Adult Aggression, Impulsivity May Have Roots in Mid-adolescent Brain

Too much exposure to dopamine in mid-adolescence may set the stage for antisocial behaviors in adulthood if the results of a new mouse study conducted by Columbia University researchers also apply to people.

The study, published Aug. 4, 2023, in the journal Molecular Psychiatry, found that the brains of mid-adolescent mice are sensitive to dopamine during this sensitive period of development, which causes changes that set the stage for aggressive and impulsive behaviors. Identifying developmental phases that impact complex behaviors, such as impulsivity and aggression, is a new area in psychiatry research and should aid in understanding the origins of psychiatric disorders, as well as their diagnosis, prevention, and treatment.

Sensitive periods in development of psychiatric illness

As organisms grow from embryo to adult, they pass through sensitive time periods when environmental factors influence developmental trajectories. While this form of developmental plasticity usually benefits the organism, normal development can sometimes be perturbed with negative consequences. 

Sensitive periods in vision and hearing development are well studied, but the role of sensitive periods in the development of psychiatric illnesses is primarily unknown.

The Columbia researchers took a close look at the brain’s dopamine system because it is implicated in several neuropsychiatric disorders, such as attention deficit disorder, depression, and schizophrenia.

Failing the mouse “marshmallow test”

To see if the development of the mouse brain is sensitive to dopamine at certain times, the researchers administered a drug that increases dopamine levels in the brain to mice. They then assessed impulsive behavior during adulthood with the mouse version of the “marshmallow test.”

The researchers found that mice exposed to extra dopamine in mid-adolescence were more impulsive and likelier to choose a small immediate reward than wait for a larger one. The mice exposed to extra dopamine in late adolescence were also more aggressive than adults but showed no differences in cognition, motivation, and working memory.

The researchers also found that physiological changes in the brain drove these changes in behavior. Mice exposed to excess dopamine in mid-adolescence had more active dopamine neurons in adulthood, and additional experiments confirmed that this biological change drove aggressive and impulsive behaviors.

These insights may help improve the diagnosis, prevention, and treatment of attention deficit disorders, schizophrenia, bipolar disorder, and substance use disorders, which frequently involve deficits in impulse control and increased aggression.

Implications for recreational drug use

Because stimulants (including amphetamines, uppers, and ecstasy) raise dopamine levels, the findings also suggest that use of these drugs during mid-adolescence may hijack normal development with potentially harmful consequences.

Psychostimulants are also prescribed to children to treat attention deficit disorders, but current study did not investigate the developmental effects of boosting dopamine in mice with dopamine deficits, as seen in ADHD.

“In a diseased state that results from dopamine deficits, transient exposure to psychostimulants during adolescence might potentially be corrective, but this hypothesis needs to be experimentally tested,” said Mark Ansorge, PhD, assistant professor of psychiatry at Columbia University Vagelos College of Physicians and Surgeons, who led the research.

“It is critical to understand the underlying biology to properly evaluate the risks and benefits of recreational or therapeutic drug exposure prior to adulthood.”