Fluoride is a ubiquitous environmental agent widely utilized in public health for the prevention of dental caries. Despite its benefits, chronic exposure, particularly during developmental windows of heightened vulnerability, has been associated with adverse neurodevelopmental outcomes. This narrative review evaluates the current evidence linking prolonged fluoride exposure via drinking water to anxiety and depression, synthesizing findings from both preclinical and human studies. Animal research robustly demonstrates that fluoride crosses the blood-brain barrier, accumulates in limbic structures such as the hippocampus, and promotes anxiety- and depression-like behaviors. These behavioral phenotypes are underpinned by multifaceted neurotoxic mechanisms, including mitochondrial dysfunction, sustained neuroinflammation, disruption of key neurotransmitter systems (glutamate, GABA, dopamine, and serotonin), and a critical reduction in brain-derived neurotrophic factor (BDNF), which is essential for synaptic plasticity and emotional regulation. In contrast, the human evidence remains sparse and less direct. While numerous epidemiological studies have reported associations between fluoride exposure and reduced cognitive performance or increased risk of attention-deficit/hyperactivity disorder, data on internalizing disorders are strikingly limited. To date, only a single study has directly assessed clinical anxiety and depression, finding an association with somatic symptoms but not core affective dimensions. This significant discrepancy underscores the considerable challenge in translating preclinical neurotoxicological findings to complex human mental health conditions. In light of the global prevalence of affective disorders and the substantial populations residing in endemic fluoride areas, there is an urgent need for rigorous longitudinal studies that utilize validated psychiatric instruments. Future research must prioritize investigating fluoride as a potential modifiable environmental risk factor for mental health, with specific attention to developmental timing and sex-specific susceptibilities.

Fluoride, Neurotoxicity, Anxiety, Depression, Environmental risk factor, Neurodevelopment, Mental health