Twin samples were used to estimate the relative importance of genetic and environmental influences on problem behavior in children, assessed by the Child Behavior Checklist (CBCL). For the younger cohort, mothers completed the CBCL/2-3, while for the older cohort the CBCL/4-18 was used. Nearly half of the older sample had also been assessed with the questionnaire for younger children at a prior date, providing tentative answers regarding continuity and change in the etiology of problem behavior. Results suggested that shared environmental influences may be more important in early childhood than in middle childhood, while the reverse holds for genetic influences.

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA ( = 42) and those without a history of ELA (control, = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69CD8 T cells ( = 0.022), increased numbers of HLA-DR CD4 and HLA-DR CD8 T cells ( < 0.001), as well as increased numbers of CD25CD8 T cells ( = 0.036). ELA also showed a trend toward higher numbers of CCR4CXCR3CCR6 CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells.

Clinical studies have shown a relationship between allergic disorders and depression, panic disorder, attention deficit/hyperactivity disorder, and social anxiety for a significant subset of patients with these disorders. The nature of the relationship, whether due to shared environmental or biologic vulnerabilities or as a result of the stress of chronic illness, has been less clear. By examining the covariance of atopic disorders and depressive symptoms in a community sample of monozygotic (MZ) and dizygotic (DZ) twins, the contribution of genetic and/or shared environmental etiological factors can be established. A Finnish sample of 1337 MZ and 2506 DZ twin pairs, ages 33-60 years, was sent questionnaires inquiring about history of asthma, eczema, and atopic rhinitis, as well as the Beck Depression Inventory (BDI). The nature of the covariation between twins of these symptoms was investigated by fitting competing genetic and environmental models. Within-person correlation between atopic symptoms and BDI was 0.103 (P < 0.001) for the total sample. Using the Mx statistical modeling program to fit the data to competing quantitative genetic models, the best fitting model estimated that 64% of the association between atopy and BDI was due to shared familial vulnerability, primarily additive genetic influences. Although the measures for allergic disorders and depression are crude, this study supports the hypothesis that there is a small shared genetic risk for atopic and depressive symptoms, and if replicated, may open research for common mechanisms between allergic and depressive disorders. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:146-153, 2000.

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n = 59) or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n = 18). No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57) in ELA. In addition, senescent T cells (CD57+) in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV) infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts.