OBJECTIVE:Cognitive Reactivity (CR) is the (re-)activation of negative cognitions by dysphoric mood. We examined whether CR predicts depressive episodes across 2 and 9 years, beyond subclinical depressive symptoms, neuroticism, and previous depressive episodes. METHODS:Participants (N = 1,734) from the Netherlands Study of Depression and Anxiety (NESDA) were never-depressed or remitted-depressed for ≥1 month prior to baseline. We examined 2-year and 9-year predictions using Cox's survival analysis and logistic regression, respectively. Two-year coefficient-based weight-points were calculated and evaluated using ROC analysis. RESULTS:CR was a statistically-significant predictor of two-year depressive episodes, with an odds ratio of 1.04, 95% CI (1.02-1.06), and over nine years, with an adjusted hazard ratio of 1.01, 95% CI (1.01-1.02). The influence of CR and subclinical depressive symptoms decreased as the number of episodes increased, especially in ≥ 3 past episodes. Calculated weight-points correctly predicted 33.5% of participants who developed 2-year depression, compared to a 17.8% base rate (sensitivity = .81, specificity = .66). CONCLUSIONS:CR is a moderately strong predictor of depressive episodes across 2 and 9 years. In participants with ≥ 3 prior episodes, depression history is such a strong predictor that a ceiling effect occurs, removing any added value of other predictors.

The Physical Symptoms Questionnaire (PSQ-51) is a Dutch-language self-report tool listing 51 physical symptoms that may occur in patients with known medical conditions, somatic symptom disorders and the general population. However, the tool is currently only available in Dutch and is yet to be translated or validated into English for utility with English-speaking populations. This study aimed to translate and validate an English version of the tool and determine the PSQ-51's factor structure in both Dutch and UK samples. An English version was translated and then validated through back-translation and refined for clarity. Data from three Dutch samples (general population [n = 1699], general practice[n = 775], and psychiatric outpatients[n = 1404]) and one UK general population sample (n = 294) were then analysed to explore the factor structure. An iterative exploratory factor analysis (EFA) on the Dutch psychiatric sample revealed a seven-factor solution including symptom clusters: General Malaise, Autonomic, Musculoskeletal, Gastrointestinal, Loss of Function, Hot Flushes, and Urogenital symptoms. Confirmatory factor analysis (CFA) tested this model across the Dutch and UK samples, with mixed results for fit indices, although good internal reliability was demonstrated. Findings indicate partial cross-cultural consistency in the factor structure. Substantial differences in symptom prevalence between Dutch and UK population samples were observed, possibly due to cultural and situational factors. The PSQ-51 shows promise for assessing somatic symptom burden, for example in multimorbidity or in complex somatic symptom disorders, where it may enhance clinical consultations by identifying symptoms to address clinical complexity. Further research is needed to explore its applicability in diverse populations and refine its factor structure for broader clinical utility.

Lithium treatment is considered the first-line option in the pharmacological treatment of bipolar disorder. At the same time, individual responses vary greatly, which complicates achieving rapid stabilization in many subjects with bipolar disorder. The neurobiological mechanism of action of lithium remains largely unknown, hindering the development of clinically applicable predictors of individual treatment responses. The recent introduction of ultra-high-field lithium magnetic resonance imaging (MRI) has opened up a promising avenue for better linking brain measures with clinical response to lithium treatment. This is an observational study involving 80 adults with bipolar disorder who begin lithium as part of their regular treatment. Within 4 weeks of reaching stable therapeutic serum lithium concentrations, brain lithium concentrations will be measured by employing a 3D lithium-7 chemical shift imaging (7Li CSI) sequence on a 7T MR system. The primary outcome is the clinical response to lithium treatment at 1 year follow-up, assessed using a validated questionnaire. Linear regression analysis will be used to establish correlations between brain lithium concentrations-measured through mean brain, voxel-wise, parcellation, and region-of-interest approaches-and clinical lithium response. The BLISS study protocol (NL80214.058.22) has been approved by the Medical Ethics Committee of Leiden, The Hague, and Delft in The Netherlands. Results will be submitted for publication in peer-reviewed journals and shared with the key population.Registration Online at clinicaltrials.gov (NCT06134349), 20 November 2023.

Introduction:When patients with persistent depressive disorder (PDD) respond insufficiently to available evidence-based treatments, depression treatment guidelines recommend psychiatric rehabilitation through self-management. Preferably, the intervention should involve the patient's informal caregiver. Methods:To gain insight into the healthcare needs of PDD patients and their caregivers and to facilitate the implementation of a self-management program, we conducted individual semi-structured interviews with 28 PDD patients and 9 informal caregivers regarding their self-management/coping and needs. Transcripts were analyzed with Grounded Theory using three sensitizing concepts (PDD experience, self-management/coping, needs). Results:Patients had 9 main themes and caregivers had 11 main themes. Patients and caregivers shared 9 main themes, pertaining to powerlessness, patients' identity changes, shame/stigma, relationship dissatisfaction, family suffering, self-management attitudes, self-management strategies, coping support, and coping complications. While self-management attitudes of patients were mixed, those of caregivers were positive. Care needs of both groups centered on psychoeducation and communication skills development. Caregivers reported urgently needing support in dealing with patients' suicidal behavior. Discussion:Our findings underscore the profound burden of PDD on both patients and their informal caregivers. We strongly recommend that healthcare professionals encourage and facilitate the development of self-management in depressed patients early in the treatment process and involve informal caregivers, particularly within suicide prevention strategies. Clinical Trial Registration:https://onderzoekmetmensen.nl/en/trial/55681, Netherlands Trial Register Identifier NL5818.

BackgroundHealthcare workers (HCW) have faced unprecedented challenges during the COVID-19, with significant impact on their well-being. We aimed to monitor stress-related symptoms and resilience in HCW over time in relation to various factors during the COVID-19 pandemic.MethodsBetween June 2020 and May 2022, data was collected among HCW of Leiden University Medical Centre (LUMC) through a digital self-monitoring application. The application included a 14-items self-monitoring tool (i.e., 7-items on Supporting factors, 7-items on Stressful burden), and a set of validated questionnaires (i.e., the Copenhagen Burnout Inventory (CBI), Impact of Event Scale – Revised (IES-R), Resilience Evaluation Scale (RES), and Depression Anxiety and Stress Scale (DASS-21).ResultsThe self-monitoring tool and validated questionnaires were completed by 1,070 and 413 participants respectively. Mean stress-related symptom scores (as measured by the self-monitoring, CBI, IES-R, and DASS-21) exhibited significant changes over time (all p’s < 0.001), which correlated with the waves of COVID-19 patients admitted and the national COVID-19 mortality rate (all p’s < 0.005). Resilience, as measured by the RES, showed a significant decrease from the start of data collection onwards (p = 0.001), whereas supporting factors showed significant decreases the first few months, followed by fluctuations after January 2021 (p = 0.02).LimitationsSelection bias may have arisen as those participating may have been more concerned with the burden on mental wellbeing.ConclusionsThe current study underscores the need for active psychosocial support for all HCW particularly during periods of increased admissions due to pandemics.

Background. Major depressive disorder (MDD) and anxiety disorders (AD) have high degrees of comorbidity and show great overlap in symptoms. The analysis of covarying depressive‐ and anxiety symptoms in longitudinal, sparse data panels has received limited attention. Dynamic time warping (DTW) analysis may help to provide new insights into symptom network properties based on diagnostic‐ and disease‐state stability criteria. Materials and Methods. In the Netherlands Study of Depression and Anxiety depressive‐, anxiety‐, and worry symptoms were assessed four or five times over the course of 9 years using self‐report questionnaires. The sample included 1,649 participants at baseline, comprising controls (n = 360), AD patients (n = 158), MDD patients (n = 265), and comorbid AD–MDD patients (n = 866). With DTW, 1,649 distance matrices were calculated, which yielded symptom networks and enabling comparison of network densities among subgroups. Results. The mean age of the sample was 41.5 years (standard deviations, 13.2), of whom 66.4% were female. The largest distance was between worry symptoms and physiological arousal symptoms, implicating the most dissimilar dynamics over time. The network density in the groups, from lowest to highest, followed the order: controls, AD, MDD, and comorbid AD–MDD. The comorbid group showed strongly connected mood and cognitive symptoms, which contrasted with the more strongly connected somatic and arousal symptoms in the AD and MDD groups. Groups that showed more transitions in disease states over follow‐up, regardless of the diagnoses, had the highest network density compared to more stable states of health or disease (beta for quadratic term = −0.095; P < 0.001). Conclusions. Symptom networks over time can be visualized by applying DTW methods on sparse panel data. Network density was highest in patients with comorbid anxiety and depressive disorders and those with more instability in disease states, suggesting that a stronger internal connectivity may facilitate “critical transitions” within the complex systems framework.

Introduction Atypical antipsychotic (AAP) drugs are the gold-standard treatment for psychotic patients but are nowadays also widely prescribed among people with other mental disorders. Notwithstanding the benefits of AAP in terms of symptom improvement, there are severe adverse effects including the metabolic syndrome. A novel hypothesis is that part of these undesirable effects of antipsychotics could be mediated by their deleterious effects on the microbiome. This may result in dysbiosis, the disruption of bacterial species of the gut microbiota. Recently, dysbiosis has been linked to poor quality of life, depression and anxiety through the gut-brain axis. Mounting evidence proposes that prebiotic consumption may be helpful in the recovery of dysbiosis, although this effect is unclear among long-term antipsychotic users. Objectives The main objective of this study is to assess the potential beneficial effects of the prebiotic Galacto-oligosaccharides (GOS) in combination with 2′-fucosyllactose (2’-FL) on the gut microbiota, by showing a relative increase in Bifidobacteria in fecal samples following intervention. The secondary objective is to assess the effects of GOS on mental wellbeing, sleep, and metabolic parameters. We hypothesize that GOS+2’FL supplementation will improve gut health, mental wellbeing, sleep, and metabolic parameters. Data will be collected 4 weeks prior to the start of the intervention during an observation only phase [t0], at baseline [t1], and after 2 [t2] and 6 [t3] weeks of GOS+2’FL intake. A follow-up will take place at week 10, 4 weeks after the intervention [t4]. Other outcomes that are assessed include the FiberScreen tool, the form of human faeces (Bristol Stool Chart), side effects and the defined daily dosis (DDD) of antipsychotic medication. Methods The study is a single-arm pilot study (non-randomized and non-blinded). We aim to include 30 psychiatric patients on long-term atypical antipsychotic use, irrespective of their specific psychiatric disorder, with a BMI > 25 kg/m2. Following a run-in period of 4 weeks (no intervention but all other aspects of the study), the participants will consume GOSplus (7.0 g BiotisTMGOS + 0.7 g 2’-FL) daily during the first consumption moment of the day (preferably in the morning) for 42 days. The GOSplus powder has a slightly sweet flavour. The primary endpoint is the change in Bifidobacteria in fecal samples from week 0 to week 6. Results The study started recruiting participants in October 2023. Conclusions Conclusions are expected by the end of 2024. Disclosure of Interest None Declared

Background Persistent depressive disorder (PDD) is prevalent and debilitating. For patients with PDD, psychiatric rehabilitation using self-management interventions is advised as the next therapeutic step after multiple unsuccessful treatment attempts. The “ Patient and Partner Education Program for All Chronic Diseases ” (PPEP4All) is a brief, structured self-management program that focuses on functional recovery for patients and their partners/caregivers. In chronic somatic disorder populations, PPEP4All has already been shown to be clinically effective. We examined whether PPEP4All adapted for PDD (PPEP4All-PDD, nine weekly group or individual sessions) is also clinically effective for adults/elderly with PDD and their partners/caregivers compared to care-as-usual (CAU) in specialized mental healthcare. Methods In this mixed-method multicenter pragmatic randomized controlled trial, 70 patients with PDD and 14 partners/caregivers were allocated to either PPEP4All-PDD (patients, n = 37; partners/caregivers, n = 14) or CAU (patients , n = 33; partners/caregivers, not included) and completed questionnaires at 0, 3, 6, and 12 months regarding depressive symptoms, psychopathology, psychosocial burden, mental resilience, and happiness/well-being. Qualitative data were collected regarding treatment satisfaction. Data were analyzed using mixed model analyses and an intention-to-treat (ITT) approach. Results There was no statistically significant difference in any outcome regarding clinical effectiveness between PPEP4All-PDD and CAU. Subgroup analysis for depressive symptoms did not show any interaction effect for any subgroup. Although 78% of participants recommended PPEP4All-PDD, there was no difference in treatment satisfaction between PPEP4All-PDD (score = 6.6; SD = 1.7) and CAU (score = 7.6; SD = 1.2), p = 0.06. Conclusion Although depressive symptoms did not improve relative to CAU, this only confirmed that treatment for patients with treatment-resistant PDD should move from symptom reduction to functional recovery. Also, functional recovery may be reflected in other outcomes than psychosocial burden, such as self-empowerment, in patients with treatment-resistant PDD. Future research on PPEP4All-PDD could focus on a longer-term program and/or online program that may also be offered earlier in the treatment process as an empowerment intervention. Trial registration Netherlands Trial Register Identifier NL5818. Registered on 20 July 2016 https://clinicaltrialregister.nl/nl/trial/20302

Introduction Manic and depressive mood states in bipolar disorder (BD) may emerge from the non-linear relations between constantly changing mood symptoms exhibited as a complex dynamic system. Dynamic Time Warp (DTW) is an algorithm that may capture symptom interactions from panel data with sparse observations over time. Objectives The current study is the first to analyze a time series of depression and manic symptoms using DTW analyses in patients with BD. We studied interactions and relative changes in symptom severity within and between participants. Methods The Young Mania Rating Scale and Quick Inventory of Depressive Symptomatology were repeatedly assessed in 141 patients with BD, with on average 5.5 assessments per patient every 3 to 6 months. DTW calculated the distance between each of the 27*27 pairs of standardized symptom scores. The changing profile of standardized symptom scores of BD patients was analyzed in individual patients, yielding symptom dimensions in aggregated group-level analyses. Using an asymmetric time-window, symptom changes that preceded other symptom changes (i.e., Granger causality) yielded a directed network. Results The mean age of the patients was 40.1 (SD 13.5) years old, and 60% were female. Idiographic symptom networks were highly variable between patients. Yet, nomothetic analyses showed five symptom dimensions: core (hypo)mania (6 items), dysphoric mania (5 items), lethargy (7 items), somatic/suicidality (6 items), and sleep (3 items). Symptoms of the ‘Lethargy’ dimension showed the highest out-strength, and its changes preceded those of ‘somatic/suicidality’, while changes in ‘core (hypo)mania’ preceded those of ‘dysphoric mania’. Image: Image 2: Image 3: Conclusions DTW may help to capture meaningful BD symptom interactions from panel data with sparse observations. It may increase insight into the temporal dynamics of symptoms, as those with high out-strength (rather than high in-strength) could be promising targets for intervention. Disclosure of Interest None Declared

Drug development for mood disorders can greatly benefit from the development of robust, reliable, and objective biomarkers. The incorporation of smartphones and wearable devices in clinical trials provide a unique opportunity to monitor behavior in a non-invasive manner. The objective of this study is to identify the correlations between remotely monitored self-reported assessments and objectively measured activities with depression severity assessments often applied in clinical trials. 30 unipolar depressed patients and 29 age- and gender-matched healthy controls were enrolled in this study. Each participant’s daily physiological, physical, and social activity were monitored using a smartphone-based application (CHDR MORE™) for 3 weeks continuously. Self-reported depression anxiety stress scale-21 (DASS-21) and positive and negative affect schedule (PANAS) were administered via smartphone weekly and daily respectively. The structured interview guide for the Hamilton depression scale and inventory of depressive symptomatology–clinical rated (SIGHD-IDSC) was administered in-clinic weekly. Nested cross-validated linear mixed-effects models were used to identify the correlation between the CHDR MORE™ features with the weekly in-clinic SIGHD-IDSC scores. The SIGHD-IDSC regression model demonstrated an explained variance (R 2 ) of 0.80, and a Root Mean Square Error (RMSE) of ± 15 points. The SIGHD-IDSC total scores were positively correlated with the DASS and mean steps-per-minute, and negatively correlated with the travel duration. Unobtrusive, remotely monitored behavior and self-reported outcomes are correlated with depression severity. While these features cannot replace the SIGHD-IDSC for estimating depression severity, it can serve as a complementary approach for assessing depression and drug effects outside the clinic.

We aimed to validate cross-culturally the Turkish, Moroccan Arabic and Moroccan Berber versions of the 48-item Symptom Questionnaire (SQ-48). Its psychometric properties were assessed in four samples: patients (n = 150) and controls (n = 103) with Turkish or Moroccan origins (n = 103) and patients (n = 189) and controls (n = 463) with native Dutch origins. Internal consistency and discriminatory power of SQ-48 subscales across groups were adequate to high. However, immigrant groups scored on average higher than Dutch native groups, but there was full configural, metric and partial scalar invariance in the immigrant groups. Although the SQ-48 is a valid measure of psychopathology in immigrant groups of Turkish and Moroccan origins, their cut-off values should likely be higher compared to natives.

Abstract Previous studies have failed to take baseline severity into account when assessing the effects of pathological personality traits (PPT) on treatment outcome. This study assessed the prognostic value of PPT (Dimensional Assessment of Personality Pathology–Short Form) on treatment outcome (Brief Symptom Inventory [BSI-posttreatment]) among patients with depressive and/or anxiety disorders (N = 5689). Baseline symptom level (BSI-pretreatment) was taken into account as a mediator or moderator variable. Results showed significant effects of PPT on outcome, of which Emotional Dysregulation demonstrated the largest association (β = 0.43, p < 0.001). When including baseline BSI score as a mediator variable, a direct effect (β = 0.11, p < 0.001) remained approximately one-third of the total effect. The effects of Emotional Dysregulation (interaction effect β = 0.061, p < 0.001) and Inhibition (interaction effect β = 0.062, p < 0.001), but not Compulsivity or Dissocial Behavior, were moderated by the baseline symptom level. PPT predicts higher symptom levels, both before and after treatment, but yields relatively small direct effects on symptom decline when the effect of pretreatment severity is taken into account.

Background Depression is a highly recurrent disorder, with more than 50% of those affected experiencing a subsequent episode. Although there is relatively little stability in symptoms across episodes, some evidence indicates that suicidal ideation may be an exception. However, these findings warrant replication, especially over longer periods and across multiple episodes. Aims To assess the relative stability of suicidal ideation in comparison with other non-core depressive symptoms across episodes. Method We examined 490 individuals with current major depressive disorder (MDD) at baseline and at least one subsequent episode during 9-year follow-up within the Netherlands Study of Depression and Anxiety (NESDA). The Inventory of Depressive Symptomatology (IDS) was used to assess DSM-5 non-core MDD symptoms (fatigue, appetite/weight change, sleep disturbance, psychomotor disturbance, concentration difficulties, worthlessness/guilt, suicidal ideation) at baseline and 2-, 4-, 6- and 9-year follow-up. We examined consistency in symptom presentation (i.e. whether the symptom met the diagnostic threshold, based on a binary categorisation of the IDS) using kappa (κ) and percentage agreement, and stability in symptom severity using Spearman correlation, based on the continuous IDS scores. Results Out of all non-core depressive symptoms, insomnia appeared the most stable across episodes ( r = 0.55–0.69, κ = 0.31–0.47) and weight decrease the least stable ( r = 0.03–0.33, κ = 0.06–0.19). For suicidal ideation, correlations across episodes ranged from r = 0.36 to r = 0.55 and consistency ranged from κ = 0.28 to κ = 0.49. Conclusions Suicidal ideation is moderately stable in recurrent depression over 9 years. Contrary to prior reports, however, it does not exhibit substantially more stability than most other non-core symptoms of depression.

Circadian rhythms have evolved in almost all organisms enabling them to anticipate alternating changes in the environment. As a consequence, the circadian clock controls a broad range of bodily functions including appetite, sleep, activity and cortisol levels. The circadian clock synchronizes itself to the external world mainly by environmental light cues and can be disturbed by a variety of factors, including shift-work, jet-lag, stress, ageing and artificial light at night. Interestingly, mood has also been shown to follow a diurnal rhythm. Moreover, circadian disruption has been associated with various mood disorders and patients suffering from depression have irregular biological rhythms in sleep, appetite, activity and cortisol levels suggesting that circadian rhythmicity is crucially involved in the etiology and pathophysiology of depression. The aim of the present review is to give an overview and discuss recent findings in both humans and rodents linking a disturbed circadian rhythm to depression. Understanding the relation between a disturbed circadian rhythm and the etiology of depression may lead to novel therapeutic and preventative strategies.

Importance:Individuals with bipolar disorder (BD) experience cognitive and emotional dysfunctions. Various brain circuits are implicated in BD but have not been investigated in a meta-analysis of functional magnetic resonance imaging (fMRI) studies.Objective:To investigate the brain functioning of individuals with BD compared with healthy control individuals in the domains of emotion processing, reward processing, and working memory.Data Sources:All fMRI experiments on BD published before March 2020, as identified in a literature search of PubMed, Embase, Web of Science, Cochrane Library, PsycInfo, Emcare, Academic Search Premier, and ScienceDirect. The literature search was conducted on February 21, 2017, and March 2, 2020, and data were analyzed from January 2021 to January 2022.Study Selection:fMRI experiments comparing adult individuals with BD and healthy control individuals were selected if they reported whole-brain results, including a task assessing at least 1 of the domains. In total, 2320 studies were screened, and 253 full-text articles were evaluated.Data Extraction and Synthesis:A total of 49 studies were included after selection procedure. Coordinates reporting significant activation differences between individuals with BD and healthy control individuals were extracted. Differences in brain region activity were tested using the activation likelihood estimation method.Main Outcomes and Measures:A whole-brain meta-analysis evaluated whether reported differences in brain activation in response to stimuli in 3 cognitive domains between individuals with BD and healthy control individuals were different.Results:The study population included 999 individuals with BD (551 [55.2%] female) and 1027 healthy control individuals (532 [51.8%] female). Compared with healthy control individuals, individuals with BD showed amygdala and hippocampal hyperactivity and hypoactivation in the inferior frontal gyrus during emotion processing (20 studies; 324 individuals with BD and 369 healthy control individuals), hyperactivation in the orbitofrontal cortex during reward processing (9 studies; 195 individuals with BD and 213 healthy control individuals), and hyperactivation in the ventromedial prefrontal cortex and subgenual anterior cingulate cortex during working memory (20 studies; 530 individuals with BD and 417 healthy control individuals). Limbic hyperactivation was only found during euthymia in the emotion and reward processing domains; abnormalities in frontal cortex activity were also found in individuals with BD with mania and depression.Conclusions and Relevance:This systematic review and meta-analysis revealed evidence for activity disturbances in key brain areas involved in cognitive and emotion processing in individuals with BD. Most of the regions are part of the fronto-limbic network. The results suggest that aberrations in the fronto-limbic network, present in both euthymic and symptomatic individuals, may be underlying cognitive and emotional dysfunctions in BD.

Introduction Childhood trauma is associated with an increased risk of anxiety and depressive disorders, but its association with anger, irritability, and related constructs has received less attention. Objectives We aimed to investigate (1) the relationship between childhood trauma and anger constructs in adulthood, and (2) which types of childhood trauma is most predictive. Methods In the Netherlands Study of Depression and Anxiety (NESDA), childhood trauma at baseline was assessed with a semi-structured interview. Childhood trauma was analyzed in relation to the Spielberger Trait Anger Subscale (STAS), the Anger Attacks Questionnaire, and the cluster B personality traits part of the Personality Disorder Questionnaire 4 (PDQ-4), measured at 4-year follow-up, using analysis of covariance (ANCOVA) and multivariable logistic regression analyses, adjusting for sex, age, level of education, BMI, smoking, alcohol dependency/abuse, disorder status. Results Participants were on average 42.1 years (SD = 13.1), and 66.3% (n = 1.508) were female. Childhood trauma showed a dose-response association with all anger constructs. Zooming in, emotional neglect, and psychological, and physical abuse were associated with all anger constructs, independently of depression or anxiety. Additionally, sexual abuse and childhood life events were associated with trait anger and borderline personality traits, and trait anger and antisocial personality traits retrospectively. Conclusions Childhood trauma is linked with anger in adulthood. Childhood trauma may cause not only anxiety and depression, but also anger, and tailored interventions (at both childhood trauma and anger itself ) might help to improve unsatisfactory relationships and prevent violent behaviors. Disclosure No significant relationships.

Introduction The Persistent Depression and Self-Management Study is a mixed-methods pragmatic randomized controlled trial that evaluated the “Patient and Partner Education Program for All Chronic Illnesses” (PPEP4All) in patients with persistent depressive disorder (PDD) compared to care as usual (CAU). PPEP4All is a brief, structured self-management program that focuses on functional recovery and involves the partner/caregiver in the program. The latter may improve patient outcomes and reduce caregiver psychosocial burden related to PDD. Objectives In addition to evaluating the cost- and clinical-effectiveness of PPEP4All, we conducted a nested qualitative study to deepen our understanding of how patients with PDD and their caregivers cope with chronic depression. Additionally we identify areas in which they require care and learn how they could benefit from a self-management program like PPEP4All. Methods In the nested qualitative study, 28 patients (16 from PPEP4All, 12 from CAU) and 9 partners/caregivers agreed to participate. The in-depth semi-structured interviews took place at participant’s home, the main research location, or over telephone. For each interview, we used a topic list, which was initially evaluated in a pilot study of patients with PDD. All interviews were audio recorded, with consent from the participant, and transcribed verbatim. Data were analyzed using Grounded Theory, with a constant comparative analysis method, using Atlas.ti version 9 software. Results Qualitative data are currently being analyzed. We expect to identify important themes relevant to the patient’s and caregiver’s personal experience and learn how they use and implement self-management in their lives. Conclusions PPEP4All may help patients with PDD and caregivers learn important self-management techniques to effectively cope with chronic depression and its consequences, and thus, it may help them meet their needs for care. Disclosure of Interest None Declared

Purpose Siblings of probands with depressive and anxiety disorders are at increased risk for psychopathology, but little is known about how risk factors operate within families to increase psychopathology for siblings. We examined the additional impact of psychosocial risk factors in probands—on top of or in combination with those in siblings—on depressive/anxious psychopathology in siblings. Methods The sample included 636 participants ( M age = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and their sibling(s) ( N = 380 proband-sibling pairs). Sixteen psychosocial risk factors were tested. In siblings, depressive and anxiety disorders were determined with standardized psychiatric interviews; symptom severity was measured using self-report questionnaires. Analyses were performed with mixed-effects models accounting for familial structure. Results In siblings, various psychosocial risk factors (female gender, low income, childhood trauma, poor parental bonding, being single, smoking, hazardous alcohol use) were associated with higher symptomatology and likelihood of disorder. The presence of the same risk factor in probands was independently associated (low income, being single) with higher symptomatology in siblings or moderated (low education, childhood trauma, hazardous alcohol use)—by reducing its strength—the association between the risk factor and symptomatology in siblings. There was no additional impact of risk factors in probands on likelihood of disorder in siblings. Conclusion Our findings demonstrate the importance of weighing psychosocial risk factors within a family context, as it may provide relevant information on the risk of affective psychopathology for individuals.