Development of a body dysmorphic disorder screener for DSM-5 (BDDS-5).

Early identification of individuals with Body dysmorphic disorder (BDD) is essential to direct them to appropriate care and to reduce the chance of developing or maintaining comorbid psychiatric disorders (like an eating disorder (ED)). The present study aimed to develop a simple screener, the Body Dysmorphic Disorder Screener for DSM-5 (BDDS-5), to overcome existing screeners' limitations and test its psychometric properties. The BDDS-5 consists of 12 statements with dichotomous answer options. Specific attention is paid to the readability of the screener for those with lower reading skills. Additional eating disorder screening questions (S section) were added to investigate whether these questions are necessary for detecting potential BDD cases. Finally, the factor structure, internal consistency, and validity of the BDDS-5 were examined within populations with a high risk of screening positive for BDD or ED. Principal axis factor analysis showed that two factors accounted for 63.5% of the variance. The factor analysis was based on polychoric correlation. Based on the BDDS-5, 33 persons (14% of N = 235) were screened as likely BDD cases. Nineteen persons were excluded as potential BDD cases based on the eating disorder related question (question D). Based on the S-section, this turned out to be largely correct for the majority, however, in 8% (n = 4) of the cases BDD was probably missed. The convergent validity appeared to be high (r > 0.80) with three other BDD measures. The BDDS-5 is a valid and widely applicable screener for BDD that may help in the early detection of BDD. The BDDS-5 uses simple wording and is thus suitable for people 8 years and older.

Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis.

Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

Social functioning in patients with depressive and anxiety disorders.

OBJECTIVE: Adaptive social functioning is severely impeded in depressive and anxiety disorders, even after remission. However, a comprehensive overview is still lacking. METHOD: Using data from the Netherlands Study of Depression and Anxiety (NESDA), behavioural (network size, social activities, social support) and affective (loneliness, affiliation, perceived social disability) indicators of social functioning were analyzed in patients with anxiety (N = 540), depressive (N = 393), comorbid anxiety and depressive disorders ('comorbid', N = 748), remitted participants (N = 621), and healthy control subjects (N = 650). RESULTS: Analyses revealed an increasing trend of social dysfunction among patient groups, in patients with comorbid anxiety and depressive disorders, showing the most severe impairments, followed by depressed and anxious patients (P's < 0.001 for all social functioning indicators). Affective indicators showed the largest effect sizes (Cohen's d range from 0.13 to 1.76). We also found impairments in social functioning among remitted patients. Furthermore, perceived social disability among patients was predictive of still having a depressive and/or anxiety diagnosis 2 years later (P < 0.01). CONCLUSIONS: Behavioural but especially affective indicators of social functioning are impaired in patients with anxiety or depressive disorders and most in patients with comorbid disorders. After remission of affective psychopathology, residual impairments tend to remain, while social dysfunction in patients seems predictive of future psychopathology.

[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.

Age of onset in obsessive-compulsive disorder: admixture analysis with a large sample.

BACKGROUND: Research into age of onset in obsessive-compulsive disorder (OCD) has indicated significant differences between patients with early and late onset of the disorder. However, multiple criteria have been used arbitrarily for differentiating between early- and late-onset OCD, rendering inconsistent results that are difficult to interpret. METHOD: In the current study, admixture analysis was conducted in a sample of 377 OC patients to determine the number of underlying populations of age of onset and associated demographic and clinical characteristics. Various measures of anxiety, depression, co-morbidity, autism, OCD, tics and attention deficit hyperactivity disorder (ADHD) symptoms were administered. RESULTS: A bimodal age of onset was established and the best-fitting cut-off score between early and late age of onset was 20 years (early age of onset ≤19 years). Patients with early age of onset were more likely to be single. Early age of onset patients demonstrated higher levels of OCD severity and increased symptoms on all OCD dimensions along with increased ADHD symptoms and higher rates of bipolar disorder. CONCLUSIONS: It is suggested that 20 years is the recommended cut-off age for the determination of early versus late age of onset in OCD. Early age of onset is associated with a generally graver OCD clinical picture and increased ADHD symptoms and bipolar disorder rates, which may be related to greater functional implications of the disorder. We propose that age of onset could be an important marker for the subtyping of OCD.

Mortality in neuropsychiatric systemic lupus erythematosus (NPSLE).

The standardized mortality ratio (SMR) for systemic lupus erythematosus (SLE) is three; SMR increases to six in case of renal involvement. Up to now data on survival in case of neuropsychiatric involvement in SLE (NPSLE) have been scarce, therefore we calculated an SMR for NPSLE. Furthermore, we identified characteristics that influenced survival by Cox regression analyses. All patients suspected of NPSLE in our center since 1989 were evaluated and included in this study when a diagnosis of primary NPSLE could be established. Patient's life/death status was tracked using the civic registries. Thirty-two (19%) of the 169 included NPSLE patients died within a median follow-up period of six years (range 0.5-24 years). This resulted in a significantly increased mortality rate compared to the general population: SMR 9.5 (95% CI 6.7-13.5). Hazard ratios (HRs) were highest in patients with acute confusional state (HR 3.4) and older age at diagnosis of NPSLE (HR 1.1). A decreased mortality risk was seen with the prescription of antiplatelet therapy (HR 0.22). The time period in which NPSLE was diagnosed did not significantly influence survival. Most frequent causes of death were infection and NPSLE itself.

[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.

A healthy dietary pattern is associated with microbiota diversity in recently diagnosed bipolar patients: The Bipolar Netherlands Cohort (BINCO) study.

BACKGROUND: Diet largely impacts the gut microbiota, and may affect mental and somatic health via the gut-brain axis. As such, the relationship between diet and the microbiota in Bipolar Disorder (BD) could be of importance, but has not been studied before. The aim was therefore to assess whether dietary quality is associated with the gut microbiota diversity in patients with recently diagnosed BD, and whether changes occur in dietary quality and microbiota diversity during their first year of treatment. METHODS: Seventy recently (<1 year) diagnosed patients with BD were included in the "Bipolar Netherlands Cohort" (BINCO), and a total of 45 participants were assessed after one year. A 203-item Food Frequency Questionnaire (FFQ) data yielded the Dutch Healthy index (DHD-15), and the microbiota composition and diversity of fecal samples were characterized by 16S rRNA gene amplicon sequencing at baseline and 1-year follow-up. Associations and changes over time were analyzed using multivariate regression analyses and t-tests for paired samples. RESULTS: Included patients had a mean age of 34.9 years (SD ± 11.2), and 58.6 % was female. Alpha diversity (Shannon diversity index), richness (Chao1 index) and evenness (Pielou's Evenness Index) were positively associated with the DHD-15 total score, after adjustment for sex, age and educational level (beta = 0.55; P < 0.001, beta = 0.39; P = 0.024, beta = 0.54; P = 0.001 respectively). The positive correlations were largely driven by the combined positive effect of fish, beans, fruits and nuts, and inverse correlations with alcohol and processed meats. No significant changes were found in DHD-15 total score, nor in microbiota diversity, richness and evenness indexes during one year follow-up and regular treatment. CONCLUSION: A healthy and varied diet is associated with the diversity of the microbiota in BD patients. Its potential consequences for maintaining mood stability and overall health should be studied further.

Dynamic reconfigurations of brain networks in depressive and anxiety disorders: The influence of antidepressants.

Major Depressive Disorder (MDD) and anxiety disorders are highly comorbid recurrent psychiatric disorders. Reduced dynamic reconfiguration of brain regions across subnetworks may play a critical role underlying these deficits, with indications of normalization after treatment with antidepressants. This study investigated dynamic reconfigurations in controls and individuals with a current MDD and/or anxiety disorder including antidepressant users and non-users in a large sample (N = 207) of adults. We quantified the number of subnetworks a region switched to (promiscuity) as well as the total number of switches (flexibility). Average whole-brain (i.e., global) values and subnetwork-specific values were compared between diagnosis and antidepressant groups. No differences in reconfiguration dynamics were found between individuals with a current MDD (N = 49), anxiety disorder (N = 46), comorbid MDD and anxiety disorder (N = 55), or controls (N = 57). Global and sensorimotor network (SMN) promiscuity and flexibility were higher in antidepressant users (N = 49, regardless of diagnosis) compared to non-users (N = 101) and controls. Dynamic reconfigurations were considerably higher in antidepressant users relative to non-users and controls, but not significantly altered in individuals with a MDD and/or anxiety disorder. The increase in antidepressant users was apparent across the whole brain and in the SMN when investigating subnetworks. These findings help disentangle how antidepressants improve symptoms.

Family history of alcohol dependence modulates functional neurophysiology in mood/anxiety disorders.

BACKGROUND: A family history (FH) of alcohol dependence (AD) not only increases the risk for AD, but is also associated with an increased risk for mood and anxiety disorders. However, it is unknown how a FH of AD affects neural substrates in patients with mood and anxiety disorders. In this study we examined the effects of an alcoholic FH on cognitive and emotional functions in these patients using functional magnetic resonance imaging (fMRI). Method In a sample of non-alcoholic patients with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA) neuroimaging study, patients with a first-degree FH of AD (FH + ; n = 31) were compared with patients without a FH (FH-; n = 77) on performance and brain activation during visuospatial planning and emotional word encoding. Results were compared with those of healthy controls (HCs) without a FH of AD (n = 31). RESULTS: FH+ patients performed slower during planning with increasing task load, coupled with stronger blood oxygen level-dependent responses in dorsal prefrontal areas compared with FH- patients and HCs. FH was not associated with performance differences during word encoding, but right insula activation during positive word encoding was present in FH+ patients, comparable with HCs, but absent in FH- patients. CONCLUSIONS: This study demonstrates subtle impairments during planning in FH+ compared with FH- patients and HCs, whereas activation during mood-incongruent stimuli in FH+ patients was similar to HCs but not FH- patients, suggesting that the presence of a FH of AD is a useful marker for the neurophysiological profile in mood/anxiety disorders and possible predictor for treatment success.

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.

[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.

Neural correlates of perception of emotional facial expressions in out-patients with mild-to-moderate depression and anxiety. A multicenter fMRI study.

BACKGROUND: Depression has been associated with limbic hyperactivation and frontal hypoactivation in response to negative facial stimuli. Anxiety disorders have also been associated with increased activation of emotional structures such as the amygdala and insula. This study examined to what extent activation of brain regions involved in perception of emotional faces is specific to depression and anxiety disorders in a large community-based sample of out-patients. METHOD: An event-related functional magnetic resonance imaging (fMRI) paradigm was used including angry, fearful, sad, happy and neutral facial expressions. One hundred and eighty-two out-patients (59 depressed, 57 anxiety and 66 co-morbid depression-anxiety) and 56 healthy controls selected from the Netherlands Study of Depression and Anxiety (NESDA) were included in the present study. Whole-brain analyses were conducted. The temporal profile of amygdala activation was also investigated. RESULTS: Facial expressions activated the amygdala and fusiform gyrus in depressed patients with or without anxiety and in healthy controls, relative to scrambled faces, but this was less evident in patients with anxiety disorders. The response shape of the amygdala did not differ between groups. Depressed patients showed dorsolateral prefrontal cortex (PFC) hyperactivation in response to happy faces compared to healthy controls. CONCLUSIONS: We suggest that stronger frontal activation to happy faces in depressed patients may reflect increased demands on effortful emotion regulation processes triggered by mood-incongruent stimuli. The lack of strong differences in neural activation to negative emotional faces, relative to healthy controls, may be characteristic of the mild-to-moderate severity of illness in this sample and may be indicative of a certain cognitive-emotional processing reserve.

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.

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.