Economic insecurity has grown in the United States since the 1970s impacting all segments of the working-class, including previously insulated sub-groups such as non-Hispanic whites. Moreover, the ...white working-class has experienced a surge in socio-cultural isolation, and disengagement with societal institutions. This analysis focuses on the health consequences of these developments, with a particular emphasis on the rising “deaths of despair” (suicide, drug poisoning, alcohol related). These deaths have been increasing since the mid-1990s and, at least until recently, tended to be clustered amongst whites without a four-year college degree. Various competing explanations have been put forth, emphasizing distinct factors such as material conditions, socio-cultural dynamics, and accessibility to opioids. Using a series of linear models this analysis examines the county-level association between economic precarity, white working-class population size, opioid accessibility, and deaths of despair. Results affirm the net effect of each predictor and illuminate an interactive relationship between opioid accessibility and precarity, as well as an interactive relationship between all three predictors. By undertaking an interdisciplinary synthesis of existing research, this study contributes to the understanding of the social determinants of mortality while providing crucial insights into an ongoing crisis in contemporary America.
•Examines increased Deaths of Despair with a focus on the white working-class.•Uses county-level data alongside linear and interactive modeling.•Economic context, socio-cultural context, and opioid accessibility shape death rates.
Depression is a widespread and severely debilitating neuropsychiatric disorder whose key clinical symptoms include low mood, anhedonia and despair (the inability or unwillingness to overcome ...stressors). Experimental animal models are widely used to improve our mechanistic understanding of depression pathogenesis, and to develop novel antidepressant therapies. In rodents, various experimental models of ‘behavioral despair’ have already been developed and rigorously validated. Complementing rodent studies, the zebrafish (Danio rerio) is emerging as a powerful model organism to assess pathobiological mechanisms of depression and other related affective disorders. Here, we critically discuss the developing potential and important translational implications of zebrafish models for studying despair and its mechanisms, and the utility of such aquatic models for antidepressant drug screening.
Abstract
Since the turn of the 21st century, during which White mortality has been rising, there has been a sharp increase in only 3 causes of death: drug use, alcohol use, and suicide. Because all 3 ...of these causes conjure notions of anguish and hopelessness, they have been conceptualized as a collective “deaths of despair” phenomenon. Simon and Masters (Am J Epidemiol. 2021;190(6)1169-1171) challenge this conceptualization by asking whether these 3 causes are empirically associated with each other. Their analyses produce small correlations, which lead them to call into question that the 3 causes are part of a unified phenomenon. We contest their work on several grounds. Their analyses suffer from several technical problems, including the fact that, for any given year and cause of death, 65.8%–97.6% of counties examined have death counts under 10. More fundamentally, it is unclear that we should expect these causes of death to rise and fall together, even if they are connected to a singular phenomenon. Instead, “despair” might manifest differently in different places (i.e., these causes might be substitutes for each other). We argue that the best answer to the authors’ important question comes from assessing whether there is a common, despair-based causal mechanism underlying all 3 of them.
Do minimum wages and the earned income tax credit (EITC) mitigate rising “deaths of despair?” We leverage state variation in these policies over time to estimate event study and ...difference-in-differences models of deaths due to drug overdose, suicide, and alcohol-related causes. Our causal models find no significant effects on drug or alcohol-related mortality, but do find significant reductions in non-drug suicides. A 10 percent minimum wage increase reduces non-drug suicides among low-educated adults by 2.7 percent, and the comparable EITC figure is 3.0 percent. Placebo tests and event-study models support our causal research design. Increasing both policies by 10 percent would likely prevent a combined total of more than 700 suicides each year.
“Deaths of despair” – deaths caused by suicide, drug use, and alcohol use – have increased among non-Hispanic whites who do not have a college degree. We analyze confidential-use data from the ...National Center for Health Statistics that contains death certificates from 2005 to 2017 (total of 21,177,490 records) linked with measures of local labor market activity. We show that deaths of despair are proportionally larger among Native Americans than non-Hispanic white Americans and that economic conditions have a different relationship with deaths of despair among Native Americans than for non-Hispanic white Americans. Improvements in economic conditions are associated with decreased deaths from drug use, alcohol use, and suicide for non-Hispanic white Americans. On the other hand, in counties with higher labor force participation rates, lower unemployment, and higher ratios of employees to residents, there are significantly higher proportions of Native American deaths attributed to alcohol and drug use.
Chronic stress induces neuronal atrophy and synaptic loss in the medial prefrontal cortex (PFC), and this leads to behavioral and cognitive impairments. Our recent findings indicate that microglia ...contribute to structural remodeling of neurons via increased colony-stimulating factor (CSF)-1 in the medial PFC. Other work shows that chronic stress induces aberrant neuronal activity in the medial PFC, and that neuronal hyperactivity increases CSF1 signaling and alters microglia function. Thus, the present studies were designed to examine the role of neuronal activity in stress-induced CSF1 signaling and microglia-mediated neuronal remodeling in the medial PFC. Additional analyses probed stress effects on the dorsal hippocampus (HPC), basolateral amygdala (BLA), and somatosensory cortex (SSCTX). Mice were exposed to chronic unpredictable stress (CUS) or handled intermittently as controls, and received daily injection of vehicle or diazepam (1 mg/kg). As anticipated, diazepam attenuated CUS-induced behavioral despair and cognitive impairments. Further studies showed that diazepam normalized Csf1 and C3 mRNA in the PFC, and prevented increases in Csf1r and Cd11b in frontal cortex microglia following CUS. Stress had no effect on neuroimmune gene expression in the HPC. Confocal imaging in Thy1-GFP(M) mice demonstrated that diazepam limited microglial engulfment of neuronal elements and blocked CUS-induced dendritic spine loss in the medial PFC. Altogether, these findings indicate that modulation of chronic stress-induced neuronal activity limits microglia-mediated neuronal remodeling in the medial PFC, and subsequent behavioral and cognitive consequences.
Life and meaning Hinchman, Edward
Philosophical explorations,
09/01/2024, 2024-09-00, 20240901, Letnik:
27, Številka:
3
Journal Article
Recenzirano
What sense could it make to describe your life as 'unlivable'? What is it not only to be alive but to have a life that you live or lead? I answer by developing a social understanding of how we pursue ...meaning in life. True to other uses of 'meaning,' I propose, meaning in a life is communicative. If you experience your life as 'unlivable,' recovery can lie in this communicative dynamic: you regain the experience of leading your life by letting others remind you of meanings you've communicated to them in leading it. My argument works from a parallel between two dimensions in which you project an investment - a care, concern, love, or the like - when you form an intention or plan. Intrapersonally, you project your investment as communicatively intelligible to your own future self at 'plan's end.' Interpersonally, you project it as communicatively intelligible to others who might come to love this thing that you love simply because you love it, as an expression of love for you. The normativity of meaning in your life puts rational pressure on you not only to abandon investments that you cannot communicate but to experience the meaning in investments that you retain.
•Personality development in a sample of college-educated women over almost 30 years.•Generativity, stagnation, ego integrity, and despair best measured separately.•Newly-developed Q-sort scales show ...good internal reliability.•Trajectories for generativity and ego integrity showed linear increases, ages 43–72.•Trajectories for stagnation and despair showed curvilinear patterns, ages 43–72.
Previous scholarship examining Erikson’s (1980) constructs of generativity versus stagnation, and ego integrity versus despair has primarily focused on generativity or ego integrity, with little examination of stagnation or despair. The current study uses four waves of longitudinal data from a total of 166 women, ages 43–72, to assess whether these characteristics are best measured via four separate or two bipolar dimensions, and to examine developmental trajectories in resulting scales. We hypothesized developmental trajectory increases for generativity and ego integrity, and declines for stagnation and despair. Results indicated that generativity and ego integrity showed linear increases with no significant decline; however, stagnation and despair showed curvilinear patterns. Findings highlight the importance of examining these constructs independently and longitudinally.
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•Zebrafish may have despair-like behavior, similarly to rodents.•Zebrafish despair-like behavior can be assessed using the Zebrafish Tail Immobilization test (ZTI).•Zebrafish ...subjected to stress prior to the ZTI test exposure increase despair-like behavior.•Exposure to antidepressant, but not anxiolytic, agents reduces the ZTI test despair-like behavior.•ZTI performance may be associated with altered serotonin and dopamine brain metabolism.
Affective disorders, especially depression and anxiety, are highly prevalent, debilitating mental illnesses. Animal experimental models are a valuable tool in translational affective neuroscience research. A hallmark phenotype of clinical and experimental depression, the learned helplessness, has become a key target for 'behavioral despair'-based animal models of depression. The zebrafish (Danio rerio) has recently emerged as a promising novel organism for affective disease modeling and CNS drug screening. Despite being widely used to assess stress and anxiety-like behaviors, there are presently no clear-cut despair-like models in zebrafish.
Here, we introduce a novel behavioral paradigm, the zebrafish tail immobilization (ZTI) test, as a potential tool to assess zebrafish despair-like behavior. Conceptually similar to rodent 'despair' models, the ZTI protocol involves immobilizing the caudal half of the fish body for 5 min, leaving the cranial part to move freely, suspended vertically in a small beaker with water.
To validate this model, we used exposure to low-voltage electric shock, alarm pheromone, selected antidepressants (sertraline and amitriptyline) and an anxiolytic drug benzodiazepine (phenazepam), assessing the number of mobility episodes, time spent 'moving', total distance moved and other activity measures of the cranial part of the body, using video-tracking. Both electric shock and alarm pheromone decreased zebrafish activity in this test, antidepressants increased it, and phenazepam was inactive. Furthermore, a 5-min ZTI exposure increased serotonin turnover, elevating the 5-hydroxyindoleacetic acid/serotonin ratio in zebrafish brain, while electric shock prior to ZTI elevated both this and the 3,4-dihydroxyphenylacetic acid/dopamine ratios. In contrast, preexposure to antidepressants sertraline and amitriptyline lowered both ratios, compared to the ZTI test-exposed fish.
The ZTI test is the first despair-like experimental model in zebrafish.
Collectively, this study suggests the ZTI test as a potentially useful protocol to assess stress-/despair-related behaviors, potentially relevant to CNS drug screening and behavioral phenotyping of zebrafish.
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