Unraveling the molecular pathways linking polystyrene exposure and depression

Polystyrene micro- and nanoplastics have become major neurotoxicants in the environment with respect to mental health in the case of depression. This review summarizes the existing experimental, epidemiological, and mechanistic data pertaining to exposure to polystyrene micro- and nanoplastics and their relationship with neurobehavioral imbalances. The particles may enter the brain by passing through the blood-brain barrier and accumulate in neural tissues, leading to in turn cause neuronal imbalance via oxidative stress, neuroinflammation, mitochondrial dysfunction, and synaptic and neurotransmitter maladaptation. These processes resemble the neurobiological foundation of major depressive disorders, such as serotonergic, dopaminergic, and glutamatergic dysfunction; dysregulation of the hypothalamic-pituitary-adrenocortical axis; and impairment of neuroplasticity. Despite limited human research, biomonitoring has shown the presence of polystyrene micro- and nanoplastics in the blood, placenta, and feces, leading to widespread and chronic exposure to these plastics. There is a risk that the most vulnerable groups (children, pregnant women, and industrial workers) may be affected disproportionately. To address these risks, human-relevant models and omics approaches, as well as longitudinal cohort studies, must be incorporated into future studies with regulatory frameworks to reduce exposure and safeguard mental health.