According to the researchers, trauma at this stage of life disrupts the balance between excitation and inhibition signals in the brain, compromising the functional stability of the organ (image: Nikolett Emmert/Freepik)
Published on 03/23/2026
By Maria Fernanda Ziegler | Agência FAPESP – Stressful situations experienced during adolescence tend to cause deeper and more lasting changes to the brain than those experienced in adulthood. A study conducted on mice at the University of São Paulo (USP) in Brazil has identified one of the neurological mechanisms behind this difference, shedding new light on the origins of psychiatric disorders such as depression and schizophrenia.
The researchers demonstrated that exposure to stress during adolescence can disrupt the balance of neurons, impairing the maturation of neural networks and increasing vulnerability to brain dysfunctions that may persist into adulthood. The results were published in the journal Cerebral Cortex.
Supported by FAPESP, the study demonstrated that stress during adolescence causes permanent changes in the circuits of the prefrontal cortex, the brain region responsible for emotional control and cognitive function.
The researchers found that trauma during this stage of life disrupts the balance between excitatory and inhibitory signals in the brain, which compromises the functional stability of the organ. However, in adult rodents, the brain showed greater resilience, with recovery mechanisms that made the effects of stress more transient.
“Epidemiological studies had already shown that the impact of severe stress is more profound during adolescence. In our study, we demonstrated that it causes an imbalance in communication between brain cells in both stages of life. However, since the adolescent brain is still developing, there is insufficient protection against this impact,” explains Felipe Gomes, a professor at the Ribeirão Preto School of Medicine (FMRP) at USP and coordinator of the study.
For the study, male mice were subjected to a stress protocol involving electric shocks to the paws and restricted movement for ten consecutive days. The experiments were conducted on two groups of animals: those between 31 and 40 days old (adolescents) and those between 65 and 74 days old (adults).
The scientists then analyzed short- and long-term changes in the activity of excitatory (glutamatergic pyramidal) and inhibitory (GABAergic interneuronal) neurons in both groups. These neurons are present in the medial prefrontal cortex.
Stress caused a persistent increase in the activity of excitatory neurons and permanently altered the functioning of inhibitory neurons in the adolescent mice. The result was a prolonged imbalance, as if the brain were revved up without a “working brake.” Although the strength of inhibitory signals returned to normal, the firing pattern remained irregular, compromising neural control.
In the adults, however, stress only temporarily reduced the activity of inhibitory interneurons without generating the hyperexcitability observed in the adolescents. This allowed the system to rebalance itself after the period of stress.
“The study also showed that malfunctioning interneurons affected brain electrical rhythms. In adolescents, there was a lasting reduction in gamma oscillations, which are fundamental to higher cognitive processes, such as attention and working memory, and which are impaired in schizophrenia. In adults, however, stress temporarily reduced theta oscillations, which regulate communication between the cortex and other regions, such as the hippocampus. The recovery of this rhythm suggests that brain connectivity was restored,” says Gomes.
Neural mechanisms
Previous studies by the same group had already shown that adolescent stress can induce behaviors similar to those seen in schizophrenia, whereas adult stress tends to cause changes associated with depression.
“Our work makes advances by revealing the neural mechanisms behind these differences, showing that the stage of life in which stress occurs is decisive for the type and duration of changes in prefrontal cortex circuits,” says Flávia Alves Verza, who is investigating this topic in her postdoctoral research supported by FAPESP.
“We were able to deepen this understanding by characterizing the impact of stress at different life stages on distinct cell types in the prefrontal cortex, a region frequently affected in psychiatric disorders,” Gomes adds.
In addition to sharing stress exposure as a common risk factor, approximately 40% of the genes associated with schizophrenia are also linked to depression. “Thus, the new study supports the hypothesis that a genetically vulnerable individual may develop schizophrenia if exposed to trauma during adolescence, while the same trauma in adulthood may trigger depression. The results reinforce the importance of preventive strategies targeting young people, especially those in situations of emotional vulnerability,” the researcher states.
The article “Adolescent and adult stress alter excitatory-inhibitory network dynamics in the medial prefrontal cortex” can be read at academic.oup.com/cercor/article-abstract/36/1/bhaf342/8422749.
Source: https://agencia.fapesp.br/57553
