Discovered potential treatment focus for addressing adolescent neuropsychiatric issues by researchers

The brain undergoes significant changes during childhood and adolescence, a critical period for brain circuitry maturation. Recent research, published in the journal eLife, has identified a potential opportunity for therapeutic intervention during this period, focusing on the dopamine system.

This research, led by senior author Kuan Hong Wang, PhD, from the University of Rochester Medical Center, builds upon previous work from the Wang Lab that identified a flexible arm of the dopamine system in the adolescent brain. The study, supported by the National Institutes of Health and the Del Monte Institute for Neuroscience pilot program, aims to develop a treatment for neuropsychiatric disorders like schizophrenia and autism, which often begin during young adulthood.

Rianne Stowell, PhD, a postdoctoral fellow in the Wang Lab at the University of Rochester Medical Center, is a co-first author on the study. Stowell and her team targeted underperforming neurons in the dopamine system that connect to the frontal cortex in mice, which is essential for higher cognitive processing and decision-making. Stimulating the cells that provide dopamine to the frontal cortex strengthened this circuit and rescued structural deficiencies in the brain that cause long-term symptoms.

New studies show dopamine modulates both fast, effortful working memory and slower reinforcement learning processes. This dual action influences how the brain balances flexible problem-solving with habit formation during adolescence. Co-first authors on the study, Surjeet Mastwal and Xinjian Li from the National Institute of Mental Health, highlight that dopamine affects not only learning but also the motivation to expend cognitive effort, which is relevant to neuropsychiatric conditions characterized by cognitive and motivational deficits.

In adolescents at clinical high risk for psychosis, co-occurring neurodevelopmental traits such as ADHD and repetitive behaviors (common in ASD) predict conversion to schizophrenia. These findings implicate disrupted dopamine-regulated circuits in the striatum and cortex that govern attention, social cognition, and executive function, suggesting that dopamine-related neurodevelopmental pathways are important targets for early intervention.

The research team used the window for plasticity in the dopamine system as an opportunity for therapeutic intervention. By targeting the right windows in development and understanding the signals at play, treatments can be developed that change the course of brain disorders. The researchers believe that future therapies may combine pharmacological modulation of dopamine signaling with behavioral training to optimize brain circuit development and improve clinical outcomes.

Experimental strategies such as immersive virtual reality training in adolescents with high functioning autism have demonstrated improvement in adaptive skills and executive function, potentially through engagement of dopaminergic circuits underpinning learning and motivation. While not a direct dopamine-targeting pharmacological approach, such behavioral interventions capitalize on neuroplasticity during adolescence to reshape affected brain networks.

Together, these findings underscore adolescence as a sensitive period when dopamine’s impact on brain circuits related to working memory, reward processing, and cognitive effort can be leveraged for intervention in schizophrenia, autism, and related disorders. The research team at the Del Monte Institute for Neuroscience at the University of Rochester continues to work on possible treatments for neuropsychiatric disorders during development that could affect brain circuitry into adulthood.

Discovered potential treatment focus for addressing adolescent neuropsychiatric issues by researchers