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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.

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.

This article describes the design and phenotype and genotype data available for sibling pairs with varying genetic relatedness in the National Longitudinal Study of Adolescent Health (Add Health). Add Health is a nationally representative longitudinal study of over 20,000 adolescents in the United States in 1994-1995 who have been followed for 15 years into adulthood. The Add Health design included oversamples of more than 3,000 pairs of individuals with varying genetic resemblance, ranging from monozygotic twins, dizygotic twins, full siblings, half siblings, and unrelated siblings who were raised in the same household. Add Health sibling pairs are therefore nationally representative and followed longitudinally from early adolescence into adulthood with four in-home interviews during the period 1994-2009. Add Health has collected rich longitudinal social, behavioral, environmental, and biological data, as well as buccal cell DNA from all sample members, including sibling pairs. Add Health has an enlightened dissemination policy and to date has released phenotype and genotype data to more than 10,000 researchers in the scientific community.

Objectives: Longitudinal examinations of associations between daily stress, diurnal cortisol concentrations, and physiological parameters in population-based studies are needed. This study evaluates issues related to consent, collection, and protocol adherence for a low-burden saliva collection protocol., Methods: In the 2007 pretest (n=193) for Wave IV of the National Longitudinal Study of Adolescent Health (Add Health) a three-sample, one-day, unsupervised saliva collection protocol was pilot tested. Embedded experiments allowed for examination of adherence and effects of monetary incentives., Results: Although most (97%) study participants consented to collection, only about 80% actually mailed back samples. Use of a time-stamping TrackCap allowed comparison of self-reported and stamp-recorded collection times. Of returned samples, self-report of collection time was missing for about a quarter, and only about one in three respondents (of those for whom adherence was calculable) fully adhered to the collection protocol, indicating significant potential for bias. Consent, return, and protocol adherence were unrelated to key sociodemographic characteristics, and did not improve with higher monetary incentives or knowledge of being monitored., Conclusions: Despite the relatively low-burden collection protocol and use of multiple strategies thought to improve collection and protocol adherence, response and adherence were poor, leading to a decision to drop cortisol measurement from the Wave IV Add Health protocol. Large field studies should carefully evaluate the feasibility of collection and protocol adherence for unsupervised collection protocols before implementing costly, and potentially unusable, biological measurements., (Copyright © 2011 Elsevier Ltd. All rights reserved.)