To the best of our knowledge, this is the first study investigating the association between all types of childhood trauma and MS. Our main finding is that patients with MS reported significantly more childhood maltreatment than adults from the general population except physical abuse and neglect. This pattern emerged using both the dimensional and the categorical scoring method of the CTQ and remained significant when age, sex, education, and current depression were accounted for. Consideration of these potentially confounding covariates is important because sociodemographic factors are differentially associated with adverse childhood experiences (13–15). In addition, adult retrospective reports of childhood trauma may be biased by current mood, particularly depression, which is frequent in patients with MS and may lead to mood-congruent memory distortions (39,40). Emotional maltreatment was more closely associated with MS than the other types of childhood trauma: the odds of having been emotionally abused was more than three-fold higher in patients with MS relative to adults from the general population (odds ratio = 3.4, 95% CI = 2.0–5.7), and the odds of emotional neglect was 2.0 (95% CI = 1.3–3.2). This finding is in keeping with recent evidence suggesting that different types of childhood trauma may predict different outcomes (41–43). Particularly, emotional abuse was found to have a significant and independent effect on adult health, and there is evidence that emotional maltreatment additionally accentuates the adverse effects of other forms of abuse and neglect, which are closely interrelated and often co-occur (41,43). In general, our findings are in line with previous research indicating that traumatic experiences in childhood negatively affect physical health in adulthood (13–15). This seems to be particularly true for conditions involving inflammatory processes such as asthma and cardiovascular and autoimmune diseases (17–19).
Among patients with MS, there were no relevant associations among childhood trauma, MS-related variables, current neurologic impairment, and disease progression as assessed by standard instruments. However, we found that patients with MS reporting severe abuse (i.e., physical and/or sexual abuse) had higher relapse rates than those without histories of severe abuse, possibly suggesting that traumatic stress in childhood may contribute to the disease course in later life. However, considering that determination of relapses was mainly derived from patients’ reports and could not be based on clear-cut definitions in concert with neurologic assessment, which is a typical shortcoming of retrospective studies, we are in need of longitudinal investigations to clarify this issue.
In sum, our data indicate that emotional and sexual childhood trauma may increase the risk of developing MS but are not related to disease course and severity (with the exception of a weak association with relapse rate). Such dissociation between disease incidence and disease severity has been reported for several well-established risk factors. For example, women have a two- to three-fold higher risk of developing MS (44), but men were reported to have a shorter time to and a younger age for conversion from relapsing-remitting to secondary progressive MS (45). Thus, being female confers a higher risk of developing MS, but the disease in males seems to be more aggressive once established. There is also evidence for a functional dichotomy between risk genes involved in MS susceptibility and those affecting the clinical phenotype (46). Conversely, other factors such as pregnancy strongly affect disease activity (47) but have no impact on disability progression (48). Thus, it is not uncommon for one factor to be linked to risk of developing MS but not to markers of disease severity in established disease or vice versa. Our finding that childhood trauma may more strongly be associated with MS susceptibility than disease progression could provide some indication that biologic mechanisms involved in pathogenesis versus progression are differentially affected by this stressor.
Potential pathways by which childhood trauma might be linked to MS have, to date, not been studied, but an effect of trauma on neuroendocrine-immune networks is a likely candidate. The nervous, endocrine, and immune systems are anatomically and functionally interconnected (49), and disturbances in the communication among these systems may play a role in MS pathogenesis (50). Interestingly, animal studies have shown that neonatal exposure to high levels of glucocorticoids (51) and early-life stressors such as maternal deprivation (52) can “prime” the immune system and lead to increased susceptibility for MS-like disease during adulthood, possibly by a lasting interference with neuroendocrine responses to inflammatory stimuli (51). In line with this notion, previous research indicated that traumatic stress in general and childhood adversities in particular are independently related to a proinflammatory state later in life (20,21). Taken together, there is indirect evidence that childhood trauma may increase the risk for MS in genetically susceptible individuals through its lasting effects on neuroendocrine-immune networks, but the exact mechanisms remain to be elucidated.
Although our study has some major strengths, for example, the assessment of childhood trauma with a psychometrically sound measure, the exclusion of individuals with cognitive impairment, and the use of a control group from the general population, some limitations merit discussion. First, because our investigation was cross-sectional, the reported associations do not allow any definite causal inferences. However, considering that the CTQ inquires about adverse events in childhood and given that the mean age at MS onset was 29.2 (SD = 7.8) years, it is very likely that the traumatic childhood experiences antedated MS onset in almost all cases. Nevertheless, we cannot rule out reverse causation, that is, patients with MS are more likely to endorse items of childhood trauma. Because humans seek explanations, a phenomenon called “effort after meaning,” it may be that patients with MS misattribute their illness to childhood maltreatment (53) particularly because effort after meaning was shown to bias memory (54).
Second, being aware of the delicate issue of asking about childhood trauma in an MS cohort, we aimed to minimize questionnaire items leading to just two screening questions for depression, which we only could compare with Beck Depression Inventory II scores of the control group. Although this drawback may compromise the validity of our results, we consider this methodological issue to be minor for several reasons. In our patients with MS, the estimate for current depression was 21.4%, similar to the 12-month prevalence of 15% to 26% reported for independent MS samples (31,55). Likewise, the 8.2% current depression rate in the control group is similar to the 4-week prevalence of 5.6% reported for unipolar depression in the German general population (56). Moreover, empirical evidence suggests that recall biases due to mood-congruent memory distortions is of minor relevance (40). Although these considerations strongly suggest that our results reflect “true” associations, we are in need of replication and prospective studies to confirm this.
Third, because we included patients with MS referred to a university department (i.e., a tertiary care setting), it remains unknown if our results can be generalized to other MS samples, for example, in primary care settings. However, the sample composition was very close to other cohort study data (57–59). In addition, the frequencies of abuse and neglect reported by our control group were very similar to those found in an independent and representative German general population study (60). Finally, some MS-related variables, that is, onset, disease duration, and relapse rate, cannot be considered highly precise data because of inherent assessment problems of retrospective studies, which can only be overcome by prospective investigations with objective criteria of worsened disability in reference to a baseline (61). However, these tools may miss numerous relapses because of insensitivity to so-called hidden symptoms, for example, fatigue. Because the numbers of relapses were taken mainly derived from patients’ reports independent of the CTQ results, we do not think that this inherent weakness in determining relapse rates biased study results.
Despite these caveats possibly limiting the generalizability of our results, we suggest that emotional childhood trauma may play a role in the complex pathogenesis of MS. Although the potential mechanisms underlying the association of MS and traumatic stress have not yet been adequately tested among patients with MS, research in this area is likely to contribute to and expand on the theory of developmental origins of adult disease and health (62). Because adverse experiences in childhood are common and MS is a chronic and often debilitating condition, future studies are warranted that focus on the impact of traumatic stress on adult chronic diseases such as MS.
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