Identifying adolescents at risk for depression : a prediction score performance in cohorts based in 3 different continents

Objective: Prediction models have become frequent in the medical literature, but most published studies are conducted in a single setting. Heterogeneity between development and validation samples has been posited as a major obstacle for the generalization of models. We aimed to develop a multivariable prognostic model using sociodemographic variables easily obtainable from adolescents at age 15 to predict a depressive disorder diagnosis at age 18 and to evaluate its generalizability in 2 samples from diverse socioeconomic and cultural settings. Method: Data from the 1993 Pelotas Birth Cohort were used to develop the prediction model, and its generalizability was evaluated in 2 representative cohort studies: the Environmental Risk (E-Risk) Longitudinal Twin Study and the Dunedin Multidisciplinary Health and Development Study. Results: At age 15, 2,192 adolescents with no evidence of current or previous depression were included (44.6% male). The apparent C-statistic of the models derived in Pelotas ranged from 0.76 to 0.79, and the model obtained from a penalized logistic regression was selected for subsequent external evaluation. Major discrepancies between the samples were identified, impacting the external prognostic performance of the model (Dunedin and E-Risk C-statistics of 0.63 and 0.59, respectively). The implementation of recommended strategies to account for this heterogeneity among samples improved the model’s calibration in both samples. Conclusion: An adolescent depression risk score comprising easily obtainable predictors was developed with good prognostic performance in a Brazilian sample. Heterogeneity among settings was not trivial, but strategies to deal with sample diversity were identified as pivotal for providing better risk stratification across samples. Future efforts should focus on developing better methodological approaches for incorporating heterogeneity in prognostic research

Is Chronic Asthma Associated with Shorter Leukocyte Telomere Length at Midlife?

RATIONALE: Asthma is prospectively associated with age-related chronic diseases and mortality, suggesting the hypothesis that asthma may relate to a general, multisystem phenotype of accelerated aging. OBJECTIVES: To test whether chronic asthma is associated with a proposed biomarker of accelerated aging, leukocyte telomere length. METHODS: Asthma was ascertained prospectively in the Dunedin Multidisciplinary Health and Development Study cohort (n = 1,037) at nine in-person assessments spanning ages 9-38 years. Leukocyte telomere length was measured at ages 26 and 38 years. Asthma was classified as life-course-persistent, childhood-onset not meeting criteria for persistence, and adolescent/adult-onset. We tested associations between asthma and leukocyte telomere length using regression models. We tested for confounding of asthma-leukocyte telomere length associations using covariate adjustment. We tested serum C-reactive protein and white blood cell counts as potential mediators of asthma-leukocyte telomere length associations. MEASUREMENTS AND MAIN RESULTS: Study members with life-course-persistent asthma had shorter leukocyte telomere length as compared with sex- and age-matched peers with no reported asthma. In contrast, leukocyte telomere length in study members with childhood-onset and adolescent/adult-onset asthma was not different from leukocyte telomere length in peers with no reported asthma. Adjustment for life histories of obesity and smoking did not change results. Study members with life-course-persistent asthma had elevated blood eosinophil counts. Blood eosinophil count mediated 29% of the life-course-persistent asthma-leukocyte telomere length association. CONCLUSIONS: Life-course-persistent asthma is related to a proposed biomarker of accelerated aging, possibly via systemic eosinophilic inflammation. Life histories of asthma can inform studies of aging

Linking stressful life events and chronic inflammation using suPAR (soluble urokinase plasminogen activator receptor)

Stressful life events have been linked to declining health, and inflammation has been proposed as a physiological mechanism that might explain this association. Using 828 participants from the Dunedin Longitudinal Study, we tested whether people who experienced more stressful life events during adulthood would show elevated systemic inflammation when followed up in midlife, at age 45. We studied three inflammatory biomarkers: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer biomarker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. Stressful life events were not associated with CRP or IL-6. However, people who experienced more stressful life events from age 38 to 44 had elevated suPAR at age 45, and had significantly greater increases in suPAR from baseline to follow up across the same period. When examining stressful life events across the lifespan, both adverse childhood experiences (ACEs) and adult stressful life events were independently associated with suPAR at age 45. ACEs moderated the association of adult stressful life events and suPAR at age 45—children with more ACEs showed higher suPAR levels after experiencing stressful life events as adults. The results suggest systemic chronic inflammation is one physiological mechanism that could link stressful life events and health, and support the use of suPAR as a useful biomarker for such research

Long-Term Cannabis Use and Cognitive Reserves and Hippocampal Volume in Midlife

OBJECTIVE: Cannabis use is increasing among midlife and older adults. We tested the hypotheses that long-term cannabis use is associated with cognitive deficits and smaller hippocampal volume in midlife, which is important because midlife cognitive deficits and smaller hippocampal volume are risk factors for dementia. METHODS: Participants are members of a representative cohort of 1,037 individuals born in Dunedin, New Zealand in 1972–73 and followed to age 45 years, with 94% retention. Cannabis use and dependence were assessed at ages 18, 21, 26, 32, 38 and 45 years. IQ was assessed at ages 7, 9, 11, and 45 years. Specific neuropsychological functions and hippocampal volume were assessed at age 45 years. RESULTS: Long-term cannabis users showed IQ decline from childhood to midlife (mean=−5.5 IQ points), poorer learning and processing speed relative to their childhood IQ, and informant-reported memory and attention problems. These deficits were specific to long-term cannabis users because they were either not present or smaller among long-term tobacco users, long-term alcohol users, midlife recreational cannabis users, and cannabis quitters. Cognitive deficits among long-term cannabis users could not be explained by persistent tobacco, alcohol, or other illicit drug use; childhood SES; low childhood self-control; or family history of substance dependence. Long-term cannabis users showed smaller hippocampal volume, but smaller hippocampal volume did not statistically mediate cannabis-related cognitive deficits. CONCLUSIONS: Long-term cannabis users showed cognitive deficits and smaller hippocampal volume in midlife. Research is needed to ascertain whether long-term cannabis users show elevated rates of dementia in later life

Childhood to Early-Midlife Systolic Blood Pressure Trajectories:Early-Life Predictors, Effect Modifiers, and Adult Cardiovascular Outcomes

Previous studies examining blood pressure change over time have modelled an “average” population trajectory. Recent research among older adults suggests there may be subgroups with different blood pressure trajectories. Identifying subgroups at risk of developing adult hypertension early in life can inform effective risk reduction efforts. We sought to identify different systolic blood pressure trajectories from childhood, their correlated risk factors and early midlife cardiovascular outcomes. Blood pressure data at ages 7, 11, 18, 26, 32 and 38 years from a longitudinal, representative birth cohort study (n=975) were used to identify four distinct trajectory groups via group-based trajectory modeling: ‘normal’ (21.8%), ‘high-normal’ (43.3%), ‘prehypertensive’ (31.6%), and ‘hypertensive’ (4.2%). The categories refer to blood pressure beginning at age 7 and most recently measured at age 38. Family history of high blood pressure (OR=43.23, 95% CI 5.27, 354.65), male gender (OR=109.48, 95% CI=26.82, 446.96), being first born (OR=2.5 95% CI=1.00, 8.69) and low birthweight (OR=2.79, 95% CI 2.49, 3.09) were associated with hypertensive group membership (compared to the normal group). Higher body mass index and cigarette smoking resulted in increasing blood pressure across trajectories, particularly for the higher blood pressure groups. Prehypertensive and hypertensive trajectory groups had worse cardiovascular outcomes by early midlife. Harmful blood pressure trajectories are identifiable in childhood, associated with both antecedent and modifiable risk factors over time, and predict adult cardiovascular disease risk. Early detection, subsequent targeted prevention and/or intervention may reduce the lifecourse burden associated with higher blood pressure