The Preeminence of Early Life Trauma as a Risk Factor for Worsened Long-Term Health Outcomes in Women

Abstract

Early life trauma (ELT) comprises an array of disturbingly common distressing experiences between conception and the beginning of adulthood with numerous and significant potential long-term, even transgenerational, health consequences of great public health concern, including depression, cardiovascular disease, and other psychiatric and medical disorders, and neurobiological, psychological, and behavioral effects which are sufficiently robust to confound many types of biomedical research. The impact of ELT on a woman's health trajectory appears to vary with the specific characteristics of the ELT (e.g., type, number of different types, severity, and timing), the individual (e.g., age, genetics, epigenetics, personality, and cognitive factors), and the individual's environment (e.g., level of social support and ongoing stressors) and to be mediated to a significant extent by persistent changes in a number of biological systems, dysregulation of those governing the stress response chief among them. Growing knowledge of the risk factors and pathophysiological mechanisms by which ELT confers diathesis to various poor health outcomes and the unique treatment-response profiles of women with ELT will lead to much needed improvements in prevention, diagnostic, and therapeutic efforts, including more effective psychotherapy and pharmacotherapy approaches, hopefully making strides toward improvements in the lives of women everywhere and ending countless cycles of intergenerational trauma-associated pathology. This article attempts to broadly summarize the current state of knowledge about the long-term sequelae of ELT for women's health.

On antidepressants and still feeling low

“…Consistent with prior findings (4,5,14), adding ELS to the model significantly increased overall performance (Δχ 2 = 5.88, Δdf = 1, P = 0.025) (Table S3). Within this model, the likelihood of achieving functional remission was negatively associated with ELS status [unstandardized beta coefficient (B) = −0.99, Wald statistic (W) = −2.12, P = 0.034] when holding covariates at a fixed value.…”

“…ELS has been shown to moderate antidepressant outcomes (4,5,14,30). Consistent with these reports, we found that the severity of exposure to ELS in childhood is associated with a greater likelihood of treatment failure across three commonly prescribed antidepressants.…”

“…Similarly, in humans, a history of ELS, particularly abuse or neglect, is a prominent risk factor for developing depression and exacerbating depression severity (3,4). Mechanisms by which ELS affects adult psychopathology are thought to involve-at least in part-engagement of the HPA axis in the immediate response to the stressor (2,6,10,11,19,26).…”

“…Moreover, amygdala reactivity in responders to both negatively and positively valenced stimuli increased toward normalization following antidepressant intervention (30). Increasing levels of ELS have also been associated with poorer outcomes to pharmacotherapy, pharmacotherapy combined with psychotherapy, and psychotherapy alone (4,5,14).…”

Human amygdala engagement moderated by early life stress exposure is a biobehavioral target for predicting recovery on antidepressants

“…amygdala | early life stress | human brain imaging | predictive biomarkers | antidepressant remission A mygdala reactivity and exposure to early life stress (ELS) are both strongly implicated in depression mechanisms in both animal and human models (1)(2)(3)(4)(5)(6). The amygdala plays an important role in emotion processing, including evaluating biologically salient emotional stimuli, generating emotional states and potentiating emotional memories (7).…”