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.

Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis.

BACKGROUND: Accumulating evidence suggests that breastfeeding benefits children's intelligence, possibly due to long-chain polyunsaturated fatty acids (LC-PUFAs) present in breast milk. Under a nutritional adequacy hypothesis, an interaction between breastfeeding and genetic variants associated with endogenous LC-PUFAs synthesis might be expected. However, the literature on this topic is controversial. METHODS: We investigated this gene × environment interaction through a collaborative effort. The primary analysis involved >12 000 individuals and used ever breastfeeding, FADS2 polymorphisms rs174575 and rs1535 coded assuming a recessive effect of the G allele, and intelligence quotient (IQ) in Z scores. RESULTS: There was no strong evidence of interaction, with pooled covariate-adjusted interaction coefficients (i.e. difference between genetic groups of the difference in IQ Z scores comparing ever with never breastfed individuals) of 0.12[(95% confidence interval (CI): -0.19; 0.43] and 0.06 (95% CI: -0.16; 0.27) for the rs174575 and rs1535 variants, respectively. Secondary analyses corroborated these results. In studies with ≥5.85 and <5.85 months of breastfeeding duration, pooled estimates for the rs174575 variant were 0.50 (95% CI: -0.06; 1.06) and 0.14 (95% CI: -0.10; 0.38), respectively, and 0.27 (95% CI: -0.28; 0.82) and -0.01 (95% CI: -0.19; 0.16) for the rs1535 variant. CONCLUSIONS: Our findings did not support an interaction between ever breastfeeding and FADS2 polymorphisms. However, subgroup analysis suggested that breastfeeding may supply LC-PUFAs requirements for cognitive development if breastfeeding lasts for some (currently unknown) time. Future studies in large individual-level datasets would allow properly powered subgroup analyses and further improve our understanding on the breastfeeding × FADS2 interaction.

Challenges in comparing the methods and findings of cohort studies of oral health: the Dunedin (New Zealand) and Pelotas (Brazil) studies.

OBJECTIVE: to systematically compare methods and some findings from two prospective cohort studies of oral health. METHODS: This paper describes and compares two such population-based birth cohort studies of younger adults: the Dunedin Multidisciplinary Health and Development Study (conducted in New Zealand); and the 1982 Pelotas Birth Cohort Study (conducted in Brazil). RESULTS: The two cohorts showed socio-demographic similarities and differences, with their gender mixes being similar, but their ethnic compositions differing markedly. There were some important similarities and differences in methods. Overall dental caries experience was higher among the Dunedin cohort. Each of the studies has examined the association between childhood-adulthood changes in socio-economic status and oral health in the mid-20s. Both studies observed the greatest disease experience among those who were of low SES in both childhood and adulthood, and the least among those who were of high SES in both childhood and adulthood. In each cohort, disease experience in the upwardly mobile and downwardly mobile groups lay between those two extremes. CONCLUSIONS AND IMPLICATIONS: There are important similarities and differences in both methods and findings. While the need for a degree of methodological convergence in future is noted, the two studies are able to use each other as replicate samples for research into chronic oral conditions.