New framework maps the complex link between psychological status and cardiovascular health

CVD remains the leading cause of death worldwide, while the global burden of mental disorders continues to rise. Depression and anxiety are associated with myocardial infarction, stroke, heart failure, and cardiovascular mortality, and patients with CVD face a higher risk of comorbid mental disorders. Despite this bidirectional relationship, most studies have examined single diseases or single mechanisms, leaving a fragmented picture of how the brain and heart communicate. Given these challenges, in-depth research is needed on the integrated mechanisms, biomarkers, and interventions that link psychological status and cardiovascular health.

The review was led by researchers at West China Hospital, Sichuan University, and West China Second University Hospital, Sichuan University, Chengdu, China. Published (DOI: 10.1093/pcmedi/pbag025) in 2026 in Precision Clinical Medicine, the article synthesizes evidence from epidemiology, neuroendocrine, autonomic, immune, and molecular studies to build the psycho-cardiovascular interaction network (PCIN) framework. It highlights how psychological factors may influence cardiovascular function through shared pathways and proposes brain-heart axis-informed strategies for assessment and treatment.

The review details six system-level mechanisms: hypothalamic-pituitary-adrenal (HPA) axis imbalance, autonomic nervous system (ANS) imbalance, chronic inflammation, platelet activation, unhealthy behaviors, and sleep/circadian disruption. These processes can raise cortisol, shift sympathetic-parasympathetic balance, increase interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), promote thrombosis, and worsen lifestyle and treatment adherence. At the molecular level, the authors focus on five pathways. BDNF signaling is protective when mature BDNF activates tropomyosin receptor kinase B (TrkB), but pro-BDNF can trigger injury through p75 neurotrophin receptor (p75NTR). PROK/PKR signaling shows receptor-specific effects: PKR1 is often cardioprotective, whereas PKR2 can drive hypertrophy and vascular leakage. MAPK branches, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, link stress and inflammation to depression, cardiac fibrosis, and remodeling. 5-hydroxytryptamine (5-HT)/ 5-HT2A receptor (5-HT2A-R) signaling influences platelet aggregation, vasoconstriction, and inflammation. NOD-like receptor protein 3 (NLRP3) inflammasome activation links stress, interleukin-1β (IL-1β), interleukin-18 (IL-18), and pyroptosis with both mental disorders and CVD. The authors stress that these pathways are not isolated. They form an interconnected network in which neurotrophic, peptidergic, kinase, monoaminergic, and inflammatory signals converge, helping explain why mental and cardiovascular conditions frequently coexist and why single-target treatments may have limited effects.

The authors said the PCIN is more than a new label for the brain-heart axis. They said it is a practical way to connect psychosocial phenotypes with measurable molecular signals, from BDNF and 5-HT to NLRP3. In their view, the most immediate opportunity is to bring mental health assessment into routine cardiovascular care, especially for patients with depression, anxiety, or chronic stress. Longer term, they said, the field needs rigorous trials testing whether pathway-targeted therapies can deliver dual mental and cardiovascular benefits without unacceptable side effects.

Clinically, the PCIN framework supports integrated risk assessment that combines psychological, molecular, genetic, and physiological data. Mental health screening and interventions such as cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR) could become part of cardiovascular management. Pharmacological strategies include selective serotonin reuptake inhibitors (SSRIs), 5-HT2A-R antagonists, NLRP3 inhibitors with central nervous system (CNS) penetration, and TrkB agonists such as 7,8-dihydroxyflavone. Adeno-associated virus (AAV)-mediated BDNF gene therapy and exosome delivery platforms remain experimental but promising. The authors call for multiomics studies, long-term randomized controlled trials, and individualized brain-heart axis-based prevention.