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Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression.

Stress in early life has been associated with insufficient glucocorticoid signaling in adulthood, possibly affecting inflammation processes. Childhood maltreatment has been linked to increased risk of adult disease with potential inflammatory origin. However, the impact of early life stress on adult inflammation is not known in humans. We tested the life-course association between childhood maltreatment and adult inflammation in a birth cohort followed to age 32 years as part of the Dunedin Multidisciplinary Health and Development Study. Regression models were used to estimate the effect of maltreatment on inflammation, adjusting for co-occurring risk factors and potential mediating variables. Maltreated children showed a significant and graded increase in the risk for clinically relevant C-reactive protein levels 20 years later, in adulthood [risk ratio (RR) ‫؍‬ 1.80, 95% confidence interval (CI) ‫؍‬ 1.26 -2.58]. The effect of childhood maltreatment on adult inflammation was independent of the influence of co-occurring early life risks (RR ‫؍‬ 1.58, 95% CI ‫؍‬ 1.08 -2.31), stress in adulthood (RR ‫؍‬ 1.64, 95% CI ‫؍‬ 1.12-2.39), and adult health and health behavior (RR ‫؍‬ 1.76, 95% CI ‫؍‬ 1.23-2.51). More than 10% of cases of low-grade inflammation in the population, as indexed by high C-reactive protein, may be attributable to childhood maltreatment. The association between maltreatment and adult inflammation also generalizes to fibrinogen and white blood cell count. Childhood maltreatment is a previously undescribed, independent, and preventable risk factor for inflammation in adulthood. Inflammation may be an important developmental mediator linking adverse experiences in early life to poor adult health.C-reactive protein ͉ development ͉ epidemiology ͉ risk factor ͉ stress

Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their "biological aging" (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, selfreported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.biological aging | cognitive aging | aging | healthspan | geroscience B y 2050, the world population aged 80 y and above will more than triple, approaching 400 million individuals (1, 2). As the population ages, the global burden of disease and disability is rising (3). From the fifth decade of life, advancing age is associated with an exponential increase in burden from many different chronic conditions (Fig. 1). The most effective means to reduce disease burden and control costs is to delay this progression by extending healthspan, years of life lived free of disease and disability (4). A key to extending healthspan is addressing the problem of aging itself (5-8).At present, much research on aging is being carried out with animals and older humans. Paradoxically, these seemingly sensible strategies pose translational difficulties. The difficulty with studying aging in old humans is that many of them already have age-related diseases (9-11). Age-related changes to physiology accumulate from early life, affecting organ systems years before disease diagnosis (12-15). Thus, intervention to reverse or delay the march toward age-related diseases must be scheduled while people are still young (16). Early interventions to slow aging can be tested in model organisms (17,18). The difficulty with these nonhuman models is that they do not typically capture the complex multifactorial risks and exposures that shape human aging. Moreover, whereas animals' brief lives make it feasible to study animal aging in the laboratory, humans' lives span many years. A solution is to study human aging in the first half of ...

Key Points Question What is the agreement between prospective and retrospective measures of childhood maltreatment? Findings This systematic review and meta-analysis of 16 unique studies and 25 471 unique participants found poor agreement between prospective and retrospective measures of childhood maltreatment, with Cohen κ = 0.19. On average, 52% of individuals with prospective observations of childhood maltreatment did not retrospectively report it, and likewise, 56% of individuals retrospectively reporting childhood maltreatment did not have concordant prospective observations. Meaning Because findings from this meta-analysis demonstrated that prospective and retrospective measures of childhood maltreatment identify largely different groups of individuals, the 2 measures cannot be used interchangeably to study the associated health outcomes and risk mechanisms.

Obesity is a prevalent global-health problem associated with substantial morbidity, impairment and economic burden. Because most readily available forms of treatment are ineffective in the long term, it is essential to advance knowledge of obesity prevention by identifying potentially modifiable risk factors. Findings from experimental studies in non-human primates suggest that adverse childhood experiences may influence obesity risk. However, observations from human studies showed heterogeneous results. To address these inconsistencies, we performed Medline, PsycInfo and Embase searches till 1 August 2012 for articles examining the association between childhood maltreatment and obesity. We then conducted a meta-analysis of the identified studies and explored the effects of various possible sources of bias. A meta-analysis of 41 studies (190 285 participants) revealed that childhood maltreatment was associated with elevated risk of developing obesity over the life-course (odds ratio=1.36; 95% confidence interval=1.26-1.47). Results were not explained by publication bias or undue influence of individual studies. Overall, results were not significantly affected by the measures or definitions used for maltreatment or obesity, nor by confounding by childhood or adult socioeconomic status, current smoking, alcohol intake or physical activity. However, the association was not statistically significant in studies of children and adolescents, focusing on emotional neglect, or adjusting for current depression. Furthermore, the association was stronger in samples including more women and whites, but was not influenced by study quality. Child maltreatment is a potentially modifiable risk factor for obesity. Future research should clarify the mechanisms through which child maltreatment affects obesity risk and explore methods to remediate this effect.

Background Adverse childhood experiences (ACEs; e.g., abuse, neglect, parental loss, etc.) have been associated with increased risk for later-life disease and dysfunction using adults’ retrospective self-reports of ACEs. Research should test whether associations between ACEs and health outcomes are the same for prospective and retrospective ACE measures. Methods We estimated agreement between ACEs prospectively-recorded throughout childhood (by Study staff at Study member ages 3, 5, 7, 9, 11, 13, and 15) and retrospectively-recalled in adulthood (by Study members when they reached age 38), in the population-representative Dunedin cohort (N=1,037). We related both retrospective and prospective ACE measures to physical, mental, cognitive, and social health at midlife measured through both objective (e.g., biomarkers and neuropsychological tests) and subjective (e.g., self-reported) means. Results Dunedin and CDC ACE distributions were similar. Retrospective and prospective measures of adversity showed moderate agreement (r=.47, p<.001; weighted Kappa = .31, 95% CI: .27–.35). Both associated with all midlife outcomes. As compared to prospective ACEs, retrospective ACEs showed stronger associations with life outcomes that were subjectively assessed, and weaker associations with life outcomes that were objectively assessed. Recalled ACEs and poor subjective outcomes were correlated regardless of whether prospectively-recorded ACEs were evident. Individuals who recalled more ACEs than had been prospectively recorded were more neurotic than average, and individuals who recalled fewer ACEs than recorded were more agreeable. Conclusions Prospective ACE records confirm associations between childhood adversity and negative life outcomes found previously using retrospective ACE reports. However, more agreeable and neurotic dispositions may respectively bias retrospective ACE measures toward underestimating the impact of adversity on objectively-measured life outcomes and overestimating the impact of adversity on self-reported outcomes. Associations between personality factors and the propensity to recall adversity were extremely modest and warrant further investigation. Risk predictions based on retrospective ACE reports should utilize objective outcome measures. Where objective outcome measurements are difficult to obtain, correction factors may be warranted.

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