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Open accessJournal ArticleDOI: 10.1080/10253890.2020.1781084

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

04 Mar 2021-Stress (Taylor & Francis)-Vol. 24, Iss: 2, pp 123-129
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.

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Open accessJournal ArticleDOI: 10.1523/JNEUROSCI.2146-20.2020
Abstract: Stress may promote emotional and cognitive disturbances, which differ by sex. Adverse outcomes, including memory disturbances, are typically observed following chronic stress, but are now being recognized also after short events, including mass shootings, assault, or natural disasters, events that consist of concurrent multiple acute stresses (MAS). Prior work has established profound and enduring effects of MAS on memory in males. Here we examined the effects of MAS on female mice and probed the role of hormonal fluctuations during the estrous cycle on MAS-induced memory problems and the underlying brain network and cellular mechanisms. Female mice were impacted by MAS in an estrous cycle-dependent manner: MAS impaired hippocampus-dependent spatial memory in early-proestrous mice, characterized by high levels of estradiol, whereas memory of mice stressed during estrus (low estradiol) was spared. As spatial memory requires an intact dorsal hippocampal CA1, we examined synaptic integrity in mice stressed at different cycle phases and found a congruence of dendritic spine density and spatial memory deficits, with reduced spine density only in mice stressed during high estradiol cycle phases. Assessing MAS-induced activation of brain networks interconnected with hippocampus, we identified differential estrous cycle-dependent activation of memory- and stress-related regions, including the amygdala. Network analyses of the cross-correlation of fos expression among these regions uncovered functional connectivity that differentiated impaired mice from those not impaired by MAS. In conclusion, the estrous cycle modulates the impact of MAS on spatial memory, and fluctuating physiological levels of sex hormones may contribute to this effect.SIGNIFICANCE STATEMENT: Effects of stress on brain functions, including memory, are profound and sex-dependent. Acute stressors occurring simultaneously result in spatial memory impairments in males, but effects on females are unknown. Here we identified estrous cycle-dependent effects of such stresses on memory in females. Surprisingly, females with higher physiological estradiol experienced stress-induced memory impairment and a loss of underlying synapses. Memory- and stress-responsive brain regions interconnected with hippocampus were differentially activated across high and low estradiol mice, and predicted memory impairment. Thus, at functional, network, and cellular levels, physiological estradiol influences the effects of stress on memory in females, providing insight into mechanisms of prominent sex differences in stress-related memory disorders, such as post-traumatic stress disorder.

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Topics: Effects of stress on memory (67%), Memory impairment (56%), Chronic stress (55%) ... show more

8 Citations


Open accessJournal ArticleDOI: 10.3389/FPSYG.2020.570196
Abstract: Introduction Tinnitus can become a strong stressor for some individuals, leading to imbalance of the autonomous nervous system with reduction of parasympathetic activity. It can manifest itself as sleep disturbances, anxiety and even depression. This condition can be reversed by bioelectrical vagal nerve stimulation (VNS). Conventional invasive VNS is an approved treatment for epilepsy and depression. Transcutaneous VNS (taVNS) stimulating the auricular branch of the vagus nerve has been shown to activate the vagal pathways similarly as an implanted VNS. Therefore, taVNS might also be a therapeutic alternative in health conditions such as tinnitus-related mental stress (TRMS). This retrospective study in 171 TRMS patients reports the clinical features, psychophysiological characteristics, and results of the heart rate variability (HRV) tests before and after test-taVNS. This study also reports the therapy outcomes of 113 TRMS patients treated with taVNS, in combination with standard tinnitus therapy. Methods Diagnostic tinnitus and hearing profiles were defined. To detect possible cardiac adverse effects, test-taVNS with heart rate monitoring as well as pre- and post-stimulation HRV tests were performed. Daily taVNS home therapy was prescribed thereafter. To assess therapeutic usefulness of taVNS, 1-year follow-up outcome was studied. Results of HRV tests were retrospectively analyzed and correlated to diagnostic data. Results The large majority of patients with TRMS suffer from associated symptoms such as sleep disturbances and anxiety. Baseline HRV data showed that more than three quarters of the 171 patients had increased sympathetic activity before test-taVNS. Test-taVNS shifted mean values of different HRV parameters toward increased parasympathetic activity in about 80% of patients. Test-taVNS did not cause any cardiac or other side effects. No significant adverse effects were reported in follow-up questionnaires. Conclusion TRMS is an example of a stress condition in which patients may benefit from taVNS. As revealed by HRV, test-taVNS improved parasympathetic function, most efficiently in patients with a low starting HRV level. Our tinnitus treatment program, including taVNS, effectively alleviated tinnitus stress and handicap. For wider clinical use, there is a great need for more knowledge about the optimal methodology and parameters of taVNS.

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Topics: Tinnitus (53%), Heart rate variability (50%)

2 Citations


Open accessJournal ArticleDOI: 10.1080/10253890.2021.1895937
Mathias V. Schmidt1, Alon Chen2Institutions (2)
22 Mar 2021-Stress
Abstract: Challenges are the spice of life, for without a little bit of pressure, excitement and uncertainty, life would be a dull endeavor. However, chronic exposure to such stressful situations can in some...

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1 Citations


Journal ArticleDOI: 10.1016/J.CCT.2020.106240
Luis A. Valdez1, Aline Gubrium1, Jefferey Markham1, Lamont Scott  +3 moreInstitutions (1)
Abstract: Low/no-income, African American men are disproportionally burdened by chronic disease resulting from a complex interplay of systemic, sociocultural, and individual factors. These disparities are related to poverty, racism, gender role strain, high levels of stress, low levels of physical activity, and malnutritious diet. Men of Color Health Awareness (MOCHA) is a community-driven movement to address the physical, mental, social, and spiritual needs of men of color. As part of ongoing programming, the MOCHA Standard intervention consists of a 10-week program including: (1) small group discussions of issues particularly relevant to men of color, (2) classes on health topics focusing on chronic disease control, such as nutrition, obesity, high blood pressure, fitness, and the social determinants of health; and (3) 60-min of moderately intensive aerobic exercise twice a week. While the MOCHA Standard intervention has yielded positive results, feedback from previous participants warranted an in-depth sociocultural tailoring of the curriculum to improve community receptiveness, in particular, revising the sessions to "narrativize" the materials to strengthen their potential effectiveness. This manuscript describes the novel recruitment strategies; the development of an enhanced MOCHA+ Stories Matter program that uses narrative communication strategies; and the methodology used to assess the comparative effectiveness of the MOCHA Standard relative to MOCHA+ Stories Matter program in lowering stress and risk of chronic diseases in a randomized controlled trial. The results of this research will contribute to the identification of effective interventions to address health disparities in low-income African-American men and the dissemination of effective chronic disease prevention programming.

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1 Citations


Open accessJournal ArticleDOI: 10.1016/J.YNSTR.2021.100408
Jing Zhang1, Alfred P. Kaye2, Jiawei Wang2, Matthew J. Girgenti2  +1 moreInstitutions (3)
Abstract: Stress is the response of an organism to demands for change, yet excessive or chronic stress contributes to nearly all psychiatric disorders. The advent of high-throughput transcriptomic methods such as single cell RNA sequencing poses new opportunities to understand the neurobiology of stress, yet substantial barriers to understanding stress remain. Stress adaptation is an organismal survival mechanism conserved across all organisms, yet there is an infinity of potential stressful experiences. Unraveling shared and separate transcriptional programs for adapting to stressful experience remains a challenge, despite methodological and analytic advances. Here we review the state of the field focusing on the technologies used to study the transcriptome for the stress neurobiologist, and also attempt to identify central questions about the heterogeneity of stress for those applying transcriptomic approaches. We further explore how postmortem transcriptome studies aided by preclinical animal models are converging on common molecular pathways for adaptation to aversive experience. Finally, we discuss approaches to integrate large genomic datasets with human neuroimaging and other datasets.

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65 results found


Journal ArticleDOI: 10.1038/NRN2639
Abstract: Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.

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Topics: Cognition (50%)

4,146 Citations


Open accessJournal ArticleDOI: 10.1016/S0893-133X(00)00159-7
Florian Holsboer1Institutions (1)
Abstract: Signs and symptoms that are characteristic for depression include changes in the setpoint of the hypothalamic-pituitary-adrenocortical (HPA) system, which in the majority of these patients result in altered regulation of corticotropin (ACTH) and cortisol secretory activity. More refined analysis of the HPA system revealed that corticosteroid receptor (CR) signaling is impaired in major depression, resulting among other changes, in increased production and secretion of corticotropin-releasing hormone (CRH, also frequently abbreviated CRF) in various brain regions postulated to be involved in the causality of depression. This article summarizes the clinical and preclinical data, supporting the concept that impaired CR signaling is a key mechanism in the pathogenesis of depression. Mouse genetics, allowing for selective inactivation of genes relevant for HPA regulation and molecular pharmacology, dissecting the intracellular cascade of CR signaling, are the most promising future research fields, suited for identifying genes predisposing to depression. Focusing on these two research lines may also allow to gain insight into understanding how current antidepressants work and further, how more specific targets for future antidepressant drugs can be identified.

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Topics: FKBP5 (51%)

1,985 Citations


Open accessJournal ArticleDOI: 10.1007/S12160-010-9210-8
Louise C. Hawkley1, John T. Cacioppo1Institutions (1)
Abstract: As a social species, humans rely on a safe, secure social surround to survive and thrive. Perceptions of social isolation, or loneliness, increase vigilance for threat and heighten feelings of vulnerability while also raising the desire to reconnect. Implicit hypervigilance for social threat alters psychological processes that influence physiological functioning, diminish sleep quality, and increase morbidity and mortality. The purpose of this paper is to review the features and consequences of loneliness within a comprehensive theoretical framework that informs interventions to reduce loneliness. We review physical and mental health consequences of loneliness, mechanisms for its effects, and effectiveness of extant interventions. Features of a loneliness regulatory loop are employed to explain cognitive, behavioral, and physiological consequences of loneliness and to discuss interventions to reduce loneliness. Loneliness is not simply being alone. Interventions to reduce loneliness and its health consequences may need to take into account its attentional, confirmatory, and memorial biases as well as its social and behavioral effects.

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Topics: Loneliness (72%), Social isolation (56%), Health psychology (50%)

1,737 Citations


Open access
01 Jan 2009-
Abstract: Sonia J. Lupien*, Bruce S. McEwen ‡ , Megan R. Gunnar § and Christine Heim || Abstract | Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.

... read more

1,243 Citations


Open accessJournal ArticleDOI: 10.1038/509282A
15 May 2014-Nature
Abstract: Janine A. Clayton and Francis S. Collins unveil policies to ensure that preclinical research funded by the US National Institutes of Health considers females and males.

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1,130 Citations


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