Kevin G. Bath, Ph.D., of Brown University, used his 2010 NARSAD Young Investigator Grant to study the role of stress and gender differences in the development of affective disorders. During adolescence, girls are at significantly greater risk than boys of developing stress-induced anxiety, depression or post-traumatic stress disorder (PTSD). Dr. Bath studies a protein called brain-derived neurotrophic factor (BDNF), known to be critically involved in the development of emotional brain centers and of affective disorders.

In a report published September 15th in the journal Biological Psychiatry, he and colleagues at Weill Cornell Medical College, including three-time NARSAD Grantee and Foundation Scientific Council Member Francis S. Lee, M.D., Ph.D., found that female mice that carry a mutation in the BDNF gene are at increased risk of developing anxiety and depressive-like behavior. This effect emerges during adolescence and is sensitive to changes in gonadal hormone expression. This effect is important, as the mutation that these mice carry is synonymous with a mutation in this same gene in humans.

More recently, Bath and colleagues published a report in the journal Neuroscience where they review work on the class of proteins called neurotrophic factors, of which the most important in the very young developing brain is BDNF. The researchers note in the paper that levels of BDNF in the blood have already been linked with stress in rodents and people. What remains unclear are the mechanisms at work when, for example, stress at the very beginning of life in some manner causes abnormal BDNF expression much later in life, during adulthood, and in some instances, but not all, greater susceptibility to developing depression and anxiety disorders.

The effects of stress on BDNF “are highly sensitive to the form, duration, and timing of the stress as well as the sex of the individual receiving the stress, and the brain region one is studying,” the scientists say. The advent of new genetic and other research tools is now making it possible to switch BDNF expression on and off, and separately the expression of the receptors that activate BDNF receptors, over specific intervals of time and in precise areas of the brain. This work, they say, is already paving the way toward identification of new targets for treatments of stress-related disorders, including depression, anxiety and PTSD.

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