2.7. Moderator and Subgroup Analyses

As described in the Introduction, demographic variables such as sex and past exposure to a major stressor, as well as methodological factors such as psychometric quality of PS measures, may confound or moderate the PS-TL relationship. Based on these hypothesized effects, we investigated 4 post hoc endpoints and subset analyses: (1) We examined the age-adjusted PS-TL correlation among only studies employing an empirically validated measure of PS. All subsequent secondary analyses were also conducted among only this subset of studies; (2) We examined the age- and sex-adjusted PS-TL correlation and the moderation effect of sex; (3) We investigated possible effects of sample heterogeneity by characterizing the PS-TL relationship according to the type of sample enrolled using 3 mutually exclusive categories: "General samples" included those not specifically selected for physical health conditions or stress exposures (these samples mostly comprised healthy adults, but subjects with physical health conditions or stress exposures were not excluded); "stress-exposed samples" included those selected for exposure (past or present) to a major stressor such as traumatic events or caregiving responsibilities for those with medical illness (this category included studies enrolling both stressed and control subjects); “physical condition samples” included those selected for the presence of a disease or other physical condition.

We did not exclude control subjects from studies recruiting stressed samples and samples with physical conditions. An alternative approach of including only samples with homogenous stressor exposure would severely limit power and could produce artificial range restriction⁴³. The ideal approach, namely using subject-level data to classify subjects by stressor exposure, was not possible given limitations in data availability. A caveat of our classification approach is potentially increased heterogeneity among “stressor-exposed” samples due to the inclusion of control subjects. Additionally, limited availability of raw data precluded assessment of the subject-level relationship between stressor exposure and PS.

Many such studies involved diseases known to be comorbid with stress or depression. In addition, in the samples that did not recruit specifically for a disease group, we coded whether there were exclusion criteria to rule out major diseases such as cardiovascular disease, diabetes, or cancer. Because specific physical conditions may have strong effects on telomere biology, these samples were not included in the stress-exposed category (which in most cases were healthy samples where major diseases were excluded; Table 1).

Characteristics of All Eligible Studies

TL assay CV = inter-assay coefficient of variation of T/S ratio.