Priorities in stress research: a view from the U.S. National Institute of Mental Health

Abstract

The mission of the National Institute of Mental Health is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. In consultation with a broad range of experts, the NIMH has identified a set of priorities for stress biology research aimed squarely at creating the basic and clinical knowledge bases for reducing and alleviating mental health burden across the lifespan. Here, we discuss these priority areas in stress biology research, which include: understanding the heterogeneity of stressors and outcomes; refining and expanding the experimental systems used to study stress and its effects; embracing and exploiting the complexity of the stress response; and prioritizing translational studies that seek to test mechanistic hypotheses in human beings. We emphasize the challenge of establishing mechanistic links across levels of analysis to explain how and when specific and diverse stressors lead to enduring changes in neural systems and produce lasting functional deficits in mental health relevant behaviors. An improved understanding of mechanisms underlying stress responses and the functional consequences of stress can and will speed translation from basic research to predictive markers of risk and to improved, personalized interventions for mental illness.

Unexpected Role of Physiological Estrogen in Acute Stress-Induced Memory Deficits

“…In conclusion, the current studies describe an important correlation of high physiological levels of estradiol to stress-induced memory impairments. This potentially deleterious role of estradiol is novel and underscores the need for careful and nuanced studies of the role of sex and sex steroids on the effects of distinct stresses in distinct contexts ( Simmons et al, 2020 ). Such studies and an improved understanding of the underlying mechanism are a prerequisite for elucidating the biology underlying sex differences in post-traumatic stress disorder and other stress and memory-related disorders.…”

Transcriptomics of the depressed and PTSD brain

“…The latter, in contrast, have typically been collected at a fixed delay after a more persistent stressful experience in order to create a contrast between two conditions (stressed and unstressed). Importantly the effects of acute and chronic stress are frequently different in terms of transcriptomic changes ( Simmons et al, 2020 ). One large gene expression atlas of different kinds of stress in rodent brain meta-analyzed gene expression data from 18 projects studying the effect of stress on the transcriptome of the brain ( Flati et al, 2020 ).…”

“…However, neurobiological research on stress has reached a major obstacle - the very “non-specific” nature of the phenomenon has blocked further study ( Simmons et al, 2020 ). The wide variety of ways to induce stress lead to diverse and often contradictory responses in neural circuits.…”

Stress and Tinnitus; Transcutaneous Auricular Vagal Nerve Stimulation Attenuates Tinnitus-Triggered Stress Reaction

“…It has been shown that the corticostriatal circuit, which includes the nucleus accumbens and ventromedial posterior frontal cortex, does indeed differ in the brains of individuals with tinnitus (Leaver et al, 2011). The corticostriatal circuit is part of the general "appraisal network", determining which sensations are important and ultimately affecting how (or whether) those sensations are experienced (Simmons et al, 2020). Our theory of the pathogenetic mechanism of NIHD is schematically summarized in Figure 6.…”