Psychiatric Risk Implications From Behavioral and Neural Effects of Adolescent Exposure to Environmental...

Adolescence is a sensitive neurodevelopmental period marked by remodeling of brain circuits that support cognitive development and emotion and behavior regulation. These maturation processes heighten psychiatric vulnerability to environmental exposures, including to toxicants such as insecticides. Epidemiological studies show widespread adolescent insecticide exposure and increasingly link this to psychiatric outcomes, but underlying neural mechanisms remain poorly understood. Preclinical studies can clarify these associations and identify insecticide-induced mechanisms that may disrupt neurodevelopment and produce consequent long-term behavioral outcomes. Here, we performed a systematic review of rodent studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fifty articles met inclusion criteria, examining neurotoxic outcomes following insecticide exposure during early (juvenile), middle, and late adolescent ages (postnatal days 21-60). Outcomes were categorized into 4 domains: neurocognitive, neuropsychiatric, neurobiological, and general neurotoxicity. Risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) Risk of Bias tool. Across studies, adolescent insecticide exposure led to learning and memory impairments and tended to increase depression-relevant behaviors, alter locomotor activity, and produce general neurotoxic effects. Mechanistic findings highlighted disruptions in cholinergic and monoaminergic signaling, oxidative stress, neuroimmune changes, and cell death and other neurodegenerative processes. Together, the findings indicate that adolescent insecticide exposure disrupts multiple neural systems, with behavioral consequences relevant to adolescent development and psychiatric risk. Future research should model real-world exposures (e.g., dose, timing) to better inform translational understanding of adolescent psychiatric vulnerability. Because many life-long neuropsychiatric disorders emerge during adolescence, identifying how modifiable environmental exposures shape risk offers an opportunity for prevention and intervention strategies to alter the course of disease across the lifespan.