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Rodent tests of depression and anxiety: Construct validity and translational relevance
Behavioral testing constitutes the primary method to measure the emotional states of nonhuman animals in preclinical research. Emerging as the characteristic tool of the behaviorist school of psychology, behavioral testing of animals, particularly rodents, is employed to understand the complex cognitive and affective symptoms of neuropsychiatric disorders. Following the symptom-based diagnosis model of the DSM, rodent models and tests of depression and anxiety focus on behavioral patterns that resemble the superficial symptoms of these disorders. While these practices provided researchers with a platform to screen novel antidepressant and anxiolytic drug candidates, their construct validity—involving relevant underlying mechanisms—has been questioned. In this review, we present the laboratory procedures used to assess depressive- and anxiety-like behaviors in rats and mice. These include constructs that rely on stress-triggered responses, such as behavioral despair, and those that emerge with nonaversive training, such as cognitive bias. We describe the specific behavioral tests that are used to assess these constructs and discuss the criticisms on their theoretical background. We review specific concerns about the construct validity and translational relevance of individual behavioral tests, outline the limitations of the traditional, symptom-based interpretation, and introduce novel, ethologically relevant frameworks that emphasize simple behavioral patterns. Finally, we explore behavioral monitoring and morphological analysis methods that can be integrated into behavioral testing and discuss how they can enhance the construct validity of these tests.
Journal Article
Global Burden of Disease and the Impact of Mental and Addictive Disorders
Purpose of Review
This contribution reviews the newest empirical evidence regarding the burden of mental and addictive disorders and weighs their importance for global health in the first decades of the twenty-first century.
Recent Findings
Mental and addictive disorders affected more than 1 billion people globally in 2016. They caused 7% of all global burden of disease as measured in DALYs and 19% of all years lived with disability. Depression was associated with most DALYs for both sexes, with higher rates in women as all other internalizing disorders, whereas other disorders such as substance use disorders had higher rates in men.
Summary
Mental and addictive disorders affect a significant portion of the global population with high burden, in particular in high- and upper-middle-income countries. The relative share of these disorders has increased in the past decades, in part due to stigma and lack of treatment. Future research needs to better analyze the role of mental and addictive disorders in shifts of life expectancy.
Journal Article
Aging Populations, Mortality, and Life Expectancy
Life expectancy has long been seen as an indicator of the quality of life as well as the health of a population. Recent trends in US life expectancy show growing inequality in life expectancy for some socioeconomic and geographic groupings but diminishing inequality by race and gender. For example, while African Americans had gains in life expectancy, non-Hispanic white women with low levels of education experienced drops. Overall, the United States continues to fall behind other countries in terms of life expectancy. One reason is our growing mortality in midlife from so-called deaths of despair. Public health programs cannot eliminate these adverse trends if they are not also accompanied by social policies supporting economic opportunity for US families.
Journal Article
The sorrows of young Werther and selected writings
One of the world's first best-sellers, this tragic masterpiece attained an instant and lasting success upon its 1774 publication. A sensitive exploration of the mind of a young artist.
Book
Chronic mild stress paradigm as a rat model of depression: facts, artifacts, and future perspectives
RationaleThe chronic mild stress (CMS) paradigm was first described almost 40 years ago and has become a widely used model in the search for antidepressant drugs for major depression disorder (MDD). It has resulted in the publication of almost 1700 studies in rats alone. Under the original CMS procedure, the expression of an anhedonic response, a key symptom of depression, was seen as an essential feature of both the model and a depressive state. The prolonged exposure of rodents to unpredictable/uncontrollable mild stressors leads to a reduction in the intake of palatable liquids, behavioral despair, locomotor inhibition, anxiety-like changes, and vegetative (somatic) abnormalities. Many of the CMS studies do not report these patterns of behaviors, and they often fail to include consistent molecular, neuroanatomical, and physiological phenotypes of CMS-exposed animals.ObjectivesTo critically review the CMS studies in rats so that conceptual and methodological flaws can be avoided in future studies.ResultsAnalysis of the literature supports the validity of the CMS model and its impact on the field. However, further improvements could be achieved by (i) the stratification of animals into ‘resilient’ and ‘susceptible’ cohorts within the CMS animals, (ii) the use of more refined protocols in the sucrose test to mitigate physiological and physical artifacts, and (iii) the systematic evaluation of the non-specific effects of CMS and implementation of appropriate adjustments within the behavioral tests.ConclusionsWe propose methodological revisions and the use of more advanced behavioral tests to refine the rat CMS paradigm, which offers a valuable tool for developing new antidepressant medications.
Journal Article
Declining mental health among disadvantaged Americans
Although there is little dispute about the impact of the US opioid epidemic on recent mortality, there is less consensus about whether trends reflect increasing despair among American adults. The issue is complicated by the absence of established scales or definitions of despair as well as a paucity of studies examining changes in psychological health, especially well-being, since the 1990s. We contribute evidence using two cross-sectional waves of the Midlife in the United States (MIDUS) study to assess changes in measures of psychological distress and well-being. These measures capture negative emotions such as sadness, hopelessness, and worthlessness, and positive emotions such as happiness, fulfillment, and life satisfaction. Most of the measures reveal increasing distress and decreasing well-being across the age span for those of low relative socioeconomic position, in contrast to little decline or modest improvement for persons of high relative position.
Journal Article