Article summary with Childhood Trauma in Adult Depressive and Anxiety Disorders: An Integrated Review on Psychological and Biological Mechanisms in the NESDA Cohort by Kuzminskaite a.o. - 2021

Introduction

Childhood trauma (CT) is one of the most robust and significant risk factors for depressive and anxiety disorders. CT is commonly defined as “all forms of physical and/or emotional ill-treatment, sexual abuse, neglect or negligent treatment or commercial or other exploitation, resulting in actual or potential harm to the child’s health, survival, development or dignity in the context of a relationship of responsibility, trust or power”. CT is operationalized as emotional (or psychological) abuse, physical abuse, and neglect (emotional or physical) before the age of 18 years.

CT has severe and long-lasting effects on both mental and somatic health across the lifespan. About one-third of all adult-onset psychiatric disorders are related to CT, with lifelong effects on morbidity and mortality. It increases the risk of negative life events, suicidality, sleep problems, and cognitive problems.

Biological research findings suggest that severe stress in early life elevates cortisol levels that over-activate glucocorticoid receptor (GR). The consequence of this glucocorticoid overproduction during early life is the abnormal development of the stress systems. Though this response may be adaptive in the short term, it comes at the cost of long-term maladaptation: a reduced capacity to respond to stress adequately and dynamically across the lifespan.

This review aims to summarize and integrate CT findings from a large longitudinal adult sample – The Netherlands Study of Depression and Anxiety (NESDA), in relation to psychopathology and discuss different psychological and biological mechanisms that may underlie the long-lasting impact of CT.

The Netherlands Study of Depression and Anxiety (NESDA)

NESDA is an ongoing longitudinal cohort study examining the course and consequences of depressive and anxiety disorders. Its sample includes Dutch-fluent adults between 18 and 65 years old with a current or remitted depressive and/or anxiety disorder. Within NESDA, CT was examined in 37 articles focused on psychopathology and potential psychological biological mechanisms underlying CT. Exposure to CT in NESDA was assessed twice: at the baseline using the structured Childhood Trauma Interview (CTI), and at a 4-year follow using the self-reported Childhood Trauma Questionnaire-Short Form (CTQ-SF). Both assess different types of CT: emotional neglect, emotional abuse, physical abuse, sexual abuse, and/or physical neglect before the age of 16, thus, while growing up.

Epidemiological Findings of CT Within NESDA

Prevalence rates of CT within NESDA (n=2970), exposure of at least once as assessed by the CTI:

• Emotional neglect (28.9%) and emotional abuse (24.8%) were most common
• Sexual (18.5%) and physical abuse (13.8%)
• Approximately half of participants (48.6%) experienced at least one type of CT

Many previous studies that reported a relationship between CT and depressive or anxiety disorders in adulthood have focused on lifetime psychopathology and the more obvious forms of maltreatment like physical and sexual abuse. Within NESDA, the emphasis was on multiple types of CT and the specificity of associations with psychopathology.

It was demonstrated that exposure to any type of CT was associated with a higher risk of current anxiety and depressive disorders in increasing strength from current anxiety to current depressive to current comorbid this order. All types of CT were also consistently and strongly associated with the presence of current anxiety and depressive disorders in adulthood.

Exposure to CT as a predictor of the 2-year course of depressive and anxiety disorders was studied in a follow-up sample of 1209 NESDA participants with a baseline diagnosis of depressive and/or anxiety disorder. Results confirmed that a reported history of CT was associated with a poor outcome, characterized by more comorbidity and chronicity.

Additionally, authors explored the differential impact of different types of CT on the onset or recurrence of anxiety, depressive, and comorbid disorders in a sub-sample of 1167 NESDA participants without current baseline depressive and/or anxiety disorder followed over a 2-year time period. It was found that a history of CT significantly predicted the first onset and recurrence of depressive and comorbid disorders, but only slightly increased the risk for anxiety disorders. Among the types, emotional neglect was the main independent predictor of first onset and recurrence of any depressive or comorbid disorder at 2-year follow-up, suggesting that the relationship between CT and psychopathology is predominantly driven by emotional neglect.

Exposure to CT may alter basic cognitive assumptions about the self and others, that over time become ingrained in an individual’s personality. The five-factor model (FFM), in which individual personality differences are grouped to the five major dimensions of neuroticism, extraversion, openness, agreeableness, and conscientiousness, presently constitutes one of the dominant models comprehensively examining personality functioning. The development of the less adaptive personality characteristics has been proposed as a potential underlying mechanism explaining the link between CT and subsequent psychopathology. The severity of CT corresponded with more maladaptive personality characteristics and cognitive reactivity styles, including higher levels of neuroticism, openness, hopelessness, rumination, and external locus of control and lower levels of extraversion, agreeableness, and conscientiousness.

Alterations in the activity of the major stress systems, namely, the hypothalamic-pituitary-adrenal (HPA)-axis, the immune-inflammatory system, and the autonomic nervous system (ANS), are at the center of the biological psychiatry research seeking to explain the enduring impact of CT. stressful life events can dysregulate the functioning of stress systems by chronically stimulating the release of cortisol, the secretion of pro-inflammatory cytokines, and the alteration of sympathetic and parasympathetic nervous system activity. These stress systems are also firmly connected by regulating each other’s functioning.

CT not only affects the brain but also extends itself to poor health behaviours and the functioning of our entire body. A recent meta-analysis showed significant associations between multiple exposures to CT and poor adult lifestyle behaviours like physical inactivity, obesity, smoking, sexual risk-taking, heavy alcohol, and illicit drug use. Within NESDA, the authors found that individuals with severe CT had significantly higher rates of smoking and body mass index (BMI) than healthy controls without CT.

Observational research shows that exposure to adverse childhood events leads to dramatically different life-course trajectories, including a two-times higher risk for premature mortality but also increased onset of various somatic conditions. CT consequently seems to be more generally linked to an increased risk for age related health conditions. This suggests that CT can generally accelerate the aging process.

Although CT is a major risk factor for depression and anxiety, considerable heterogeneity exists in outcomes after exposure to CT. Many theories posit that the impact of CT may depend on individual characteristics. But these characteristics are generally hard to identify due to methodological heterogeneity and lack of replicated findings.

Discussion & Conclusion

This review summarized and integrated the potential mechanisms through which CT exerts its adverse effects using finding from the large longitudinal adult NESDA cohort. NESDA results indicated that CT has a negative impact on the onset and the course of affective disorders, both for depression and/or anxiety disorders and their comorbidity. These findings are in line with a large body of literature showing that CT negatively impact mental health across the lifespan and is, therefore, one of the most prominent public health risks for poor mental outcomes. Findings also suggested existing interindividual differences, with some individuals exposed to CT being at significant risk for psychopathology or further biological CT-related alterations.

It’s important to determine the mechanisms by which CT exerts its adverse outcomes to better understand who is at risk and ultimately develop personalized (preventative) interventions. Findings demonstrated the complexity of an organism, suggesting that the impact of CT on poor mental health outcomes is probably a result of a complex interaction of genes, brain processes, environment, and psychological factors. We have to be careful with causal inferences, as its currently unknown how different system interact due to a lack of theoretic underpinnings and comprehensive longitudinal projects integrating psychological, environmental, and biological factors in the same samples in the context of CT.

To advance our knowledge, there are currently several unmet needs in psychiatric research concerning CT and affective disorders:

• Lack of comprehensive longitudinal projects investigating how multiple systems interact to result in affective disorders
• How these different interactions sustain and proliferate symptomatology

It is essential to elucidate the time path between CT, its underlying mechanisms, and psychopathology, as well as investigate how genes and environment are both involved in adverse CT outcomes.

The current review also has limitations as it focuses on CT findings within one cohort, and replications of integrative approaches related to CT are essential. But this is also a strength as findings are comparable since the assessment of CT and other methodology were homogenous.

Overall, this review has shown that CT impacts the functioning of the brain, mind, and body. All these aspects most likely work together and contribute to a higher vulnerability for affective disorders across the lifespan. An integration of mechanistic explanations at different psychological, biological, and environmental levels is essential to better understand the life-long adverse effects of CT in the context of affective disorders.