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An abstract of the article "Need for Alternative Ways of Phenotyping of Mood, Anxiety, and Somatoform Disorders in Biological Research," by G. Veen and colleagues is presented.

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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: No somatic treatment has been found to be effective for chronic fatigue syndrome (CFS). Antidepressant therapy is commonly used. Fluoxetine is recommended in preference to tricyclic agents because it has fewer sedative and autonomic nervous system effects. However, there have been no randomised, placebo-controlled, double-blind studies showing the effectiveness of antidepressant therapy in CFS. We have carried out such a study to assess the effect of fluoxetine in depressed and non-depressed CFS patients.Methods: In this randomised, double-blind study, we recruited 44 patients to the depressed CFS group, and 52 to the non-depressed CFS group. In each group participants were randomly assigned to receive either fluoxetine (20 mg once daily) or placebo for 8 weeks. The effect of fluoxetine was assessed by questionnaires, self-observation lists, standard neuropsychological tests, and a motion-sensing device (Actometer), which were applied on the day treatment started and on the last day.Findings: The two groups were well matched in terms of age, sex distribution, employment and marital status, and duration of CFS. There were no significant differences between the placebo and fluoxetine-treated groups in the change during the 8-week treatment period for any dimension of CFS. There was no change in subjective assessments of fatigue, severity of depression, functional impairment, sleep disturbances, neuropsychological function, cognitions, or physical activity in the depressed or the non-depressed subgroup.Interpretation: Fluoxetine in a 20 mg daily dose does not have a beneficial effect on any characteristic of CFS. The lack of effect of fluoxetine on depressive symptoms in CFS suggests that processes underlying the presentation of depressive symptoms in CFS may differ from those in patients with major depressive disorder. [ABSTRACT FROM AUTHOR]

Rationale, Aims, and Objectives: People worldwide are affected by psychiatric disorders that lack a "best" treatment option. The role of shared decision-making (SDM) in psychiatric care seems evident, yet remains limited. Research on SDM in specialized mental health is scarce, concentrating on patients with depressive disorder or psychiatric disorders in general and less on patients with anxiety and obsessive-compulsive disorder (OCD). Furthermore, recent research concentrates on the evaluation of interventions to promote and measure SDM rather than on the feasibility of SDM in routine practice. This study investigated patients' and clinicians' perspectives on SDM to treat depression, anxiety disorders, and OCD as to better understand SDM in specialized psychiatric care and its challenges in clinical practice., Methods: Transcripts of eight focus groups with 17 outpatients and 33 clinicians were coded, and SDM-related codes were analysed using thematic analyses., Results: Motivators, responsibilities, and preconditions regarding SDM were defined. Patients thought SDM should be common practice given the autonomy they have over their own bodies and felt responsible for their treatments. Clinicians value SDM for obtaining patients' consent, promoting treatment adherence, and establishing a good patient-clinician relationship. Patients and clinicians thought clinicians assumed the most responsibility regarding the initiation and achievement of SDM in clinical practice. According to clinicians, preconditions were often not met, were influenced by illness severity, and formed important barriers (eg, patient's decision-making capacity, treatment availability, and clinicians' preferences), leading to paternalistic decision-making. Patients recognized these difficulties, but felt none of these preclude the implementation of SDM. Personalized information and more consultation time could facilitate SDM., Conclusions: Patients and clinicians in specialized psychiatric care value SDM, but adapting it to daily practice remains challenging. Clinicians are vital to the implementation of SDM and should become versed in how to involve patients in the decision-making process, even when this is difficult., (© 2019 John Wiley & Sons, Ltd.)

Objective: To investigate treatment selection in a naturalistic sample of MDD outpatients and the factors influencing treatment selection in specialized psychiatric care., Method: Multinomial Logistic Regression analysis investigated associations between treatment selection and patients' sociodemographic and clinical characteristics, using retrospective chart review data and Routine Outcome Monitoring (ROM) data of MDD outpatients., Results: Of the patients included for analyses (N = 263), 34% received psychotherapy, 32% received an antidepressant (AD) and 35% received a combination. Men were more likely than women to receive AD with reference to psychotherapy (OR AD  = 5.57, 95% CI 2.38-13.00). Patients with severe depression and patients with AD use upon referral, prescribed by their general practitioner, were more likely to receive AD (OR severe depression  = 5.34, 95% CI 1.70-16.78/OR AD GP  = 9.26, 95% CI 2.53-33.90) or combined treatment (OR severe depression  = 6.32, 95% CI 1.86-21.49/OR AD GP  = 22.36, 95% CI 5.89-83.59) with respect to psychotherapy. More severe patients with AD upon referral received combined treatment less often compared to psychotherapy (OR = 0.14, 95% CI 0.03-0.68)., Conclusion: AD prescriptions in primary care, severity and gender influenced treatment selection for depressive disorders in secondary psychiatric care. Other factors such as the accessibility of treatment and patient preferences may have played a role in treatment selection in this setting and need further investigation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Standardized Diagnostic Interviews (SDIs) such as the Mini International Neuropsychiatric Interview (MINI) are widely used to systematically screen for psychiatric disorders in research. To support generalizability of results to clinical practice, we assessed agreement between the MINI and clinical diagnoses., Methods: Agreement was assessed in a large, real life dataset (n = 7016) using concordance statistics such as sensitivity, specificity, efficiency and area under the curve (AUC)., Results: 41.5% of clinical diagnoses were mood disorders, 26.5% were anxiety disorders. Overall, we found moderate agreement between MINI and clinical diagnoses (median efficiency: 0.92, median AUC: 0.79). For mood disorders, the AUC for all participants showed a range between 0.55 and 0.81 (median: 0.73), and for anxiety disorders the AUC ranged from 0.78 to 0.88 (median: 0.83). The AUC showed better agreement for mood disorders in the single diagnosis group than in the total group (median 0.77 vs. 0.71). For anxiety disorders, the AUC for the single diagnosis group was comparable to the AUC of the total group (median: 0.81 vs. 0.83 respectively). Numbers of false positives were high for both mood and anxiety diagnoses, but less so in the single diagnosis group., Limitations: Time lag between MINI and clinical diagnosis, the availability of only the primary clinical diagnosis, and relatively high severity of the current sample are limitations of the current study., Conclusions: Agreement between MINI and clinical diagnoses was moderate at best, which partly reflects the difference between the different measures used in the current study., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Rationale, Aims and Objectives: To assess (feasibility) of adherence to treatment guidelines among outpatients with common mental disorders in a routine Dutch clinical outpatient setting for common mental disorders using administrative data., Methods: In a retrospective cohort study, we analysed routinely collected administrative data of 5346 patients, treated for mood, anxiety or somatoform disorders with pharmacotherapy, psychotherapy or a combination of both. Available administrative data allowed assessment of guideline adherence with a disorder-independent set of five quality indicators, assessing psychotherapy, pharmacotherapy, a combination of both and routine outcome measurements (ROM) during diagnostic and therapeutic phases. Associations between the socio-demographic variables age, gender, clinical diagnosis and treatment type on the one hand and non-adherence to guidelines were tested using logistic regression analysis., Results: Patients were aged 39.5 years (SD 13.0) on average. The majority of patients were treated with a combination of pharmacotherapy and psychotherapy (50.1%), followed by psychotherapy (44.2%) and pharmacotherapy (5.6%). The majority of patients were suffering from a mood disorder (50.0%), followed by anxiety (43.9%) and somatoform disorders (6.1%). A diagnosis of anxiety or somatoform disorder was associated with higher odds of suboptimal duration [odds ratio (OR): 1.55 and 1.82[ and suboptimal frequency of psychotherapeutic treatment (OR of 0.89 and 0.63), and absence of ROM in the diagnostic phase (ORs 1.31 and 1.36, respectively) compared with depressive disorders. No ROM in the diagnostic phase was also predicted for by increasing age (ORs for the age categories of 56 and older of 1.48)., Conclusions: In this proof of principal study, we were able to assess some key indicators assessing adherence to clinical guidelines by using administrative data. Also, we could identify predictors of adherence with simple parameters available in every administrative data. Administrative data could help to monitor and aid guideline adherence in routine care, although quality may vary between settings., (© 2015 John Wiley & Sons, Ltd.)

Early onset is regarded as an important characteristic of anxiety disorders, associated with higher severity. However, previous findings diverge, as definitions of early onset vary and are often unsubstantiated. We objectively defined early onset in social phobia, panic disorder, agoraphobia, and generalised anxiety disorder, using cluster analysis with data gathered in the general population. Resulting cut-off ages for early onset were ≤22 (social phobia), ≤31 (panic disorder), ≤21 (agoraphobia), and ≤27 (generalised anxiety disorder). Comparison of psychiatric comorbidity and general wellbeing between subjects with early and late onset in the general population and an outpatient cohort, demonstrated that among outpatients anxiety comorbidity was more common in early onset agoraphobia, but also that anxiety- as well as mood comorbidity were more common in late onset social phobia. A major limitation was the retrospective assessment of onset. Our results encourage future studies into correlates of early onset of psychiatric disorders., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Depressive and anxiety disorders contribute to a high disease burden. This paper investigates whether concise formats of cognitive behavioral- and/or pharmacotherapy are equivalent with longer standard care in the treatment of depressive and/or anxiety disorders in secondary mental health care., Methods: A pragmatic randomized controlled equivalence trial was conducted at five Dutch outpatient Mental Healthcare Centers (MHCs) of the Regional Mental Health Provider (RMHP) 'Rivierduinen'. Patients (aged 18-65 years) with a mild to moderate anxiety and/or depressive disorder, were randomly allocated to concise or standard care. Data were collected at baseline, 3, 6 and 12 months by Routine Outcome Monitoring (ROM). Primary outcomes were the Brief Symptom Inventory (BSI) and the Web Screening Questionnaire (WSQ). We used Generalized Estimating Equations (GEE) to assess outcomes., Results: Between March 2010 and December 2012, 182 patients, were enrolled (n=89 standard care; n=93 concise care). Both intention-to-treat and per-protocol analyses demonstrated equivalence of concise care and standard care at all time points. Severity of illness reduced, and both treatments improved patient's general health status and subdomains of quality of life. Moreover, in concise care, the beneficial effects started earlier., Discussion: Concise care has the potential to be a feasible and promising alternative to longer standard secondary mental health care in the treatment of outpatients with a mild to moderate depressive and/or anxiety disorder. For future research, we recommend adhering more strictly to the concise treatment protocols to further explore the beneficial effects of the concise treatment. The study is registered in the Netherlands Trial Register, number NTR2590. Clinicaltrials.gov identifier: NCT01643642., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: A strong association has been established between migraine and depression. However, this is the first study to differentiate in a large sample of migraine patients for symptom dimensions of the affective disorder spectrum., Methods: Migraine patients (n=3174) from the LUMINA (Leiden University Medical Centre Migraine Neuro-analysis Program) study and patients with current psychopathology (n=1129), past psychopathology (n=477), and healthy controls (n=561) from the NESDA (Netherlands Study of Depression and Anxiety) study, were compared for three symptom dimensions of depression and anxiety. The dimensions -lack of positive affect (depression specific); negative affect (nonspecific); and somatic arousal (anxiety specific)- were assessed by a shortened adaptation of the Mood and Anxiety Symptom Questionnaire (MASQ-D30). Within the migraine group, the association with migraine specific determinants was established. Multivariate regression analyses were conducted., Results: Migraine patients differed significantly (p<0.001) from healthy controls for all three dimensions: Cohen's d effect sizes were 0.37 for lack of positive affect, 0.68 for negative affect, and 0.75 for somatic arousal. For the lack of positive affect and negative affect dimensions, migraine patients were predominantly similar to the past psychopathology group. For the somatic arousal dimension, migraine patients scores were more comparable with the current psychopathology group. Migraine specific determinants for high scores on all dimensions were high frequency of attacks and cutaneous allodynia during attacks., Conclusion: This study shows that affective symptoms in migraine patients are especially associated with the somatic arousal component., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Depression and anxiety disorders are highly comorbid and share neurobiological characteristics. However, this is usually not explicitly addressed in studies on intrinsic brain functioning in these disorders. Contrary to previous resting-state reports on small, monodiagnostic subsets of the current sample, we investigated resting-state functional connectivity (RSFC) in medication-free patients with depression, anxiety, comorbid depression and anxiety, and a healthy control group. RSFC was investigated in 140 medication-free subjects: 37 major depressive disorder patients (MDD), 30 patients with one or more anxiety disorders (ANX), 25 patients with MDD and one or more anxiety disorders (COM), and 48 healthy controls (HC). RSFC networks were calculated using a probabilistic independent component analysis. Using a dual regression approach, individuals׳ timecourses were extracted and regressed to obtain subjects-specific spatial maps, which were used for group comparisons in four networks of interest (limbic, default mode, salience and sensory-motor networks). When compared to HC, the COM group showed increased RSFC of the limbic network with a cluster containing the bilateral precuneus, intracalcarine cortex, lingual gyrus, and posterior cingulate, and with a cluster including the right precentral gyrus, inferior frontal gyrus, and middle frontal gyrus. This effect was specific for comorbid depression and anxiety. No abnormal RSFC of other networks or in the MDD and ANX groups was observed. No association was found between strength of RSFC and symptom severity. These results indicate that altered RSFC of cortical regions with a limbic network could be specific for comorbid depression and anxiety., (Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.)

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.

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., (© International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

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.

Little is known about the predictors of outcome in anxiety disorders in naturalistic outpatient settings. We analyzed 2-year follow-up data collected through Routine Outcome Monitoring (ROM) in a naturalistic sample of 917 outpatients in psychiatric specialty care in order to identify factors predicting outcome. We included patients with panic disorder with or without agoraphobia, agoraphobia without panic, social phobia, or generalized anxiety disorder. Main findings from Cox regression analyses demonstrated that several socio-demographic variables (having a non-Dutch ethnicity [HR = 0.71)], not having a daily occupation [HR = 0.76]) and clinical factors (having a diagnosis of agoraphobia [HR = 0.67], high affective lability [HR = 0.80] and behavior problems [HR = 0.84]) decreased chances of response (defined as 50% reduction of anxiety severity) over the period of two years. Living with family had a protective predictive value [HR = 1.41]. These results may imply that factors that could be thought to limit societal participation, are associated with elevated risk of poor outcome. A comprehensive ROM screening process at intake may aid clinicians in the identification of patients at risk of chronicity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In the last decade, early-onset of affective illness has been recognized as a major public health problem. However, clinical studies indicate that although children experience the symptoms of anxiety and depression in much the same way as adults, they display and react to those symptoms differently (Bostic et al., 2005). Recently, we have demonstrated that similar differences in symptoms are found also between adult and juvenile rats (Jacobson-Pick and Richter-Levin, 2010). Especially the hippocampus is believed to be vulnerable to stress-related illness, as this brain region has a high density of corticoid receptors. The hippocampus is known to finalize its development, and particularly that of GABA-related functions, into adolescence (Bergmann et al., 1991; Harris et al., 1992; Nurse and Lacaille, 1999; Lopez-Tellez et al., 2004; Jacobson-Pick et al., 2008) and may thus be differentially sensitive to environmental challenges in childhood and in adulthood. In this study we explored the differences in activity and plasticity of the dentate gyrus between pre-pubertal and adult rats in vivo. Furthermore, we have examined the impact of exposure to stress either during pre-puberty or in adulthood on dentate gyrus electrophysiology. In both male and female rats, marked differences were found for intrinsic excitability and local circuit activity between pre-pubertal and adult animals. Exposure to forced swim stress resulted in significant alterations of dentate gyrus activity and plasticity in male rats with differences between adult and pre-pubertal animals. Stress had far less impact on females' dentate electrophysiology. The results are in agreement with the differences in behavioral response to stress between pre-pubertal and adult rats, and with reported differences for the sensitivity of male and female rats in performing hippocampus-dependent tasks under stress, such as the active avoidance task., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

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.

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.

Background: Different types of adverse events may have general or specific effects on depression and anxiety symptomatology. We examined the effects of adversities on the dimensions of the tripartite model: general distress, anhedonic depression and anxious arousal., Methods: Data were from 2615 individuals from the Netherlands Study for Depression and Anxiety (NESDA), with or without depressive or anxiety disorders. We analysed associations of childhood trauma, childhood life events (childhood trauma interview), and recent life events (List of Threatening Events Questionnaire, LTE-Q) with anhedonic depression, anxious arousal, and general distress (assessed by the adapted Mood and Anxiety Symptoms Questionnaire, MASQ-D30)., Results: We controlled for co-occurrence of adversities. Regarding childhood trauma, only emotional neglect was associated with all three symptom dimensions. Psychological and sexual abuse were associated with general distress and anxious arousal, whereas physical abuse was associated only with anxious arousal. Particularly strong associations were seen for emotional neglect with anhedonic depression and for sexual abuse with anxious arousal. Childhood life events showed no associations with symptom dimensions. The recent life events 'Serious problems with friend', 'Serious financial problems', and 'Becoming unemployed' were associated with all three dimensions. The recent life event 'death of parent/child/sibling' was associated with anxious arousal. Several associations remained significant when controlled for current diagnosis of depression or anxiety., Limitations: Our cross-sectional analyses do not allow for causal interpretation., Conclusions: Distinct childhood traumas had different effects on the symptom dimensions, whereas most recent adult life events were associated with all three symptom dimensions. Our observations help to understand the often reported associations of these adversities with depressive and anxiety symptomatology. In addition, symptom dimensions of the tripartite model were shown to capture effects of adverse events on top of those captured by diagnostic categories., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Self-report measures of psychological distress or psychopathology are widely used and can be easily implemented as psychiatric screening tools. Positive psychological constructs such as vitality/optimism and work functioning have scarcely been incorporated. We aimed to develop and validate a psychological distress instrument, including measures of vitality and work functioning. A patient sample with suspected depressive, anxiety, and somatoform disorders (N=242) and a reference sample of the general population (N=516) filled in the 48-item Symptom Questionnaire (SQ-48) plus a battery of observer-rated and self-report scales (MINI Plus, MADR, BAS, INH, BSI), using a web-based ROM programme. The resulting SQ-48 is multidimensional and includes the following nine subscales: Depression (MOOD, six items), Anxiety (ANXI, six items), Somatization (SOMA, seven items), Agoraphobia (AGOR, four items), Aggression (AGGR, four items), Cognitive problems (COGN, five items), Social Phobia (SOPH, five items), Work functioning (WORK, five items), and Vitality (VITA, six items). The results showed good internal consistency as well as good convergent and divergent validity. The SQ-48 is meant to be available in the public domain for Routine Outcome Monitoring (ROM) and can be used as a screening/ monitoring tool in clinical settings (psychiatric and non-psychiatric), as a benchmark tool, or for research purposes., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Comorbidity among anxiety and depressive disorders is the rule rather than the exception. The Integrative Hierarchical Model proposes that each of these disorders contains general (common to all), specific (common to some) and unique components. However, research into this model is limited and hampered by small (clinical) sample sizes. The aim of the present study is to investigate the incremental validity of the cognitive constructs Anxiety Sensitivity, Pathological Worry and Cognitive Reactivity to sad mood over and above the personality traits neuroticism and extraversion. Symptomatic (N = 1,111) and remitted (N = 834) patients were selected from the 2,981 participants of the Netherlands Study of Depression and Anxiety (NESDA). Results revealed both specific and unique cognitive components of anxiety and depression. Across symptomatic and remitted groups, Anxiety Sensitivity was specific to social anxiety disorder and panic disorder, Aggression Reactivity was a unique component of dysthymia, and Rumination on Sadness was unique to major depressive disorder. We conclude that cognitive constructs have additional value in understanding anxiety and depressive disorders. Moreover, they prove to be more than mere epiphenomena of current disorders.

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., (© 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.)

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., (© 2012 John Wiley & Sons A/S.)

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.

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.

Background: Not only is the heterogeneous concept of depression too comprehensive, it is also insufficiently differentiated. This serves as a barrier to scientific research and obscures the symptoms that should indicate what treatment is required., Aim: To describe an accurate model for staging and profiling depression., Method: We placed depressive disorders in the context of the entire course of the disorder and we regarded the course as a continuum of psychopathology., Results: First of all we distinguish five stages: (1) the prodromal phase, (2) the first depressive episode, (3) residual symptoms following an episode, (4) the relapse episode and (5) the chronic and/or treatment-resistant depression. The higher the stage, the greater the need for complex and specialised treatment. As characteristics for profiling we distinguish (a) aetiological and pathophysiological variables and (b) clinical factors. The latter are the ones that mainly influence treatment from stage 2 onwards., Conclusion: In our article we give a tentative overview of possible characteristics for profiling. At the moment the clinical factors are the ones used most for assessment. Current research into the value of aetiological characteristics for profiling will increase the applicability of a staging and profiling model.

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.

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., (© 2011 John Wiley & Sons A/S.)

Introduction: The hypothalamus-pituitary-adrenal (HPA)-axis is often found to be dysregulated in bipolar disorder (BD) while stress and changes in day-night rhythms can trigger a new mood episode. Genetic variants of the glucocorticoid receptor (GR)- and mineralocorticoid receptor (MR)-gene influence both the reactivity of the stress-response and associate with changes in mood. In this study we tested the hypothesis that these polymorphisms associate with different clinical characteristics of BD., Methods: We studied 326 outpatients with BD and performed GR genotyping of the TthIIII, ER22/23EK, N363S, BclI, and 9β polymorphisms, as well as MR genotyping of the 2G/C and I180V variants. All patients were interviewed for clinical characteristics., Results: Seasonal patterns of hypomania are related to the BclI haplotype and the TthIIII+9β haplotype of the GR gene (respectively, crude p=.007 and crude p=.005). Carriers of the ER22/23EK polymorphism had an almost 8 years earlier onset of their first (hypo)manic episode than non-carriers (crude p=.004, after adjustment p=.016). No evidence for a role of the MR in modifying clinical manifestations was found., Conclusion: Polymorphisms of the GR-gene are factors which influence some clinical manifestations of BD, with respect to seasonal pattern of (hypo)mania and age of onset., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

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., (© 2011 John Wiley & Sons A/S.)

Introduction: Psychogenic Non Epileptic Seizures (PNES) have been theorized to reflect a learned pattern of avoidant behavior to deal with stressors. Although such observation may be relevant for our understanding of the etiology of PNES, evidence for this theory is largely build on self-report investigations and no studies have systematically tested actual avoidance behavior in patients with PNES. In this study, we tested automatic threat avoidance tendencies in relation to stress and cortisol levels in patients with PNES and healthy controls (HCs)., Methods: The approach and avoidance (AA) task was administered to 12 patients with PNES and 20 matched HCs at baseline and following stress-induction using the Cold Pressor Test (CPT). The AA task requires participants to evaluate the emotional valence of pictures of angry and happy faces by making arm movements (arm flexion or extension) that are either affect-congruent (avoid-angry; approach-happy) or affect-incongruent (approach-angry; avoid-happy) with their intuitive action tendencies. Saliva cortisol was measured throughout the experiment., Results: Patients, but not HCs, showed increased approach-avoidance congruency-effects for angry faces on the AA task at baseline, with relatively slower approach of angry faces, which was overall associated with basal pre-task cortisol. This congruency-effect disappeared after the CPT., Discussion: The present findings provide an objective confirmation of previous suggestions from self-report studies indicating that PNES patients show relatively increased avoidance tendencies to social threat cues. The registering of threat avoidance behavior may prove to be a clinically valuable contribution to evaluate psychological treatment effectiveness and perhaps even PNES prognosis., (Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

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.

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.

Background: Several interventions aiming at discontinuation of long-term benzodiazepine use have been proven effective in the short term. However, data on the persistence of discontinuation are lacking., Objectives: To assess 10-year follow-up status in patients who succeeded in stopping benzodiazepine use after a discontinuation letter from the patient's own GP. To identify determinants of successful discontinuation on the long term., Methods: Follow-up data of patients who participated in a large prospective, controlled stepped care intervention programme among long-term benzodiazepine users in primary care., Results: At 10-year follow-up, the percentage of benzodiazepine abstinence was 58.8%. Non-abstinent patients used lower doses of benzodiazepine. Being abstinent at 21 months after the intervention predicted abstinence at 10-year follow-up., Conclusions: Ten years after a minimal intervention to decrease long-term benzodiazepine use, the majority of patients who were able to discontinue benzodiazepine use initially, does not use benzodiazepines at 10-year follow-up. Patients who did not succeed in maintaining abstinence from benzodiazepines appear to use lower or average dosages.

The synthetic vasopressin (AVP) analogue desmopressin (dDAVP) has been used as pharmacological function test to quantify vasopressinergic co-activation of the hypothalamus-pituitary-adrenal (HPA) axis in the past. Such exogenous vasopressinergic stimulation may induce confounding cardiovascular, pro-coagulatory and anti-diuretic effects and low endogenous corticotrophin-releasing-hormone (CRH) levels may limit its potential to reliably assess co-activation. Alternatively, the dopamine-2-(D2)-antagonist metoclopramide is believed to induce co-activation indirectly by releasing endogenous AVP. We investigated this indirect co-activation with metoclopramide under conditions of low and enhanced endogenous CRH release in healthy volunteers. A randomized, double-blind, placebo-controlled, four-way crossover study was performed in 12 healthy males. CRH release was induced by administering an oral 5-hydroxytryptophan (5-HTP) 200 mg function test. Co-activation was investigated by administering metoclopramide 10mg intravenously around the expected maximal effect of 5-HTP. The neuroendocrine effects were compared to those of metoclopramide alone, the 5-HTP test alone and matching placebo. Metoclopramide safely induced HPA-axis activation by itself, and potently synergized 5-HTP-induced corticotrophinergic activation of the HPA axis. These findings are indicative of vasopressinergic co-activation and suggest a role for metoclopramide as a practical function test for co-activation of the HPA axis. However, its application will be hampered pending clarification of the exact pharmacological mechanism by which metoclopramide induces co-activation of the HPA axis., (Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.)

To examine the nature of the association between depression and obesity and to determine possible underlying (demographic) factors, we conducted a meta-analysis of cross-sectional studies in the general population. We searched in major bibliographical databases (PubMed, Embase and PsycInfo) for studies examining the association between obesity and depression in the adult, general population. Seventeen studies were included with a total of 204,507 participants. We calculated an overall pooled mean effect size and conducted subgroup analyses on gender, age, continent of residence, year of publication and several differences in measurement methods. After removing two outliers, the overall association for depression and obesity was very significant. Subgroup analyses showed a trend indicating a possible significant difference between males and females. We found a significant positive association for females and a smaller non-significant association for males. The results of other subgroup analyses showed no significant differences. According to the findings of this study, there is a significant positive association between depression and obesity in the general population, which appeared to be more marked among women. Further research should focus on underlying factors and examine causal pathways between depression and obesity., (Copyright 2009 Elsevier Ltd. All rights reserved.)

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.

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.

Aim: The aim of the current study was to develop scales that assess symptoms of depression and anxiety and can adequately differentiate between depression and anxiety disorders, and also can distinguish within anxiety disorders. As point of departure, we used the tripartite model of Clark and Watson that discerns three dimensions: negative affect, positive affect and physiological hyperarousal., Methods: Analyses were performed on the data of 1449 patients, who completed the Mood and Anxiety Symptoms Questionnaire (MASQ) and the Brief Symptom Inventory (BSI). From this, 1434 patients were assessed with a standardized diagnostic interview., Results: A model with five dimensions was found: depressed mood, lack of positive affect, somatic arousal, phobic fear and hostility. The scales appear capable to differentiate between patients with a mood and with an anxiety disorder. Within the anxiety disorders, somatic arousal was specific for patients with panic disorder. Phobic fear was associated with panic disorder, simple phobia and social anxiety disorder, but not with generalized anxiety disorder., Conclusions: We present a five-factor model as an extension of the tripartite model. Through the addition of phobic fear, anxiety is better represented than in the tripartite model. The new scales are capable to accurately differentiate between depression and anxiety disorders, as well as between several anxiety disorders., ((c) 2009 Elsevier Masson SAS. All rights reserved.)

Introduction and Purpose: Functional proton magnetic resonance spectroscopy (MRS) can be applied to measure pharmacodynamic effects of central nervous system (CNS)-active drugs. The serotonin precursor 5-hydroxytryptophan (5-HTP), administered together with carbidopa and granisetron to improve kinetics and reduce adverse effects, acutely enhances central serotonergic neurotransmission and induces hypothalamus-pituitary-adrenal-(HPA) axis activation. We studied the hypothalamic levels of glutamate/glutamine (Glx), choline (Chol), N-acetyl-aspartate (NAA) and creatine using 7-Tesla (7T) MRS, and adrenocorticotropic hormone (ACTH) and cortisol in peripheral blood, after the administration of the 5-HTP function test in healthy volunteers., Methods: A randomized, double blind, placebo-controlled, two-way cross-over study was performed in 12 healthy males with a 7day wash-out period. After administration of the oral 5-HTP function test, ACTH and cortisol were measured over 4h and MRS scans at 7T were performed every 30min over 3h measuring Glx:Creatine, Chol:Creatine and NAA:Creatine ratios., Results: In the hypothalamus, the administration of 5-HTP had no effect on the average Glx, Chol or NAA levels over 180min but induced a significant decrease of Glx at 60min on post-hoc analysis. 5-HTP-induced significant ACTH release reaching an E(max) of 60.2ng/L at 80min followed by cortisol with an E(max) of 246.4ng/mL at 110min., Conclusions: The reduction in hypothalamic Glx levels after serotonergic stimulation is compatible with activation of excitatory neurons in this region, which is expected to cause depletion of local glutamate stores. The hypothalamic MRS-response reached its maximum prior to subsequent increases of ACTH and cortisol, which support the functional relevance of hypothalamic Glx-depletion for activation of the HPA-axis. This exploratory study shows that MRS is capable of detecting neuronal activation following functional stimulation of a targeted brain area., (Copyright 2010 Elsevier Inc. All rights reserved.)

The aim of this study was to validate the Dutch version of the Kessler-10 (K10) as well as an extended version (EK10) in screening for depressive and anxiety disorders in primary care. Data are from 1607 participants (18 through 65 years, 68.8% female) of the Netherlands Study of Depression and Anxiety (NESDA), recruited from 65 general practitioners. Participants completed the K10, extended with five additional questions focusing on core anxiety symptoms, and were evaluated with the WHO Composite International Diagnostic Interview (CIDI lifetime version 2.1) to assess DSM-IV disorders (major depressive disorder, dysthymia, generalized anxiety disorder, social phobia, panic disorder, agoraphobia). Reliability (Cronbach's alpha) of the Dutch K10 was 0.94. Based on Receiver Operating Characteristics (ROC) analysis, the area under the curve (AUC) for the K10 for any depressive and/or anxiety disorder was found to be 0.87. The extended questions on the EK10 significantly improved the detection of anxiety disorders in particular. With a cut-off point of 20, the K10 reached a sensitivity of 0.80 and a specificity of 0.81 for any depressive and/or anxiety disorder. For the EK10, a cut-off point of 20 and/or at least one positive answer on the additional questions provided a sensitivity of 0.90 and a specificity of 0.75 for detecting any depressive and/or anxiety disorder. The Dutch version of the K10 is appropriate for screening depressive disorders in primary care, while the EK10 is preferred in screening for both depressive and anxiety disorders., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: Chronic phantom limb pain (PLP) is a disabling chronic pain syndrome for which regular pain treatment is seldom effective. Pain memories resulting from long-lasting preamputation pain or pain flashbacks, which are part of a traumatic memory, are reported to be powerful elicitors of PLP., Objective: To investigate whether a psychological treatment directed at processing the emotional and somatosensory memories associated with amputation reduces PLP., Methods: Ten consecutive participants (six men and four women) with chronic PLP after leg amputation were treated with eye movement desensitization and reprocessing (EMDR). Pain intensity was assessed during a two-week period before and after treatment (mean number of sessions = 5.9), and at short- (three months) and long-term (mean 2.8 years) follow-up., Results: Multivariate ANOVA for repeated measures revealed an overall time effect (F[2, 8]=6.7; P<0.02) for pain intensity. Pairwise comparison showed a significant decrease in mean pain score before and after treatment (P=0.00), which was maintained three months later. All but two participants improved and four were considered to be completely pain free at three months follow-up. Of the six participants available at long-term follow-up (mean 2.8 years), three were pain free and two had reduced pain intensity., Conclusions: These preliminary results suggest that, following a psychological intervention focused on trauma or pain-related memories, substantial long-term reduction of chronic PLP can be achieved. However, larger outcome studies are required.