Phthalates and Bisphenols as Endocrine-Disrupting Chemicals: Possible Determinants of Mood Disorders
Major depressive disorder (MDD) accounts for a substantial share of global disability-adjusted life years and remains inadequately treated despite pharmacological advances. Growing evidence implicates endocrine-disrupting chemicals (EDCs)—particularly phthalates and bisphenols—as environmental contributors to the onset of these conditions. This narrative review examines evidence from PubMed, Scopus, and Web of Science (January 2000–March 2025) on the relationship between early-life exposure to these compounds and the development of mood disorders, with emphasis on molecular and neurobiological mechanisms. Phthalates such as di(2-ethylhexyl) phthalate (DEHP), and bisphenols such as bisphenol A (BPA), are detected ubiquitously in human urine, blood, placenta, and umbilical cord blood. Key mechanisms identified include Nrf2/HO-1-driven oxidative stress and neuronal apoptosis, disruption of calcium signalling and synaptic plasticity via CREB phosphorylation deficits, epigenetic suppression of brain-derived neurotrophic factor (BDNF) via promoter hypermethylation, NF-κB/NLRP3/IL-1β neuroinflammatory cascades, interference with thyroid hormone bioavailability through transthyretin competition, and PPAR-mediated disruption of brain lipid metabolism. Prenatal and early-life exposure has been associated with ADHD, cognitive impairment, autism spectrum disorder, and elevated risk of depressive and anxiety phenotypes in epidemiological cohorts. Psychological vulnerability factors—perceived stress, deficient emotion regulation, and adverse childhood experiences—likely amplify this biological susceptibility through HPA axis sensitisation. Methodological limitations of current evidence, including reliance on single-spot urine samples and residual confounding, are critically appraised. Future research priorities include longitudinal biomonitoring cohorts, brain organoid mechanistic models, and integration of validated psychiatric assessments into environmental health study designs.