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A set of new findings suggest that anxiety and depression in middle adulthood act synergistically with childhood maltreatment to accelerate biological aging.¹ Previous studies have suggested that psychiatric symptoms are associated with accelerated biological aging, while childhood maltreatment is associated both with an increase in the rate of psychiatric symptoms in adulthood and with accelerated biological aging.^2-6

How psychiatric symptoms affect the relationship between childhood maltreatment and biological aging is unclear. Psychiatric symptoms could be mediators of the relationship in a temporal pathway. They could also be moderators by acting synergistically with childhood maltreatment to accelerate biological aging, or they may act independently to promote biological aging.

In a new report of a long-term prospective study of abused and neglected children, investigators described the use of association, mediation, and moderation analyses to try to clarify the role of psychiatric symptoms in the relationship between childhood maltreatment and biological aging.

Study design

Participants in the cohort were children aged 11 years or younger with a history of abuse or neglect identified through a US Midwestern county court system from 1967 to 1971. They were matched to control children without a history of maltreatment by age, sex, race or ethnicity, and social class.

In adulthood, the participants were interviewed three times.

• Interview 1: From 1989 to 1995, the participants underwent psychiatric assessments for current and previous posttraumatic stress disorder (PTSD), major depressive disorder, and generalized anxiety disorder using the National Institute of Mental Health Diagnostic Interview Schedule, Version III, Revised.
• Interview 2: From 2000 to 2002, participants were assessed for current symptoms of PTSD, major depressive disorder, and generalized anxiety disorder. Assessments were performed with a modified version of the Composite International Diagnostic Interview PTSD module, the Center for Epidemiologic Studies Depression Scale, and the Beck Anxiety Inventory.
• Interview 3: From 2003 to 2005, blood samples were collected from each participant to assess biomarkers of biological age. The biomarkers analyzed included albumin, alkaline phosphatase, creatinine, C-reactive protein, glycated hemoglobin, lymphocyte percentage, mean cell volume, red cell distribution width, and white blood cell count. Biological age relative to chronological age was modeled using the Klemera-Doubal method.⁷

For the hypothesis that psychiatric symptoms mediated the effects of childhood maltreatment on biological aging, the investigators used path analysis. The independent variable was childhood maltreatment, and the biological age in middle adulthood (Interview 3) was the outcome.

For the hypothesis that psychiatric symptoms moderated the relationship between childhood maltreatment and biological aging, the investigators used linear regression for each psychiatric symptom assessed at Interview 1 and Interview 2 and analyzed the interaction between symptoms and maltreatment.

Participant characteristics

The new report included 627 participants with documented childhood maltreatment and 497 matched controls who completed Interview 1. Of these, 48.8% were female, and 65.4% were non鈥揌ispanic White, and the mean (SD) age at Interview 1 was 29 years. At Interview 2, there were 457 in the maltreatment group and 376 in the control group, with a combined mean age of 40 years. At Interview 3, there were 357 in the maltreatment group and 250 in the control group, with a combined mean age of 41 years.

At Interview 1, participants in the maltreatment group had significantly higher scores compared with the control group on assessments of lifetime symptoms of PTSD (mean [SD] score, 6.1 [6.0] vs 4.1 [5.1]; P<.001), major depressive disorder (mean [SD] score, 3.6 [2.7] vs 3.1 [2.7]; P=.004), and generalized anxiety disorder (mean [SD] score, 4.4 [5.6] vs 3.7 [4.6]; P=.011).

Similarly, at Interview 2, participants in the maltreatment group had significantly higher scores compared with the control group on assessments of current symptoms of PTSD (mean [SD] score, 7.0 [4.8] vs 5.8 [4.5]; P<.001), major depressive disorder (mean [SD] score, 14.8 [11.6] vs 10.6 [10.0]; P<.001), and generalized anxiety disorder (mean [SD] score, 10.6 [11.3] vs 7.8 [8.7]; P<.001).

The mean (SD) biological age in the maltreatment group was 鈥�0.6 (8.2) years lower than the chronological age. However, the difference between the mean (SD) biological age and chronological age was even greater for the control group (鈥�2.2 [7.4] years). The difference between biological and chronological ages significantly differed between groups and indicated accelerated aging in the maltreatment group compared with the control group (P=.018).

Prediction, mediation, and moderation

Among the entire cohort, the investigators found that lifetime PTSD symptoms at Interview 1 in young adulthood predicted biological age acceleration at Interview 3 in middle adulthood (尾 [SE], .01 [.007]; P=.04). At Interview 2 for current symptoms in middle adulthood, PTSD (尾 [SE], 0.02 [.01]; P=.05), depression (尾 [SE], 0.01 [.004]; P=.02), and anxiety (尾 [SE], .009 [.004]; P=.03) predicted biological age acceleration.

Path analysis of Interviews 1 and 2 data showed that PTSD symptoms predicted biological age acceleration, maltreatment predicted psychiatric symptoms, and some psychiatric symptoms predicted biological age acceleration. However, the path of maltreatment to psychiatric symptom to biological age acceleration was not significant for any psychiatric symptom. These results suggested that the psychiatric symptoms did not mediate the relationship between maltreatment and accelerated aging.

For example, for path analysis of Interview 2 assessment data, the path from maltreatment to biological age acceleration was significant (尾 [SE], .09 [0.04]; 95% confidence interval [CI], .01-.17; P=.03), as was the path from maltreatment to depression (尾 [SE], 0.18 [.03]; 95% CI, .12-.25; P<.001) and the path from depression to biological age acceleration (尾 [SE], .08 [.04]; 95% CI, .01-.17; P=.04). However, the full path from maltreatment to depression to biological age acceleration was not significant (P=.06).

The investigators found some evidence for moderation. For the maltreatment group only, there was a significant relationship between current depression symptoms in Interview 2 and biological age acceleration (尾 [SE], .01 [.004]; 95% CI, .004-.03). Similarly, higher levels of anxiety were predictive of biological age acceleration in the maltreatment group (尾 [SE], .01 [.005]; 95% CI, .004-.02). These relationships were not significant in the control group.

Who is most at risk of accelerated aging?

The study confirmed an increase in psychiatric symptoms and biological age acceleration in individuals with a history of childhood maltreatment and suggested that psychiatric symptoms moderated biological aging.

The investigators did not know why short-term depression and anxiety symptoms in middle adulthood would moderate biological aging in individuals with childhood maltreatment, but long-term symptoms in young adulthood would not.

鈥淚dentifying and understanding the role of critical moderators has the potential to help direct limited resources toward those who are most likely to benefit from them and may have implications for the development of personalized clinical care for people with histories of childhood maltreatment,鈥� they wrote.

The maltreatment participants in this study came from the court system and mostly from low-income families. Consequently, the investigators wrote that their results may not be generalizable to cases that were unreported, unsubstantiated, or from middle- or high-income families. Another limitation to generalizability may be from a difference in support services available to children today compared with those who were abused or neglected in the 1960s or 1970s. The investigators were also unable to assess the effects of substance use on the relationships between psychiatric symptoms and biological aging.

Published: August 08, 2024