between mental health and blood pressure that may be involved in the development of HTN. In people who develop HTN, this relationship seems to be altered, such that higher blood pressure is required to sustain mental health, potentially offering a novel perspective for developing preventive and therapeutic measures

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

Mental and cardiovascular health interact in complex ways. Here, the authors demonstrate an association of blood pressure with depressive symptoms, well-being, and emotion-related brain activity that may be relevant to the development of hypertension

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

Affective experience and cognitive abilities are key human traits that are interrelated in behavior and brain. Individual variation of affective and cognitive 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 twin-based Human Connectome Project sample (N = 1091). Both affective and cognitive 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, which was driven by shared genetic effects. Quantitative functional decoding of this region yielded associations 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

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

Funder: International Max Planck Research School on Neuroscience of Communication: Function, Structure, and PlasticityFunder: Canada First Research Excellence FundFunder: Max-Planck-GesellschaftFunder: Azrieli Center for Autism ResearchThe 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