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.
Perinatal hypoxia-ischemia (HI) is a leading cause of morbidity and mortality among newborns. Infants with HI encephalopathy may experience lasting consequences, such as depression, in adulthood. In ...this study, we examined depressive-like behavior, neuronal population, and markers of monoaminergic and synaptic plasticity in the prefrontal cortex (PFC) of adolescent rats subjected to a prenatal HI model. Pregnant rats underwent a surgery in which uterine and ovarian blood flow was blocked for 45 min at E18 (HI procedure). Sham-operated subjects were also generated (SH procedure). Behavioral tests were conducted on male and female pups from P41 to P43, and animals were histologically processed or dissected for western blotting at P45. We found that the HI groups consumed less sucrose in the sucrose preference test and remained immobile for longer periods in the forced swim test. Additionally, we observed a significant reduction in neuronal density and PSD95 levels in the HI group, as well as a smaller number of synaptophysin-positive cells. Our results underscore the importance of this model in investigating the effects of HI-induced injuries, as it reproduces an increase in depressive-like behavior and suggests that the HI insult affects circuits involved in mood modulation.
•Prenatal hypoxia-ischemia increased depressive-like behavior in young rats.•A reduced number of neurons in the PFC was a result of prenatal hypoxia-ischemia.•This model of prenatal hypoxia-ischemia may affect synaptic activity in rats.
The adipocyte-derived hormone adiponectin has a broad spectrum of functions beyond metabolic control. We previously reported that adiponectin acts in the brain to regulate depression-related ...behaviors. However, its underlying neural substrates have not been identified. Here we show that adiponectin receptor 1 (AdipoR1) is expressed in the dorsal raphe nucleus (DRN) and colocalized with tryptophan hydroxylase 2 (TPH2), a marker of serotonin (5-HT) neurons. Selective deletion of AdipoR1 in 5-HT neurons induced anhedonia in male mice, as indicated by reduced female urine sniffing time and saccharin preference, and behavioral despair in female mice and enhanced stress-induced decrease in sucrose preference in both sexes. The expression levels of TPH2 were downregulated with a concurrent reduction of 5-HT-immunoreactivity in the DRN and its two major projection regions, the hippocampus and medial prefrontal cortex (mPFC), in male but not female mice lacking AdipoR1 in 5-HT neurons. In addition, serotonin transporter (SERT) expression was upregulated in both DRN projection fields of male mice but only in the mPFC of female mice. These changes presumably lead to decreased 5-HT synthesis and/or increased 5-HT reuptake, thereby reducing 5-HT transmission. The augmented behavioral responses to the selective serotonin reuptake inhibitor fluoxetine but not desipramine, a selective norepinephrine reuptake inhibitor, observed in conditional knockout male mice supports deficient 5-HT transmission underlying depression-related phenotypes. Our results indicate that adiponectin acts on 5-HT neurons through AdipoR1 receptors to regulate depression-related behaviors in a sex-dependent manner.
The effects of activation of N-methyl-D-aspartate (D-cycloserine) and dopamine D sub(1) (SKF 38393) receptors on the acquisition and extinction of a conditioned passive avoidance reflex were studied ...in normal mice and after formation of "behavioral despair." The data demonstrated that D-cycloserine and SKF 38393 had no effect on acquisition of the conditioned reflex. In normal mice, SKF 38393 had no effect on the dynamics of extinction, while D-cycloserine promoted faster decreases in the level of reproduction of the memory trace on testing without punishment. On simultaneous administration of the two agents, the dynamics of extinction were similar to those seen with D-cycloserine alone. In mice with the "behavioral despair" reaction, D-cycloserine and SKF 38393 reduced the deficit of extinction of the conditioned passive avoidance reflex typical of "depressive" individuals not given agents. Simultaneous activation of NMDA and D sub(1) receptors led to acceleration of the onset of extinction and the development of complete extinction of the memory trace relating to the pain factor as compared with animals given either D-cycloserine or SKF 38393 separately.
Sirtuin 1 (SIRT1), an NAD
-dependent deacetylase, is a key regulator of cellular metabolism. Recent genome-wide association studies identified genetic variants of SIRT1 linked to major depressive ...disorders. SIRT1 is widely expressed in the brain; however, neuronal substrates that mediate SIRT1 action on depressive behaviors remain largely unknown. Here we show that selective deletion of SIRT1 in forebrain excitatory neurons causes depression-like phenotypes in male but not female mice. AAV-Cre-mediated SIRT1 knockdown in the medial prefrontal cortex (mPFC) of adult male mice induces depressive-like behaviors. Whole-cell patch-clamp recordings demonstrate that loss of SIRT1 decreases intrinsic excitability and spontaneous excitatory synaptic transmission in layer V pyramidal neurons in the prelimbic mPFC. Consistent with neuronal hypoexcitability, SIRT1 knockout reduces mitochondrial density and expression levels of genes involved in mitochondrial biogenesis and dynamics in the prelimbic mPFC. When a SIRT1 activator (SRT2104) is injected into the mPFC or lateral ventricle of wild-type mice, it reverses chronic unpredictable stress-induced anhedonia and behavioral despair, indicating an antidepressant-like effect. These results suggest that SIRT1 in mPFC excitatory neurons is required for normal neuronal excitability and synaptic transmission and regulates depression-related behaviors in a sex-specific manner.
The article considers McCarthy’s novel No Country for Old Men from the perspective of the existentialist motif of despair in the characters’ network. Being philosophical in nature, the book raises ...existential questions of the value of human life and the purpose of human existence. The subject of the study is the existentialist motif of despair. The problem is the peculiarities of representation of this existentialist motif in modern literature. The aim of the study is to explore the literary representation of the existentialist motif of despair in No Country for Old Men. The applied methods include close reading, which serves for the identification of the motif of despair in the novel, and character analysis, which helps examine the main characters’ experiences of despair and reveal their psychological and emotional responses to the existential challenges they face. The novelty of the study lies in offering a fresh perspective on the analysis of the novel in the context of existentialist motifs, especially the motif of despair.
The results of the study show that in No Country for Old Men the existentialist motif of despair arises from the awareness of the inherent meaninglessness and absurdity of existence. The main characters constantly experience despair because the society they live in is devoid of meaning and is ruled by cruelty, which reveals profound changes of modern civilization. The protagonists belong to diverse generations and differ in their positions and ways of thinking, but they share a common experience of descending into the depths of despair at some point of their lives. The despair that they feel is caused by the changes that society undergoes. These transformations, also on the global scale, provoke alteration in the ethical norms engendering a pervasive sense of dissonance and moral ambiguity. The characters seem to assume that violence becomes necessary for survival, since justice proves its insufficiency, money and drugs take a leading place and substitute religion, and the value of human life deteriorates. The world seems absurd and devoid of meaning; however, the protagonists desperately try to find their path through the darkness and struggle to uncover meaning and authenticity in a seemingly indifferent and chaotic world.
In times of a prevailing sense of crisis and disorder in modern politics, there is a growing sentiment that anger, despair or resignation are more appropriate attitudes to navigate the world than ...hope. Political philosophers have long shared this suspicion and shied away from theorising hope more systematically. The aim of this article is to resist this tendency by showing that hope constitutes an integral part of democratic politics in particular. In making this argument I draw on Kant’s conceptualisation of hope as a psychological condition on action under circumstances where the chances of making a difference are dim. Given that the Kantian agent avoids the threat of despair in the pursuit of political goals by placing trust in her fellow citizens, hope has the potential to positively transform democratic practices.
Recent research has suggested that increases in mortality among middle-aged US Whites are being driven by suicides and poisonings from alcohol and drug use. Increases in these 'despair' deaths have ...been argued to reflect a cohort-based epidemic of pain and distress among middle-aged US Whites.
We examine trends in all-cause and cause-specific mortality rates among younger and middle-aged US White men and women between 1980 and 2014, using official US mortality data. We estimate trends in cause-specific mortality from suicides, alcohol-related deaths, drug-related deaths, 'metabolic diseases' (i.e. deaths from heart diseases, diabetes, obesity and/or hypertension), and residual deaths from extrinsic causes (i.e. causes external to the body). We examine variation in mortality trends by gender, age and cause of death, and decompose trends into period- and cohort-based variation.
Trends in middle-aged US White mortality vary considerably by cause and gender. The relative contribution to overall mortality rates from drug-related deaths has increased dramatically since the early 1990s, but the contributions from suicide and alcohol-related deaths have remained stable. Rising mortality from drug-related deaths exhibit strong period-based patterns. Declines in deaths from metabolic diseases have slowed for middle-aged White men and have stalled for middle-aged White women, and exhibit strong cohort-based patterns.
We find little empirical support for the pain- and distress-based explanations for rising mortality in the US White population. Instead, recent mortality increases among younger and middle-aged US White men and women have likely been shaped by the US opiate epidemic and an expanding obesogenic environment.
For organizational leaders, implementing change in a workplace means influencing employees to do something new or behave differently. For employees, implementing a change at work requires detaching ...from familiar routines and social systems, learning and practicing the change, and imagining a future in which the change is valued by the organization. As they apply their agency to implement change, employees may experience loss, uncertainty, and frustration that manifests as despair, which can jeopardize the change process and its outcomes. We assemble a meta-theoretical framework using human agency theory, the Valley of Despair model of organizational change, and Full-Range Leadership Theory to explore ways that leaders' behaviors relate to employees' agentic orientations and behaviors during the implementation phase of the organizational change process. Taking both organizational change leaders' and employees' perspectives into account, the theory derived from our meta-framework argues that leaders' behaviors can shape employees' agency and their behaviors during the implementation stage of change in two important ways: 1) certain leader behaviors are likely to prime agentic orientations that facilitate changing, and 2) certain leader behaviors may help to mitigate employees' despair, enabling the firm to derive value from employees' change implementation behaviors.
•Human agency includes habitual iteration oriented toward the past, practical evaluation in the present, and imaginative future projection.•A leader's behaviors differentially relate to employees' dominant agentic orientation in the chordal triad of human agency.•When implementing change, employees may experience despair that reflects loss, frustration, uncertainty, and disruptions to social systems.•Despair may moderate the relationship between employees' implementation behaviors and the value to be derived from the change.•Transactional and transformational leadership behaviors can mitigate the depth and duration of employees' implementation despair.
Traumatic experience changes health, relation patterns and conflict reactions. Threatening events can cause desperation and can profoundly damage personality structure capacities and bonding ...qualities like trust. A structured process of treatment back to confidence and a balanced everyday life starting with stabilization phases, leading to integration is described.
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