Both humans and animals experience stress. Ideally, stress serves as a survival tool, allowing organisms to adapt and overcome adversity in an unpredictable environment. As a result, higher-order animals have developed complex systems to perceive, react to, and adapt to psychological stress, ensuring that they can respond to environmental dangers that might harm or kill them. But for some, the response to stress can go awry, and what started as a natural response to a changing environment can ultimately become a chronic disease such as depression, anxiety disorder, or posttraumatic stress disorder (PTSD). A recent review in Nature Neuroscience explores how innovative findings in animals can advance our understanding of stress-related mental disorders in humans.

 

The review, written by Dr. Ahmad Hariri, Duke University, and Dr. Andrew Holmes, NIAAA Laboratory of Behavioral and Genomic Neuroscience, notes that the neural circuits and underlying genes that control the stress response are similar across species. Hence, studies in animals (known as preclinical studies) have revealed much about the systems that play a central role in psychological stress, such as the hypothalamic–pituitary–adrenal axis, a complex interaction between three endocrine glands. Based on preclinical work, scientists also have an important understanding of how the brain perceives and processes stressful experiences. Across species, the amygdala, hippocampus, and prefrontal cortex work together to play a critical role in both short-term and long-term response to stress. Using animal models, scientists have also been able to identify genetic variants that contribute to stress-related disorders. These candidate genes could help identify people at risk for such disorders and provide possible targets for developing treatments.

 

Preclinical models have been developed for a wide range of disorders. The authors note that “translational stress research is thus positioned to be a standard bearer for the charge toward the recasting of mental illness as manifestations of disordered brain circuits and the behavioral processes they subserve.”