Does Despair Really Kill? A Roadmap for an Evidence-Based Answer.

Two seemingly associated demographic trends have generated considerable interest: income stagnation and rising premature mortality from suicides, drug poisoning, and alcoholic liver disease among US non-Hispanic Whites with low education. Economists interpret these population-level trends to indicate that despair induced by financial stressors is a shared pathway to these causes of death. Although we now have the catchy term "deaths of despair," we have yet to study its central empirical claim: that conceptually defined and empirically assessed "despair" is indeed a common pathway to several causes of death. At the level of the person, despair consists of cognitive, emotional, behavioral, and biological domains. Despair can also permeate social relationships, networks, institutions, and communities. Extant longitudinal data sets feature repeated measures of despair-before, during, and after the Great Recession-offering resources to test the role that despair induced by economic decline plays in premature morbidity and mortality. Such tests must also focus on protective factors that could shield individuals. Deaths of despair is more than a phrase; it constitutes a hypothesis that deserves conceptual mapping and empirical study with longitudinal, multilevel data.

Assisted reproductive technology and association with childhood cancer subtypes.

OBJECTIVES: To investigate the association between assisted reproductive technology (ART) use and childhood cancer subtype. STUDY DESIGN: We deployed a cross-sectional survey of 1701 parents of children with cancer about their ART use, demographics, and gestational and perinatal factors. Multivariable logistic regression modeled the association between ART use, birthweight and multiple gestation status with childhood cancer, by subtype. RESULTS: ART use was highest among children with osteosarcoma relative to children with other cancer types, and this association was statistically significant in multivariable models (OR = 4.4; 95% CI = 1.7-11.3; p = 0.0020). ART use was also elevated among children with hepatoblastoma, but this relationship appeared to be due to the strong associations between ART use and lower birthweight in our sample. No specific ART modality appeared to drive these associations. In univariate models, multiple gestation was associated with a 2.7-fold increased odds of hepatoblastoma (OR = 2.71; 95% CI = 1.14-6.42; p = 0.02) and a 1.6-fold increased odds of neuroblastoma (OR = 1.62; 95% CI = 1.03-2.54; p = 0.03), but these associations were not retained in multivariable models. CONCLUSIONS: Associations between ART use and hepatoblastoma risk may be attributable to birthweight, a known hepatoblastoma risk factor. ART use may also be associated with osteosarcoma, independent of birthweight, an association not previously observed in studies limited to cancers diagnosed before adolescence. Evaluating long-term health outcomes in children conceived by ART, throughout adolescence and potentially into adulthood, appears warranted.

Adult Psychiatric, Substance, and Functional Outcomes of Different Definitions of Early Cannabis Use.

OBJECTIVE: Research on associations of early cannabis use with adult functioning reports mixed findings. This may be due, in part, to wide variations in the definitions of early cannabis use. This study aims to compare associations of 4 commonly used definitions of early cannabis use-related to timing, dose, duration, and associated symptoms-with adult outcomes. METHOD: Analyses were based on a 20+-year longitudinal, community-representative study of 1,420 participants. Between ages 9 and 21 years (8,806 observations), participants were assessed for cannabis use and DSM-5 cannabis use disorder. In early adulthood (ages 24-26 and 30; 2,424 observations of 1,266 subjects), participants were also assessed for psychiatric, substance use, and functional outcomes. RESULTS: All definitions of early use were associated with multiple adult outcomes in models that adjusted for sex and race/ethnicity. In models that also adjusted for childhood psychiatric problems and family adversities, only daily use and a persistent developmental subtype (defined as daily/problematic use that began in adolescence and continued into early adulthood) were associated with later substance use/disorders, poorer functional outcomes, and derailments in the transition to adulthood. CONCLUSION: Daily, continued-over-time cannabis use beginning on adolescence was most problematic for a range of adult outcomes. Cessation of early use did not fully eliminate later risks; but was associated with fewer negative outcomes, with weaker effect sizes.

Long-term Outcomes of Childhood Family Income Supplements on Adult Functioning.

Importance: During an ongoing longitudinal cohort study, a casino opening created a natural cash transfer experiment. Some participating families received income supplements, and others did not. The children in this study are now adults. Objective: To assess the long-term outcomes of family income supplements received in childhood. Design, Setting, and Participants: This community-representative longitudinal cohort study set in western North Carolina assessed 1266 participants aged 9, 11, and 13 years at intake up to 11 times up to age 30 years from January 1993 to December 2015. Data were analyzed from January to December 2021. Exposures: In 1996, a southeastern American Indian tribe implemented a cash transfer program of approximately $5000 annually per person for tribal members. Participants were compared on whether their family ever received the cash transfers (American Indian vs non-American Indian), the duration of the transfers, and annual amount based on the number of parents. Main Outcomes and Measures: Participants were followed up at ages 25 and 30 years to assess mental health symptoms, substance use symptoms, and functional outcomes (physical health, risky or illegal behaviors, and financial and social functioning). Results: Of 1266 included participants, 320 (25.3%) were American Indian and 581 (49.7%) were female. Participants whose families received cash transfers during childhood reported fewer anxiety symptoms (relative risk [RR], 0.33; 95% CI, 0.25-0.44), depressive symptoms (RR, 0.51; 95% CI, 0.42-0.62), and cannabis symptoms (RR, 0.47; 95% CI, 0.27-0.82). They also reported improved physical health (RR, 0.66; 95% CI, 0.55-0.80) and financial functioning (RR, 0.78; 95% CI, 0.67-0.89) and fewer risky or illegal behaviors (RR, 0.57; 95% CI, 0.46-0.72) compared with those who did not receive the cash transfer. This pattern was supported by a series of heterogeneity analyses in which children whose families received the transfers for the longest duration and whose families received the largest transfer (due to having multiple American Indian parents) had the lowest levels of symptoms and the highest levels of functioning. Conclusions and Relevance: In this natural experiment, a family cash transfer in childhood was associated with positive adult functioning 20 years later. The findings support programs like the child tax credit or universal basic income that provide cash directly to families with children.

Prevalence and Childhood Precursors of Opioid Use in the Early Decades of Life.

Importance: Opioid use disorder and opioid deaths have increased dramatically in young adults in the US, but the age-related course or precursors to opioid use among young people are not fully understood. Objective: To document age-related changes in opioid use and study the childhood antecedents of opioid use by age 30 years in 6 domains of childhood risk: sociodemographic characteristics; school or peer problems; parental mental illness, drug problems, or legal involvement; substance use; psychiatric illness; and physical health. Design, Setting, and Participants: This community-representative prospective longitudinal cohort study assessed 1252 non-Hispanic White individuals and American Indian individuals in rural counties in the central Appalachia region of North Carolina from January 1993 to December 2015. Data were analyzed from January 2019 to January 2020. Exposures: Between ages 9 and 16 years, participants and their parents were interviewed up to 7 times using the Child and Adolescent Psychiatric Assessment and reported risk factors in 6 risk domains. Main Outcomes and Measures: Participants were assessed again at ages 19, 21, 25, and 30 years for nonheroin opioid use (any and weekly) and heroin use using the structured Young Adult Psychiatric Assessment. Results: Of 1252 participants, 342 (27%) were American Indian. By age 30 years, 322 participants had used a nonheroin opioid (24.2%; 95% CI, 21.8-26.5), 155 had used a nonheroin opioid weekly (8.8%; 95% CI, 7.2-10.3), and 95 had used heroin (6.6%; 95% CI, 5.2-7.9). Childhood risk markers for later opioid use included male sex, tobacco use, depression, conduct disorder, cannabis use, having peers exhibiting social deviance, parents with legal involvement, and elevated systemic inflammation. In final models, childhood tobacco use, depression, and cannabis use were most robustly associated with opioid use in young adulthood (ages 19 to 30 years). Chronic depression and dysthymia were strongly associated with any nonheroin opioid use (OR. 5.43; 95% CI, 2.35-12.55 and OR, 7.13; 95% CI, 1.99-25.60, respectively) and with weekly nonheroin opioid use (OR, 8.89; 95% CI, 3.61-21.93 and OR, 11.51; 95% CI, 3.05-42.72, respectively). Among young adults with opioid use, those with heroin use had the highest rates of childhood psychiatric disorders and comorbidities. Conclusions and Relevance: Childhood tobacco use and chronic depression may be associated with impaired reward system functioning, which may increase young adults' vulnerability to opioid-associated euphoria. Preventing and treating early substance use and childhood mental illness may help prevent later opioid use.

Associations of Despair With Suicidality and Substance Misuse Among Young Adults.

Importance: Deaths of despair is a term that has recently been used to describe the increases in premature mortality from suicides, drug overdoses (particularly from opiates), and alcohol-related liver disease among US adults. Despite the use of the term despair, its role in these causes of premature death has not been empirically tested. Objective: To test whether despair among young adults is associated with suicidal thoughts and behavior, alcohol misuse, and drug misuse. Design, Setting, and Participants: The Great Smoky Mountains Study is a Southeastern, mixed urban-rural population-based cohort study conducted from November 10, 1992, to September 22, 2015. A total of 1420 participants originally 9, 11, and 13 years of age were followed up 11 times to 30 years of age (11 230 person-observations). A total of 1154 of 1400 living participants (82.4%) were assessed at 30 years of age. Statistical analysis was performed from May 7, 2019, to April 10, 2020. Exposures: Participants were assessed with structured interviews for indicators of despair (eg, hopelessness, helplessness, low self-worth, and feeling unloved). Despair was assessed with items from structured interviews: the Child and Adolescent Psychiatric Assessment and the Young Adult Psychiatric Assessment. Main Outcomes and Measures: Structured interviews were used to assess suicidal thoughts and behavior, substance use, and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) alcohol use disorder and drug use disorder (including opioids) in young adulthood (2424 observations of 1266 individuals between 25 and 30 years of age). Results: This study included 1420 individuals (790 male individuals). During young adulthood (25 and 30 years of age), the 3-month weighted prevalence of any despair was 19.5% (476 of 2424 observations) with 7.6% of participants (201 of 2424 observations) reporting 2 or more despair items. In longitudinal, lagged models, despair scores (range, 0-3) were associated with more suicidal thoughts and behaviors (odds ratio [OR], 1.5; 95% CI, 1.1-2.0), illicit drug use (OR, 1.7; 95% CI, 1.2-2.5), and opioid use (OR, 1.9; 95% CI, 1.1-3.3) but not alcohol use disorder (OR, 0.8; 95% CI, 0.6-1.2). These associations persisted after accounting for sociodemographic factors (eg, poverty and educational level), lagged outcome status, and lagged depression status. The associations between despair and study outcomes were stronger in models accounting for long-term measures of despair extending back to childhood. There was no consistent pattern of moderation by sociodemographic factors. Conclusions and Relevance: This study's findings suggest an empirical basis for longitudinal associations between despair and several, but not all, precursors of "deaths of despair" in rural Appalachia. Individual despair should be studied as a potential factor associated with morbidity and impairment in young adulthood.

Association of Parental Incarceration With Psychiatric and Functional Outcomes of Young Adults.

Importance: In 2016, an estimated 8% of US children younger than 18 years had experienced the incarceration of a parent, and rates were substantially higher among children from racial and ethnic minority backgrounds and disadvantaged groups. Little is known about whether parental incarceration during childhood is associated with adult psychiatric problems and functional outcomes. Objective: To examine whether parental incarceration is associated with increased levels of psychiatric diagnosis and poor outcomes in health, legal, financial, and social domains in adulthood. Design, Setting, and Participants: This cohort study used data from the community-representative, prospective, longitudinal Great Smoky Mountains Study. Children and their parents were interviewed up to 8 times from January 1993 to December 2000 (ages 9-16 years; 6674 observations of 1420 participants) using the Child and Adolescent Psychiatric Assessment, which assessed parental incarceration, childhood psychiatric diagnoses, and other adversities. Young adults were followed up at ages 19, 21, 25, and 30 years from January 1999 to December 2015 (4556 observations of 1334 participants) to assess psychiatric diagnoses and functional outcomes indicative of a disrupted transition to adulthood. Data analysis was conducted from June 2018 to June 2019. Results: By age 16 years, 475 participants (weighted percentage, 23.9%) had a parental figure who had been incarcerated, including 259 young men (22.2%) and 216 young women (25.5%). Parental incarceration was associated with higher prevalence of childhood psychiatric diagnoses (eg, any depressive diagnosis: adjusted odds ratio [aOR], 2.5; 95% CI, 1.3-4.6; P = .006; attention-deficit/hyperactivity disorder: aOR, 2.3; 95% CI, 1.0-5.5; P = .06; and conduct disorder: aOR, 2.5; 95% CI, 1.4-4.3; P = .001). After accounting for childhood psychiatric diagnoses and adversity exposure, parental incarceration remained associated with increased odds of having an adult anxiety disorder (aOR, 1.7; 95% CI, 1.0-3.0; P = .04), having an illicit drug use disorder (aOR, 6.6; 95% CI, 2.6-17.0; P < .001), having a felony charge (aOR, 3.4; 95% CI, 1.8-6.5; P < .001), incarceration (aOR, 2.8; 95% CI, 1.4-5.4; P = .003), not completing high school (aOR, 4.4; 95% CI, 2.2-8.8; P < .001), early parenthood (aOR, 1.7; 95% CI, 1.0-3.0; P = .04), and being socially isolated (aOR, 2.2; 95% CI, 1.2-4.0; P = .009). Conclusions and Relevance: This study suggests that parental incarceration is associated with a broad range of psychiatric, legal, financial, and social outcomes during young adulthood. Parental incarceration is a common experience that may perpetuate disadvantage from generation to generation.

Systematic review of character development and childhood chronic illness.

AIM: To review empirical evidence on character development among youth with chronic illnesses. METHODS: A systematic literature review was conducted using PubMed and PSYCHINFO from inception until November 2013 to find quantitative studies that measured character strengths among youth with chronic illnesses. Inclusion criteria were limited to English language studies examining constructs of character development among adolescents or young adults aged 13-24 years with a childhood-onset chronic medical condition. A librarian at Duke University Medical Center Library assisted with the development of the mesh search term. Two researchers independently reviewed relevant titles (n = 549), then abstracts (n = 45), and finally manuscripts (n = 3). RESULTS: There is a lack of empirical research on character development and childhood-onset chronic medical conditions. Three studies were identified that used different measures of character based on moral themes. One study examined moral reasoning among deaf adolescents using Kohlberg's Moral Judgement Instrument; another, investigated moral values of adolescent cancer survivors with the Values In Action Classification of Strengths. A third study evaluated moral behavior among young adult survivors of burn injury utilizing the Tennessee Self-Concept, 2(nd) edition. The studies observed that youth with chronic conditions reasoned at less advanced stages and had a lower moral self-concept compared to referent populations, but that they did differ on character virtues and strengths when matched with healthy peers for age, sex, and race/ethnicity. Yet, generalizations could not be drawn regarding character development of youth with chronic medical conditions because the studies were too divergent from each other and biased from study design limitations. CONCLUSION: Future empirical studies should learn from the strengths and weaknesses of the existing literature on character development among youth with chronic medical conditions.

Comparison of Positive Youth Development for Youth With Chronic Conditions With Healthy Peers.

PURPOSE: Adolescents with childhood-onset chronic condition (COCC) are at increased risk for physical and psychological problems. Despite being at greater risk and having to deal with traumatic experiences and uncertainty, most adolescents with COCC do well across many domains. The Positive Youth Development (PYD) perspective provides a framework for examining thriving in youth and has been useful in understanding positive outcomes for general populations of youth as well as at-risk youth. This study aimed to compare levels of PYD assets between youth with COCC and youth without illness. METHODS: Participants with COCC were recruited from specialty pediatric clinics while healthy participants were recruited from a large pediatric primary care practice. Inclusion criteria for participants included being (1) English speaking, (2) no documented intellectual disability in electronic medical record, and (3) aged between 13 and 18 years during the recruitment period. Univariate and bivariate analyses on key variables were conducted for adolescents with and without COCC. Finally, we performed multivariable linear regressions for PYD and its subdomains. RESULTS: There were no significant differences between overall PYD or any of the subdomains between the two groups. Multivariable linear regression models showed no statistically significant relationship between chronic condition status and PYD or the subdomains. CONCLUSIONS: The findings from this study support the application of the PYD perspective to this population of youth. The results of this study suggest that approaches shown to benefit healthy youth, could be used to promote positive outcomes for youth with COCC.