The World of Women's Despair: An Unfolding Unitary Conceptual Journey.

In looking back over 3 decades since the development of his interest in developing a unitary conceptualization of despair, nurse scholar W. Richard Cowling, III, had new insights and revelations. The purpose of this dialogue article is to re-envision this journey as one of unfolding, seen with the gift of new eyes. Revisiting this journey allowed him to understand and appreciate it anew. Horizons of possibilities of this conceptual journey are explained in terms of conceptual-theoretical development, inquiry, and the advancement of discipline-specific knowledge, and improving the lives of women in despair. It is his sincere hope, as with all meaningful scholarly endeavors, that a wider discourse occurs with the persistent inclusion of women's voices and experiences.

Environmental enrichment enhances the antidepressant effect of ketamine and ameliorates spatial memory deficits in adult rats.

Ketamine is a rapid-acting antidepressant associated with various cognitive side effects. To mitigate these side effects while enhancing efficacy, it can be co-administered with other antidepressants. In our study, we adopted a similar strategy by combining ketamine with environmental enrichment, a potent sensory-motor paradigm, in adult male Wistar rats. We divided the animals into four groups based on a combination of housing conditions and ketamine versus vehicle injections. The groups included those housed in standard cages or an enriched environment for 50 days, which encompassed a 13-day-long behavioral testing period. Each group received either two doses of ketamine (20 mg/kg, IP) or saline as a vehicle. We tested the animals in the novel object recognition test (NORT), forced swim test (FST), open field test (OFT), elevated plus maze (EPM), and Morris water maze (MWM), which was followed by ex vivo c-Fos immunohistochemistry. We observed that combining environmental enrichment with ketamine led to a synergistic antidepressant effect. Environmental enrichment also ameliorated the spatial memory deficits caused by ketamine in the MWM. There was enhanced neuronal activity in the habenula of the enrichment only group following the probe trial of the MWM. In contrast, no differential activity was observed in enriched animals that received ketamine injections. The present study showed how environmental enrichment can enhance the antidepressant properties of ketamine while reducing some of its side effects, highlighting the potential of combining pharmacological and sensory-motor manipulations in the treatment of mood disorders.

Midlife diseases of despair and cardiometabolic risk: testing shared origins in adolescent psychopathology.

BACKGROUND: Rising midlife mortality in the United States is largely attributable to 'deaths of despair' (deaths from suicide, drug poisonings, and alcohol-related diseases) and deaths from cardiometabolic conditions. Although despair- and cardiometabolic-related mortality are increasing concurrently, it is unclear whether they share common developmental origins. We tested adolescent psychopathology as a potential common origin of midlife diseases of despair and cardiometabolic risk. METHODS: Participants (N = 4578) were from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative cohort followed from adolescence to early midlife. Adolescent psychopathology included depression, anxiety, eating disorders, PTSD, conduct disorder, and ADHD at ages 11-18. Diseases of despair (suicidality, substance misuse, pain, and sleep problems) and cardiometabolic risk (hypertension, hyperlipidemia, high-risk waist circumference, diabetes, and cardiovascular conditions) were multi-modally measured at ages 33-43. RESULTS: At midlife, adolescents who experienced psychopathology exhibited more indicators of despair-related diseases and cardiometabolic risk (IRRs = 1.67 [1.46-1.87] and 1.13 [1.04-1.21], respectively), even after accounting for demographics, adolescent SES, and adolescent cognitive ability. Associations were evident for internalizing and externalizing conditions, and in a dose-response fashion. In mediation analyses, low education explained little of these associations, but early-adult substance use explained 21.5% of psychopathology's association with despair-related diseases. Midlife despair-related diseases and cardiometabolic risk co-occurred within individuals (IRR = 1.12 [1.08-1.16]). Adolescent psychopathology accounted for 8.3% of this co-occurrence, and 16.7% together with adolescent SES and cognitive ability. CONCLUSIONS: Adolescent psychopathology precedes both diseases of despair and cardiometabolic risk. Prevention and treatment of psychopathology may mitigate multiple causes of poor midlife health, reducing premature mortality.

Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors.

Depression is a prevalent psychological condition with limited treatment options. While its etiology is multifactorial, both chronic stress and changes in microbiome composition are associated with disease pathology. Stress is known to induce microbiome dysbiosis, defined here as a change in microbial composition associated with a pathological condition. This state of dysbiosis is known to feedback on depressive symptoms. While studies have demonstrated that targeted restoration of the microbiome can alleviate depressive-like symptoms in mice, translating these findings to human patients has proven challenging due to the complexity of the human microbiome. As such, there is an urgent need to identify factors upstream of microbial dysbiosis. Here we investigate the role of mucin 13 as an upstream mediator of microbiome composition changes in the context of stress. Using a model of chronic stress, we show that the glycocalyx protein, mucin 13, is selectively reduced after psychological stress exposure. We further demonstrate that the reduction of Muc13 is mediated by the Hnf4 transcription factor family. Finally, we determine that deleting Muc13 is sufficient to drive microbiome shifts and despair behaviors. These findings shed light on the mechanisms behind stress-induced microbial changes and reveal a novel regulator of mucin 13 expression.

The role of mGluR5 on the therapeutic effects of ketamine in Wistar rats.

RATIONALE: Ketamine produces dissociative, psychomimetic, anxiolytic, antidepressant, and anesthetic effects in a dose dependent manner. It has a complex mechanism of action that involve alterations in other glutamate receptors. The metabotropic glutamate receptor 5 (mGluR5) has been investigated in relation to the psychotic and anesthetic properties of ketamine, while its role in mediating the therapeutic effects of ketamine remains unknown. OBJECTIVES: We investigated the role of mGluR5 on the antidepressant, anxiolytic and fear memory-related effects of ketamine in adult male Wistar rats. METHODS: Two sets of experiments were conducted. We first utilized the positive allosteric modulator CDPPB to investigate how acute mGluR5 activation regulates the therapeutic effects of ketamine (10 mg/kg). We then tested the synergistic antidepressant effect of mGluR5 antagonism and ketamine by combining MTEP with a sub-effective dose of ketamine (1 mg/kg). Behavioral despair, locomotor activity, anxiety-like behavior, and fear memory were respectively assessed in the forced swim test (FST), open field test (OFT), elevated plus maze (EPM), and auditory fear conditioning. RESULTS: Enhancing mGluR5 activity via CDPPB occluded the antidepressant effect of ketamine without changing locomotor activity. Furthermore, concomitant administration of MTEP and ketamine exhibited a robust synergistic antidepressant effect. The MTEP + ketamine treatment, however, blocked the anxiolytic effect observed by sole administration of MTEP or the low dose ketamine. CONCLUSIONS: These findings suggest that suppressed mGluR5 activity is required for the antidepressant effects of ketamine. Consequently, the antagonism of mGluR5 enhances the antidepressant effectiveness of low dose ketamine, but eliminates its anxiolytic effects.

"Deaths of despair" over the business cycle: New estimates from a shift-share instrumental variables approach.

This study presents new evidence of the effects of short-term economic fluctuations on suicide, fatal drug overdose, and alcohol-related mortality among working-age adults in the United States from 2003-2017. Using a shift-share instrumental variables approach, I find that a one percentage point increase in the aggregate employment rate decreases current-year non-drug suicides by 1.7 percent. These protective effects are concentrated among working-age men and likely reflect a combination of individual labor market experiences as well as the indirect effects of local economic growth. I find no consistent evidence that short-term business cycle changes affect drug or alcohol-related mortality. While the estimated protective effects are small relative to secular increases in suicide in recent decades, these findings are suggestive of important, short-term economic factors affecting specific causes of death and should be considered alongside the longer-term and multifaceted social, economic, and cultural determinants of America's "despair" epidemic.

Reevaluating the "deaths of despair" narrative: Racial/ethnic heterogeneity in the trend of psychological distress-related death.

Despite the significant scientific advancement in deciphering the "deaths of despair" narrative, most relevant studies have focused on drug-, alcohol-, and suicide-related (DAS) deaths. This study directly investigated despair as a determinant of death and the temporal variation and racial heterogeneity among individuals. We used psychological distress (PD) as a proxy for despair and drew data from the US National Health Interview Survey-Linked Mortality Files 1997 to 2014, CDC (Centers for Disease Control and Prevention) Multiple Cause of Death database 1997 to 2014, CDC bridged-race population files 1997 to 2014, Current Population Survey 1997 to 1999, and the American Community Survey 2000 to 2014. We used Cox proportional hazards models to estimate mortality hazard ratios of PD and compared age-standardized PD- and DAS-related mortality rates by race/ethnicity and over time. We found that while Whites had a lower prevalence of PD than Blacks and Hispanics throughout the whole period, they underwent distinctive increases in PD-related death and have had a higher PD-related mortality rate than Blacks and Hispanics since the early 2000s. This was predominantly due to Whites' relatively high and increasing vulnerability to PD less the prevalence of PD. Furthermore, PD induced a more pervasive mortality consequence than DAS combined for Whites and Blacks. In addition, PD- and DAS-related deaths displayed a concordant trend among Whites but divergent patterns for Blacks and Hispanics. These findings suggest that 1) DAS-related deaths underestimated the mortality consequence of despair for Whites and Blacks but overestimated it for Hispanics; and 2) despair partially contributed to the DAS trend among Whites but probably not for Blacks and Hispanics.

Socioeconomic inequalities in deaths of despair: Age heterogeneity in Canada's working age population.

PURPOSE: Although prior literature documented socioeconomic inequalities in deaths of despair among working age population, it is unclear whether and how (a) the link between socioeconomic status and deaths of despair differs by age (b) each measure of socioeconomic status has independent effects on deaths of despair. This study aims to reduce these knowledge gaps. METHODS: Using data from a large scale nationally representative linked dataset (2011 Canadian Census Health and Environment Cohorts), this study employed Fine-Gray subdistribution hazard models to estimate the link between socioeconomic status and deaths of despair due to suicide, drug overdose, and alcoholic liver disease among working age population (N = 4,076,530). Age stratified analysis was conducted to examine age heterogeneity. RESULTS: Socioeconomic status, such as housing tenure, employment status, household income, and education level, was associated with deaths of despair among working age population. Age differences in the association between socioeconomic status and deaths of despair were found. While education level was pronounced for deaths of despair for younger adults, a combination of socioeconomic status was significantly associated with deaths of despair for those in late adulthood. CONCLUSIONS: Socioeconomic inequalities in deaths of despair are manifest among Canadian working age population. This study lends support the social and health policies aimed at reducing gaps in mortalities.

Income inequality and deaths of despair risk in Canada, identifying possible mechanisms.

BACKGROUND: Declines in life expectancy in developed countries have been attributed to increases in drug-related overdose, suicide, and liver cirrhosis, collectively referred to as deaths of despair. Income inequality is proposed to be partly responsible for increases in deaths of despair rates. This study investigated the associations between income inequality, deaths of despair risk in Canada, and potential mechanisms (stress, social cohesion, and access to health services). METHODS: We obtained data from the Canadian Community Health Survey and the Canadian Vital Statistics Database from 2007 to 2017. A total of 504,825 Canadians were included in the analyses. We used multilevel survival analyses, as measured by the Gini coefficient, to examine the relationships between income inequality and mortality attributed to drug overdose, suicide, death of despair, and all-cause. We then used multilevel path analyses to investigate whether each mediator (stress, social cohesion, and access to mental health professionals), which were investigated using separate mediation models, influenced the relationship between income inequality and drug overdose, suicide, deaths of despair, and all-cause death. RESULTS: Adjusted multilevel survival analyses demonstrated significant relationships between a one-SD increase in Gini coefficient was associated with an increased hazard for drug overdose (HRadj. = 1.28; 95 CI = 1.05, 1.55), suicide (HRadj. = 1.24; 95 CI = 1.06, 1.46), deaths of despair (HRadj. = 1.26; 95 CI = 1.12, 1.40), and all-cause death (HRadj. = 1.04; 95 CI = 1.02, 1.07). Adjusted path analyses indicated that stress, social cohesion, and access to mental health professionals significantly mediated the association between income inequality and mortality outcomes. CONCLUSION: Income inequality is associated with deaths of despair and this relationship is mediated by stress, social cohesion, and access to mental health professionals. Findings should be applied to develop programs to address income inequality in Canada.

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.

Socio-economic vulnerability and deaths of despair in Brazilian counties.

Over the past few years, there has been a progressive increase in premature deaths attributable to suicide, drug overdose, and alcohol-related liver disease that impact life expectancy. Regarding the relationship with contextual effects, the evidence is developing, especially in countries with a peripheral economy, as is the case of Brazil. We carried out an analysis aimed at estimating the relationship between socioeconomic insecurity and deaths due to despair in Brazilian cities. We used 5,570 counties' data to create clusters concerning socioeconomic development and then analyzed age-adjusted mortality rates (ASMR) from each of them and compared them using the ANOVA test. Cluster analysis generated two groups of Brazilian municipalities. DoD rates are consistently higher in the group that experiences more deprivation. However, considering differences between 2010 and 2019, the increase in rates was higher in the group with less deprivation experience (48.82 % vs. 39.53 %) We verified an existing gap between the clusters before the beginning of economic stagnation in 2010 The gap between those two groups decreased from 20.58 % (p < 0.001) in 2010 to 14.03 % in 2019 (p = 0.034). The conjuncture of economic crises creates mortality differentials in certain population groups. Also, significant inequalities explain how causes of death from despair affect different subpopulations. Our first approach assessed this assumption, and we could check those differentials at an ecological level. Public policies should focus on reducing the difference in mortality from despair between higher and lower socioeconomic strata.

Risk factors for deaths of despair in England: An ecological study of local authority mortality data.

Deaths of Despair (DoD) are socially patterned fatalities encompassing those attributable to drug and alcohol misuse and suicide. DoD occur much more frequently in socially deprived communities. This ecological study aimed to yield new knowledge on the spatial distribution of DoD, and socioeconomic factors that predict DoD risk in England. Via ICD-10 coding, deaths nationally during 2019-2021 were classified to non-overlapping categories of drug-related death, alcohol-specific death, and suicide. The proportion of DoD from each of these causes was calculated and age standardised DoD rates were generated for local authorities. A multivariable regression model for DoD risk was developed using 25 socioeconomic indicators. In 2019-2021, an estimated 46,200 people lost their lives due to DoD. Rates were higher in the North and in coastal areas (p < 0.001), ranging regionally from 25.1/100,000 (SD 6.3) in London to 54.7/100,000 (SD 9.5) in the North East. Alcohol-specific deaths were the largest contributor of DoD, accounting for 44.1% (95%CI 43.5-44.8%) of all such deaths. Living in the North, unemployment, White British ethnicity, living alone, economic inactivity, employment in elementary occupations, and living in urban areas were significantly associated with elevated DoD risk. DoD in England are spatially patterned, with northern regions experiencing a much higher burden of mortality from these avoidable causes. This study provides novel insights into the area-level factors associated with DoD in England. Potential ecological error is a key limitation.

Brain-heart interaction disruption in major depressive disorder: disturbed rhythm modulation of the cardiac cycle on brain transient theta bursts.

Brain neurons support arousal and cognitive activity in the form of spectral transient bursts and cooperate with the peripheral nervous system to adapt to the surrounding environment. However, the temporal dynamics of brain-heart interactions have not been confirmed, and the mechanism of brain-heart interactions in major depressive disorder (MDD) remains unclear. This study aimed to provide direct evidence for brain-heart synchronization in temporal dynamics and clarify the mechanism of brain-heart interaction disruption in MDD. Eight-minute resting-state (closed eyes) electroencephalograph and electrocardiogram signals were acquired simultaneously. The Jaccard index (JI) was used to measure the temporal synchronization between cortical theta transient bursts and cardiac cycle activity (diastole and systole) in 90 MDD patients and 44 healthy controls (HCs) at rest. The deviation JI was used to reflect the equilibrium of brain activity between diastole and systole. The results showed that the diastole JI was higher than the systole JI in both the HC and MDD groups; compared to HCs, the deviation JI attenuated at F4, F6, FC2, and FC4 in the MDD patients. The eccentric deviation JI was negatively correlated with the despair factor scores of the HAMD, and after 4 weeks of antidepressant treatment, the eccentric deviation JI was positively correlated with the despair factor scores of the HAMD. It was concluded that brain-heart synchronization existed in the theta band in healthy individuals and that disturbed rhythm modulation of the cardiac cycle on brain transient theta bursts at right frontoparietal sites led to brain-heart interaction disruption in MDD.

Suicides, drug poisonings, and alcohol-related deaths cluster with health and social disadvantage in 4.1 million citizens from two nations.

BACKGROUND: Deaths from suicides, drug poisonings, and alcohol-related diseases ('deaths of despair') are well-documented among working-age Americans, and have been hypothesized to be largely specific to the U.S. However, support for this assertion-and associated policies to reduce premature mortality-requires tests concerning these deaths in other industrialized countries, with different institutional contexts. We tested whether the concentration and accumulation of health and social disadvantage forecasts deaths of despair, in New Zealand and Denmark. METHODS: We used nationwide administrative data. Our observation period was 10 years (NZ = July 2006-June 2016, Denmark = January 2007-December 2016). We identified all NZ-born and Danish-born individuals aged 25-64 in the last observation year (NZ = 1 555 902, Denmark = 2 541 758). We ascertained measures of disadvantage (public-hospital stays for physical- and mental-health difficulties, social-welfare benefit-use, and criminal convictions) across the first nine years. We ascertained deaths from suicide, drugs, alcohol, and all other causes in the last year. RESULTS: Deaths of despair clustered within a population segment that disproportionately experienced multiple disadvantages. In both countries, individuals in the top 5% of the population in multiple health- and social-service sectors were at elevated risk for deaths from suicide, drugs, and alcohol, and deaths from other causes. Associations were evident across sex and age. CONCLUSIONS: Deaths of despair are a marker of inequalities in countries beyond the U.S. with robust social-safety nets, nationwide healthcare, and strong pharmaceutical regulations. These deaths cluster within a highly disadvantaged population segment identifiable within health- and social-service systems.

Pro-Environmental Behavior and Climate Change Anxiety, Perception, Hope, and Despair According to Political Orientation.

The main objective of this paper is to assess pro-environmental behavior, climate change anxiety, perception, hope, and despair in different political orientations. Our specific aims included to assess the validity of all the instruments used; to assess whether the factor structure of the scales were valid across political orientations; to evaluate their reliability; to assess differences concerning age, gender, and political orientation; to learn the variables that explain pro-environmental behavior; and to evaluate the moderating role of climate change perception, despair, and hope in the relationship between climate change anxiety and pro-environmental behavior. Confirmatory factor analyses (CFAs), multi-group CFAs (to calculate measurement invariance), multiple linear regressions, and moderations were performed. Results showed that pro-environmental behavior and climate change hope achieved the four assessed levels of invariance across different political orientations; climate change anxiety achieved the first three levels of invariance; and climate change perception and climate change despair achieved configural invariance. Climate change anxiety, personal experience with climate change, and climate change perception (total, reality, and consequences) presented higher values for the left political orientation than for the right or the center. Climate change anxiety variables contributed most to explaining pro-environmental behaviors. Hope, despair, and climate change perception (consequences) moderated the relationship between climate change anxiety and pro-environmental behavior. These results open up new avenues for investigation, specifically to understand why high levels of anxiety lead to more pro-environmental behaviors.

"Just the Facts Ma'am": Moral and Ethical Considerations for Artificial Intelligence in Medicine and its Potential to Impact Patient Autonomy and Hope.

Applying machine-based learning and synthetic cognition, commonly referred to as artificial intelligence (AI), to medicine intimates prescient knowledge. The ability of these algorithms to potentially unlock secrets held within vast data sets makes them invaluable to healthcare. Complex computer algorithms are routinely used to enhance diagnoses in fields like oncology, cardiology, and neurology. These algorithms have found utility in making healthcare decisions that are often complicated by seemingly endless relationships between exogenous and endogenous variables. They have also found utility in the allocation of limited healthcare resources and the management of end-of-life issues. With the increase in computing power and the ability to test a virtually unlimited number of relationships, scientists and engineers have the unprecedented ability to increase the prognostic confidence that comes from complex data analysis. While these systems present exciting opportunities for the democratization and precision of healthcare, their use raises important moral and ethical considerations around Christian concepts of autonomy and hope. The purpose of this essay is to explore some of the practical limitations associated with AI in medicine and discuss some of the potential theological implications that machine-generated diagnoses may present. Specifically, this article examines how these systems may disrupt the patient and healthcare provider relationship emblematic of Christ's healing mission. Finally, this article seeks to offer insights that might help in the development of a more robust ethical framework for the application of these systems in the future.

Factors Influencing Despair, Self-blame, and Acceptance Among Parents of Children with Autism Spectrum Disorder (ASD): A Malaysian Perspective.

PURPOSE: Accepting and adapting to the child's diagnosis of Autism Spectrum Disorder (ASD) can be challenging for parents. We aimed to assess domains of parental adjustment namely despair, self-blame, and acceptance among parents whose children were diagnosed with ASD. METHODS: A cross-sectional study was conducted among 111 parents of children with autism who attended Child and Adolescent Psychiatry Unit (CAPU), in a university teaching hospital in Kuala Lumpur, Malaysia. Sociodemographic profiles of both parents and children were gathered. Parental adjustment focusing on parental self-blame, despair and acceptance were assessed using self-reported questionnaires namely Adjustment to the Diagnosis of Autism (ADA). RESULTS: Higher level of despair was associated with parents who have medical illness (ß = 0.214, p = 0.016) and children who received antipsychotic medications (ß = 0.329, p < 0.001). Parents with tertiary education (ß = -0.207, p = 0.023) and those with autistic child attended school (ß = -0.200, p = 0.037) have lower level of despair. Parents with medical illness (ß = 0.245, p = 0.008), child receiving antipsychotic medications (ß = 0.251, p = 0.005), Chinese ethnicity (ß = 0.185, p = 0.04), and child's gender (ß = 0.283, p = 0.003) were significantly associated with higher level of self-blame. Lower acceptance was found among Chinese parents (ß = -0.264, p = 0.005) while married parents had higher acceptance levels (ß = 0.215, p = 0.022). CONCLUSION: Parental adjustment involving domains of despair, self-blame, and acceptance were significantly associated with ethnicity of parents, educational level, parents' marital status and medical illness, as well as the ASD children's schooling status and type of medications used.

"Why me?": Qualitative research on why patients ask, what they mean, how they answer and what factors and processes are involved.

Patients often ask, "why me?" but questions arise regarding what this statement means, how, when and why patients ask, how they answer and why. Interviews were conducted as part of several qualitative research studies exploring how patients view and cope with various conditions, including HIV, cancer, Huntington's disease and infertility. A secondary qualitative analysis was performed. Many patients ask, "why me?" but this statement emerges as having varying meanings, and entailing complex psychosocial processes. Patients commonly recognize that this question may lack a clear answer and that asking it is irrational, but they ask nonetheless, given the roles of unknown factors and chance in disease causation, psychological stresses of illness and lack of definitive answers. Patients may focus on different aspects of the question - e.g., on possible causes of illness (Why me? - whether God or randomness is involved) and/or on whether they are being singled out and/or punished (Why me vs. someone else?). Patients frequently undergo dynamic processes, confronting this question at various points, and arriving at different answers, looking for explanations that have narrative coherence for them, and make sense to them emotionally. Social contexts can affect these processes, with friends, family, providers or others rejecting or accepting patients' responses to this question (e.g., beliefs about whether the patient is being punished and/or these questions are worth asking). Anger, depression, despair and/or resistance to notions about the roles of randomness or chaos can also shape these processes. While prior studies have each operationalized "why me?" in differing ways, focusing on varying aspects of it, the concept emerges here as highly multidimensional, involving complex processes and often affected by social contexts. These data, the first to examine key aspects and meanings of the phrase, "why me?" have critical implications for future practice, research and education.

Disentangling opioids-related overdose syndemics: a scoping review.

This article reviews research investigating the synergistic interaction of opioid-related morbidity and mortality with other social, psychiatric, and biological conditions, to describe how and why it is syndemic. Opioid-related overdose syndemics are driven by commercial interests, emerging in communities facing social and economic disadvantage, and interacting with a range of other health conditions. We included articles that empirically investigated an opioid-related syndemic, discussed syndemic co-factors associated with opioid use, or framed opioid consumption conceptually in relation to syndemics. Most articles were conducted in and first authored by investigators from North America. These articles were published in journals focused on general public health (n = 20), drug use and addiction (n = 18), and infectious disease or HIV (n = 15). Most original research articles (n = 60) employed quantitative methods. Unlike scholarship from other disciplines, specifically the controversial "Deaths of Despair" (DoD) framework, most research on opioid-related overdose syndemics fails to fully articulate the macro-structural drivers of localized disease clustering. Instead, the syndemics scholarship emphasizes the clinical manifestations of opioid and substance use, illustrating a problem in translation at the heart of syndemic theory. Moreover, syndemics scholarship on opioid impacts remains largely disconnected from the wider DoD discourse, which represents a missed opportunity for equity-oriented research. Re-directing attention to the sociopolitical forces that shape opioid-related overdose syndemics is necessary to prevent future commercially-driven health crises and repair lives harmed by these deadly syndemics.

The needle and the damage done: Deaths of despair, economic precarity, and the white working-class.

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.