Detoxification in medication-overuse headache, a retrospective controlled follow-up study: Does care by a headache nurse lead to cure?

AIM: J.A.P. and M.A.L. contributed equally to this manuscript.The aim of this article is to determine whether support by a headache nurse in the treatment of medication-overuse headache (MOH) increases successful withdrawal, and to study determinants of response to withdrawal therapy. METHODS: A retrospective, controlled follow-up study was performed with 416 MOH patients. All patients were treated with outpatient withdrawal therapy, with two treatment arms: with or without the support of a specialised headache nurse. The outcome measures were: i) successful withdrawal, defined as discontinuation of all headache medication according to the study protocol; and ii) the responder rate, defined as the percentage of patients with ≥ 50% reduction in headache days after successful withdrawal and iii) relative reduction in headache days after successful withdrawal. RESULTS: Successful withdrawal percentages were significantly higher in the group supported by the headache nurse than in the group without support (73.1% vs. 60.7%; p = 0.008), which was confirmed in multivariate analysis (OR 1.73, 95% CI 1.11-2.71, p = 0.016). Support by a headache nurse was not associated with response. The underlying primary headache diagnosis, determined after withdrawal, was significantly correlated with response. CONCLUSION: The support by a headache nurse results in an increased adherence to detoxification.

[The generalisability of depression trials to clinical practice]. / Generaliseerbaarheid van depressietrials naar de dagelijkse praktijk.

BACKGROUND: Evidence-based therapies for major depression, as described in the clinical guidelines, are based on results from randomised controlled trials (RCTs). So far, it is not known to what extent results of RCTs on major depression can be generalised to 'real life' clinical practice. AIM: To compare treatment results for major depression from RCTs (efficacy) and results from daily practice (effectiveness); furthermore, to assess to what extent eligibility criteria and (un)intended selection by recruitment procedures influences treatment outcomes in daily practice. METHOD: In a 'real life' patient population (n=1653) suffering from major depression (established by the MINIplus) and assessed in routine outcome monitoring at baseline, we explored how many patients met the eligibility criteria for antidepressant and psychotherapy efficacy trials. Furthermore we explored to what extent RCT participants differed in socio-demographic and socio-economic status from 'daily practice' patients. 626 of the ROM patients had at least one follow-up assessment. In this follow-up group we compared the treatment outcome (assessed by the MADRS and BDI-II) to the results of 15 meta-analyses of RCTs. We also explored to what extent patient selection based on eligibility criteria and socio-demographic/socio-economic status influenced treatment outcome. RESULTS: Remission percentages (21-27% in ROM versus 34-58% in RCTs) and effect sizes (0.85 in ROM versus 1.71 in RCTs, within-group data) were lower in daily practice than in RCTs. ROM patients differed from RCT participants in many disease-specific and socio-economic features. These differences are due to patient selection in RCTs. However, the influence of patient selection based on eligibility criteria and socio-demographic differences in treatment outcome were very modest (explained variances 1-11%). CONCLUSION: Treatment success for major depression is lower in daily practice than in RCTs and 'real life' patients differ in many features from RCT participants. However, these differences cannot explain the difference between efficacy and effectiveness. The generalisability of the results of depression trials to daily practice might not be jeopardised by the use of eligibility criteria and recruitment procedures to the extent suggested in earlier research.

Allodynia is associated with a higher prevalence of depression in migraine patients.

INTRODUCTION: There is a strong association between migraine and depression. The aim of this study is to identify migraine-specific factors involved in this association. METHODS: We conducted a cross-sectional study in a large, well-defined cohort of migraine patients (n=2533). We assessed lifetime depression using validated questionnaires, and diagnosed migraine based on the International Classification of Headache Disorders III-beta criteria. Multivariate regression analyses were conducted. RESULTS: Of the 2533 migraineurs that were eligible, 1137 (45%) suffered from lifetime depression. The following independent factors were associated with an increased depression prevalence: i) migraine-specific risk factors: high migraine attack frequency and the presence of allodynia, ii) general factors: being a bad sleeper, female gender, high BMI, being single, smoking, and a low alcohol consumption. CONCLUSION: This study identified allodynia, in addition to high migraine attack frequency, as a new migraine-specific factor associated with depression.

[The Leiden Routine Outcome Monitoring Study: mood, anxiety and somatoform disorders in patients attending a day clinic]. / De Leiden Routine Outcome Monitoring Studie: beloop van stemmings-, angst- en somatoforme stoornissen in de poliklinische praktijk.

BACKGROUND: Routine outcome monitoring (rom) is a method for the systematic monitoring of treatment-progression. Because rom data are collected regularly and systematically, we believe it should be possible to use these data in clinical epidemiological research. AIM: To describe, on the basis of publications of the Leiden Routine Outcome Monitoring Study, a number of potential research topics in which rom data can play a role. METHOD: We used rom data of patients referred, between 2004 and 2009, to secondary or tertiary care for treatment of a mood, anxiety or somatoform disorder. RESULTS: We describe three cross-sectional studies and one prospective study in which we aimed to identify predictors of outcome. CONCLUSION: These studies demonstrate clearly that it is feasible to use rom data to supplement clinical epidemiological research done on patients. Together these findings can be a useful addition to data derived from randomised clinical trials.

Resting-state functional connectivity in adults with childhood emotional maltreatment.

BACKGROUND: Childhood emotional maltreatment (CEM) has been associated with disturbances in emotional and behavioral functioning, and with changes in regional brain morphology. However, whether CEM has any effect on the intrinsic organization of the brain is not known. In this study, we investigated the effects of CEM on resting-state functional connectivity (RSFC) using seeds in the limbic network, the default-mode network (DMN) and the salience network, and the left dorsomedial prefrontal cortex (dmPFC). Method Using 3-T magnetic resonance imaging (MRI), resting-state functional MRI (RS-fMRI) scans were obtained. We defined seeds in the bilateral amygdala, the dorsal anterior cingulate cortex (dACC), the posterior cingulate cortex (PCC) and the left dmPFC, and used these to examine whether individuals reporting CEM (n=44) differed from individuals reporting no CEM (n=44) in RSFC with other brain regions. The two groups were matched for age, gender, handedness and the presence of psychopathology. RESULTS: CEM was associated with decreased RSFC between the right amygdala and the bilateral precuneus and a cluster extending from the left insula to the hippocampus and putamen. In addition, CEM was associated with decreased RSFC between the dACC and the precuneus and also frontal regions of the brain. CONCLUSIONS: We found that CEM has a profound effect on RSFC in the limbic network and the salience network. Regions that show aberrant connectivity are related to episodic memory encoding, retrieval and self-processing operations.

Influence of sociodemographic and socioeconomic features on treatment outcome in RCTs versus daily psychiatric practice.

PURPOSE: Sociodemographic and socioeconomic characteristics of participants in antidepressant and psychotherapy efficacy trials (AETs and PETs) for major depressive disorder (MDD) may limit the generalizability of the results. We compared trial participants with daily practice patients. We subsequently assessed the influence of socio-demographic and socioeconomic status on treatment outcome in daily practice. METHODS: Data on daily practice patients were derived through routine outcome monitoring (ROM). We included 626 patients with MDD according to the MINIplus. Distributions of age, gender, race, marital status and employment status were compared with participants in 63 selected AETs and PETs. Influence of these features on treatment outcome was explored through multivariate regression analysis. RESULTS: Trial participants were older, more often male (diff. 4 %, p = 0.05), white (diff. 4 %, p < 0.001) and not married (diff. 7 %, p = 0.003). Although significant, most differences were relatively small. However, the difference in employment status was striking: 34 % of the ROM patients were currently working versus 68 % of the trial participants (diff. 34 %, p < 0.001). Being employed contributed to a positive treatment outcome: OR 1.8 for response [50 % reduction of Montgomery Asberg Rating Scale for Depression (MADRS)], OR 1.9 for remission (MADRS ≤10). CONCLUSIONS: Employment status should be taken into account while interpreting results from randomized controlled trials and as predictor of treatment success in daily practice.

Genetic risk profiles for depression and anxiety in adult and elderly cohorts.

The first generation of genome-wide association studies (GWA studies) for psychiatric disorders has led to new insights regarding the genetic architecture of these disorders. We now start to realize that a larger number of genes, each with a small contribution, are likely to explain the heritability of psychiatric diseases. The contribution of a large number of genes to complex traits can be analyzed with genome-wide profiling. In a discovery sample, a genetic risk profile for depression was defined based on a GWA study of 1738 adult cases and 1802 controls. The genetic risk scores were tested in two population-based samples of elderly participants. The genetic risk profiles were evaluated for depression and anxiety in the Rotterdam Study cohort and the Erasmus Rucphen Family (ERF) study. The genetic risk scores were significantly associated with different measures of depression and explained up to ∼0.7% of the variance in depression in Rotterdam Study and up to ∼1% in ERF study. The genetic score for depression was also significantly associated with anxiety explaining up to 2.1% in Rotterdam study. These findings suggest the presence of many genetic loci of small effect that influence both depression and anxiety. Remarkably, the predictive value of these profiles was as large in the sample of elderly participants as in the middle-aged samples.

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

OBJECTIVE: Data on the impact of childhood life events and childhood trauma on the clinical course of depressive and anxiety disorders are limited. METHOD: Longitudinal data were collected from 1209 adult participants in the Netherlands Study of Depression and Anxiety (NESDA). Childhood life events and trauma at baseline were assessed with a semi-structured interview and the clinical course after 2 years with a DSM-IV-based diagnostic interview and Life Chart Interview. RESULTS: At baseline, 18.4% reported at least one childhood life event and 57.8% any childhood trauma. Childhood life events were not predictive of any measures of course trajectory. Emotional neglect, psychological and physical abuse, but not sexual abuse, were associated with persistence of both depressive and comorbid anxiety and depressive disorder at follow-up. Emotional neglect and psychological abuse were associated with a higher occurrence of a chronic course. Poor course outcomes were mediated mainly through a higher baseline severity of depressive symptoms. CONCLUSION: Childhood trauma, but not childhood life events, was associated with an increased persistence of comorbidity and chronicity in adults with anxiety and/or depressive disorders. More unfavourable clinical characteristics at baseline mediate the relationship between childhood trauma and a poorer course of depressive and anxiety disorders.

Utility of the Brief Symptom Inventory (BSI) in psychiatric outpatients with intellectual disabilities.

BACKGROUND: Diagnostics and care for people with intellectual disabilities (ID) and psychiatric disorders need to be improved. This can be done by using assessment instruments to routinely measure the nature and severity of psychiatric symptoms. Up until now, in the Netherlands, assessment measures are seldom used in the psychiatric care for this population. The objective of the present paper is to evaluate the use of the Brief Symptom Inventory (BSI), a widely used standardised questionnaire in general psychiatry, in a well-defined sample of people with borderline intellectual functioning or mild ID diagnosed with one or more psychiatric disorders. METHODS: A total of 224 psychiatric outpatients with either borderline intellectual functioning or mild ID participated in this study. All participants were new patients of Kristal, Centre for Psychiatry and Intellectual Disability in the Netherlands, in the period between 1 April 2008 and 1 October 2009. All participants were assessed by a multidisciplinary team, including a certified psychiatrist. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria were applied. The mean total intelligence quotient was measured with the Wechsler Adult Intelligence Scale (WAIS-III). The BSI was administered in an assisted fashion. Utility and psychometric properties of the BSI were investigated. Internal consistency coefficients (Cronbach's alphas) were computed. Bivariate correlations between the sub-scales were computed to assess differentiation between the scales. Mean sub-scale scores were compared between different DSM-IV-TR subgroups to investigate the discriminant abilities of the scales. A confirmatory factor analysis was conducted. RESULTS: The results suggest that the BSI is practically useful. Internal consistencies ranged from 0.70 to 0.96 and thus are considered good to adequate. Sub-scale inter-correlations showed there is a degree of differentiation between the sub-scales. Discriminant validity was shown for the sub-scales depression, anxiety and phobic anxiety. Confirmatory factor analysis showed that the underlying structure of the BSI could be described by the same nine-factor model as reported in previous studies. CONCLUSIONS: As a result of the psychometric properties illustrated, this study supports the use of the BSI as a screener for psychopathology and a general outcome measure in people with ID.

[Staging, profiling and routine outcome monitoring]. / Stagering, profilering en routine outcome monitoring.

BACKGROUND: Staging and profiling can make a valuable contribution to more effective and tailor-made treatments. In psychiatry these techniques have so far played only a very limited role. Routine outcome monitoring ROM ) may be able to alter the situation. AIM: To describe the criteria of a ROM-system that is ideal for staging and profiling and to find out to what extent some existing rom-systems satisfy these criteria. METHOD: The method used was to investigate to what extent the minimal dataset of the Stichting Benchmark GGZ and the ROM of the Leiden Routine Outcome Monitoring Study meet the criteria formulated in this article for an ideal ROM and provide a 'proof of principle'. RESULTS: The minimal dataset of the Stichting Benchmark ggz satisfies fewer criteria than the ROM of the Leiden Routine Outcome Monitoring Study, but neither fulfils all the criteria. Nevertheless, even without adequate datasets the Leiden Routine Outcome Monitoring Study can make a useful contribution to the staging of depression and mental health in general and to the profiling of depression. CONCLUSION: ROM is an important instrument for the development of staging and profiling in psychiatry.

[ROM in mood, anxiety and somatoform disorders: a promising technique with pleasing results]. / ROM bij stemmings-, angst- en somatoforme stoornissen; bemoedigende resultaten.

BACKGROUND: Since 2002 the Leiden University Medical Center and the psychiatric hospital Rivierduinen have been using routine outcome monitoring in patients suffering from mood, anxiety and somatoform disorders (ROM). AIM: To describe the ROM-MAS set-up, explain how the system was implemented and report on the data-based scientific research that ensued. METHOD: The study is mainly descriptive. RESULTS: Circa 80% of the patients were assessed at intake, 50% via follow-up measurements. ROM-MAS has become a regular component of patient care. However, it has proved difficult to make full use of the outcomes in clinical practice and particularly in benchmarking. The data for 8357 patients have generated various publications relating to psychometrics, epidemiology and effects of treatment. CONCLUSION: ROM-MAS is now generally accepted and has been introduced in most psychiatric clinics. The next step is to make better use of the results for clinical practice and for benchmarking. ROM-MAS provides valuable data and generates publications relating to a naturalistic secondary-care cohort.

[Empirical evidence for the effectiveness of Routine Outcome Monitoring. A study of the literature]. / Empirische evidence voor de effectiviteit van routine outcome monitoring; een literatuuronderzoek.

BACKGROUND: Routine Outcome Monitoring ROM is an important instrument for measuring the effectiveness of treatment and has been implemented in the Dutch mental health care system. AIM: To review the effectiveness of ROM with regard to diagnosis, treatment, and other outcomes. METHOD: The literature study focused on randomised controlled trials RCT's of ROM performed on patients of all age groups, some being general patients, others being psychiatric patients. The main search words were 'routine outcome monitoring' or 'routine outcome measurement'. RESULTS: 52 RCTs on adult patients were included in the study; 45 of these trials were performed on patients with mental health problems, but not always in a psychiatric setting or as primary outcome measure. rom appears to have positive effects on diagnosis and treatment and on the communication between patient and therapist. Other results were less clear. CONCLUSION: ROM seems to be particularly effective for the monitoring of treatments which have not been entirely successful. Further research needs to be done into the clinical and cost-effectiveness of ROM when used with adults and children who have mental health problems.

The generalizability of antidepressant efficacy trials to routine psychiatric out-patient practice.

BACKGROUND: Generalizability of antidepressant efficacy trials (AETs) to daily practice is questioned because of their very stringent patient selection. This study aims to determine eligibility for AETs of out-patients suffering from major depression in a routine out-patient setting and investigates influence of eligibility on treatment outcome. METHOD: Data collection (n = 1653) was performed through routine outcome monitoring by independent trained research nurses. The Mini-International Neuropsychiatric Interview Plus and the Dimensional Assessment of Personality Pathology, short Dutch version were used for diagnostic assessment and personality pathology screening. The Montgomery-Asberg Depression Rating Scale (MADRS) was used for assessment of baseline severity and treatment outcome. Eligibility was assessed by stepwise application of commonly used exclusion criteria. Influence of eligibility on treatment outcome was investigated in a subsample of the 1653 patients who had at least one follow-up assessment (n = 626). Eligible and non-eligible patients were compared on proportion of response (50% reduction) and remission on MADRS (MADRS ≤ 10). RESULTS: Altogether, 17-25% of the patients were eligible for AETs. The most common reasons for exclusion would be 'not meeting minimum baseline severity' and 'presence of co-morbid Axis I disorder'. Eligible and non-eligible patients did not differ in treatment outcome. Only 'meeting the minimum baseline severity' is associated with remission. CONCLUSIONS: The majority of 'real life' out-patients are not eligible for AETs. However, the influence of eligibility on treatment outcome seems to be small. This suggests that stringent patient selection by eligibility criteria is not the major reason for lack of generalizability of AETs. Exclusion of less severely depressed patients from the analyses resulted in better treatment outcome. Milder depression is highly prevalent in daily practice and more research into treatment effectiveness in milder depression is warranted.

Pre-adult versus adult onset major depressive disorder in a naturalistic patient sample: the Leiden Routine Outcome Monitoring Study.

BACKGROUND: Pre-adult onset of major depressive disorder (MDD) may predict a more severe phenotype of depression. As data from naturalistic psychiatric specialty care settings are scarce, we examined phenotypic differences between pre-adult and adult onset MDD in a large sample of consecutive out-patients. METHOD: Altogether, 1552 out-patients, mean age 39.2 ± 11.6 years, were diagnosed with current MDD on the Mini-International Neuropsychiatric Interview Plus diagnostic interview as part of the usual diagnostic procedure. A total of 1105 patients (71.2%) had complete data on all variables of interest. Pre-adult onset of MDD was defined as having experienced the signs and symptoms of a first major depressive episode before the age of 18 years. Patients were stratified according to the age at interview (20-40/40-65 years). Correlates of pre-adult onset were analysed using logistic regression models adjusted for age, age squared and gender. RESULTS: Univariate analyses showed that pre-adult onset of MDD had a distinct set of demographic (e.g. less frequently living alone) and clinical correlates (more co-morbid DSM-IV - Text Revision diagnoses, more social phobia, more suicidality). In the multivariate model, we found an independent association only for a history of suicide attempts [odds ratio (OR) 3.15, 95% confidence intervals (CI) 1.97-5.05] and current suicidal thoughts (OR 1.81, 95% CI 1.26-2.60) in patients with pre-adult versus adult onset MDD. CONCLUSIONS: Pre-adult onset of MDD is associated with more suicidality than adult onset MDD. Age of onset of depression is an easy to ascertain characteristic that may help clinicians in weighing suicide risk.

Functional MRI correlates of visuospatial planning in out-patient depression and anxiety.

OBJECTIVE: Major depressive disorder (MDD) has been associated with executive dysfunction and related abnormal prefrontal activity, whereas the status of executive function (EF) in frequently co-occurring anxiety disorders and in comorbid depression-anxiety is unclear. We aimed to study functional MRI correlates of (visuospatial) planning in MDD and anxiety disorders and to test for the effects of their comorbidity. METHOD: Functional MRI was employed during performance of a parametric Tower of London task in out-patients with MDD (n = 65), MDD with comorbid anxiety (n = 82) or anxiety disorders without MDD (n = 64), and controls (n = 63). RESULTS: Moderately/severely depressed patients with MDD showed increased left dorsolateral prefrontal activity as a function of task load, together with subtle slowing during task execution. In mildly depressed and remitted MDD patients, in anxiety patients, and in patients with comorbid depression-anxiety, task performance was normal and no activation differences were observed. Medication use and regional brain volume were not associated with altered visuospatial planning. CONCLUSION: Prefrontal hyperactivation during high planning demands is not a trait characteristic, but a state characteristic of MDD without comorbid anxiety, occurring independent of SSRI use. Disturbances in planning or the related activation are probably not a feature of anxiety disorders with or without comorbid MDD, supporting the current distinction between anxiety disorders and depression.

Positive and negative life events and personality traits in predicting course of depression and anxiety.

OBJECTIVE: To examine the prognostic value of personality dimensions and negative and positive life events for diagnostic and symptom course trajectories in depressive and anxiety disorder. METHOD: A total of 1209 subjects (18-65 years) with depressive and/or anxiety disorder were recruited in primary and specialized mental health care. Personality dimensions at baseline were assessed with the NEO-FFI and incidence and date of life events retrospectively with a structured interview at 2-year follow-up. DSM-IV-based diagnostic interviews as well as life chart assessments allowed course assessment at both the diagnostic and symptom trajectory level over 2 years. RESULTS: Life events were significantly related to diagnostic and symptom course trajectories of depression and anxiety also after correcting for sociodemographic and clinical characteristics. Only negative life events prospectively predicted longer time to remission of depressive disorder. Prospective associations of neuroticism and extraversion with prognosis of anxiety and depression were greatly reduced after correcting for baseline severity and duration of index disorder. Personality traits did not moderate the effect of life events on 2-year course indicators. CONCLUSIONS: Negative life events have an independent effect on diagnostic and symptom course trajectories of depression and to a lesser extent anxiety unconfounded by sociodemographic, clinical, and personality characteristics.

Routine outcome monitoring in the Netherlands: practical experiences with a web-based strategy for the assessment of treatment outcome in clinical practice.

Routine outcome monitoring (ROM) is a method devised to systematically collect data on the effectiveness of treatments in everyday clinical practice. ROM involves documenting the outcome of treatments through repeated assessments. Assistants are employed who perform a baseline assessment comprising a standardized diagnostic interview, administration of rating scales and completion of several self-report measures by the patient. At fixed time intervals, assessments are repeated. Dedicated Web-based software has been developed to assist in this task. ROM informs therapists and patients on the severity of the complaints at intake, and the waxing and waning of symptoms over the course of treatment. Researchers can use ROM for effectiveness research, and managers can use it for benchmarking. The use of ROM for research is illustrated by presenting data on the diagnostic status of patients participating in ROM and data on treatment outcome of a subgroup of patients (with panic disorder) in our database. The results show that implementation of ROM is feasible, and after some initial reservations, most therapists now consider ROM to be a necessary and important adjunct to the clinical treatment. In addition, ROM furthers research as the data can be used to study the phenomenology of psychiatric disorders and the outcome of treatments delivered in everyday practice.

Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo.

Major depressive disorder (MDD) is a common complex trait with enormous public health significance. As part of the Genetic Association Information Network initiative of the US Foundation for the National Institutes of Health, we conducted a genome-wide association study of 435 291 single nucleotide polymorphisms (SNPs) genotyped in 1738 MDD cases and 1802 controls selected to be at low liability for MDD. Of the top 200, 11 signals localized to a 167 kb region overlapping the gene piccolo (PCLO, whose protein product localizes to the cytomatrix of the presynaptic active zone and is important in monoaminergic neurotransmission in the brain) with P-values of 7.7 x 10(-7) for rs2715148 and 1.2 x 10(-6) for rs2522833. We undertook replication of SNPs in this region in five independent samples (6079 MDD independent cases and 5893 controls) but no SNP exceeded the replication significance threshold when all replication samples were analyzed together. However, there was heterogeneity in the replication samples, and secondary analysis of the original sample with the sample of greatest similarity yielded P=6.4 x 10(-8) for the nonsynonymous SNP rs2522833 that gives rise to a serine to alanine substitution near a C2 calcium-binding domain of the PCLO protein. With the integrated replication effort, we present a specific hypothesis for further studies.

Metabolic syndrome abnormalities are associated with severity of anxiety and depression and with tricyclic antidepressant use.

OBJECTIVE: The metabolic syndrome (MetSyn) predisposes to cardiovascular disease and diabetes mellitus. There might also be an association between the MetSyn and anxiety and depression, but its nature is unclear. We aimed to investigate whether diagnosis, symptom severity and antidepressant use are associated with the MetSyn. METHOD: We addressed the odds for the MetSyn and its components among 1217 depressed and/or anxious subjects and 629 controls, and their associations with symptom severity and antidepressant use. RESULTS: Symptom severity was positively associated with prevalence of the MetSyn, [adjusted odds ratio (OR) 2.21 for very severe depression: 95% confidence interval (CI): 1.06-4.64, P = 0.04], which could be attributed to abdominal obesity and dyslipidemia. Tricyclic antidepressant (TCA) use also increased odds for the MetSyn (OR 2.30, 95% CI: 1.21-4.36, P = 0.01), independent of depression severity. CONCLUSION: The most severely depressed people and TCA users more often have the MetSyn, which is driven by abdominal adiposity and dyslipidemia.

Childhood life events and childhood trauma in adult patients with depressive, anxiety and comorbid disorders vs. controls.

OBJECTIVE: To investigate the association between childhood life events, childhood trauma and the presence of anxiety, depressive or comorbid anxiety and depressive disorders in adulthood. METHOD: Data are from 1931 adult participants in the Netherlands Study of Depression and Anxiety (NESDA). Childhood life events included divorce of parents, early parental loss and 'placed in care', whereas childhood trauma was assessed as experienced emotional neglect, psychological, physical and sexual abuse prior to age 16. RESULTS: Childhood life events were not associated with psychopathology, except for 'placed in care' in the comorbid group. All types of childhood trauma were increasingly prevalent in the following order: controls, anxiety, depression, and comorbid group (P < 0.001). The higher the score was on the childhood trauma index, the stronger the association with psychopathology (P < 0.001). CONCLUSION: Childhood trauma rather than childhood life events are related to anxiety and depressive disorders. The strong associations with the comorbid group suggest that childhood trauma contributes to the severity of psychopathology. Our study underscores the importance of heightened awareness of the possible presence of childhood trauma, especially in adult patients with comorbid anxiety and depressive disorders.