Depression is a risk factor for cardiometabolic diseases, but the extent to which this is attributable to genetic (rather than environmental) factors is unclear. Mendelian randomisation (MR) uses genetic variants to infer causality. We aimed to investigate the bidirectional association between respective genetic susceptibility to depression and cardiometabolic diseases. We conducted a systematic review and meta-analysis of MR studies (unidirectional or bidirectional) in adults that assessed associations between genetic variants related to depression and any cardiometabolic disease. A comprehensive literature search of MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus, Web of Science, and Cochrane Library was performed to capture relevant articles published between database inception to June 20, 2024. This search was updated on April 23, 2025. Reference lists of included articles were manually searched for additional records. Articles published in English or translated into English were included. Primary outcomes of interest included cardiovascular diseases (six) and metabolic diseases (three). Contextually similar studies were pooled and sub-grouped based on population ancestry, study design, and outcome definition. A customised risk of bias tools for Mendelian randomisation was used to assess the risk of bias across five domains. Heterogeneity was assessed via I2 and tau-squared (τ2) statistics and publication bias was assessed via visual inspection of contour-enhanced funnel plots. This work is registered with PROSPERO, CRD42023460334. We included 79 studies (294 MR analyses) in the systematic review and 21 studies (29 MR analyses) in the meta-analysis. For the primary outcomes eligible for pooling, genetic susceptibility to depression was associated with increased odds of coronary artery disease (odds ratio 1.12, 95% CI 1.05–1.19; k = 3, τ² = 0.00, I² = 0%), myocardial infarction (1.13, 1.10–1.17; k = 3, τ² = 0.00, I² = 0%), and elevated triglycerides (1.10, 1.06–1.14; k = 3, τ² = 0.00, I² = 0); but not with diabetes (1.08, 0.96–1.21; k = 3, τ² = 0.01, I² = 75%), high-density lipoproteins (0.97, 0.92–1.01; k = 3, τ² = 0.00, I² = 37%), or low-density lipoproteins (1.12, 0.99–1.28; k = 4, τ² = 0.00, I² = 87%). Leave-one-out analyses showed that some studies altered the results more than the others. Our findings suggest that depression and cardiometabolic diseases are associated with each other. Though the observed effects are small and of limited immediate clinical relevance, our findings reflect the genetic component of the association separately to the behavioural and environmental influences. Treatment strategies identifying those at risk could benefit both diseases; however, high heterogeneity warrants cautious interpretation of our findings. None.

Patients with asthma experience elevated rates of mental illness. However, the molecular links underlying such lung–brain crosstalk remain ambiguous. Hypothalamic dysfunction is observed in many psychiatric disorders, particularly those with an inflammatory component due to many hypothalamic regions being unprotected by the blood–brain barrier. To gain a better insight into such neuropsychiatric sequelae, this study investigated gene expression differences in the hypothalamus following lung inflammation (asthma) induction in mice, using RNA transcriptome profiling. BALB/c mice were challenged with either bacterial lipopolysaccharide (LPS, E. coli) or ovalbumin (OVA) allergens or saline control (n = 7 per group), and lung inflammation was confirmed via histological examination of postmortem lung tissue. The majority of the hypothalamus was micro-dissected, and total RNA was extracted for sequencing. Differential expression analysis identified 31 statistically significant single genes (false discovery rate FDR5%) altered in expression following LPS exposure compared to controls; however, none were significantly changed following OVA treatment, suggesting a milder hypothalamic response. When gene sets were examined, 48 were upregulated and 8 were downregulated in both asthma groups relative to controls. REACTOME enrichment analysis suggests these gene sets are involved in signal transduction metabolism, immune response and neuroplasticity. Interestingly, we identified five altered gene sets directly associated with neurotransmitter signaling. Intriguingly, many of these altered gene sets can influence mental health and or/neuroinflammation in humans. These findings help characterize the links between asthma-induced lung inflammation and the brain and may assist in identifying relevant pathways and therapeutic targets for future intervention.

Mammalian sperm has a high metabolic activity and primarily relies on glycolysis and mitochondrial oxidative phosphorylation for energy supply. It has been reported that imiquimod (R837), a specific ligand of TLR7 protein, reduces the motility of sperm. However, the specific molecular mechanism by which TLR7 modulates boar sperm is unclear. In this study, the effect of R837, a Toll-like receptor 7 (TLR7) agonist, on boar sperm motility was investigated. Sperm samples were incubated with varying concentrations of R837 (0 to 0.8 µM) at different time points (30, 60, and 90 min). Findings reveal for the first time that TLR7 protein, a key component of the immune system’s Toll-like receptors, is predominantly localized in the middle section of the boar sperm tail, with a smaller concentration observed in the neck. Also, immunofluorescence (IF) revealed that approximately half of the boar sperm sample expressed TLR7. Furthermore, the TLR7 agonist influenced glycolytic hexokinase activity and mitochondrial function via the PI3K-GSK3β signaling pathway. It also selectively inhibited motility in the lower-layer sperm, while motility in the upper-layer sperm remained unaffected. Additionally, this study determined that incubation conditions for boar sperm with 0.2 μM R837 at 37 °C for 60 min yielded the most pronounced inhibition of forward motility in the lower layer of sperm, without compromising the integrity of the acrosome or plasma membrane. The present study reveals the crucial role of R837 in boar sperm motility and highlights TLR7 as an important protein that regulates boar sperm energy metabolism.

Aims: Mental health is a critical component of recovery following an acute cardiac event, yet the factors shaping mental health across the care continuum are complex and interconnected. This study aimed to co-develop a shared understanding of factors influencing mental health following a cardiac event and to identify priority areas for intervention, informed by consumers with lived experience and key stakeholders. Methods and results: Group model building was used to collaboratively explore and visually map factors shaping mental health experiences after an acute cardiac event. A national sample of consumers with lived experience of a cardiac event (n = 3) and relevant stakeholders (n = 9) participated in facilitated workshops to reflect on factors influencing mental health across the cardiac healthcare journey. Eight interconnected domains were identified: knowledge, skills, health system context, personal context, emotional response, social influences, behavioural regulation, and beliefs about capabilities. Participants highlighted health literacy, systemic support for health services, ability to navigate services, and person-centred approaches as key priorities for future action. Conclusion: Supporting mental health following a cardiac event requires coordinated, multi-level interventions that address interacting individual, service-level, and community factors.