Loneliness in OCD and its determinants.

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and repetitive behaviors, affecting approximately 1.3 % of the population. Loneliness has serious consequences for future health outcomes. Although it has been extensively studied in depression, its prevalence in obsessive-compulsive disorder (OCD) has hardly been investigated. The current study sought to examine the association between loneliness and OCD, through an exploratory investigation of their demographic and clinical correlates. This cross-sectional study utilized data from the Netherlands Obsessive-Compulsive Disorder Association (NOCDA) study, designed to investigate determinants, course, and consequences of OCD in a large clinical sample. In this data base, a cohort of 363 OCD adult patients underwent assessment for loneliness severity, OCD symptomatology, comorbid conditions, and demographic variables. Findings reveal a high prevalence of loneliness among OCD patients, with nearly three-quarters (73.6 %) experiencing elevated levels. Loneliness was associated with greater depression severity and specific demographic factors such as gender, age, and education level. However, the relationship between OCD severity and loneliness was explained by depression severity. Clinical and theoretical implications are discussed as well as limitations and directions for future research.

The Mood and Resilience in Offspring (MARIO) project: a longitudinal cohort study among offspring of parents with and without a mood disorder.

BACKGROUND: One of the most robust risk factors for developing a mood disorder is having a parent with a mood disorder. Unfortunately, mechanisms explaining the transmission of mood disorders from one generation to the next remain largely elusive. Since timely intervention is associated with a better outcome and prognosis, early detection of intergenerational transmission of mood disorders is of paramount importance. Here, we describe the design of the Mood and Resilience in Offspring (MARIO) cohort study in which we investigate: 1. differences in clinical, biological and environmental (e.g., psychosocial factors, substance use or stressful life events) risk and resilience factors in children of parents with and without mood disorders, and 2. mechanisms of intergenerational transmission of mood disorders via clinical, biological and environmental risk and resilience factors. METHODS: MARIO is an observational, longitudinal cohort study that aims to include 450 offspring of parents with a mood disorder (uni- or bipolar mood disorders) and 100-150 offspring of parents without a mood disorder aged 10-25 years. Power analyses indicate that this sample size is sufficient to detect small to medium sized effects. Offspring are recruited via existing Dutch studies involving patients with a mood disorder and healthy controls, for which detailed clinical, environmental and biological data of the index-parent (i.e., the initially identified parent with or without a mood disorder) is available. Over a period of three years, four assessments will take place, in which extensive clinical, biological and environmental data and data on risk and resilience are collected through e.g., blood sampling, face-to-face interviews, online questionnaires, actigraphy and Experience Sampling Method assessment. For co-parents, information on demographics, mental disorder status and a DNA-sample are collected. DISCUSSION: The MARIO cohort study is a large longitudinal cohort study among offspring of parents with and without mood disorders. A unique aspect is the collection of granular data on clinical, biological and environmental risk and resilience factors in offspring, in addition to available parental data on many similar factors. We aim to investigate the mechanisms underlying intergenerational transmission of mood disorders, which will ultimately lead to better outcomes for offspring at high familial risk.

Long-term remission rates and trajectory predictors in obsessive-compulsive disorder: Findings from a six-year naturalistic longitudinal cohort study.

BACKGROUND: This naturalistic study, utilizing data from the Netherlands Obsessive-Compulsive Disorder Association (NOCDA) cohort, investigated the long-term remission rates and predictors of different trajectories of obsessive-compulsive disorder (OCD) within a clinical population. METHODS: A sample of 213 participants was classified into three illness trajectories: "Chronic," "Episodic, "and "Remitted-OCD." Long-term remission rates were calculated based on three follow-up measurements over a 6-year period. A multinomial logistic regression model, incorporating five selected predictors with high explanatory power and one covariate, was employed to analyze OCD trajectory outcomes. RESULTS: The long-term full remission rates, calculated from all the measurements combined (14%), were significantly lower than what was observed in earlier studies and when compared to assessments at each individual follow-up (∼30%). Moreover, high baseline symptom severity and early age of onset were identified as significant risk factors for a chronic course of OCD, while male sex and younger age predicted a more favorable trajectory. Notably, the likelihood of an episodic course remained high even without identified risk factors. LIMITATIONS: The bi-annual data collection process is unable to capture participants' clinical conditions between assessments. Additionally, no data was collected regarding the specific type and duration of psychological treatment received. Regarding the type of treatment participants received. CONCLUSIONS: Results suggest that long-term remission rates may be lower than previously reported. Consequently, employing multiple assessment points in longitudinal studies is necessary for valid estimation of long-term full remission rates. The results emphasize the importance of personalized clinical care and ongoing monitoring and maintenance for most OCD cases.

The impact of COVID-19-pandemic-related adversity on mental health: longitudinal study in Dutch populations with and without mental health disorders.

BACKGROUND: Despite growing concerns about mental health during the COVID-19 pandemic, particularly in people with pre-existing mental health disorders, research has shown that symptoms of depression and anxiety were generally quite stable, with modest changes in certain subgroups. However, individual differences in cumulative exposure to COVID-19 stressors have not been yet considered. AIMS: We aimed to quantify and investigate the impact of individual-level cumulative exposure to COVID-19-pandemic-related adversity on changes in depressive and anxiety symptoms and loneliness. In addition, we examined whether the impact differed among individuals with various levels of pre-pandemic chronicity of mental health disorders. METHOD: Between April 2020 and July 2021, 15 successive online questionnaires were distributed among three psychiatric case-control cohorts that started in the 2000s (N = 1377). Outcomes included depressive and anxiety symptoms and loneliness. We developed a COVID-19 Adversity Index (CAI) summarising up to 15 repeated measures of COVID-19-pandemic-related exposures (e.g. exposure to COVID-19 infection, negative economic impact and quarantine). We used linear mixed linear models to estimate the effects of COVID-19-related adversity on mental health and its interaction with pre-pandemic chronicity of mental health disorders and CAI. RESULTS: Higher CAI scores were positively associated with higher increases in depressive symptoms, anxiety symptoms and loneliness. Associations were not statistically significantly different between groups with and without (chronic) pre-pandemic mental health disorders. CONCLUSIONS: Individual differences in cumulative exposure to COVID-19-pandemic-related adversity are important predictors of mental health, but we found no evidence for higher vulnerability among people with (chronic) pre-pandemic mental health disorders.

Predictors of the 6-year outcome of obsessive-compulsive disorder: Findings from the Netherlands Obsessive-Compulsive Disorder Association study.

OBJECTIVE: Obsessive-compulsive disorder is characterized by a chronic course that can vary between patients. The knowledge on the naturalistic long-term outcome of obsessive-compulsive disorder and its predictors is surprisingly limited. The present research was designed to identify clinical and psychosocial predictors of the long-term outcome of obsessive-compulsive disorder. METHODS: We included 377 individuals with a current diagnosis of obsessive-compulsive disorder, who participated in the Netherlands Obsessive Compulsive Disorder Association study, a multicenter naturalistic cohort study. Predictors were measured at baseline using self-report questionnaires and clinical interviews. Outcome was assessed using the Yale-Brown Obsessive Compulsive Scale at 2-, 4- and 6-year follow-up. RESULTS: The overall course of obsessive-compulsive disorder was characterized by two prominent trends: the first reflected an improvement in symptom severity, which was mitigated by the second, worsening trend in the long term. Several determinants affected the course variations of obsessive-compulsive disorder, namely, increased baseline symptom severity, late age of onset, history of childhood trauma and autism traits. CONCLUSION: The long-term outcome of obsessive-compulsive disorder in naturalistic settings was characterized by an overall improvement in symptom severity, which was gradually halted to the point of increased worsening. However, after 6 years, the severity of symptoms remained below the baseline level. While certain determinants predicted a more favorable course, their effect diminished over time in correspondence to the general worsening trend. The results highlight the importance of a regular and continuous monitoring for symptom exacerbations as part of the management of the obsessive-compulsive disorder, regardless of the presence of putative predictors.

Rivastigmine for ECT-induced cognitive adverse effects in late life depression (RECALL study): A multicenter, randomized, double blind, placebo-controlled, cross-over trial in patients with depression aged 55 years or older: Rationale, objectives and methods.

Background: Cognitive side-effects are an important reason for the limited use of electroconvulsive therapy (ECT). Cognitive side-effects are heterogeneous and occur frequently in older persons. To date, insight into these side-effects is hampered due to inconsistencies in study designs and small sample sizes. Among all cognitive side-effects, confusion and delirious states are especially troublesome for patients, relatives and clinicians. In particular inter-ictal delirium-like states are worrisome, since they may lead to premature treatment discontinuation. Besides a need for further insight into determinants of cognitive side-effects of ECT, there is a great need for treatment options. Methods and design: The Rivastigmine for ECT-induced Cognitive Adverse effects in Late Life depression (RECALL) study combines a multicenter, prospective cohort study on older patients with depression, treated with ECT, with an embedded randomized, placebo-controlled cross-over trial to examine the effect of rivastigmine on inter-ictal delirium. Patients are recruited in four centers across the Netherlands and Belgium. We aim to include 150 patients into the cohort study, in order to be able to subsequently include 30 patients into the trial. Patients are included in the trial when inter-ictal delirium, assessed by the Confusion Assessment method (CAM), or a drop in Mini Mental State Examination (MMSE) score of ≥4 during ECT, develops. In the cohort study, comprehensive measurements of ECT-related cognitive side-effects-and their putative determinants-are done at baseline and during the ECT-course. The primary outcome of the clinical trial is the effectiveness of rivastigmine on inter-ictal delirium-severity, assessed with a change in the Delirium Rating Scale-Revised-98. Secondary outcomes of the clinical trial are several ECT-characteristics and side-effects of rivastigmine. Discussion: This study is the first clinical trial with a focus on ECT-induced, inter-ictal delirium. The cohort provides the basis for recruitment of patients for the cross-over trial and additionally provides an excellent opportunity to unravel cognitive side-effects of ECT and identify putative determinants. This paper describes the rationale and study protocol. Clinical trial registration: EudraCT 2014-003385-24.

Predictors of mental health deterioration from pre- to post-COVID-19 outbreak.

BACKGROUND: Mental health was only modestly affected in adults during the early months of the COVID-19 pandemic on the group level, but interpersonal variation was large. AIMS: We aim to investigate potential predictors of the differences in changes in mental health. METHOD: Data were aggregated from three Dutch ongoing prospective cohorts with similar methodology for data collection. We included participants with pre-pandemic data gathered during 2006-2016, and who completed online questionnaires at least once during lockdown in The Netherlands between 1 April and 15 May 2020. Sociodemographic, clinical (number of mental health disorders and personality factors) and COVID-19-related variables were analysed as predictors of relative changes in four mental health outcomes (depressive symptoms, anxiety and worry symptoms, and loneliness), using multivariate linear regression analyses. RESULTS: We included 1517 participants with (n = 1181) and without (n = 336) mental health disorders. Mean age was 56.1 years (s.d. 13.2), and 64.3% were women. Higher neuroticism predicted increases in all four mental health outcomes, especially for worry (ß = 0.172, P = 0.003). Living alone and female gender predicted increases in depressive symptoms and loneliness (ß = 0.05-0.08), whereas quarantine and strict adherence with COVID-19 restrictions predicted increases in anxiety and worry symptoms (ß = 0.07-0.11).Teleworking predicted a decrease in anxiety symptoms (ß = -0.07) and higher age predicted a decrease in anxiety (ß = -0.08) and worry symptoms (ß = -0.10). CONCLUSIONS: Our study showed neuroticism as a robust predictor of adverse changes in mental health, and identified additional sociodemographic and COVID-19-related predictors that explain longitudinal variability in mental health during the COVID-19 pandemic.

The effectiveness of intensive home treatment as a substitute for hospital admission in acute psychiatric crisis resolution in the Netherlands: a two-centre Zelen double-consent randomised controlled trial.

BACKGROUND: Although de-institutionalisation has been underway for decades, admission to hospital followed by low-intensity outpatient care remains the usual treatment for patients with an acute psychiatric crisis. Intensive home treatment has been developed for patients in a severe psychiatric crisis as an alternative to inpatient care. This study aimed to evaluate the potential of intensive home treatment to reduce bed-days and its clinical effectiveness compared with treatment as usual. METHODS: We did a two-armed, two-centre, open-label, Zelen, double-consent, pragmatic randomised controlled trial. Patients aged 18-65 years were recruited at the psychiatric emergency service and psychiatric emergency wards of the two major mental health institutions (Arkin and GGZ inGeest) in Amsterdam, the Netherlands. Patients diagnosed with at least one DSM-IV-TR or DSM-5 disorder and in a psychiatric crisis and for whom psychiatrists had indicated or completed a clinical admission could be included. Trained psychiatric emergency service and hospital professionals did the automated web-based pre-randomisation procedure upon first contact with the patient. A seeded pseudo-random number generator allocated patients (2:1) to intensive home treatment or treatment as usual. Informed consent was obtained after randomisation as soon as the patient was mentally capable within 14 days. Due to the nature of this study, patients and professionals were not masked to treatment. Intensive home treatment was tailored to the nature of the crisis and goals of patients and relatives, and developed in collaboration with them and a multidisciplinary professional team. All main analyses were intention-to-treat, and the primary outcome was the total number of admission days 12 months after randomisation. To investigate the effect of treatment conditions on the outcome measures, linear mixed modelling analyses using restricted maximum likelihood estimation were done. This trial was prospectively registered with Trialregister.nl, NL-6020 (NTR-6151). FINDINGS: Between Nov 15, 2016, and Oct 15, 2018, 246 patients were included in the study (183 patients with intensive home treatment vs 63 patients with treatment as usual). 135 women (55%) and 111 men (45%) were included, with a mean age of 41·01 years (range 18-65; SD 12·68). 114 participants (46%) were born in the Netherlands and 85 (35%) elsewhere (missing data on 47 [19%] participants). Ethnicity data were not available. After 12 months, the mean number of admission days in the intensive home treatment condition was 42·47 (SD 53·92) versus 67·02 (SD 79·03) for treatment as usual, a reduction of 24·55 days (SD 10·73) or 36·6% (p=0·033). 26 adverse events were registered, 23 (89%) of which were suicide attempts. The number of patients with a reported adverse event did not differ significantly between the groups (15 [8%] in the intensive home treatment group vs five [8%] in the treatment as usual group; p=0·950). Five patients died by suicide (three [2%] in the intensive home treatment group vs two [3%] in the treatment as usual group; p=0·610). No treatment-related deaths occurred. INTERPRETATION: Intensive home treatment is a safe and effective partial substitute for conventional psychiatric crisis care that led to a reduction in admission days, causing patients to stay longer in their social environment, with similar clinical effects, patient satisfaction and adverse events. FUNDING: De Stichting tot Steun Vereniging voor Christelijke Verzorging van Geestes-en Zenuwzieken.

Cannabidiol enhancement of exposure therapy in treatment refractory patients with social anxiety disorder and panic disorder with agoraphobia: A randomised controlled trial.

Preclinical research suggests that enhancing CB1 receptor agonism may improve fear extinction. In order to translate this knowledge into a clinical application we examined whether cannabidiol (CBD), a hydrolysis inhibitor of the endogenous CB1 receptor agonist anandamide (AEA), would enhance the effects of exposure therapy in treatment refractory patients with anxiety disorders. Patients with panic disorder with agoraphobia or social anxiety disorder were recruited for a double-blind parallel randomised controlled trial at three mental health care centres in the Netherlands. Eight therapist-assisted exposure in vivo sessions (weekly, outpatient) were augmented with 300 mg oral CBD (n = 39) or placebo (n = 41). The Fear Questionnaire (FQ) was assessed at baseline, mid- and post-treatment, and at 3 and 6 months follow-up. Primary analyses were on an intent-to-treat basis. No differences were found in treatment outcome over time between CBD and placebo on FQ scores, neither across (ß = 0.32, 95% CI [-0.60; 1.25]) nor within diagnosis groups (ß = -0.11, 95% CI [-1.62; 1.40]). In contrast to our hypotheses, CBD augmentation did not enhance early treatment response, within-session fear extinction or extinction learning. Incidence of adverse effects was equal in the CBD (n = 4, 10.3%) and placebo condition (n = 6, 15.4%). In this first clinical trial examining CBD as an adjunctive therapy in anxiety disorders, CBD did not improve treatment outcome. Future clinical trials may investigate different dosage regimens.

Cluster B versus Cluster C Personality Disorders: A Comparison of Comorbidity, Suicidality, Traumatization and Global Functioning.

A general clinical assumption states that cluster B personality disorders (PDs) represent a more severe form of PD than cluster C PDs. Consequently, most PD research is centered on cluster B PDs (especially borderline PD). Yet, prevalence ratings of cluster C PDs exceed those of cluster B PDs. In this explorative, cross-sectional study, we compared cluster B and C PD patients (N = 94) on a wide range of clinically-relevant severity measures, including comorbidity, suicidality, (childhood) traumatization and global functioning. Results showed that, although cluster B PD patients suffered more often from substance use disorders and lifetime suicide attempts, no difference could be established between groups for all other severity measures, including trauma variables. In our study, we additionally included a group of combined cluster B and C PDs, who were largely similar to both other groups. Although our study is insufficiently powered to claim a significant non-difference, these findings emphasize that high rates of comorbidity, suicidality, childhood traumatization and functional impairment apply to both cluster B and C patients. As such, our findings encourage more research into cluster C PDs, ultimately leading to more evidence-based treatments for this prevalent patient group. In addition, the high level of traumatization across groups calls for a routine trauma screening, especially since PD treatment may benefit from concurrent trauma treatment.

Associations of three major physiological stress systems with suicidal ideation and suicide attempts in patients with a depressive and/or anxiety disorder.

BACKGROUND: People with depressive and/or anxiety disorders are at increased risk of suicidal ideation and suicide attempts, but biological correlates signaling such risk remain unclear. Independent and cumulative dysregulations in physiological stress systems, in particular the hypothalamic-pituitaryadrenal axis (HPA-axis), immune-inflammatory system, and autonomous nervous system (ANS), may contribute to this risk. However, findings have either been heterogeneous or absent thus far. METHODS: Associations between individual markers and cumulative indices of the HPA-axis (cortisol awakening response and evening cortisol), immune-inflammatory system (C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor-α), and the ANS (heart rate, respiratory sinus arrhythmia, and pre-ejection period) and the outcomes no suicide ideation with suicide attempt (SI-SA+), suicide ideation without suicide attempt (SI+SA-) and suicide ideation with suicide attempt (SI+SA+) were investigated in 1749 persons with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA). RESULTS: High levels of CRP and IL-6 were associated with SI-SA+ and SI+SA+ respectively when compared to non-suicidal patients after adjusting for confounders and multiple testing. Also, cumulative immune-inflammatory dysregulations were positively associated with SI+SA+, suggesting a dose-response effect. No significant associations were found between HPA-axis or ANS indicators and suicide-outcomes and between immune-inflammatory system markers or cumulative stress system dysregulations and SI+SA-. CONCLUSION: Although stress system markers could not differentiate between SI+SA- and non-suicidal patients, findings indicate that dysregulations of individual and cumulative immune-inflammatory markers are associated with suicide attempts in depressive and/or anxiety patients. Thus, immune-inflammatory system dysregulation may be involved in the pathophysiology of suicidal behavior, supporting further examination of the effects of anti-inflammatory interventions on suicidality.

Mental health and perceived impact during the first Covid-19 pandemic year: A longitudinal study in Dutch case-control cohorts of persons with and without depressive, anxiety, and obsessive-compulsive disorders.

BACKGROUND: Little is known about the longer-term impact of the Covid-19 pandemic beyond the first months of 2020, particularly for people with pre-existing mental health disorders. Studies including pre-pandemic data from large psychiatric cohorts are scarce. METHODS: Between April 2020 and February 2021, twelve successive online questionnaires were distributed among participants of the Netherlands Study of Depression and Anxiety, Netherlands Study of Depression in Older Persons, and Netherlands Obsessive Compulsive Disorder Association Study (N = 1714, response rate 62%). Outcomes were depressive symptoms, anxiety, worry, loneliness, perceived mental health impact of the pandemic, fear of Covid-19, positive coping, and happiness. Using linear mixed models we compared trajectories between subgroups with different pre-pandemic chronicity of disorders and healthy controls. RESULTS: Depressive, anxiety and worry symptoms were stable since April-May 2020 whereas happiness slightly decreased. Furthermore, positive coping steadily decreased and loneliness increased - exceeding pre-Covid and April-May 2020 levels. Perceived mental health impact and fear of Covid-19 fluctuated in accordance with national Covid-19 mortality rate changes. Absolute levels of all outcomes were poorer with higher chronicity of disorders, yet trajectories did not differ among subgroups. LIMITATIONS: The most vulnerable psychiatric groups may have been underrepresented and results may not be generalizable to lower income countries. CONCLUSIONS: After a year, levels of depressive and worry symptoms remained higher than before the pandemic in healthy control groups, yet not in psychiatric groups. Nevertheless, persistent high symptoms in psychiatric groups and increasing loneliness in all groups are specific points of concern for mental health care professionals.

Prediction of illness remission in patients with Obsessive-Compulsive Disorder with supervised machine learning.

INTRODUCTION: The course of OCD differs widely among OCD patients, varying from chronic symptoms to full remission. No tools for individual prediction of OCD remission are currently available. This study aimed to develop a machine learning algorithm to predict OCD remission after two years, using solely predictors easily accessible in the daily clinical routine. METHODS: Subjects were recruited in a longitudinal multi-center study (NOCDA). Gradient boosted decision trees were used as supervised machine learning technique. The training of the algorithm was performed with 227 predictors and 213 observations collected in a single clinical center. Hyper-parameter optimization was performed with cross-validation and a Bayesian optimization strategy. The predictive performance of the algorithm was subsequently tested in an independent sample of 215 observations collected in five different centers. Between-center differences were investigated with a bootstrap resampling approach. RESULTS: The average predictive performance of the algorithm in the test centers resulted in an AUROC of 0.7820, a sensitivity of 73.42%, and a specificity of 71.45%. Results also showed a significant between-center variation in the predictive performance. The most important predictors resulted related to OCD severity, OCD chronic course, use of psychotropic medications, and better global functioning. LIMITATIONS: All recruiting centers followed the same assessment protocol and are in The Netherlands. Moreover, the sample of the data recruited in some of the test centers was limited in size. DISCUSSION: The algorithm demonstrated a moderate average predictive performance, and future studies will focus on increasing the stability of the predictive performance across clinical settings.

Associations between personality traits and suicidal ideation and suicide attempts in patients with personality disorders.

INTRODUCTION: People with personality disorders (PDs) have an elevated suicide risk. However, correlates of suicidal ideation (SI) and suicide attempts (SA) remain largely unknown in this population. A growing body of literature highlights the contribution of the Big Five personality traits in suicide-outcomes. Therefore, the present study investigates the association between the Big Five personality traits and SI and SA in people with PDs while applying the ideation-to-action framework. METHOD: Data were obtained from 105 treatment-seeking individuals diagnosed with PDs participating in the Trauma tO Personality Spectrum Study (TOPSS). Multinomial logistic regression analyses were used to analyze the association between the NEO Five-Factor Inventory and the three category suicide-outcome: non-suicidal, SI, and SA. RESULTS: After controlling for age, gender, a comorbid depressive disorder, the severity of borderline manifestations, and other personality traits from the Big Five taxonomy, significantly lower levels of extraversion were observed in participants with SI compared to non-suicidal participants (OR = 0.27, 95% CI 0.10-0.72) but not in SA participants. In contrast, higher levels of extraversion were associated with SA when compared to SI (OR = 3.52, 95% CI 1.33-9.32). Other Big Five traits were not independently associated with suicide-outcomes. CONCLUSIONS: Of the Big Five traits, the introversion-extraversion dimension most clearly distinguishes individuals with SI from non-suicidal individuals, as well as those with a SA in the past from those with SI only. Prospective studies are required to investigate if this personality trait can predict the progression from being non-suicidal to having SI and from having SI to performing an attempt.

The Effect of Rapport on Data Quality in Face-to-Face Interviews: Beneficial or Detrimental?

The benefits of rapport between interviewers and respondents, in terms of recruiting the latter and motiving them to participate in research, have been generally endorsed. However, there has been less clarity with regard to the association between rapport and data quality. In theory, rapport could be beneficial if it motivates people to give complete and honest responses. On the other hand, efforts to maintain rapport by exhibiting pleasing and socially desirable behaviour could well be detrimental to data quality. In a large longitudinal epidemiological sample, generalized estimating equations (GEE) analyses were used to examine the association between rapport and the following three quality indicators: missing responses, responses to sensitive questions, and consistency of responses. The results of these analyses indicate an association between a high level of rapport and fewer missing responses. In contrast, we found more socially desirable responses for the high-rapport group. Finally, the high-rapport group did not differ from the low-rapport group in terms of the consistency of their responses.

Common and specific determinants of 9-year depression and anxiety course-trajectories: A machine-learning investigation in the Netherlands Study of Depression and Anxiety (NESDA).

BACKGROUND: Given the strong relationship between depression and anxiety, there is an urge to investigate their shared and specific long-term course determinants. The current study aimed to identify and compare the main determinants of the 9-year trajectories of combined and pure depression and anxiety symptom severity. METHODS: Respondents with a 6-month depression and/or anxiety diagnosis (n=1,701) provided baseline data on 152 sociodemographic, clinical and biological variables. Depression and anxiety symptom severity assessed at baseline, 2-, 4-, 6- and 9-year follow-up, were used to identify data-driven course-trajectory subgroups for general psychological distress, pure depression, and pure anxiety severity scores. For each outcome (class-probability), a Superlearner (SL) algorithm identified an optimally weighted (minimum mean squared error) combination of machine-learning prediction algorithms. For each outcome, the top determinants in the SL were identified by determining variable-importance and correlations between each SL-predicted and observed outcome (ρpred) were calculated. RESULTS: Low to high prediction correlations (ρpred: 0.41-0.91, median=0.73) were found. In the SL, important determinants of psychological distress were age, young age of onset, respiratory rate, participation disability, somatic disease, low income, minor depressive disorder and mastery score. For course of pure depression and anxiety symptom severity, similar determinants were found. Specific determinants of pure depression included several types of healthcare-use, and of pure-anxiety course included somatic arousal and psychological distress. LIMITATIONS: Limited sample size for machine learning. CONCLUSIONS: The determinants of depression- and anxiety-severity course are mostly shared. Domain-specific exceptions are healthcare use for depression and somatic arousal and distress for anxiety-severity course.

The correlates of social phobia in OCD: Findings from a large clinical sample.

OBJECTIVES: Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder, often complicated with comorbidities. Social phobia (SP) is the most frequent co-occurring anxiety disorder in OCD, associated with increased clinical severity. However, no study had examined the relevance of interpersonal processes in this comorbidity, which are at the core of SP. This study characterized the clinical (i.e., symptom profile, age of onset, chronicity, and comorbidity), vulnerability (i.e., childhood trauma, negative life events), and interpersonal (attachment style, expressed emotion, and social support) correlates of comorbid SP in a large sample of OCD patients. METHODS: We analysed the data of 382 OCD patients participating in the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study. We examined the correlates of SP in OCD using self-report questionnaires and structured clinical interviews. In addition, data of 312 non-OCD SP patients were drawn from the Netherlands Study of Depression and Anxiety (NESDA), to compare the age of onset of SP between groups. Descriptive univariate analyses were followed by backward stepwise logistic regression analyses. RESULTS: Social phobia was present among approximately 20% of OCD patients. Social phobia in OCD was associated with increased depression severity and decreased ratings of secure attachment style. Among OCD patients, SP had a significantly earlier age onset as compared to SP in non-OCD patients. CONCLUSION: Social phobia in OCD might render a vulnerable clinical picture, characterized with early onset of SP symptoms, insecure attachment style, and increased depressive symptoms. Future studies should use prospective designs to better understand the nature of comorbid SP in OCD. PRACTITIONER POINTS: Approximately one fifth of OCD patients were diagnosed with comorbid social phobia in a large representative clinical sample. OCD patients with comorbid social phobia presented with a vulnerable clinical picture, characterized with increased depression severity and decreased ratings of secure attachment style. Social phobia in OCD was associated with an earlier AOO as compared to the AOO of social phobia without OCD. The findings are limited by a cross-sectional design; thus, causality could not be assessed. Research is needed to further examine the mechanisms of comorbid social phobia in OCD.

Cohort profile of the longitudinal Netherlands Study of Depression and Anxiety (NESDA) on etiology, course and consequences of depressive and anxiety disorders.

INTRODUCTION: The Netherlands Study of Depression and Anxiety (NESDA, www.nesda.nl) is a longitudinal, multi-site, naturalistic, case-control cohort study set up to examine the etiology, course and consequences of depressive and anxiety disorders. This paper presents a cohort profile of NESDA. METHODS AND RESULTS: The NESDA sample recruited initially 2329 persons with a remitted or current DSM-IV based depressive (major depressive disorder, dysthymia) and/or anxiety disorder (panic disorder, social phobia, agoraphobia, generalized anxiety disorder), 367 of their siblings and 652 healthy controls, yielding a total of 3348 participants. Half-day face-to-face assessments of participants started in 2004 and since then have been repeated six times over a period of 9 years. A 13-year follow-up assessment is ongoing, at what time we also recruit offspring of participants. Retention rates are generally high, ranging from 87.1% (after 2 years) to 69.4% (after 9 years). Psychiatric diagnostic interviews have been administered at all face-to-face assessments, as was monitoring of clinical characteristics, psychosocial functioning and somatic health. Assessed etiological factors include e.g. early and current environmental risk factors, psychological vulnerability and resilience factors as well as (neuro)biology through hypothesis-driven biomarker assessments, genome-wide and large-scale '-omics' assessments, and neuroimaging assessments. LIMITATIONS: The naturalistic design allows research into course and consequences of affective disorders but is limited in treatment response interpretation. CONCLUSIONS: NESDA provides a strong research infrastructure for research into depressive and/or anxiety disorders. Its data have been used for many scientific papers describing either NESDA-based analyses or joint collaborative consortia-projects, and are in principle available to researchers outside the NESDA consortium.

Prevalence, course, and determinants of suicide ideation and attempts in patients with a depressive and/or anxiety disorder: A review of NESDA findings.

BACKGROUND: Depressive and anxiety disorders are often associated with suicide ideation (SI) and attempt (SA). However, analyses of prevalence, course, and more specific risk mechanisms are needed to improve knowledge and detection of high risk individuals with depressive and anxiety disorders. Previous studies often lacked statistical power, assessment of detailed determinants and follow-up measurements. METHODS: The Netherlands Study of Depression and Anxiety (NESDA), a large cohort study, overcomes some earlier limitations. Scale for Suicide Ideation and Compositive Interview Diagnostic Instrument data were analyzed to report on prevalence of SI and SA. Additionally, important sociodemographic, clinical, psychological, environmental, and neurobiological determinants and course of SI and SA identified in depressive and/or anxiety disorder respondents in 16 NESDA articles were summarized. RESULTS: Within respondents with 12-month diagnosis (n=1,783), SI and 12-month SA prevalence ranged from 17.1-20.1% and 0.8-3.0% respectively across 5 waves during 9-year follow-up and SI was highly recurrent. Both SI and SA were especially associated with comorbid depression and anxiety, higher clinical severity, sleep dysfunctions, higher aggression and hopelessness, and childhood trauma. In the (neuro)biological domain, SI was linked with immune dysregulation and SA with abnormal brain activity during emotion processing and genetic risk. LIMITATIONS: Most articles were cross-sectional in nature, preventing causal inferences and no conclusions could be drawn about the overall magnitude of results. CONCLUSION: SI and SA are multifactorial phenomena and especially prevalent amongst comorbid depressive and anxiety respondents. Considering many overlapping SI and SA determinants, more neurobiological determinants and use of innovative methodological techniques are desirable.

The mental health impact of the COVID-19 pandemic on people with and without depressive, anxiety, or obsessive-compulsive disorders: a longitudinal study of three Dutch case-control cohorts.

BACKGROUND: The impact of the COVID-19 pandemic on mental health in people with pre-existing mental health disorders is unclear. In three psychiatry case-control cohorts, we compared the perceived mental health impact and coping and changes in depressive symptoms, anxiety, worry, and loneliness before and during the COVID-19 pandemic between people with and without lifetime depressive, anxiety, or obsessive-compulsive disorders. METHODS: Between April 1 and May 13, 2020, online questionnaires were distributed among the Netherlands Study of Depression and Anxiety, Netherlands Study of Depression in Older Persons, and Netherlands Obsessive Compulsive Disorder Association cohorts, including people with (n=1181) and without (n=336) depressive, anxiety, or obsessive-compulsive disorders. The questionnaire contained questions on perceived mental health impact, fear of COVID-19, coping, and four validated scales assessing depressive symptoms, anxiety, worry, and loneliness used in previous waves during 2006-16. Number and chronicity of disorders were based on diagnoses in previous waves. Linear regression and mixed models were done. FINDINGS: The number and chronicity of disorders showed a positive graded dose-response relation, with greater perceived impact on mental health, fear, and poorer coping. Although people with depressive, anxiety, or obsessive-compulsive disorders scored higher on all four symptom scales than did individuals without these mental health disorders, both before and during the COVID-19 pandemic, they did not report a greater increase in symptoms during the pandemic. In fact, people without depressive, anxiety, or obsessive-compulsive disorders showed a greater increase in symptoms during the COVID-19 pandemic, whereas individuals with the greatest burden on their mental health tended to show a slight symptom decrease. INTERPRETATION: People with depressive, anxiety, or obsessive-compulsive disorders are experiencing a detrimental impact on their mental health from the COVID-19 pandemic, which requires close monitoring in clinical practice. Yet, the COVID-19 pandemic does not seem to have further increased symptom severity compared with their prepandemic levels. FUNDING: Dutch Research Council.