The clinical effectiveness of a self-management intervention for patients with persistent depressive disorder and their partners/caregivers: results from a multicenter, pragmatic randomized controlled trial.

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.

Suicidal ideation across depressive episodes: 9-year longitudinal cohort study.

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.

The role of the circadian system in the etiology 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.

Association Between the Fronto-Limbic Network and Cognitive and Emotional Functioning in Individuals With Bipolar Disorder: A Systematic Review and Meta-analysis.

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.

Weighing psychosocial factors in relatives for the risk of psychopathology: a study of patients with depressive and anxiety disorders and their siblings.

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 (Mage = 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.

Translation and cross-cultural validation of the Turkish, Moroccan Arabic and Moroccan Berber versions of the 48-item Symptom Questionnaire (SQ-48).

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.

Dietary supplements for aggressive behaviour in people with intellectual disabilities: A randomised controlled crossover trial.

BACKGROUND: Aggressive incidents are common in people with intellectual disabilities. Therefore, we aimed to assess whether supplementation of multivitamins, minerals, and omega-3 fatty acids (FA) reduces aggressive incidents. METHODS: We conducted a randomised, triple blind, placebo controlled, single crossover intervention trial. People with intellectual disabilities or borderline intellectual functioning, between 12 and 40 years of age, and showing aggressive behaviour were included. Participants received either a daily dose of dietary supplements, or placebo. Primary outcome was the number of aggressive incidents, measured using the Modified Overt Aggression Scale (MOAS). RESULTS: there were 113 participants (placebo, n = 56), of whom 24 (placebo, n = 10) participated in the crossover phase of the trial. All 137 trajectories were included in the analyses. There was no significant difference in mean number of aggressive incidents per day between those assigned to supplements and those who received placebo (rate ratio = 0.93: 95% Confidence Interval [CI] = 0.59-1.45). CONCLUSION: In this pragmatic trial, we did not find significant differences in the outcomes between the supplement and placebo arms. The COVID-19 pandemic started midway through our trial, this may have affected the results.

Within-day bidirectional associations between physical activity and affect: A real-time ambulatory study in persons with and without depressive and anxiety disorders.

BACKGROUND: Ambulatory assessments offer opportunities to study physical activity level (PAL) and affect at the group and person-level. We examined bidirectional associations between PAL and affect in a 3-h timeframe and evaluated whether associations differ between people with and without current or remitted depression/anxiety. METHODS: Two-week ecological momentary assessment (EMA) and actigraphy data of 359 participants with current (n = 93), remitted (n = 176), or no (n = 90) Composite International Diagnostic Interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Positive affect (PA) and negative affect (NA) were assessed by EMA 5 times per day. Average PAL between EMA assessments were calculated from actigraphy data. RESULTS: At the group-level, higher PAL was associated with subsequent higher PA (b = 0.109, p < .001) and lower NA (b = -0.043, p < .001), while higher PA (b = 0.066, p < .001) and lower NA (b = -0.053, p < .001) were associated with subsequent higher PAL. The association between higher PAL and subsequent lower NA was stronger for current depression/anxiety patients than controls (p = .01). At the person-level, analyses revealed heterogeneity in bidirectional associations. CONCLUSIONS: Higher PAL may improve affect, especially among depression/anxiety patients. As the relationships vary at the person-level, ambulatory assessments may help identify who would benefit from behavioral interventions.

Prognostic Value of Pathological Personality Traits for Treatment Outcome in Anxiety and Depressive Disorders: The Leiden Routine Outcome Monitoring Study.

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 ( ß = 0.43, p < 0.001). When including baseline BSI score as a mediator variable, a direct effect ( ß = 0.11, p < 0.001) remained approximately one-third of the total effect. The effects of Emotional Dysregulation (interaction effect ß = 0.061, p < 0.001) and Inhibition (interaction effect ß = 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.

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.

Effects of multivitamin, mineral and n-3 polyunsaturated fatty acid supplementation on aggression among long-stay psychiatric in-patients: randomised clinical trial.

BACKGROUND: Aggression and violent incidents are a major concern in psychiatric in-patient care. Nutritional supplementation has been found to reduce aggressive incidents and rule violations in forensic populations and children with behavioural problems. AIMS: To assess whether multivitamin, mineral and n-3 polyunsaturated fatty acid supplementation would reduce the number of aggressive incidents among long-stay psychiatric in-patients. METHOD: The trial was a pragmatic, multicentre, randomised, double-blind placebo-controlled study. Data were collected from 25 July 2016 to 29 October 2019, at eight local sites for mental healthcare in The Netherlands and Belgium. Participants were randomised (1:1) to receive 6-month treatment with either three supplements containing multivitamins, minerals and n-3 polyunsaturated fatty acid, or placebo. The primary outcome was the number of aggressive incidents, determined by the Staff Observation Aggression Scale - Revised (SOAS-R). Secondary outcomes were patient quality of life, affective symptoms and adverse events. RESULTS: In total, 176 participants were randomised (supplements, n = 87; placebo, n = 89). Participants were on average 49.3 years old (s.d. 14.5) and 64.2% were male. Most patients had a psychotic disorder (60.8%). The primary outcome of SOAS-R incidents was similar in supplement (1.03 incidents per month, 95% CI 0.74-1.37) and placebo groups (0.90 incidents per month, 95% CI 0.65-1.19), with a rate ratio of 1.08 (95% CI 0.67-1.74, P = 0.75). Differential effects were not found in sensitivity analyses on the SOAS-R or on secondary outcomes. CONCLUSIONS: Six months of nutritional supplementation did not reduce aggressive incidents among long-stay psychiatric in-patients.

Lessons learned from two clinical trials on nutritional supplements to reduce aggressive behaviour.

BACKGROUND: Setting up and conducting a randomised controlled trial (RCT) has many challenges-particularly trials that include vulnerable individuals with behavioural problems or who reside in facilities that focus on care as opposed to research. These populations are underrepresented in RCTs. APPROACH: In our paper, we describe the challenges and practical lessons learned from two RCTs in two care settings involving long-stay psychiatric inpatients and people with intellectual disabilities. We describe five main difficulties and how these were overcome: (1) multisite setting, (2) inclusion of vulnerable participants, (3) nutritional supplements and placebos, (4) assessment of behavioural outcomes, and (5) collecting bio samples. CONCLUSIONS: By sharing these practical experiences, we hope to inform other researchers how to optimally design their trials, while avoiding and minimising the difficulties that we encountered, and to facilitate the implementation of a trial. Both trials were registered in the Clinical Trials Register (RCT A: NCT02498106; RCT B: NCT03212092).

Familial risk for depressive and anxiety disorders: associations with genetic, clinical, and psychosocial vulnerabilities.

BACKGROUND: In research and clinical practice, familial risk for depression and anxiety is often constructed as a simple Yes/No dichotomous family history (FH) indicator. However, this measure may not fully capture the liability to these conditions. This study investigated whether a continuous familial loading score (FLS), incorporating family- and disorder-specific characteristics (e.g. family size, prevalence of depression/anxiety), (i) is associated with a polygenic risk score (PRS) for major depression and with clinical/psychosocial vulnerabilities and (ii) still captures variation in clinical/psychosocial vulnerabilities after information on FH has been taken into account. METHODS: Data came from 1425 participants with lifetime depression and/or anxiety from the Netherlands Study of Depression and Anxiety. The Family Tree Inventory was used to determine FLS/FH indicators for depression and/or anxiety. RESULTS: Persons with higher FLS had higher PRS for major depression, more severe depression and anxiety symptoms, higher disease burden, younger age of onset, and more neuroticism, rumination, and childhood trauma. Among these variables, FH was not associated with PRS, severity of symptoms, and neuroticism. After regression out the effect of FH from the FLS, the resulting residualized measure of FLS was still associated with severity of symptoms of depression and anxiety, rumination, and childhood trauma. CONCLUSIONS: Familial risk for depression and anxiety deserves clinical attention due to its associated genetic vulnerability and more unfavorable disease profile, and seems to be better captured by a continuous score that incorporates family- and disorder-specific characteristics than by a dichotomous FH measure.

Identifying mismatch and match between clinical needs and mental healthcare use trajectories in people with anxiety and depression: Results of a longitudinal study.

BACKGROUND: Mismatch between need and mental healthcare (MHC) use (under-and overuse) has mainly been studied with cross-sectional designs, not accurately capturing patterns of persistence or change in clinical burden and MHC-use among persons with depressive and/or anxiety disorders. AIMS: Determining and describing [mis]match of longitudinal trajectories of clinical burden and MHC-use. METHODS: Six-year longitudinal burden and MHC-use data came from the Netherlands Study of Depression and Anxiety (n=2981). The sample was split into four subgroups: I) no clinical burden but constant MHC use, II) constant clinical burden but no MHC-use, III) changing clinical burden and MHC-use, and IV) healthy non-users. Within subgroups I)-III), specific clinical burden and MHC trajectories were identified (growth mixture modeling). The resulting classes' associations with predisposing, enabling, and need factors were investigated (regression analysis). RESULTS: Subgroups I-III revealed different trajectories. I) increasing MHC without burden (4.1%). II) slightly increasing (1.9%), strongly increasing (2.4%), and decreasing (9.5%) burden without MHC. III) increasing (41.4%) or decreasing (19.4%) burden and concurrently increasing MHC use (first underuse, then matched care), thus revealing delayed MHC-use. Only having suicidal ideation (p<.001, Cohen's d= .6-1.5) was a significant determinant of being in latter classes compared to underusers (strongly increasing burden without MHC-use). LIMITATIONS: More explanatory factors are needed to explain [mis]match. CONCLUSION: Mismatch occurred as constant underuse or as delayed MHC-use in a high-income country (Netherlands). Additionally, no meaningful class revealed constantly matched care on average. Presence of suicidal ideation could influence the probability of symptomatic individuals receiving matched MHC or not.

The 9-year clinical course of depressive and anxiety disorders: New NESDA findings.

BACKGROUND: In longitudinal research, switching between diagnoses should be considered when examining patients with depression and anxiety. We investigated course trajectories of affective disorders over a nine-year period, comparing a categorical approach using diagnoses to a dimensional approach using symptom severity. METHOD: Patients with a current depressive and/or anxiety disorder at baseline (N = 1701) were selected from the Netherlands Study of Depression and Anxiety (NESDA). Using psychiatric diagnoses, we described 'consistently recovered,' 'intermittently recovered,' 'intermittently recurrent', and 'consistently chronic' at two-, four-, six-, and nine-year follow-up. Additionally, latent class growth analysis (LCGA) using depressive, anxiety, fear, and worry symptom severity scores was used to identify distinct classes. RESULTS: Considering the categorical approach, 8.5% were chronic, 32.9% were intermittently recurrent, 37.6% were intermittently recovered, and 21.0% remained consistently recovered from any affective disorder at nine-year follow-up. In the dimensional approach, 66.6% were chronic, 25.9% showed partial recovery, and 7.6% had recovered. LIMITATIONS: 30.6% of patients were lost to follow-up. Diagnoses were rated by the interviewer and questionnaires were completed by the participant. CONCLUSIONS: Using diagnoses alone as discrete categories to describe clinical course fails to fully capture the persistence of affective symptoms that were observed when using a dimensional approach. The enduring, fluctuating presence of subthreshold affective symptoms likely predisposes patients to frequent relapse. The commonness of subthreshold symptoms and their adverse impact on long-term prognoses deserve continuous clinical attention in mental health care as well further research.

The clinical and cost-effectiveness of a self-management intervention for patients with persistent depressive disorder and their partners/caregivers: study protocol of a multicenter pragmatic randomized controlled trial.

BACKGROUND: After regular treatment, patients with persistent depressive disorder (PDD) may remain in specialized psychiatric outpatient care without achieving remission. Lacking other options, these patients often receive long-term, non-protocolized care as usual (CAU) that does not involve the partner/caregiver of the patient. Although the revised depression treatment guidelines suggest focusing on psychiatric rehabilitation and self-management as the next treatment step for PDD, an evidence-based cost-effective self-management protocol for PDD is lacking. This study investigates the "Patient and Partner Education Program for All Chronic Illnesses" (PPEP4All) as a brief self-management protocol that could lead to lower costs, higher quality of life, and less disease burden in PDD patients and their partners/caregivers. METHODS: Presented is the rationale and methods of a multicenter pragmatic randomized controlled trial to evaluate the clinical efficacy and cost-effectiveness of PPEP4All for patients with PDD and their partners/caregivers. In accordance with current recommendations, a mixed methods research approach is used with both quantitative and qualitative data. A total of 178 eligible outpatients with PDD and their partners/caregivers are recruited and randomized to either PPEP4All or CAU. Those assigned to PPEP4All receive nine weekly self-management sessions with a trained PPEP4All therapist. Primary and secondary outcome measurements are at 0, 3, 6, and 12 months. DISCUSSION: This project will result in the implementation of a self-management intervention for patients with PDD, meeting an urgent need in mental healthcare. Using PPEP4All can optimize the quality and efficiency of care for both patients with PDD and their partners/caregivers. TRIAL REGISTRATION: Netherlands Trial Register Identifier NTR5973 . Registered on 20 July 2016.

Toxoplasma gondii seropositivity in patients with depressive and anxiety disorders.

INTRODUCTION: Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that is estimated to be carried by one-third of the world population. Latent T. gondii infection has been linked to several neuropsychiatric mood disorders and behaviors. The aim of the present study was to examine whether T. gondii seropositivity is associated with affective disorders, as well as with aggression reactivity and suicidal thoughts. METHODS: In the Netherlands Study of Depression and Anxiety (NESDA), T. gondii antibodies were assessed in patients with current depressive (n â€‹= â€‹133), anxiety (n â€‹= â€‹188), comorbid depressive and anxiety (n â€‹= â€‹148), and remitted disorders (n â€‹= â€‹889), as well as in healthy controls (n â€‹= â€‹373) based on DSM-IV criteria. Seropositivity was analyzed in relation to disorder status, aggression reactivity and suicidal thoughts using multivariate analyses of covariance and regression analyses. RESULTS: Participants were on average 51.2 years (SD â€‹= â€‹13.2), and 64.4% were female. Seropositivity was found in 673 participants (38.9%). A strong positive association between T. gondii seropositivity and age was observed. No significant associations were found between T. gondii seropositivity and disorder status, aggression reactivity and suicidal thoughts. The adjusted odds ratio (OR) for any remitted disorder versus controls was 1.13 (95% CI: 0.87-1.49), and for any current disorder versus controls was 0.94 (95% CI: 0.69-1.28). CONCLUSIONS: No evidence was found for a relationship between affective disorders and T. gondii infection in the current sample.

Basal and LPS-stimulated inflammatory markers and the course of anxiety symptoms.

A cross-sectional relationship between low-grade inflammation -characterized by increased blood levels of C-reactive protein (CRP) and pro-inflammatory cytokines- and anxiety has been reported, but the potential longitudinal relationship has been less well studied. We aimed to examine whether basal and lipopolysaccharide (LPS-)induced levels of inflammatory markers are associated with anxiety symptom severity over the course of nine years. We tested the association between basal and LPS-induced inflammatory markers with anxiety symptoms (measured with the Beck's Anxiety Inventory; BAI, Fear Questionnaire; FQ and Penn's State Worry Questionnaire; PSWQ) at 5 assessment waves over a period up nine years. We used multivariate-adjusted mixed models in up to 2867 participants of the Netherlands Study of Depression and Anxiety (NESDA). At baseline, 43.6% of the participants had a current anxiety disorder, of which social phobia (18.5%) was most prevalent. Our results demonstrated that baseline inflammatory markers were significantly associated with several outcomes of anxiety at baseline over nine subsequent years. BAI subscale of somatic (arousal) symptoms of anxiety, and FQ subscale of agoraphobia demonstrated the strongest effects with standardized beta-coefficients of up to 0.14. The associations were attenuated by 25%-30% after adjusting for the presence of (comorbid) major depressive disorder (MDD), but remained statistically significant. In conclusion, we found that participants with high levels of inflammatory markers have on average high levels of anxiety consisting of physical arousal and agoraphobia, which tended to persist over a period of nine years, albeit with small effect sizes. These associations were partly driven by co-morbid depression.

Dynamic time warp analysis of individual symptom trajectories in depressed patients treated with electroconvulsive therapy.

BACKGROUND: Although electroconvulsive therapy (ECT) effectively improves severity scores of depression, its effects on its individual symptoms has scarcely been studied. We aimed to study which depressive symptom trajectories dynamically cluster together in individuals as well as groups of patients during ECT using Dynamic Time Warp (DTW) analysis. METHODS: We analysed the standardized weekly scores on the 25-item abbreviated version of the Comprehensive Psychopathological Rating Scale (CPRS) in depressed patients before and during their first six weeks of ECT treatment. DTW analysis was used to analyse the (dis)similarity of time series of items scores at the patient level (300 'DTW distances' per patient) as well as on the group level. Hierarchical cluster, network, and Distatis analyses yielded symptom dimensions. RESULTS: We included 133 patients, 64.7% female, with an average age of 60.4 years (SD 15.1). Individual DTW distance matrices and networks revealed marked differences in hierarchical and network clusters among patients. Based on cluster analyses of the aggregated matrices, four symptom clusters emerged. In patients who reached remission, the average DTW distance between their symptoms was significantly smaller than non-remitters, reflecting denser symptom networks in remitters than non-remitters (p=0.04). LIMITATIONS: The assessments were done only weekly during the first six weeks of ECT treatment. The use of individual items of the abbreviated CPRS may have led to measurement error as well as floor and ceiling effects. CONCLUSION: DTW offers an efficient new approach to analyse symptom trajectories within individuals as well as groups of patients, aiding personalized medicine of psychopathology.

The cumulation of ill health and low agency in socially excluded city dwellers in the Netherlands: how to better identify high-risk/high-need population segments with public health survey data.

BACKGROUND: Population segmentation and risk stratification are important strategies for allocating resources in public health, health care and social care. Social exclusion, which is defined as the cumulation of disadvantages in social, economic, cultural and political domains, is associated with an increased risk of health problems, low agency, and as a consequence, a higher need for health and social care. The aim of this study is to test social exclusion against traditional social stratifiers to identify high-risk/high-need population segments. METHODS: We used data from 33,285 adults from the 2016 Public Health Monitor of four major cities in the Netherlands. To identify at-risk populations for cardiovascular risk, cancer, low self-rated health, anxiety and depression symptoms, and low personal control, we compared relative risks (RR) and population attributable fractions (PAF) for social exclusion, which was measured with the Social Exclusion Index for Health Surveys (SEI-HS), and four traditional social stratifiers, namely, education, income, labour market position and migration background. RESULTS: The analyses showed significant associations of social exclusion with all the health indicators and personal control. Particular strong RRs were found for anxiety and depression symptoms (7.95) and low personal control (6.36), with corresponding PAFs of 42 and 35%, respectively. Social exclusion was significantly better at identifying population segments with high anxiety and depression symptoms and low personal control than were the four traditional stratifiers, while the two approaches were similar at identifying other health problems. The combination of social exclusion with a low labour market position (19.5% of the adult population) captured 67% of the prevalence of anxiety and depression symptoms and 60% of the prevalence of low personal control, as well as substantial proportions of the other health indicators. CONCLUSIONS: This study shows that the SEI-HS is a powerful tool for identifying high-risk/high-need population segments in which not only ill health is concentrated, as is the case with traditional social stratifiers, but also a high prevalence of anxiety and depression symptoms and low personal control are present, in addition to an accumulation of social problems. These findings have implications for health care practice, public health and social interventions in large cities.