Childhood abuse v. neglect and risk for major psychiatric disorders.

BACKGROUND: Childhood maltreatment (CM) is a strong risk factor for psychiatric disorders but serves in its current definitions as an umbrella for various fundamentally different childhood experiences. As first step toward a more refined analysis of the impact of CM, our objective is to revisit the relation of abuse and neglect, major subtypes of CM, with symptoms across disorders. METHODS: Three longitudinal studies of major depressive disorder (MDD, N = 1240), bipolar disorder (BD, N = 1339), and schizophrenia (SCZ, N = 577), each including controls (N = 881), were analyzed. Multivariate regression models were used to examine the relation between exposure to abuse, neglect, or their combination to the odds for MDD, BD, SCZ, and symptoms across disorders. Bidirectional Mendelian randomization (MR) was used to probe causality, using genetic instruments of abuse and neglect derived from UK Biobank data (N = 143 473). RESULTS: Abuse was the stronger risk factor for SCZ (OR 3.51, 95% CI 2.17-5.67) and neglect for BD (OR 2.69, 95% CI 2.09-3.46). Combined CM was related to increased risk exceeding additive effects of abuse and neglect for MDD (RERI = 1.4) and BD (RERI = 1.1). Across disorders, abuse was associated with hallucinations (OR 2.16, 95% CI 1.55-3.01) and suicide attempts (OR 2.16, 95% CI 1.55-3.01) whereas neglect was associated with agitation (OR 1.24, 95% CI 1.02-1.51) and reduced need for sleep (OR 1.64, 95% CI 1.08-2.48). MR analyses were consistent with a bidirectional causal effect of abuse with SCZ (IVWforward = 0.13, 95% CI 0.01-0.24). CONCLUSIONS: Childhood abuse and neglect are associated with different risks to psychiatric symptoms and disorders. Unraveling the origin of these differences may advance understanding of disease etiology and ultimately facilitate development of improved personalized treatment strategies.

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.

Psychological Symptoms and Quality of Life After Simultaneous Kidney and Pancreas Transplantation.

Patients that have undergone successful simultaneous pancreas/kidney (SPK) transplantation attain normoglycemia and are free from dialysis. However, only a minor improvement in quality of life (QOL) has been demonstrated. Here, we evaluated the role of psychological symptoms in QOL after SPK transplantation. METHODS: We assessed patients with type 1 diabetes and end-stage renal disease waitlisted for SPK transplantation (pre-SPK, n = 47), and recipients of an SPK transplant (post-SPK, n = 72). Matched patients with type 1 diabetes without end-stage renal disease were included as reference group (type 1 diabetes [T1D] reference group, n = 42). The brief symptom inventory (BSI) was used to measure psychological symptoms. The Short Form-36 (SF-36) was used to determine QOL. RESULTS: Post-SPK patients scored slightly better on the SF-36 than pre-SPK patients ("General health" 47.2 ± 23.1 versus 37.5 ± 18.1 [P = 0.017]). In the T1D reference group, this score was 60.6 ± 22.3. Post- and pre-SPK patients had similar BSI scores (0.54 ± 0.55 and 0.45 ± 0.42, respectively [P = 0.34]). This score was better in the T1D reference group (BSI score 0.32 ± 0.33). The BSI score inversely correlated with the SF-36 (r = -0.61, P < 0.001). CONCLUSIONS: Psychological symptoms are prevalent in both pre-SPK and post-SPK patients and could play an important role in the reduced QOL observed in these groups.

CHILDHOOD MALTREATMENT AND THE COURSE OF DEPRESSIVE AND ANXIETY DISORDERS: THE CONTRIBUTION OF PERSONALITY CHARACTERISTICS.

BACKGROUND: We investigated the effect of childhood maltreatment on predicting the 4-year course of depressive and anxiety disorders and the possible mediating role of personality characteristics in the association between childhood maltreatment and illness course. METHODS: Longitudinal data in a large sample of participants with baseline depressive and/or anxiety disorders (n = 1,474, 18-65 years) were collected in the Netherlands Study of Depression and Anxiety. At baseline, childhood maltreatment was assessed with a semistructured interview. Personality trait questionnaires (Neuroticism-Extroversion-Openness Five Factor Inventory, Mastery scale, and Leiden Index of Depression Sensitivity), recent stressful life events (List of Threatening Experiences Questionnaire), and psychosocial variables were administered. The Life Chart Interview was used to determine the time to remission of depressive and/or anxiety disorders. RESULTS: At baseline, 846 participants (57.4%) reported any childhood maltreatment. Childhood maltreatment had a negative impact on psychosocial functioning and was predictive of more unfavorable personality characteristics and cognitive reactivity styles (P < 0.001). Childhood maltreatment was a significant predictor of lower likelihood of remission of depressive and/or anxiety disorders (HR = 0.94, P < 0.001). High levels of neuroticism, hopelessness, external locus of control, and low levels of extraversion were mediating the relationship between childhood maltreatment and 4-year remission of depressive and anxiety disorders. CONCLUSIONS: Certain personality characteristics are key players in the mechanism linking childhood maltreatment to an adverse illness course of depressive and anxiety disorders. Early interventions--reducing neuroticism and hopelessness, and enhancing extraversion and locus of control--might contribute to a better prognosis in a "high-risk" group of depressive and anxiety disorders.

Impact of childhood life events and childhood trauma on the onset and recurrence of depressive and anxiety disorders.

OBJECTIVE: To investigate the effect of childhood life events and childhood trauma on the onset and recurrence of depressive and/or anxiety disorders over a 2-year period in participants without current psychopathology at baseline. METHOD: Longitudinal data in a large sample of participants without baseline DSM-IV depressive or anxiety disorders (n = 1,167, aged 18 to 65 years; assessed between 2004-2007) were collected in the Netherlands Study of Depression and Anxiety (NESDA). Childhood life events and childhood trauma were assessed at baseline with a semistructured interview. The Composite International Diagnostic Interview, based on DSM-IV criteria, was used to diagnose first onset or recurrent depressive and/or anxiety disorders over a 2-year period. RESULTS: At baseline, 172 participants (14.7%) reported at least 1 childhood life event, and 412 (35.3%) reported any childhood trauma. During 2 years of follow-up, 226 participants (19.4%) developed a new (n = 58) or recurrent (n = 168) episode of a depressive and/or anxiety disorder. Childhood life events did not predict the onset and recurrence of depressive or anxiety disorders. Emotional neglect and psychological, physical, and sexual abuse were all associated with an increased risk of first onset and recurrence of either depressive or comorbid disorders (P < .001), but not of anxiety disorders. In multivariate models, emotional neglect was the only significant independent predictor of first onset and recurrence of any depressive or comorbid disorder (P = .002). These effects were primarily mediated by the severity of (subclinical) depressive symptoms at baseline and, to a lesser extent, by a prior lifetime diagnosis of a depressive and/or anxiety disorder. CONCLUSIONS: Childhood maltreatment is a key environmental risk factor, inducing vulnerability to develop new and recurrent depressive and comorbid anxiety and depressive episodes.

Fetal, neonatal and developmental outcomes of lithium-exposed pregnancies.

INTRODUCTION: Many women with a bipolar disorder are of reproductive age and will need to continue lithium treatment during pregnancy. The teratogenic and perinatal effects of lithium are known, but not the long-term effects of lithium on neurodevelopment of the children. This study investigates growth, neurological, cognitive and behavioral development of children exposed to lithium in utero. METHOD: In an observational retrospective cohort study 15 children who were exposed to lithium in utero were investigated at 3-15 years of age. Neurological development was tested using the Hempel or Touwen examination. Cognitive development was assessed with the Bayley Scales of Infant Development III, Wechsler Preschool and Primary Scale of Intelligence or the Wechsler Intelligence Scale for Children. Parents completed the Child Behavior Checklist to assess behavioral development and a standard questionnaire about general development of the child since birth. RESULTS: One child had signs of a minor neurological dysfunction, but without further clinical implications. The results of the cognitive tests were within normal limits, although most children had lower scores on the performance IQ subtest. Growth, behavior and general development were within the normal range. CONCLUSIONS: Continuing lithium therapy during pregnancy did not cause adverse effects on growth, neurological, cognitive and behavioral development of exposed children.

The effects of neuroticism, extraversion, and positive and negative life events on a one-year course of depressive symptoms in euthymic previously depressed patients versus healthy controls.

We investigated a) the concurrent impact of positive and negative life events on the course of depressive symptoms in persons remitted from depression and healthy controls, b) whether the impact of life events on symptom course is moderated by the history of depression and the personality traits of neuroticism and extraversion, and c) whether life events mediate possible relationships of history of depression and personality traits with symptom course. Using data from the Netherlands Study of Depression and Anxiety, we examined 239 euthymic participants with a previous depressive disorder based on DSM-IV and 450 healthy controls who completed a) baseline assessments of personality dimensions (NEO Five-Factor Inventory) and depression severity (Inventory of Depressive Symptoms [IDS]) and b) 1-year follow-up assessments of depression severity and the occurrence of positive and negative life events during the follow-up period (List of Threatening Events Questionnaire). Remitted persons reported higher IDS scores at 1-year follow-up than did the controls. Extraversion and positive and negative life events independently predicted the course of depressive symptoms. The impact of life events on symptom course was not moderated by history of depression or personality traits. The effect of extraversion on symptom course was partly caused by differential engagement in positive life events.

The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders.

BACKGROUND: Although several studies have shown that life adversities play an important role in the etiology and maintenance of both depressive and anxiety disorders, little is known about the relative specificity of several types of life adversities to different forms of depressive and anxiety disorder and the concurrent role of neuroticism. Few studies have investigated whether clustering of life adversities or comorbidity of psychiatric disorders critically influence these relationships. METHODS: Using data from the Netherlands Study of Depression and Anxiety (NESDA), we analyzed the association of childhood adversities and negative life experiences across the lifespan with lifetime DSM-IV-based diagnoses of depression or anxiety among 2288 participants with at least one affective disorder. RESULTS: Controlling for comorbidity and clustering of adversities the association of childhood adversity with affective disorders was greater than that of negative life events across the life span with affective disorders. Among childhood adversities, emotional neglect was specifically associated with depressive disorder, dysthymia, and social phobia. Persons with a history of emotional neglect and sexual abuse were more likely to develop more than one lifetime affective disorder. Neuroticism and current affective disorder did not affect the adversity-disorder relationships found. LIMITATIONS: Using a retrospective study design, causal interpretations of the relationships found are not warranted. CONCLUSIONS: Emotional neglect seems to be differentially related to depression, dysthymia and social phobia. This knowledge may help to reduce underestimation of the impact of emotional abuse and lead to better recognition and treatment to prevent long-term disorders.

The importance of childhood trauma and childhood life events for chronicity of depression in adults.

BACKGROUND: Childhood trauma is linked to adult depression and might be a risk factor for a more chronic course of depression. However, the link between childhood trauma and chronicity of depression has not been investigated using a large and representative sample in which other depression characteristics, such as severity, age at onset, and comorbid psychopathology, were taken into account. METHOD: Baseline data, collected during 2004 through 2007, were drawn from the Netherlands Study of Depression and Anxiety (NESDA). Participants had a current DSM-IV-TR diagnosis of major depressive disorder (MDD) and were recruited from the community, primary care settings, and specialized mental health care facilities (N = 1230). Relationships between both childhood trauma and childhood life events and chronicity of depression were examined using multiple logistic regression models. Chronicity of depression was defined as being depressed for 24 months or more in the past 4 years. RESULTS: Chronicity of depression was associated with a significantly higher prevalence of childhood trauma but was not associated with childhood life events. We found the strongest association for those with the highest score on a cumulative index summarizing frequency of childhood trauma (OR = 3.26; 95% CI = 1.86 to 5.72, p < .001). After controlling for comorbid anxiety disorders, severity of depressive symptoms, and age at onset of depression, we found that the association between childhood trauma index and chronicity of depression remained significant (OR = 2.06; 95% CI = 1.13 to 3.73, p = .02). CONCLUSIONS: These results suggest that multiple childhood traumas can be seen as an independent determinant of chronicity of depression. For treatment of depressed patients, it is therefore important to detect the presence of childhood trauma.