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.

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.

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.

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.

Suicide ideation versus suicide attempt: Examining overlapping and differential determinants in a large cohort of patients with depression and/or anxiety.

OBJECTIVE: Individuals with a depressive and/or anxiety disorder are known to have an elevated risk of suicide. However, these diagnoses alone are insufficient at differentiating patients with suicide ideation that attempt suicide from those that do not. Few studies examined such differences in an ideation-to-action framework. Using this framework, extensive multivariate testing was performed to examine differences between suicidal patients with and without a suicide attempt. METHOD: Data were from 1576 respondents with a depressive and/or anxiety disorder, participating in the Netherlands Study of Depression and Anxiety. Logistic regression analyses were used to analyze associations between sociodemographic, clinical, personality, and psychosocial risk factors and suicide ideation and attempt. RESULTS: Patients with suicide ideation could be uniquely distinguished from non-suicidal patients by more years of education, presence of a depressive disorder (vs anxiety disorder) and higher introversion. Patients with suicide ideation and a past suicide attempt could be uniquely distinguished from non-suicidal patients by a younger age of onset, a lifetime alcohol use disorder, more external locus of control and lower levels of social support. Within the group of patients with suicide ideation, patients with a suicide attempt were more likely to have childhood trauma and lower education, and be of non-Western descent than patients with suicide ideation and no past attempt. CONCLUSION: This study found that although various clinical, personality and psychosocial characteristics distinguish patients with suicide ideation from non-suicidal patients, many of these often-cited factors do not distinguish patients with a suicide attempt from those who only think about suicide. However, childhood trauma, lower education and non-Western descent could aid in detecting suicide attempt risk among patients with suicide ideation.

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.

A 6-year longitudinal study of predictors for suicide attempts in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD), represent a major source of risk for suicidality. However, knowledge about risk factors for future suicide attempts (SAs) within MDD is limited. The present longitudinal study examined a wide range of putative non-clinical risk factors (demographic, social, lifestyle, personality) and clinical risk factors (depressive and suicidal indicators) for future SAs among persons with MDD. Furthermore, we examined the relationship between a number of significant predictors and the incidence of a future SA. METHODS: Data are from 1713 persons (18-65 years) with a lifetime MDD at the baseline measurement of the Netherlands Study of Depression and Anxiety who were subsequently followed up 2, 4 and 6 years. SAs were assessed in the face-to-face measurements. Cox proportional hazard regression analyses were used to examine a wide range of possible non-clinical and clinical predictors for subsequent SAs during 6-year follow-up. RESULTS: Over a period of 6 years, 3.4% of the respondents attempted suicide. Younger age, lower education, unemployment, insomnia, antidepressant use, a previous SA and current suicidal thoughts independently predicted a future SA. The number of significant risk factors (ranging from 0 to 7) linearly predicted the incidence of future SAs: in those with 0 predictors the SA incidence was 0%, which increased to 32% incidence in those with 6+ predictors. CONCLUSION: Of the non-clinical factors, particularly socio-economic factors predicted a SA independently. Furthermore, preexisting suicidal ideation and insomnia appear to be important clinical risk factors for subsequent SA that are open to preventative intervention.

Chronic obsessive-compulsive disorder: prognostic factors.

BACKGROUND: The course of illness in obsessive-compulsive disorder (OCD) varies significantly between patients. Little is known about factors predicting a chronic course of illness. The aim of this study is to identify factors involved in inducing and in maintaining chronicity in OCD. METHODS: The present study is embedded within the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study, an ongoing multicenter naturalistic cohort study designed to identify predictors of long-term course and outcome in OCD. For this study, 270 subjects with a current diagnosis of OCD were included. Chronicity status at 2-year follow-up was regressed on a selection of baseline predictors related to OCD, to comorbidity and to stress and support. RESULTS: Psychotrauma [odds ratio (OR) 1.98, confidence interval (CI) 1.22-3.22, p = 0.006], recent negative life events (OR 1.42, CI 1.01-2.01, p = 0.043), and presence of a partner (OR 0.28, CI 0.09-0.85, p = 0.025) influenced the risk of becoming chronic. Longer illness duration (OR 1.46, CI 1.08-1.96, p = 0.013) and higher illness severity (OR 1.09, CI 1.03-1.16, p = 0.003) increased the risk of remaining chronic. CONCLUSIONS: External influences increase the risk of becoming chronic, whereas the factors involved in maintaining chronicity are illness-related. As the latter are potentially difficult to modify, treatment should be devoted to prevent chronicity from occurring in the first place. Therapeutic strategies aimed at alleviating stress and at boosting social support might aid in achieving this goal.

Attempted suicide of ethnic minority girls with a Caribbean and Cape Verdean background: rates and risk factors.

BACKGROUND: WHO data shows that female immigrants in Europe attempt suicide at higher rates than 'native' women and 'native' and immigrant men. Empirical studies addressing attempted suicide of female immigrants of Caribbean (Antillean-Dutch and Creole-Surinamese-Dutch) as well as Cape Verdean descent in Europe are however scarce. We aim to increase knowledge about rates and risk factors of girls of Caribbean and Cape Verdean descent living in the Netherlands. METHODS: We conducted logistic regression on a dataset that consisted of self-reported health and well-being surveys filled out by 5611 female students, age 14-16, in Rotterdam, the Netherlands (Antillean Dutch N = 357, Creole-Surinamese-Dutch N = 130, and Cape Verdean-Dutch N = 402, and Dutch 'natives' N = 4691). We studied if girls of these minority groups had elevated risk for attempted suicide. Risk indicators that were suspected to play a role were investigated i.e. household composition, socio-economic class, externalizing problems, emotional problems and sexual abuse. RESULTS: We found that rates of attempted suicide among Antillean (14%), Creole-Surinamese young women (15.4%) were higher than of 'native' Dutch girls (9.1%), while rates of Cape-Verdean girls (8.3%) were rather similar to those of 'native' girls. Not living with two biological parents was a risk factor for 'native' girls, but not for girls of Caribbean and Cape Verdean descent. Emotional problems and sexual abuse seems to be a risk indicator for suicidality across all ethnicities. Aggressive behaviour was a risk factor for Antillean Dutch and 'native' girls. CONCLUSIONS: Our findings underscore the need for developing suicide prevention programs for minority girls in multicultural cities in western Europe, in particular those of Caribbean descent. Results suggest the importance of addressing socio-economic class and educational background for suicide prevention, which bear particular relevance for Caribbean populations. Referral in the case of sexual trauma and low psychological wellbeing seems critical for reducing suicidal behaviour in girls, regardless of ethnicity.

Longitudinal Associations Between Biopsychosocial Factors and Sustainable Return to Work of Sick-Listed Workers with a Depressive or Anxiety Disorder.

PURPOSE: Only a limited number of studies have investigated return to work of sick-listed workers with mental health problems, and more knowledge is needed about the influence of non-disorder-related factors. This study aimed to identify longitudinal associations between demographic, personality, disorder-related and work-related characteristics and sustainable return to work of sicklisted workers with a depressive or anxiety disorder. METHODS: We used data of a large Dutch cohort study to prospectively study longitudinal associations between biopsychosocial factors and sustainable return to work in 2 years. Associations were studied by means of univariable and multivariable logistic regression analysis. Participants who were sick-listed at baseline and had a lifetime diagnosis of a depressive and/or anxiety disorder were included in this study (N = 215). RESULTS: In 2 years, 51.6% of the participants returned to work sustainably. Age, household income, extraversion, employment status, skill discretion and job security were significantly (P B 0.05) associated with sustainable RTW in 2 years in the univariable analyses. The multivariable analysis revealed significant associations between sustainable return to work and age (OR per 10 years = 0.67; 95% CI 0.47­0.95), household income (OR per 100 Euro's a month = 1.04; 95% CI 1.00­1.08) and being on sickness benefit versus being (self-)employed (OR 0.39; 95% CI 0.20­0.77). CONCLUSIONS: In the long-run not disorder-related factors, but an older age, the absence of a job and a low household income seem to complicate return to work. Policy and research should focus on facilitators and barriers for return to work of workers with these characteristics.

Inference-Based Approach versus Cognitive Behavioral Therapy in the Treatment of Obsessive-Compulsive Disorder with Poor Insight: A 24-Session Randomized Controlled Trial.

OBJECTIVE: Obsessive-compulsive disorder (OCD) with poor insight has severe consequences for patients; nonetheless, no randomized controlled trial has ever been performed to evaluate the effectiveness of any treatment specifically for poor-insight OCD. A new psychotherapy for OCD, the inference-based approach (IBA), targets insight in OCD by strengthening normal sensory-driven reality testing. The goal of the present study is to compare the effectiveness of this new treatment to the effectiveness of cognitive behavior therapy (CBT) for patients with OCD with poor insight. METHOD: A randomized controlled trial was conducted, in which 90 patients with OCD with poor insight received either 24 CBT sessions or 24 IBA sessions. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS). Secondary outcome measures were level of insight, anxiety and depressive symptoms, and quality of life. Mixed-effects models were used to determine the treatment effect. RESULTS: In both conditions, a significant OCD symptom reduction was reached, but no condition effects were established. Post hoc, in a small subgroup of patients with the worst insight (n = 23), it was found that the patients treated with the IBA reached a significantly higher OCD symptom reduction than the patients treated with CBT [estimated marginal mean = -7.77, t(219.45) = -2.4, p = 0.017]. CONCLUSION: Patients with OCD with poor insight improve significantly after psychological treatment. The results of this study suggest that both CBT and the IBA are effective treatments for OCD with poor insight. The IBA might be more promising than CBT for patients with more extreme poor insight.

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.

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 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.

Cognitive therapy versus fluvoxamine as a second-step treatment in obsessive-compulsive disorder nonresponsive to first-step behavior therapy.

BACKGROUND: To compare the effectiveness of second-step treatment with cognitive therapy (CT) versus fluvoxamine in patients with obsessive-compulsive disorder (OCD) who are nonresponsive to exposure in vivo with response prevention (ERP). METHODS: A 12-week randomized controlled trial at an outpatient clinic in the Netherlands comparing CT with fluvoxamine in OCD. Of 118 subjects with OCD treated with 12 weeks of ERP, 48 appeared to be nonresponders (Y-BOCS improvement score of less than one third). These nonresponders were randomized to CT (n = 22) or fluvoxamine (n = 26). The main outcome measure was the Y-BOCS severity scale. Statistical analyses were conducted in the intention-to-treat sample (n = 45) on an 'as randomized basis' and in the per-protocol sample (n = 30). Due to selective dropout in the fluvoxamine group, two additional sensitivity analyses were performed. RESULTS: Complete data could be obtained from 45 subjects (94%) after 12 weeks. Fifty percent of the patients refused fluvoxamine after randomization compared to 13% who refused CT [χ(2)(1) = 7.10; p = 0.01]. CT as a second-step treatment did not appear to be effective in this sample of nonresponders. Fluvoxamine was significantly superior to CT in the intention-to-treat sample, in the per-protocol sample and in the two separately defined samples in which the sensitivity analyses were performed. CONCLUSIONS: OCD patients who are nonresponsive to ERP may benefit more from a switch to treatment with an antidepressant instead of switching to CT. In clinical practice, it may be important to motivate this subgroup of patients to undergo psychopharmacological treatment, as this may improve their outcome considerably.

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.

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.

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.

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.

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.