Ozone causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Rho kinase (ROCK) is a key regulator of smooth muscle cell contraction and inflammatory cell migration. To determine the contribution of the two ROCK isoforms ROCK1 and ROCK2 to ozone-induced AHR, we exposed wild-type, ROCK1(+/-), and ROCK2(+/-) mice to air or ozone (2 ppm for 3 h) and evaluated mice 24 h later. ROCK1 or ROCK2 haploinsufficiency did not affect airway responsiveness in air-exposed mice but significantly reduced ozone-induced AHR, with a greater reduction in ROCK2(+/-) mice despite increased bronchoalveolar lavage (BAL) inflammatory cells in ROCK2(+/-) mice. Compared with wild-type mice, ozone-induced increases in BAL hyaluronan, a matrix protein implicated in ozone-induced AHR, were lower in ROCK1(+/-) but not ROCK2(+/-) mice. Ozone-induced increases in other inflammatory moieties reported to contribute to ozone-induced AHR (IL-17A, osteopontin, TNFα) were not different in wild-type vs. ROCK1(+/-) or ROCK2(+/-) mice. We also observed a dose-dependent reduction in ozone-induced AHR after treatment with the ROCK1/ROCK2 inhibitor fasudil, even though fasudil was administered after induction of inflammation. Ozone increased pulmonary expression of ROCK2 but not ROCK1 or RhoA. A ROCK2 inhibitor, SR3677, reduced contractile forces in primary human airway smooth muscle cells, confirming a role for ROCK2 in airway smooth muscle contraction. Our results demonstrate that ozone-induced AHR requires ROCK. Whereas ROCK1-dependent changes in hyaluronan may contribute to ROCK1's role in O3-induced AHR, the role of ROCK2 is downstream of inflammation, likely at the level of airway smooth muscle contraction.

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This 17-year prospective study applied a social-development lens to the challenge of identifying long-term predictors of adult depressive symptoms. A diverse community sample of 171 individuals was repeatedly assessed from age 13 to age 30 using self-, parent-, and peer-report methods. As hypothesized, competence in establishing close friendships beginning in adolescence had a substantial long-term predictive relation to adult depressive symptoms at ages 27–30, even after accounting for prior depressive, anxiety, and externalizing symptoms. Intervening relationship difficulties at ages 23–26 were identified as part of pathways to depressive symptoms in the late twenties. Somewhat distinct paths by gender were also identified, but in all cases were consistent with an overall role of relationship difficulties in predicting long-term depressive symptoms. Implications both for early identification of risk as well as for potential preventive interventions are discussed.

This randomized controlled trial examined the impact of The Connection Project, an experiential, relationship‐focused intervention designed to improve school belongingness and decrease symptoms of depression and loneliness among new college students. Participants were 438 first‐year and transfer students (232 treatment, 206 waitlist‐control) at a medium‐sized, 4years, predominantly White public university in the Southeastern United States. At postintervention, the treatment group reported significant relative increases in school belonging and significant relative reductions in levels of loneliness and depressive symptoms in comparison to waitlist‐controls. Program effects were stronger for students from marginalized racial or ethnic backgrounds, students from lower socioeconomic status households, and transfer students. Results are interpreted as suggesting the utility of experiential, peer‐support prevention programming to promote college students' well‐being, particularly college students who hold identities that are traditionally disadvantaged in this context.

This study examined struggles to establish autonomy and relatedness with peers in adolescence and early adulthood as predictors of advanced epigenetic aging assessed at age 30. Participants (N = 154; 67 male and 87 female) were observed repeatedly, along with close friends and romantic partners, from ages 13 through 29. Observed difficulty establishing close friendships characterized by mutual autonomy and relatedness from ages 13 to 18, an interview-assessed attachment state of mind lacking autonomy and valuing of attachment at 24, and self-reported difficulties in social integration across adolescence and adulthood were all linked to greater epigenetic age at 30, after accounting for chronological age, gender, race, and income. Analyses assessing the unique and combined effects of these factors, along with lifetime history of cigarette smoking, indicated that each of these factors, except for adult social integration, contributed uniquely to explaining epigenetic age acceleration. Results are interpreted as evidence that the adolescent preoccupation with peer relationships may be highly functional given the relevance of such relationships to long-term physical outcomes.