Diurnal salivary cortisol profiles are valuable indicators of adrenocortical functioning in epidemiological research and clinical practice. However, normative reference values derived from a large number of participants and across a wide age range are still missing. To fill this gap, data were compiled from 15 independently conducted field studies with a total of 104,623 salivary cortisol samples obtained from 18,698 unselected individuals (mean age: 48.3 years, age range: 0.5 to 98.5 years, 39% females). Besides providing a descriptive analysis of the complete dataset, we also performed mixed-effects growth curve modeling of diurnal salivary cortisol (i.e., 1 to 16 hours after awakening). Cortisol decreased significantly across the day and was influenced by both, age and sex. Intriguingly, we also found a pronounced impact of sampling season with elevated diurnal cortisol in spring and decreased levels in autumn. However, the majority of variance was accounted for by between-participant and between-study variance components. Based on these analyses, reference ranges (LC/MS-MS calibrated) for cortisol concentrations in saliva were derived for different times across the day, with more specific reference ranges generated for males and females in different age categories. This integrative summary provides important reference values on salivary cortisol to aid basic scientists and clinicians in interpreting deviations from the normal diurnal cycle.

Background Depression is a major public health problem among youth, currently estimated to affect as many as 9% of US children and adolescents. The recognition that both genes (“nature”) and environments (“nurture”) are important for understanding the etiology of depression has led to rapid growth in research exploring gene–environment interactions (GxE). However, there has been no systematic review of GxE in youth depression to date. Methods The goal of this article was to systematically review evidence on the contribution of GxE to the risk of child and adolescent depression. Though a search of PubMed and PsycINFO databases to 1 April 2010, we identified 20 candidate gene–environment interaction studies focused on depression in youth (up to age 26) and compared each study in terms of the following characteristics: research design and sample studied; measure of depression and environment used; genes explored; and GxE findings in relation to these factors. Results In total 80% of studies (n=16) found at least one significant GxE association. However, there was wide variation in methods and analyses adopted across studies, especially with respect to environmental measures used and tests conducted to estimate GxE. This heterogeneity made it difficult to compare findings and evaluate the strength of the evidence for GxE. Conclusions The existing body of GxE research on depression in youth contains studies that are conceptually and methodologically quite different, which contributes to mixed findings and makes it difficult to assess the current state of the evidence. To decrease this heterogeneity, we offer 20 recommendations that are focused on: (1) reporting GxE research; (2) testing and reporting GxE effects; (3) conceptualizing, measuring, and analyzing depression; (4) conceptualizing measuring, and analyzing environment; (5) increasing power to test for GxE; and (6) improving the quality of genetic data used. Although targeted to GxE research on depression, these recommendations can be adopted by GxE researchers focusing on other mental health outcomes.

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