With support from a 2011 Brain & Behavior Research Foundation NARSAD Distinguished Investigator Grant, Akira Sawa, M.D., Ph.D. and Johns Hopkins University colleagues have shown that when mice with a genetic predisposition to mental illness experience stress as adolescents they are more likely to go on to develop severe mental illness such as schizophrenia and depression. The researchers observed raised cortisol (stress hormone) levels among mice placed in social isolation during adolescence—a critical brain development period. The results of their study were published in the Jan. 18, 2013 issue of Science.
 
"We have discovered a mechanism for how environmental factors, such as stress hormones, can affect the brain's physiology and bring about mental illness," says study leader Akira Sawa, M.D., Ph.D., Brain & Behavior Research Foundation Scientific Council member; Professor, psychiatry and behavioral sciences and Director, Schizophrenia Center, Johns Hopkins University School of Medicine. "We've shown in mice that stress in adolescence can affect the expression of a gene that codes for a key neurotransmitter related to mental function and psychiatric illness. While many genes are believed to be involved in the development of mental illness, my gut feeling is environmental factors are critically important to the process."

A group of mice that experienced a period of three weeks of isolation exhibited behaviors associated with mental illness, such as hyperactivity and lack of interest in certain activities, and had lower levels of the neurotransmitter dopamine in areas of the brain that play a role in emotional control and cognition. Symptoms subsided when a compound that blocks cells from receiving cortisol, RU486, was administered. A control group of mice without a genetic predisposition to mental illness did not show the negative responses to social isolation that were experienced by the other group. According to Sawa, the new study highlights the need for better preventive care in teenagers who have mental illness in their families, and also sheds light on the cascade of events that occurs when cortisol levels are elevated, furthering researchers’ ability to develop new treatments with fewer side effects than RU486 has.

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