A key aim of our experiments was to identify background strains that might enable us to develop such a model. Strikingly, the long-lived D2?Tor1aDE/DE pups exhibited a noticeable tremor, abnormal limb placement and limb weakness, and a delayed righting reflex. While this abnormal motor behavior likely results from torsinA-related neural dysfunction, these pups do not feed well and appear generally ill, a confounding factor that complicates the interpretation of this phenotype. This finding was nevertheless encouraging, and we tried to build on it to create healthy mice that display abnormal motor function. Because we studied a mixed population of leukocytes, our findings could be influenced by the relative composition of these cells, which can be altered during infection and other conditions. Glucocorticoids have strong anti-inflammatory effects, and glucocorticoid receptors are present in several leukocyte cell types, including lymphocytes, neutrophils, eosinophils, and macrophages. However, it is unlikely that inflammatory conditions explain our findings because 1) we excluded subjects with acute or chronic illness, allergy symptoms, abnormal blood counts, or the use of antibiotics, antihistamines, or corticosteroids, and 2) any such confounding effect would have to occur differentially in those with adversity. In summary, we found that early-life stress, in the form of loss of a parent during childhood, maltreatment, and low parental care, was associated with epigenetic changes to the promoter region of the glucocorticoid receptor gene. In addition, methylation of the promoter region of this gene was linked to alterations in HPA axis function. These findings, together with previous research in rodents and two prior studies in humans, provide preliminary support for the hypothesis that altered expression of the glucocorticoid receptor due to cytosine methylation of the gene promoter could be a mechanism of the neuroendocrine effects of early-life stress, and could predispose to the development of major depression and post-traumatic stress disorder. However, our effect sizes tended to be modest in magnitude, different CpG sites were associated with the associations of childhood adversity measures and the cortisol response to the Dex/CRH test, and we did not have gene expression data available. This study will need to be replicated in order to draw firm conclusions about the findings. Further work is also needed to determine whether these findings are specific to lymphocytes and whether this reflects changes in central regulation of the glucocorticoid receptor in brain regions involved in stress responses and mood and anxiety disorders. Lymphatic filariasis is a disabling disease transmitted by mosquitoes that infects more than 120 million people throughout the tropics. The infection is caused by filarial nematodes that reside in the lymphatic vasculature.