Depression is a multifactorial, chronic disorder and represents a leading cause of disability, with women exhibiting nearly twice the lifetime prevalence compared to men. Growing evidence indicates th Show more
Depression is a multifactorial, chronic disorder and represents a leading cause of disability, with women exhibiting nearly twice the lifetime prevalence compared to men. Growing evidence indicates that this disparity cannot be explained by hormonal or psychosocial factors, but rather by dynamic interactions between environmental exposures, neuroendocrine signaling, and epigenetic regulation across development. This mini-narrative review aimed to examine how sex-specific exposome components interact with epigenetic mechanisms and synaptic remodeling processes to influence vulnerability to Major Depressive Disorder in women. The reviewed evidence demonstrates that fluctuations in ovarian hormones modulate HPA axis responsivity, neuroinflammatory signaling, and glutamatergic transmission through epigenetic regulation of stress-responsive genes such as Show less
Chronic pain, marked by nociceptive sensitization and maladaptive neuroplasticity, affects 30% of the global population with escalating socioeconomic burdens. Epidemiological data show a 2-3-fold incr Show more
Chronic pain, marked by nociceptive sensitization and maladaptive neuroplasticity, affects 30% of the global population with escalating socioeconomic burdens. Epidemiological data show a 2-3-fold increase in neuropsychiatric co-morbidities among individuals with chronic pain, where epigenetic dysregulation serves as a key mechanism linking ongoing pain to emotional disorders. This review systematically explores epigenetic signatures in supraspinal integration hubs, notably the limbic-paralimbic networks and prefrontal regulatory circuits. The identified epigenetic signatures encompass dysregulation of DNA methyltransferases (DNMTs), RNA modifications, histone post-translational modifications and locus-specific alterations, including aberrant methylation at the brain-derived neurotrophic factor (BDNF), opioid μ receptor and transient receptor potential ankyrin 1 (TRPA1) gene loci. Additionally, they involve dysfunction of the glucocorticoid receptor (GR)/corticotropin-releasing factor (CRF) axis via epigenetic modulation. Building on these findings, we evaluate therapeutic strategies addressing epigenetic dysregulation. While preclinical data demonstrate the efficacy of histone deacetylase (HDAC) and DNMT inhibitors, clinical translation faces significant barriers, including limited blood-brain barrier permeability. Notably, our analysis highlights the benefits of combining pharmacological interventions with non-invasive neuromodulation for enhanced co-morbidity management. Looking forward, this review proposes innovative approaches that leverage CRISPR-based chromatin editing platforms, biomimetic nanocarriers for neuron-specific delivery and closed-loop neuromodulation integrating real-time biomarker feedback, collectively establishing a precision medicine framework for pain or neuropsychiatric co-morbidities. Show less