Day-to-day affect fluctuations in adults with childhood trauma history: a two-week ecological momentary assessment study.

BACKGROUND: Childhood trauma (CT) may increase vulnerability to psychopathology through affective dysregulation (greater variability, autocorrelation, and instability of emotional symptoms). However, CT associations with dynamic affect fluctuations while considering differences in mean affect levels across CT status have been understudied. METHODS: 346 adults (age = 49.25 ± 12.55, 67.0% female) from the Netherlands Study of Depression and Anxiety participated in ecological momentary assessment. Positive and negative affect (PA, NA) were measured five times per day for two weeks by electronic diaries. Retrospectively-reported CT included emotional neglect and emotional/physical/sexual abuse. Linear regressions determined associations between CT and affect fluctuations, controlling for age, sex, education, and mean affect levels. RESULTS: Compared to those without CT, individuals with CT reported significantly lower mean PA levels (Cohen's d = -0.620) and higher mean NA levels (d = 0.556) throughout the two weeks. CT was linked to significantly greater PA variability (d = 0.336), NA variability (d = 0.353), and NA autocorrelation (d = 0.308), with strongest effects for individuals reporting higher CT scores. However, these effects were entirely explained by differences in mean affect levels between the CT groups. Findings suggested consistency of results in adults with and without lifetime depressive/anxiety disorders and across CT types, with sexual abuse showing the smallest effects. CONCLUSIONS: Individuals with CT show greater affective dysregulation during the two-week monitoring of emotional symptoms, likely due to their consistently lower PA and higher NA levels. It is essential to consider mean affect level when interpreting the impact of CT on affect dynamics.

Childhood trauma and LPS-stimulated inflammation in adulthood: Results from the Netherlands Study of Depression and Anxiety

BACKGROUND: Childhood trauma (CT) is robustly associated with psychiatric disorders including major depressive and anxiety disorders across the life span. The innate immune system may play a role in the relation between CT and stress-related psychopathology. However, whether CT influences the innate production capacity of cytokine levels following ex vivo stimulation by lipopolysaccharide (LPS), is currently unknown. METHODS: Using data from the Netherlands Study of Depression and Anxiety (NESDA, n=1237), we examined whether CT (emotional neglect, emotional, physical, and sexual abuse before the age of 16), assessed by the Childhood Trauma Interview, was associated with levels in supernatants of interferon (IFN)γ, interleukin-2 (IL-2), IL-4, IL-6, IL-8, IL-10, IL-18, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1ß, matrix metalloproteinase-2 (MMP-2), TNFα and TNFß after ex vivo stimulation with LPS. Cytokines were analysed individually and cumulatively (overall inflammation index and number of cytokines in high-risk quartile (HRQ)) using linear regression analyses. RESULTS: After adjustment for demographic, lifestyle, and health-related covariates, total CT severity was associated with the overall inflammation index (ß = 0.085, PFDR = 0.011), the number of cytokines in HRQ (ß = 0.063, PFDR = 0.036), and individual markers of IL-2 (ß = 0.067, PFDR = 0.036), IL-6 (ß = 0.091 PFDR = 0.011), IL-8 (ß = 0.085 PFDR = 0.011), IL-10 (ß = 0.094 PFDR = 0.011), MCP-1 (ß = 0.081 PFDR = 0.011), MIP-1α (ß = 0.061 PFDR = 0.047), MIP1-ß (ß = 0.077 PFDR = 0.016), MMP-2 (ß = 0.070 PFDR = 0.027), and TNFß (ß = 0.078 PFDR = 0.016). Associations were strongest for individuals with severe CT, reporting multiple types or higher frequencies of trauma. Half of the findings persisted after adjustment for psychiatric status. The findings were consistent across different CT types. CONCLUSION: Childhood Trauma is associated with increased LPS-stimulated cytokine levels, with evidence for a dose-response relationship. Our results highlight a dysregulated innate immune system capacity in adults with CT, which could contribute to an increased vulnerability for psychopathology and somatic disorders across the lifespan.

Childhood trauma and its impact on depressive and anxiety symptomatology in adulthood: A 6-year longitudinal study.

BACKGROUND: Childhood trauma (CT) is a risk factor for depressive and anxiety disorders. However, whether CT is more strongly linked to specific clinical features of these disorders remains inconclusive. The current study comprehensively examined cross-sectional and longitudinal associations between CT and depressive/anxiety symptomatology in a large adult sample with current and remitted depressive and/or anxiety disorders. METHODS: Baseline (n = 1803), 2-year (n = 1735), 4-year (n = 1585), and 6-year follow-up (n = 1475) data from the Netherlands Study of Depression and Anxiety were used. CT (emotional neglect, emotional/physical/sexual abuse) was assessed at baseline, while depressive/anxiety symptomatology with relevant dimensions (e.g., mood/cognitive, melancholic, general distress, and somatic depression) was assessed at each wave using self-reported questionnaires. Linear regressions and linear mixed models determined cross-sectional and longitudinal associations. RESULTS: Individuals with CT, especially, severe CT, compared to those without CT, had significantly higher scores in overall depressive symptomatology (Cohen's d = 0.674), mood/cognitive depression (d = 0.691), melancholic depression (d = 0.587), general distress (d = 0.561), and somatic depression severity (d = 0.549). Differences were lower, but still highly significant for anxiety (d = 0.418), worry (d = 0.362), and fear/phobic symptomatology (d = 0.359). Effects were consistent across CT types and maintained over six years. LIMITATIONS: Retrospectively-reported CT. CONCLUSIONS: CT is a risk factor for depressive and anxiety symptomatology across all dimensions and enduring over multiple years. Screening for CT is essential to identify individuals at risk for more severe and chronic manifestations of affective disorders.

Patient Choice in Depression Psychotherapy: Outcomes of Patient-Preferred Therapy Versus Randomly Allocated Therapy.

OBJECTIVE: Patient choice is recognized as a factor that influences clinical outcomes and treatment evaluation in mental health care. However, research on how having a choice affects patients with depression has been rare. This Dutch study examined whether patients randomly selected to choose between two types of depression psychotherapy benefited more from treatment than patients randomly assigned to an intervention. METHODS: Data were derived from a trial of outpatients with depression who were randomly assigned to cognitive therapy (CT), interpersonal psychotherapy (IPT), or a 2-month waitlist control condition followed by the patient's choice of CT or IPT. Treatment groups were combined into a no-choice condition (N=151), with the waitlist as the choice condition (N=31). Multilevel regression was used to compare depression severity (measured with the Beck Depression Inventory-II [BDI-II]) and general psychological distress (measured with the Brief Symptom Inventory [BSI]) posttreatment and at the 5-month follow-up. Differences in patients' pretreatment expectations, beliefs about treatment credibility, and posttreatment evaluation were examined. RESULTS: No significant differences in clinical outcomes were found between the choice and no-choice conditions (mean difference: BDI-II posttreatment=-0.55, 95% confidence interval [CI]=-5.25 to 4.15; follow-up=2.10, 95% CI=-4.01 to 8.20; BSI posttreatment=-1.89, 95% CI=-15.35 to 11.58; follow-up=3.13, 95% CI=-12.32 to 18.57). Patients in both groups reported comparable scores on pretreatment expectations, credibility beliefs, and posttreatment evaluation. Neither expectations nor credibility beliefs were predictive of clinical outcomes. CONCLUSIONS: Our findings did not support the value of patient choice. Considering the exploratory nature of the trial, future studies designed to examine the effects of choice in depression treatment are recommended.

Patient Choice in Depression Psychotherapy: Outcomes of Patient-Preferred Therapy Versus Randomly Allocated Therapy.

OBJECTIVE: Patient choice is recognized as a factor that influences clinical outcomes and treatment evaluation in mental health care. However, research on how having a choice affects patients with depression has been rare. This Dutch study examined whether patients randomly selected to choose between two types of depression psychotherapy benefited more from treatment than patients randomly assigned to an intervention. METHODS: Data were derived from a trial of outpatients with depression who were randomly assigned to cognitive therapy (CT), interpersonal psychotherapy (IPT), or a 2-month waitlist control condition followed by the patient's choice of CT or IPT. Treatment groups were combined into a no-choice condition (N=151), with the waitlist as the choice condition (N=31). Multilevel regression was used to compare depression severity (measured with the Beck Depression Inventory-II [BDI-II]) and general psychological distress (measured with the Brief Symptom Inventory [BSI]) posttreatment and at the 5-month follow-up. Differences in patients' pretreatment expectations, beliefs about treatment credibility, and posttreatment evaluation were examined. RESULTS: No significant differences in clinical outcomes were found between the choice and no-choice conditions (mean difference: BDI-II posttreatment=-0.55, 95% confidence interval [CI]=-5.25 to 4.15; follow-up=2.10, 95% CI=-4.01 to 8.20; BSI posttreatment=-1.89, 95% CI=-15.35 to 11.58; follow-up=3.13, 95% CI=-12.32 to 18.57). Patients in both groups reported comparable scores on pretreatment expectations, credibility beliefs, and posttreatment evaluation. Neither expectations nor credibility beliefs were predictive of clinical outcomes. CONCLUSIONS: Our findings did not support the value of patient choice. Considering the exploratory nature of the trial, future studies designed to examine the effects of choice in depression treatment are recommended.

Childhood Trauma in Adult Depressive and Anxiety Disorders: An Integrated Review on Psychological and Biological Mechanisms in the NESDA Cohort.

BACKGROUND: Childhood trauma (CT) has adverse consequences on mental health across the lifespan. The understanding of how CT increases vulnerability for psychiatric disorders is growing. However, lack of an integrative approach to psychological and biological mechanisms of CT hampers further advancement. This review integrates CT findings across explanatory levels from a longitudinal adult cohort - the Netherlands Study of Depression and Anxiety (NESDA). METHODS: We reviewed all studies (k = 37) from the NESDA cohort (n = 2981) published from 2009 to 2020 containing CT findings related to psychopathology and potential psychological and biological mechanisms of CT. RESULTS: CT was associated with a higher risk of anxiety and depressive disorders with the strongest associations in the comorbid group. CT predicted the onset of these disorders, recurrence, and poorer outcomes (more comorbidity and chronicity). CT was associated with maladaptive personality characteristics and cognitions (e.g., higher neuroticism and negative self-associations), mild stress systems dysregulations (heightened levels of cortisol and inflammation), advanced biological aging (increased epigenetic aging and telomere attrition), poorer lifestyle (higher smoking rate and body mass index), somatic health decline (e.g., increased metabolic syndrome dysregulations), and brain alterations (e.g., reduced mPFC volume and increased amygdala reactivity). LIMITATIONS: Literature review of one cohort using mixed analytical approaches. CONCLUSION: CT impacts the functioning of the brain, mind, and body, which together may contribute to a higher vulnerability for affective disorders. It is essential to employ an integrative approach combining different sources of data to understand the mechanisms of CT better.

An integrated approach to understand biological stress system dysregulation across depressive and anxiety disorders.

BACKGROUND: Affective disorders involve dysregulation of major biological stress systems (hypothalamic-pituitary-adrenal (HPA)-axis, immune system, autonomic nervous system (ANS)). Suchdysregulationshave rarely beensimultaneously examined across different stress systems. METHODS: In the Netherlands Study of Depression and Anxiety (n=2789), we investigated whether current or remitted depressive and/or anxiety disorders (based on the CIDI semi-structured interview), including specific symptom profiles, were associated with separate markers and cumulative indexes of the HPA-axis (cortisol awakening response, evening cortisol, dexamethasone suppression test cortisol), immune system (C-reactive protein, interleukin-6, tumor necrosis factor-α), and ANS (heart rate, respiratory sinus arrhythmia, pre-ejection period). RESULTS: Depressive andanxiety disorderswere significantlyassociated with changes in three biological stress systemsincluding HPA-axis hyperactivity, increased inflammatory activity, and a higher ANS tone, particularly for integrative and cumulative indexes of these stress systems (pFDR <.05) vs. controls. The strongest associations were seen with current disorders andcumulative indexes of the HPA-axis (ß=.124, pFDR=.001), the immune system (ß =.057, pFDR=.032), and total cumulative index across stress systems (ß=.102, pFDR=.004). Atypical, energy-related depression severity was linked to immune system markers (pFDR<0.001), melancholic depression severity to HPA-axis markers (pFDR=.032), and anxiety arousal severity to both HPA-axis and immune system markers (pFDR<0.05). Findings were partially explained by poorer lifestyle, more chronic diseases,or (especially for ANS-function) antidepressant use. LIMITATIONS: Cross-sectional analyses limit examination of temporal associations. CONCLUSION: Patients withdepressive and anxiety disorders showed consistent dysregulation across biological stress systems, particularly for current episodes.To understand stress system functionality in affective disorders, an integrated approach capturing cumulative stress indices within and across biological stress systems is important.

Childhood trauma and dysregulation of multiple biological stress systems in adulthood: Results from the Netherlands Study of Depression and Anxiety (NESDA).

BACKGROUND: Childhood trauma (CT) is a risk factor for depressive and anxiety disorders. Although dysregulated biological stress systems may underlie the enduring effect of CT, the relation between CT and separate and cumulative activity of the major stress systems, namely, the hypothalamic-pituitary-adrenal (HPA)-axis, the immune-inflammatory system, and the autonomic nervous system (ANS), remains inconclusive. METHODS: In the Netherlands Study of Depression and Anxiety (NESDA, n = 2778), we determined whether self-reported CT (as assessed by the Childhood Trauma Interview) was associated with separate and cumulative markers of the HPA-axis (cortisol awakening response, evening cortisol, dexamethasone suppression test cortisol), the immune-inflammatory system (C-reactive protein, interleukin-6, tumor necrosis factor-α), and the ANS (heart rate, respiratory sinus arrhythmia, pre-ejection period) in adulthood. RESULTS: Almost all individuals with CT (n = 1330) had either current or remitted depressive and/or anxiety disorder (88.6%). Total-sample analyses showed little evidence for CT being significantly associated with the separate or cumulative stress systems' activity in adulthood. These findings were true for individuals with and without depressive and/or anxiety disorders. To maximize contrast, individuals with severe CT were compared to healthy controls without CT. This yielded slight, but significantly higher levels of cortisol awakening response (AUCg, ß = .088, p = .007; AUCi, ß = .084, p = .010), cumulative HPA-axis markers (ß = .115, p = .001), C-reactive protein (ß = .055, p = .032), interleukin-6 (ß = .053, p = .038), cumulative inflammation (ß = .060, p = .020), and cumulative markers across all systems (ß = .125, p = .0003) for those with severe CT, partially explained by higher rates of smoking, body mass index, and chronic diseases. CONCLUSION: While our findings do not provide conclusive evidence on CT directly dysregulating stress systems, individuals with severe CT showed slight indications of dysregulations, partially explained by an unhealthy lifestyle and poorer health.

Short report: Social communication difficulties and restricted repetitive behaviors as predictors of anxiety in adults with autism spectrum disorder.

Autism spectrum disorder and anxiety are highly comorbid conditions. Understanding the underlying traits of anxiety in autism spectrum disorder is crucial to prevent and treat it efficiently. Hence, this study determined whether social communication difficulties or restricted repetitive behaviors are stronger risk factors for anxiety symptoms in autistic adults in a large cohort. Data on 742 autistic adults from the Netherlands Autism Register were included in the study. Hierarchical regression was implemented to evaluate whether social communication difficulties (Autism-Spectrum Quotient social behavior factor) and restricted repetitive behaviors (Adult Routines Inventory) were predictive of anxiety (Hospital Anxiety and Depression Scale) controlling for age and sex. When considered together, restricted repetitive behaviors stood out as significant positive predictors of anxiety symptoms (lower-order restricted repetitive behaviors, ß = 0.32, p < 0.001; higher-order restricted repetitive behaviors, ß = 0.15, p = 0.001), whereas social communication difficulties did not (ß = 0.06, p = 0.11). Sex did not moderate these associations (p > 0.05). Non-social autistic traits are stronger predictors of anxiety symptoms than social traits in autistic adults. Increased attention to restricted repetitive behaviors should be given to improve current support programs for autistic adults with anxiety and to identify autistic individuals at risk.