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Background: Depression is generally perceived from the perspective of the common‐cause disease model. However, the network perspective assumes mutual influence of individual symptoms and stresses the importance of investigating symptom dynamics. Gaining a better understanding of symptom dynamics within individuals might contribute to more effective treatments. Methods: Current exploratory longitudinal research studied the associations and directionality between 43 symptoms from the generic questionnaire Symptom Questionnaire‐48 (SQ‐48) using dynamic time warp (DTW) analyses, in which trajectories with similar time‐dependent patterns can be identified. Data from individuals were analysed first, yielding distance matrices for all symptom trajectories, after which the data were aggregated. Results: The 148 included patients were all admitted for the treatment of their clinical depression. Undirected DTW analyses of three patients with longer time series but otherwise randomly chosen showed large variability among individuals. Group‐level undirected DTW analyses showed numerous significant edges between symptoms, largely clustering symptoms according to the eight pre‐existing subscales of the SQ‐48. Group‐level directed DTW analyses showed five symptoms with significant outstrength: 'hopeless', 'restless', 'down/depressed', 'feeling tense' and 'no enjoyment', meaning that change in these key symptoms preceded change in other symptoms. Limitations: The 43 included symptoms of the SQ‐48 primarily focus on internalizing problems in severely depressed inpatients, potentially limiting generalizability. Conclusions: DTW networks provided us with five key symptoms based on the dynamics of symptom scores. Future studies could explore whether process‐based therapy targeted at symptoms with high outstrength might result in more effectivity as part of personalized treatment. [ABSTRACT FROM AUTHOR]

Speech contains neuromuscular, physiological and cognitive components, and so is a potential biomarker of mental disorders. Previous studies indicate that speaking rate and pausing are associated with major depressive disorder (MDD). However, results are inconclusive as many studies are small and underpowered and do not include clinical samples. These studies have also been unilingual and use speech collected in controlled settings. If speech markers are to help understand the onset and progress of MDD, we need to uncover markers that are robust to language and establish the strength of associations in real-world data. We collected speech data in 585 participants with a history of MDD in the United Kingdom, Spain, and Netherlands as part of the RADAR-MDD study. Participants recorded their speech via smartphones every two weeks for 18 months. Linear mixed models were used to estimate the strength of specific markers of depression from a set of 28 speech features. Increased depressive symptoms were associated with speech rate, articulation rate and intensity of speech elicited from a scripted task. These features had consistently stronger effect sizes than pauses. Our findings are derived at the cohort level so may have limited impact on identifying intra-individual speech changes associated with changes in symptom severity. The analysis of features averaged over the entire recording may have underestimated the importance of some features. Participants with more severe depressive symptoms spoke more slowly and quietly. Our findings are from a real-world, multilingual, clinical dataset so represent a step-change in the usefulness of speech as a digital phenotype of MDD. • Collected of a unique multilingual clinical speech dataset • Identified three multilingual speech phenotypes of MDD • Pausing not universally impacted by MDD across the three languages • Slowing of speech is most likely due to psychomotor impairments. [ABSTRACT FROM AUTHOR]

We examined whether childhood abuse is related to body mass index (BMI) in young adults and whether this relationship is mediated by depression and anxiety. Data are from the Dutch longitudinal cohort study TRAILS (nfemales = 836, nmales = 719). At wave 4, childhood sexual, physical and verbal abuse, and lifetime major depressive disorder (MDD) and generalized anxiety disorder (GAD) were assessed. BMI was measured at wave 4 and 5 (mean age = 19.2/22.4 years). Sex-stratified structural equation models were estimated. Females who had experienced sexual abuse had a higher BMI at wave 4 (B = 0.97, 95%CI = [−0.01,1.96]) and a higher increase in BMI between wave 4 and 5 (B = 0.52, 95%CI = [0.04,1.01]) than females who had not experienced sexual abuse. Additionally, MDD and BMI at wave 4 were related in females (B = 1.35, 95%CI = [0.52,2.18]). MDD mediated the relationship between sexual abuse and BMI at wave 4 in females. In addition, sexual abuse moderated the relationship between MDD and BMI at wave 4. The relationship was stronger among females who had experienced sexual abuse than among females who had not. Prevention of BMI changes among females who experienced sexual abuse may thus be warranted, particularly when they developed MDD. MDD treatment, such as abuse-focused psychotherapy, may aid this prevention. [ABSTRACT FROM AUTHOR]

Background: The pandemic of the coronavirus disease 2019 (COVID-19) has led to an increased burden on mental health.Aims: To investigate the development of major depressive disorder (MDD), generalized anxiety disorder (GAD), and suicidal ideation in the Netherlands during the first fifteen months of the pandemic and three nation-wide lockdowns.Method: Participants of the Lifelines Cohort Study -a Dutch population-based sample-reported current symptoms of MDD and GAD, including suicidal ideation, according to DSM-IV criteria. Between March 2020 and June 2021, 36,106 participants (aged 18-96) filled out a total of 629,811 questionnaires across 23 time points. Trajectories over time were estimated using generalized additive models and analyzed in relation to age, sex, and lifetime history of MDD/GAD.Results: We found non-linear trajectories for MDD and GAD with a higher number of symptoms and prevalence rates during periods of lockdown. The point prevalence of MDD and GAD peaked during the third hard lockdown at 2.88 % (95 % CI: 2.71 %-3.06 %) and 2.92 % (95 % CI: 2.76 %-3.08 %), respectively, in March 2021. Women, younger adults, and participants with a history of MDD/GAD reported significantly more symptoms. For suicidal ideation, we found a significant linear increase over time in younger participants. For example, 20-year-old participants reported 4.14× more suicidal ideation at the end of June 2021 compared to the start of the pandemic (4.64 % (CI: 3.09 %-6.96 %) versus 1.12 % (CI: 0.76 %-1.66 %)).Limitations: Our findings should be interpreted in relation to the societal context of the Netherlands and the public health response of the Dutch government during the pandemic, which may be different in other regions in the world.Conclusions: Our study showed greater prevalence of MDD and GAD during COVID-19 lockdowns and a continuing increase in suicidal thoughts among young adults suggesting that the pandemic and government enacted restrictions impacted mental health in the population. Our findings provide actionable insights on mental health in the population during the pandemic, which can guide policy makers and clinical care during future lockdowns and epi/pandemics. [ABSTRACT FROM AUTHOR]

Background: Considering the heterogeneity of depression, distinct depressive symptom dimensions may be differentially associated with more objective actigraphy-based estimates of physical activity (PA), sleep and circadian rhythm (CR). We examined the association between PA, sleep, and CR assessed with actigraphy and symptom dimensions (i.e. mood/cognition, somatic/vegetative, sleep). Methods: Fourteen-day actigraphy data of 359 participants were obtained from the Netherlands Study of Depression and Anxiety. PA, sleep, and CR estimates included gross motor activity (GMA), sleep duration (SD), sleep efficiency (SE), relative amplitude between daytime and night-time activity (RA) and sleep midpoint. The 30-item Inventory of Depressive Symptomatology was used to assess depressive symptoms, which were categorised in three depression dimensions: mood/cognition, somatic/vegetative, and sleep. Results: GMA and RA were negatively associated with higher score on all three symptom dimensions: mood/cognition (GMA: β = −0.155, p < 0.001; RA: β = −0.116, p = 0.002), somatic/vegetative (GMA: β = −0.165, p < 0.001; RA: β = −0.133, p < 0.001), sleep (GMA: β = −0.169, p < 0.001; RA: β = −0.190, p < 0.001). The association with sleep was more pronounced for two depression dimensions: longer SD was linked to somatic/vegetative (β = 0.115, p = 0.015) dimension and lower SE was linked to sleep (β = −0.101, p = 0.011) dimension. Conclusion: As three symptom dimensions were associated with actigraphy-based low PA and dampened CR, these seem to be general indicators of depression. Sleep disturbances appeared more linked to the somatic/vegetative and sleep dimensions; the effectiveness of sleep interventions in patients reporting somatic/vegetative symptoms may be explored, as well as the potential of actigraphy to monitor treatment response to such interventions. [ABSTRACT FROM AUTHOR]

Background: Individuals with depression often show an adverse cardiometabolic risk profile and might represent a distinct depression subtype. The aim of this study was to investigate whether a cardiometabolic depression subtype could be identified and to investigate its association with demographics and clinical characteristics (severity, symptomatology, anti-depressant use, persistence and cognitive functioning).Methods: We used data from The Maastricht Study, a population-based cohort in the southern part of The Netherlands. A total of 248 participants with major depressive disorder were included (mean [SD] age, 58.8 ± 8.5 years; 121 [48.8 %] were men). Major depressive disorder was assessed at baseline by the Mini-International Neuropsychiatric Interview. Cardiometabolic risk factors were defined as indicators of the metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. We measured severity and persistence of depressive symptoms by use of the 9-item Patient Health Questionnaire.Results: Latent class analysis resulted in two subtypes, one with cardiometabolic depression (n = 145) and another with non-cardiometabolic depression (n = 103). The cardiometabolic depression subtype was characterized by being male, low education, more severe depressive symptoms, less symptoms of depressed mood and more symptoms of loss of energy, more use of antidepressant medication and lower cognitive functioning.Limitations: No conclusions can be made about causality.Conclusions: Latent class analysis suggested a distinct cardiometabolic depression subtype. Participants with cardiometabolic depression differed from participants with non-cardiometabolic depression in terms of demographics and clinical characteristics. The existence of a cardiometabolic depression subtype may indicate the need for prevention and treatment targeting cardiometabolic risk management. [ABSTRACT FROM AUTHOR]

Background: Traditionally tricyclic antidepressants (TCAs) have an important place in treatment of major depressive disorder (MDD). Today, often other antidepressant medications are considered as first step in the pharmacological treatment of MDD, mainly because they are associated with less adverse effects, whereby the position of TCAs appears unclear. In this study we aimed to examine the current practice of TCAs in treatment of unipolar MDD. Methods: A mixed methods approach was applied. First, a selection of leading international and national guidelines was reviewed. Second, actual TCA prescription was examined by analyzing health records of 75 MDD patients treated with the TCAs nortriptyline, clomipramine or imipramine in different centers in the Netherlands. Third, promotors and barriers influencing the choice for TCAs and dosing strategies were explored using semi-structured interviews with 24 Dutch psychiatrists. Results: Clinical practice guidelines were sometimes indirective and inconsistent with each other. Health records revealed that most patients (71%) attained therapeutic plasma concentrations within two months of TCA use. Patients who achieved therapeutic plasma concentrations reached them on average after 19.6 days (SD 10.9). Both health records and interviews indicated that therapeutic nortriptyline concentrations were attained faster compared to other TCAs. Various factors were identified influencing the choice for TCAs and dosing by psychiatrists. Conclusions: Guideline recommendations and clinical practice regarding TCA prescription for MDD vary. To increase consistency in clinical practice we recommend development of an up-to-date guideline integrating selection and dosing of TCAs, including the roles of therapeutic drug monitoring and pharmacogenetics. Such a guideline is currently lacking and would contribute to optimal TCA treatment, whereby efficacy and tolerability may be increased. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a common mood disorder, with a heritability of around 34%. Molecular genetic studies made significant progress and identified genetic markers associated with the risk of MDD; however, progress is slowed down by substantial heterogeneity as MDD is assessed differently across international cohorts. Here, we used a standardized online approach to measure MDD in multiple cohorts in the Netherlands and evaluated whether this approach can be used in epidemiological and genetic association studies of depression. Methods: Within the Biobank Netherlands Internet Collaboration (BIONIC) project, we collected MDD data in eight cohorts involving 31 936 participants, using the online Lifetime Depression Assessment Self-report (LIDAS), and estimated the prevalence of current and lifetime MDD in 22 623 unrelated individuals. In a large Netherlands Twin Register (NTR) twin-family dataset (n ≈ 18 000), we estimated the heritability of MDD, and the prediction of MDD in a subset (n = 4782) through Polygenic Risk Score (PRS). Results: Estimates of current and lifetime MDD prevalence were 6.7% and 18.1%, respectively, in line with population estimates based on validated psychiatric interviews. In the NTR heritability estimates were 0.34/0.30 (s.e. = 0.02/0.02) for current/lifetime MDD, respectively, showing that the LIDAS gives similar heritability rates for MDD as reported in the literature. The PRS predicted risk of MDD (OR 1.23, 95% CI 1.15–1.32, R2 = 1.47%). Conclusions: By assessing MDD status in the Netherlands using the LIDAS instrument, we were able to confirm previously reported MDD prevalence and heritability estimates, which suggests that this instrument can be used in epidemiological and genetic association studies of depression. [ABSTRACT FROM AUTHOR]

Background: Ambulatory assessments offer opportunities to evaluate daily dynamics of sleep and momentary affect using mobile technologies. This study examines day-to-day bidirectional associations between sleep and affect using mobile monitoring, and evaluates whether these associations differ between people without and with 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) CIDI depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective sleep duration (SD) and efficiency were obtained from actigraphy data. Self-reported SD, sleep quality (SQ), positive affect (PA) and negative affect (NA) were assessed by electronic diaries through EMA.Results: A bidirectional longitudinal association was found between self-reported SQ and affect, while no association was found for self-reported SD and objective SD and efficiency. Better SQ predicted affect the same day (higher PA: b = 0.035, p < 0.001; lower NA: b = -0.022, p < 0.001), while lower NA on the preceding day predicted better SQ (b = -0.102, p = 0.001). The presence of current depression/anxiety disorders moderated the association between better SQ and subsequent lower NA; it was stronger for patients compared to controls (p = 0.003).Limitations: Observational study design can only point to areas of interest for interventions.Conclusions: This 2-week ambulatory monitoring study shows that, especially among depression/anxiety patients, better self-reported SQ predicts higher PA and lower NA the same day, while lower NA predicts better self-reported SQ. The value of mobile technologies to monitor and potentially intervene in patients to improve their affect should be explored. [ABSTRACT FROM AUTHOR]

Background: Affective disorders involve dysregulation of major biological stress systems (hypothalamic-pituitary-adrenal (HPA)-axis, immune system, autonomic nervous system (ANS)). Suchdysregulationshave rarely beensimultaneously examined across different stress systems.Methods: In the Netherlands Study of Depression and Anxiety (n=2789), we investigated whether current or remitted depressive and/or anxiety disorders (based on the CIDI semi-structured interview), including specific symptom profiles, were associated with separate markers and cumulative indexes of the HPA-axis (cortisol awakening response, evening cortisol, dexamethasone suppression test cortisol), immune system (C-reactive protein, interleukin-6, tumor necrosis factor-α), and ANS (heart rate, respiratory sinus arrhythmia, pre-ejection period).Results: Depressive andanxiety disorderswere significantlyassociated with changes in three biological stress systemsincluding HPA-axis hyperactivity, increased inflammatory activity, and a higher ANS tone, particularly for integrative and cumulative indexes of these stress systems (pFDR <.05) vs. controls. The strongest associations were seen with current disorders andcumulative indexes of the HPA-axis (β=.124, pFDR=.001), the immune system (β =.057, pFDR=.032), and total cumulative index across stress systems (β=.102, pFDR=.004). Atypical, energy-related depression severity was linked to immune system markers (pFDR<0.001), melancholic depression severity to HPA-axis markers (pFDR=.032), and anxiety arousal severity to both HPA-axis and immune system markers (pFDR<0.05). Findings were partially explained by poorer lifestyle, more chronic diseases,or (especially for ANS-function) antidepressant use.Limitations: Cross-sectional analyses limit examination of temporal associations.Conclusion: Patients withdepressive and anxiety disorders showed consistent dysregulation across biological stress systems, particularly for current episodes.To understand stress system functionality in affective disorders, an integrated approach capturing cumulative stress indices within and across biological stress systems is important. [ABSTRACT FROM AUTHOR]

Background: The importance of the hippocampus and amygdala for disrupted emotional memory formation in depression is well-recognized, but it remains unclear whether functional abnormalities are state-dependent and whether they are affected by the persistence of depressive symptoms. Methods: Thirty-nine patients with major depressive disorder and 28 healthy controls were included from the longitudinal functional magnetic resonance imaging (fMRI) sub-study of the Netherlands Study of Depression and Anxiety. Participants performed an emotional word-encoding and -recognition task during fMRI at baseline and 2-year follow-up measurement. At baseline, all patients were in a depressed state. We investigated state-dependency by relating changes in brain activation over time to changes in symptom severity. Furthermore, the effect of time spent with depressive symptoms in the 2-year interval was investigated. Results: Symptom change was linearly associated with higher activation over time of the left anterior hippocampus extending to the amygdala during positive and negative word-encoding. Especially during positive word encoding, this effect was driven by symptomatic improvement. There was no effect of time spent with depression in the 2-year interval on change in brain activation. Results were independent of medication- and psychotherapy-use. Conclusion: Using a longitudinal within-subjects design, we showed that hippocampal–amygdalar activation during emotional memory formation is related to depressive symptom severity but not persistence (i.e. time spent with depression or 'load'), suggesting functional activation patterns in depression are not subject to functional 'scarring' although this hypothesis awaits future replication. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder (MDD) has a negative impact on individuals ability to work, and is often associated with long phases of sick leave. Consequently, interventions facilitating return to work in patients with MDD gained increased attention during last decades. We here report results of a feasibility study where a "return-to-work" (RTW) module published by Lagerveld and colleagues in the Netherlands was integrated in cognitive behavioral therapy in depressed patients with long-term sick leaves in Germany. Our study aimed to answer the following questions: Is RTW accepted by patients and therapists? Do RTW interventions lead to return-to-work? Do depressive symptoms improve? Methods: Twenty patients with MDD (15 female; mean age, 45 ± 9 years) were included. Patients received cognitive-behavioral therapy with an integrated, standardized return-to-work module (W-CBT). Psychometric measurements included Beck Depression Inventory (BDI-2) and work ability index (WAI). Further, time until return-to-work was measured, and acceptability of W-CBT was assessed using visual analog scales and open questions. Results: Mean sick leave days in depressed patients were 127 ± 97, and 75% of patients were sick leave for more than 6 weeks. After treatment, 11/20 patients had returned to their former occupation (55%), 5/20 were in occupational re-deployment or started a new job (25%), and 3/20 patients were still on sick leave (2/20; 10%) or received a pension (1/20; 5%). One patient dropped out. BDI-2 sum score improved from 23 ± 8 to 8 ± 5 (p < 0.001), and WAI improved from 28 ± 6 to 39 ± 7 (p < 0.001). Acceptability of W-CBT in patients and therapists was high. Conclusion: We here demonstrate feasibility and acceptability of an RTW module integrated in standard cognitive behavioral therapy. W-CBT leads to improvement of work ability, paralleled by improvement of depressive symptoms. Despite the limitations of this uncontrolled study, the results propose that W-CBT may be feasible in the treatment of depressed patients with long sick leaves and justify a controlled trial evaluating the efficacy of W-CBT. [ABSTRACT FROM AUTHOR]

Objective: Omega‐3 (n‐3) and omega‐6 (n‐6) polyunsaturated fatty acid (PUFA) alterations in patients with major depressive disorder (MDD) have been shown to persist after remission. Whether these alterations are risk factors for MDD recurrence remains unknown. Here, we examined whether fatty acids predict time until MDD recurrence in remitted MDD patients. Methods: Data were used from remitted MDD patients of the Netherlands Study of Depression and Anxiety (n = 356) and the Depression Evaluation Longitudinal Therapy Assessment studies (n = 118). Associations of FAs with time until MDD recurrence up to 8‐year follow‐up were analyzed using Cox regression analyses. Study‐specific estimates were pooled using mega‐ and meta‐analysis techniques. Results: 27.5% (NESDA) and 56.8% (DELTA) participants had an MDD recurrence. Pooled results showed that no FA was significantly associated with time until MDD recurrence (n‐3 PUFAs: hazard ratio (HR) = 1.17, 95% confidence interval (CI) = 0.98–1.41, P = 0.082; n‐6 PUFAs: HR = 1.08, 95% CI = 0.84–1.38, P = 0.55). Conclusion: In remitted MDD patients, circulating PUFAs were not associated with prospective risk of MDD recurrence. Consequently, circulating PUFAs are unlikely to reflect a vulnerability marker for recurrence, so correcting n‐3 PUFA 'deficits' through supplementation does not seem a promising option to prevent MDD recurrence. [ABSTRACT FROM AUTHOR]

• A history of chronic depression and level of neuroticism are associated to similar symptom profiles. • Chronic depression is associated to mood and cognitive symptoms and to a lesser extent to somatic/vegetative symptoms. • Neuroticism is associated to mood and cognitive symptoms but on average not to somatic vegetative symptoms. • Patients with chronic depression and/or high levels of neuroticism report particularly on low self-esteem and high interpersonal sensitivity items. This may be of importance in the development of personalized treatment. The large between-person differences in symptomatology suggest that major depressive disorder (MDD) is a heterogeneous psychiatric disorder. However, symptom-specific prospective studies are scarce. We hypothesized that chronicity (i.e., being depressed for 24 months during a patient's preceding 48 months at baseline) and neuroticism at baseline would predict adverse course trajectories over 9 years of follow up with differential magnitudes for individual depressive symptoms. In total, 560 patients with a current MDD were included from the Netherlands Study of Depression and Anxiety (NESDA-cohort). We used a multivariate linear mixed model with repeated measures, with a history of chronicity and neuroticism separately as main independent variables and with Inventory of Depressive Symptomatology self-report (IDS-SR) item scores as outcome variables. For each individual symptom, the model was adjusted for age, gender, and baseline depression severity. Patients were on average 42.7 (SD = 12.1) years old and 64.7% were women. Patients with chronic depression or high levels of neuroticism showed similar absolute rates of decline over time compared to their counterparts. However, because symptoms had higher starting points for mood, cognitive, and somatic/vegetative symptoms (in that order), symptom severity remained higher over time. Chronicity and neuroticism were especially linked to persistent low self-esteem and high interpersonal sensitivity. Neuroticism is partly state dependent and likely affected by depression severity. Chronicity and neuroticism predict long-term persistence of diverse psychiatric symptoms, in particular low self-esteem and high interpersonal sensitivity. [ABSTRACT FROM AUTHOR]

Highlights • Genetic methods were used to untangle the nature of the association between depression and short telomere length. • Polygenic risk scores for depression and telomere length showed strong same-trait but no cross-trait associations. • The genetic correlation between depression and telomere length was small and not significant. • The association between depression and telomere length is unlikely due to shared underlying genetic vulnerability. Abstract Objective While there is robust evidence for a cross-sectional association between depression and shorter telomere length, suggestive of advanced biological aging, the nature of this association remains unclear. Here, we tested whether both traits share a common genetic liability with novel methods using genomics. Methods Data were from 2032 participants of the Netherlands Study of Depression and Anxiety (NESDA) with genome-wide genetic information and multiple waves of data on DSM-IV lifetime depression diagnosis, depression severity, neuroticism and telomere length. Polygenic risk scores (PRS) for both traits were built using summary results from the largest genome-wide association studies (GWAS) on depression (59,851 cases and 113,154 controls) and telomere length (37,684 samples). Additionally, a PRS for neuroticism was built (337,000 samples). Genetic overlap between the traits was tested using PRS for same- and cross-trait associations. Furthermore, GWAS summary statistics were used to estimate the genome-wide genetic correlation between traits. Results In NESDA data, the PRS for depression was associated with lifetime depression (odds ratio = 1.36; p = 6.49e-7) and depression severity level (β = 0.13; p = 1.24e-8), but not with telomere length. Similar results were found for the PRS for neuroticism. Conversely, the PRS for telomere length was associated with telomere length (β = 0.07; p = 8.42e-4) and 6-year telomere length attrition rate (β = 0.04; p = 2.15e-2), but not with depression variables. In summary-level analyses, the genetic correlation between the traits was small and not significant (rg=-0.08; p =.300). Conclusion The use of genetic methods in this paper indicated that the established phenotypic association between telomere length and depression is unlikely due to shared underlying genetic vulnerability. Our findings suggest that short telomeres in depressed patients may simply represent a generic marker of disease or may originate from non-genetic environmental factors. [ABSTRACT FROM AUTHOR]

Background: Suicidality could be associated with specific combinations of biological, social and psychological factors. Therefore, depressive episodes with suicidal ideation could be different from depressive episodes without suicidal ideation in terms of latent variable structures.Methods: In this study we compared latent variable structures between suicidal and non-suicidal depressed patients using confirmatory factor analysis (CFA), following a measurement invariance test procedure. Patients (N = 919) suffering from major depressive disorder were selected from the Netherlands Study of Depression and Anxiety (NESDA) and split into a group that showed no symptoms of suicidal ideation (non-SI; N = 691) and a suicidal ideation (SI) group that had one or more symptoms of suicidal ideation (N = 228). Depression and anxiety symptoms were measured using the short form of the Mood and Anxiety Symptoms Questionnaire (MASQ-D30).Results: CFA implied a difference in latent variable structures between the non-SI sample (CFI 0.957; RMSEA 0.041) and the SI sample (CFI 0.900; RMSEA 0.056). Subsequent multiple-group CFA showed violations of measurement invariance. The General distress and Anhedonic depression subscales were best indicated by hopelessness and lack of optimism in the SI sample and by dissatisfaction and not feeling lively in the non-SI sample. Overall, the SI sample had higher scores and lower inter-item correlations on the Anhedonic depression items.Limitations: We have included very mild cases of suicidal ideation in our SI sample.Conclusions: On a latent variable level, depression with suicidal ideation differs from depression without suicidal ideation. Results encourage further research into the symptom structure of depression among suicidal patients. [ABSTRACT FROM AUTHOR]

Social jetlag, the misalignment between the internal clock and the socially required timing of activities, is highly prevalent, especially in people with an evening chronotype and is hypothesized to be related to the link between the evening chronotype and major depressive disorder. Although social jetlag has been linked to depressive symptoms in non-clinical samples, it has never been studied in patients with major depressive disorder (MDD). This study is aimed to study social jetlag in patients with major depressive disorder and healthy controls, and to further examine the link between social jetlag and depressive symptomatology. Patients with a diagnosis of MDD (n = 1084) and healthy controls (n = 385), assessed in a clinical interview, were selected from the Netherlands Study of Depression and Anxiety. Social jetlag was derived from the Munich Chronotype Questionnaire, by calculating the absolute difference between the midsleep on free days and midsleep on work days. Depression severity was measured with the Inventory of Depressive Symptomatology. It was found that patients with MDD did not show more social jetlag compared to healthy controls, neither in a model without medication use (β = 0.06, 95% CI: −0.03–0.15,p = 0.17) nor in a model where medication use is accounted for. There was no direct association between the amount of social jetlag and depressive symptoms, neither in the full sample, nor in the patient group or the healthy control group. This first study on social jetlag in a clinical sample showed no differences in social jetlag between patients with MDD and healthy controls. [ABSTRACT FROM PUBLISHER]

Background: Uric acid has neuroprotective effects, owing to its antioxidant properties. Lowered antioxidant capacity, causing increased oxidative stress, may be involved in affective disorders and might be altered by antidepressants. This study investigated the association of plasma uric acid, the greatest contributor to blood antioxidant capacity, with major depressive disorder (MDD) and anxiety disorders.Methods: Data were from the Netherlands Study of Depression and Anxiety including patients with current (N = 1648), remitted (N = 609) MDD and/or anxiety disorders (of which N = 710 antidepressant users) and 618 controls. Diagnoses were established with the Composite International Diagnostic Interview. Symptom severity was assessed with the Inventory of Depressive Symptoms-Self Report, Beck Anxiety Inventory and Fear Questionnaire. Uric acid was measured in plasma. Analyses were adjusted for sociodemographic, health and lifestyle variables.Results: Plasma uric acid adjusted mean levels were lower in current MDD and/or anxiety disorder(s) (289μmol/l) compared to remitted disorders (298μmol/l, p < .001) and controls (299μmol/l, p < .001; Cohen's d .10). This finding was independent of antidepressant use. Depressive (β-.05, p = .0012), anxiety (β-.04, p = .009) and phobic (β-.03, p = .036) symptom severity, and symptom duration (β-.04, p = .009) were negatively associated with uric acid.Limitations: Limitations include the lack of data on dietary intake which could be a potential confounding factor. From these cross-sectional findings, the association between uric acid and psychopathology cannot be inferred to be causal.Conclusion: This large scale study finds plasma uric acid levels are lower in current, but not remitted, MDD and/or anxiety disorders, according to a dose-response gradient. This suggests the involvement of decreased antioxidant status in affective disorders, and points to their potential as an avenue for treatment. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is often handled as an episodic and isolated disorder, resulting in an optimistic view about its prognosis. Herein, we test the idea that the prognosis of MDD changes if we vary the perspective in terms of (1) a longer time frame and (2) a broader diagnostic conceptualisation including dysthymia, (hypo)mania and anxiety disorders as relevant outcomes.Methods: Patients with current MDD at baseline (n = 903) and available 2-, 4-, and/or 6-year follow-up assessments were selected from the Netherlands Study of Depression and Anxiety, a psychiatric cohort study. Combining psychiatric DSM-IV-based diagnoses and life-chart data, patient course trajectories were classified as (1) recovered (no diagnoses at 2-year follow-up or thereafter), (2) recurrent without chronic episodes, (3) recurrent with chronic episodes or (4) consistently chronic since baseline. A chronic episode was defined as having a current diagnosis at the follow-up assessment and consistent symptoms over 2 years. Proportions of course trajectories were provided moving from a short, narrow perspective (2-year follow-up, considering only MDD diagnosis) to a long, broad perspective (6-year follow-up, including MDD, dysthymia, (hypo)mania and anxiety diagnoses).Results: With the short, narrow perspective, the recovery rate was 58% and 21% had a chronic episode. However, in the long, broad perspective the recovery rate was reduced to 17%, while 55% of the patients experienced chronic episodes.Conclusions: Results from a long and rigorous follow-up in a large cohort suggests that most MDD patients have an unfavourable prognosis. Longer follow-up and broader diagnostic conceptualisation show that the majority of patients have a disabling and chronic disorder. Conceptualising and handling MDD as a narrowly defined and episodic disorder may underestimate the prognosis of the majority of depressed patients and, consequently, the type of care that is appropriate. [ABSTRACT FROM AUTHOR]

BackgroundOxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD) and anxiety disorders and may be influenced by antidepressant use. This study investigated the association of oxidative stress, measured by plasma levels of F2-isoprostanes and 8-hydroxy-2′-deoxyguanosine (8-OHdG) reflecting oxidative lipid and DNA damage respectively, with MDD, anxiety disorders and antidepressant use in a large cohort.MethodData was derived from the Netherlands Study of Depression and Anxiety including patients with current (N = 1619) or remitted (N = 610) MDD and/or anxiety disorder(s) (of which N = 704 antidepressant users) and 612 controls. Diagnoses were established with the Composite International Diagnostic Interview. Plasma 8-OHdG and F2-isoprostanes were measured using LC-MS/MS. ANCOVA was performed adjusted for sampling, sociodemographic, health and lifestyle variables.ResultsF2-isoprostanes did not differ between controls and patients, or by antidepressant use. Patients with current disorders had lower 8-OHdG (mean 42.1 pmol/l, 95% CI 40.4–43.8) compared to controls (45.0 pmol/l, 95% CI 42.9–47.2; p < 0.001) after adjustment for sampling, sociodemographics and lifestyle, but these differences disappeared after further adjustment for antidepressant use (p = 0.562). Antidepressant users had lower 8-OHdG levels (38.2 pmol/l, 95% CI 36.5–39.9) compared to controls (44.9 pmol/l, 95% CI 43.2–46.6; Cohen's d = 0.21, p < 0.001). Results for 8-OHdG were comparable across disorders (MDD and/or anxiety disorders), and all antidepressant types (SSRIs, TCAs, other antidepressants).ConclusionContrary to previous findings this large-scale study found no increased oxidative stress in MDD and anxiety disorders. Antidepressant use was associated with lower oxidative DNA damage, suggesting antidepressants may have antioxidant effects. [ABSTRACT FROM PUBLISHER]

Background: Depression is common in patients with diabetes type 2 (DM2) and/or coronary heart disease (CHD), with high personal and societal burden and may even be preventable. Recently, a cluster randomized trial of stepped care to prevent depression among patients with DM2 and/or CHD and subthreshold depression in Dutch primary care (Step-Dep) versus usual care showed no effectiveness. This paper presents its process evaluation, exploring in-depth experiences from a patient and practice nurse perspective to further understand the results. Methods: A qualitative study was conducted. Using a purposive sampling strategy, data were collected through semi-structured interviews with 24 participants (15 patients and nine practice nurses). All interviews were audiotaped and transcribed verbatim. Atlas.ti 5.7.1 software was used for coding and structuring of themes. A thematic analysis of the data was performed. Results: The process evaluation showed, even through a negative trial, that Step-Dep was perceived as valuable by both patients and practice nurses; perceived effectiveness on improving depressive symptoms varied greatly, but most felt that it had been beneficial for patients' well-being. Facilitators were: increased awareness of mental health problems in chronic disease management and improved accessibility and decreased experienced stigma of receiving mental health care. The Patient Health Questionnaire 9 (PHQ-9), used to determine depression severity, functioned as a useful starting point for the conversation on mental health and patients gained more insight into their mental health by regularly filling out the PHQ-9. However, patients and practice nurses did not widely support its use for monitoring depressive symptoms or making treatment decisions. Monitoring mental health was deemed important in chronically ill patients by both patients and practice nurses and was suggested to start at the time of diagnosis of a chronic disease. Appointed barriers were that patients were primarily motivated to participate in scientific research rather than their intrinsic need to improve depressive symptoms. Additionally, various practice nurses preferred offering individually based therapy over pre-determined interventions in a protocolled sequence and somatic practice nurses expressed a lack of competence to recognise and treat mental health problems. Conclusion: This study demonstrates both the benefits and unique demands of programs such as Step-Dep. The appointed facilitators and barriers could guide the development of future studies aiming to prevent depression in similar patient groups. [ABSTRACT FROM AUTHOR]

BackgroundThe heterogeneous aetiology of major depressive disorder (MDD) might affect the presentation of depressive symptoms across the lifespan. We examined to what extent a range of mood, cognitive, and somatic/vegetative depressive symptoms were differentially present depending on patient's age.MethodData came from 1404 participants with current MDD (aged 18–88 years) from two cohort studies: the Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Study of Depression in Older Persons (NESDO). Associations between age (per 10 years) and 30 depressive symptoms as well as three symptom clusters (mood, cognitive, somatic/vegetative) were assessed using logistic and linear regression analyses.ResultsDepression severity was found to be stable with increasing age. Nevertheless, 20 (67%) out of 30 symptoms were associated with age. Most clearly, with ageing there was more often early morning awakening [odds ratio (OR) 1.47, 95% confidence interval (CI) 1.36–1.60], reduced interest in sex (OR 1.42, 95% CI 1.31–1.53), and problems sleeping during the night (OR 1.33, 95% CI 1.24–1.43), whereas symptoms most strongly associated with younger age were interpersonal sensitivity (OR 0.72, 95% CI 0.66–0.79), feeling irritable (OR 0.73, 95% CI 0.67–0.79), and sleeping too much (OR 0.75, 95% CI 0.68–0.83). The sum score of somatic/vegetative symptoms was associated with older age (B = 0.23, p < 0.001), whereas the mood and cognitive sum scores were associated with younger age (B = −0.20, p < 0.001; B = −0.04, p = 0.004).ConclusionsDepression severity was found to be stable across the lifespan, yet depressive symptoms tend to shift with age from being predominantly mood-related to being more somatic/vegetative. Due to the increasing somatic presentation of depression with age, diagnoses may be missed. [ABSTRACT FROM AUTHOR]

BackgroundThere is a paucity of valid, brief instruments for the assessment of lifetime major depressive disorder (MDD) that can be used in, for example, large-scale genomics, imaging or biomarker studies on depression. We developed the LIfetime Depression Assessment Self-report (LIDAS), which assesses lifetime MDD diagnosis according to DSM criteria, and is largely based on the widely used Composite International Diagnostic Interview (CIDI). Here, we tested the feasibility and determined the sensitivity and specificity for measuring lifetime MDD with this new questionnaire, with a regular CIDI as reference.MethodSensitivity and specificity analyses of the online lifetime MDD questionnaire were performed in adults with (n = 177) and without (n = 87) lifetime MDD according to regular index CIDIs, selected from the Netherlands Study of Depression and Anxiety (NESDA) and Netherlands Twin Register (NTR). Feasibility was tested in an additional non-selective, population-based sample of NTR participants (n = 245).ResultsOf the 753 invited persons, 509 (68%) completed the LIDAS, of which 419 (82%) did this online. User-friendliness of the instrument was rated high. Median completion time was 6.2 min. Sensitivity and specificity for lifetime MDD were 85% [95% confidence interval (CI) 80–91%] and 80% (95% CI 72–89%), respectively. This LIDAS instrument gave a lifetime MDD prevalence of 20.8% in the population-based sample.ConclusionsMeasuring lifetime MDD with an online instrument was feasible. Sensitivity and specificity were adequate. The instrument gave a prevalence of lifetime MDD in line with reported population prevalences. LIDAS is a promising tool for rapid determination of lifetime MDD status in large samples, such as needed for genomics studies. [ABSTRACT FROM AUTHOR]

Experience sampling studies into daily-life affective reactivity indicate that depressed individuals react more strongly to both positive and negative stimuli than non-depressed individuals, particularly on negative affect (NA). Given the different mean levels of both positive affect (PA) and NA between patients and controls, such findings may be influenced by floor/ceiling effects, leading to violations of the normality and homoscedasticity assumptions underlying the used statistical models. Affect distributions in prior studies suggest that this may have particularly influenced NA-reactivity findings. Here, we investigated the influence of floor/ceiling effects on the observed PA- and NA-reactivity to both positive and negative events. Data came from 346 depressed, non-depressed, and remitted participants from the Netherlands Study of Depression and Anxiety (NESDA). In PA-reactivity analyses, no floor/ceiling effects and assumption violations were observed, and PA-reactivity to positive events, but not negative events, was significantly increased in the depressed and remitted groups versus the non-depressed group. However, NA-scores exhibited a floor effect in the non-depressed group and naively estimated models violated model assumptions. When these violations were accounted for in subsequent analyses, group differences in NA-reactivity that had been present in the naive models were no longer observed. In conclusion, we found increased PA-reactivity to positive events but no evidence of increased NA-reactivity in depressed individuals when accounting for violations of assumptions. The results indicate that affective-reactivity results are very sensitive to modeling choices and that previously observed increased NA-reactivity in depressed individuals may (partially) reflect unaddressed assumption violations resulting from floor effects in NA., Competing Interests: Declaration of competing interest We declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Treatment resistant depression (TRD) is common in daily practice. An empirical, widely accepted and applicable measure to quantify TRD is lacking. Previously, the Maudsley Staging Method (MSM) showed good validity. We aimed to improve the MSM by refining and extending its items resulting in the Dutch Measure for quantification of TRD (DM-TRD).Methods: In addition to duration, severity and failed treatments in the current depressive episode, we added items for functional impairment, comorbid anxiety, personality disorders and psychosocial stressors. We extended the augmentation section and added items for failed psychotherapy and intensified treatment. We examined psychometric properties of the DM-TRD and tested prediction of future depressive symptoms and remission after 16 weeks in 274 (DSM-IV) depressed in- and outpatients entering naturalistic treatment.Results: The DM-TRD showed excellent inter-/intra-rater reliability. Higher scores were associated with more symptoms and less remission during follow-up. The DM-TRD outperformed the MSM in prediction of future depressive symptomatology. Remission was predicted equally well by both measures. Longer duration of the current episode, larger functional impairment and larger baseline symptom severity were the strongest predictors of symptomatology at follow-up. Longer duration and larger functional impairment were negatively associated with remission.Limitations: Longer follow-up could have increased predictive power. Addition of items for somatic co-morbidity, childhood adversity and psychotic features must be investigated further.Conclusion: The DM-TRD has excellent psychometric properties and better predictive validity for clinical outcome than other sophisticated measure published to date. Its use in clinical practice and research will improve treatment planning in TRD-patients. [ABSTRACT FROM AUTHOR]

BackgroundMajor depressive disorder (MDD) and generalized anxiety disorder (GAD) often co-occur with somatic symptomatology. Little is known about the contributions of individual symptoms to this association and more insight into their relationships could help to identify symptoms that are central in the processes behind the co-occurrence. This study explores associations between individual MDD/GAD symptoms and somatic symptoms by using the network approach.MethodMDD/GAD symptoms were assessed in 2704 participants (mean age 41.7 years, 66.1% female) from the Netherlands Study of Depression and Anxiety using the Inventory of Depressive Symptomatology. Somatic symptoms were assessed with the somatization scale of the Four-Dimensional Symptom Questionnaire. The technique eLasso was used to estimate the network of MDD/GAD and somatic symptoms.ResultsThe network structure showed numerous associations between MDD/GAD and somatic symptoms. In general, neurovegetative and cognitive/affective MDD/GAD symptoms showed a similar strength of connections to the somatic domain. However, associations varied substantially across individual symptoms. MDD/GAD symptoms with many and strong associations to the somatic domain included anxiety and fatigue, whereas hypersomnia and insomnia showed no connections to somatic symptoms. Among somatic symptoms, excessive perspiration and pressure/tight feeling in chest were associated with the MDD/GAD domain, while muscle pain and tingling in fingers showed only a few weak associations.ConclusionsIndividual symptoms show differential associations in the co-occurrence of MDD/GAD with somatic symptomatology. Strongly interconnected symptoms are important in furthering our understanding of the interaction between the symptom domains, and may be valuable targets for future research and treatment. [ABSTRACT FROM PUBLISHER]

Background: High rates of psychiatric comorbidity are subject of debate: To what extent do they depend on classification choices such as diagnostic thresholds? This paper investigates the influence of different thresholds on rates of comorbidity between major depressive disorder (MDD) and generalized anxiety disorder (GAD).Methods: Point prevalence of comorbidity between MDD and GAD was measured in 74,092 subjects from the general population (LifeLines) according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria. Comorbidity rates were compared for different thresholds by varying the number of necessary criteria from ≥ 1 to all nine symptoms for MDD, and from ≥ 1 to all seven symptoms for GAD.Results: According to DSM thresholds, 0.86% had MDD only, 2.96% GAD only, and 1.14% both MDD and GAD (odds ratio (OR) 42.6). Lower thresholds for MDD led to higher rates of comorbidity (1.44% for ≥ 4 of nine MDD symptoms, OR 34.4), whereas lower thresholds for GAD hardly influenced comorbidity (1.16% for ≥ 3 of seven GAD symptoms, OR 38.8). Specific patterns in the distribution of symptoms within the population explained this finding: 37.3% of subjects with core criteria of MDD and GAD reported subthreshold MDD symptoms, whereas only 7.6% reported subthreshold GAD symptoms.Conclusions: Lower thresholds for MDD increased comorbidity with GAD, but not vice versa, owing to specific symptom patterns in the population. Generally, comorbidity rates result from both empirical symptom distributions and classification choices and cannot be reduced to either of these exclusively. This insight invites further research into the formation of disease concepts that allow for reliable predictions and targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: In recent years, researchers have used various techniques to elucidate the heterogeneity in depressive symptoms. This study seeks to resolve the extent to which variations in depression reflect qualitative differences between symptom categories and/or quantitative differences in severity.Methods: Data were used from the Netherlands Mental Health Survey and Incidence Study-2, a nationally representative face-to-face survey of the adult general population. In a subsample of respondents with a lifetime key symptom of depression at baseline and who participated in the first two waves (n=1388), symptom profiles at baseline were based on symptoms reported during their worst lifetime depressive episode. Depressive symptoms and DSM-IV diagnoses were assessed with the Composite International Diagnostic Interview 3.0. Three latent variable techniques (latent class analysis, factor analysis, factor mixture modelling) were used to identify the best subtyping model.Results: A latent class analysis, adjusted for local dependence between weight change and appetite change, described the data best and resulted in four distinct depressive subtypes: severe depression with anxiety (28.0%), moderate depression with anxiety (29.3%), moderate depression without anxiety (23.6%) and mild depression (19.0%). These classes showed corresponding clinical correlates at baseline and corresponding course and outcome indicators at follow-up (i.e., class severity was linked to lifetime mental disorders at baseline, and service use for mental health problems and current disability at follow-up).Limitations: Although the sample was representative of the population on most parameters, the findings are not generalisable to the most severely affected depressed patients.Conclusions: Depression could best be described in terms of both qualitative differences between symptom categories and quantitative differences in severity. In particular anxiety was a distinguishing feature within moderate depression. This study stresses the central position anxiety occupies in the concept of depression. [ABSTRACT FROM AUTHOR]

Background.Childhood maltreatment (CM) may modify the relationship between major depressive disorder (MDD) and hippocampal volume reduction. To disentangle the impact of MDD and CM on hippocampal volume we investigated the association between MDD and hippocampal volume in persons with and without a history of CM in two independent cohorts.Method.We used data of 262 participants from the Netherlands Study of Depression and Anxiety (NESDA) (mean age 37 years, 32% male) and 636 participants from the SMART-Medea study (mean age 61 years, 81% male). In both studies a 12-month diagnosis of MDD and CM were assessed using a diagnostic interview. Hippocampal volume was measured in NESDA using FreeSurfer software on 3-T magnetic resonance (MR) images and in SMART it was manually outlined on 1.5-T MR images. With analysis of covariance adjusted for intracranial volume, age, gender and lifestyle factors we estimated the effects of MDD and CM on hippocampal volume.Results.In both cohorts CM was not significantly associated with hippocampal volume. After pooling the data MDD was associated with smaller hippocampal volume (B = −138.90 mm3, p = 0.05) and the interaction between MDD and CM reached significance (p = 0.04); in participants with CM, MDD was related to smaller hippocampal volume (NESDA: B = −316.8 mm3, p = 0.02; SMART: B = −407.6, p = 0.046), but not in participants without CM (p > 0.05).Conclusions.Our study shows that in two independent cohorts, particularly in individuals with CM, a diagnosis of MDD is related to smaller hippocampal volume. Prospective studies are needed to further determine through which mechanism CM may amplify the relationship between MDD and hippocampal volume. [ABSTRACT FROM PUBLISHER]

Objective We aimed to systematically compare patients with major depressive disorder from three different treatment settings (a primary care outpatient, a secondary care outpatient and one inpatient sample), with regard to metabolic syndrome (MetSyn) prevalences, individual MetSyn components and related metabolic variables. Method The outpatient samples were drawn from the ongoing Netherlands Study of Depression and Anxiety (302 primary care and 445 secondary care outpatients). The inpatient sample (n=80) was recruited from five Dutch mental health hospitals. The assessments of MetSyn and related variables [waist circumference (WC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, glucose, systolic and diastolic blood pressure (SBP, DBP), body mass index (BMI), waist-hip ratio (WHR), LDL and total cholesterol (TC)] were compared using analysis of (co)variance and regression analysis, whereas medication analyses examined the extent to which clinical differences (e.g., depression severity or medication use) mediated the observed metabolic differences across setting. Results MetSyn prevalences (26% primary, 24% secondary care and 28% inpatients) did not significantly differ (P=.71). WC, BMI, LDL cholesterol, glucose and DBP were not significantly different across settings. However, WHR, TC and triglyceride levels were higher in inpatients than in both outpatients groups, while HDL cholesterol levels and SBP were lower. There was some mediating role for tricyclic and non-selective serotonin-reuptake inhibitor antidepressant use, but overall, the mediating role of clinical differences was limited. Conclusions Although overall MetSyn prevalences did not differ, patterns of individual MetSyn-related variables differed more markedly across depressed inpatients and outpatients. Inpatients showed more adverse WHR and serum lipid profiles, while SBP levels were lower. [ABSTRACT FROM AUTHOR]

Objectives: Late-life major depressive disorder (MDD) can be conceptualized as a complex dynamic system. However, it is not straightforward how to analyze the covarying depressive symptoms over time in case of sparse panel data. Dynamic time warping (DTW) analysis may yield symptom networks and dimensions both at the patient and group level., Methods: In the Netherlands Study of Depression in Older People (NESDO) depressive symptoms were assessed every 6 months using the 30-item Inventory of Depressive Symptomatology (IDS) with up to 13 assessments per participant. Our sample consisted of 182 persons, aged ≥ 60 years, with an IDS total score of 26 or higher at baseline. Symptom networks dimensions, and centrality metrics were analyzed using DTW and Distatis analyses., Results: The mean age was 69.8 years (SD 7.1), with 69.0% females, and a mean IDS score of 38.0 (SD = 8.7). DTW enabled visualization of an idiographic symptom network in a single NESDO participant. In the group-level nomothetic approach, four depressive symptom dimensions were identified: "core symptoms", "lethargy/somatic", "sleep", and "appetite/atypical". Items of the "internalizing symptoms" dimension had the highest centrality, whose symptom changes over time were most similar to those changes of other symptoms., Conclusions: DTW revealed symptom networks and dimensions based on the within-person symptom changes in older MDD patients. Its centrality metrics signal the most influential symptoms, which may aid personalized care., (© 2022 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

BackgroundKnowledge of the risk of recurrence after recovery from major depressive disorder (MDD) in the general population is scarce.MethodData were derived from 687 subjects in the general population with a lifetime DSM-III-R diagnosis of MDD but without a current major depressive episode (MDE) or dysthymia. Participants had to be at least 6 months in remission, and were recruited from The Netherlands Mental Health Survey and Incidence Study (NEMESIS), using the Composite International Diagnostic Interview (CIDI). Recency and severity of the last MDE were assessed retrospectively at baseline. Recurrence of MDD was measured prospectively during the 3-year follow-up. Kaplan–Meier survival curves were used to measure time to recurrence. Determinants of time to recurrence were analyzed using proportional hazard models.ResultsThe estimated cumulative recurrence of MDD was 13.2% at 5 years, 23.2% at 10 years and 42.0% at 20 years. In bivariate analysis, the following variables predicted a shorter time to recurrence: younger age, younger age of onset, higher number of previous episodes, a severe last depressive episode, negative youth experiences, ongoing difficulties before recurrence and high neuroticism. Multivariably, younger age, a higher number of previous episodes, a severe last depressive episode, negative youth experiences and ongoing difficulties remained significant.ConclusionsIn this community sample, the long-term risk of recurrence was high, but lower than that found in clinical samples. Subjects who had had an MDE had a long-term vulnerability for recurrence. Factors predicting recurrence included illness- and stress-related factors. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: This study assessed the cost-effectiveness of escitalopram for the treatment of depression in the Netherlands from a societal perspective. Methods: A decision tree model was constructed using decision analytical techniques. Data sources included published literature, clinical trials, official price/tariff lists, national population statistics, and Delphi panel data. The comparators were venlafaxine XR and citalopram. The primary perspective of this health economic evaluation was that of the society in the Netherlands in 2010. The time horizon was 26 weeks. The effectiveness outcomes of the study were quality-adjusted life-years (QALYs). Results: Escitalopram was associated with a cost savings per patient of €263 versus venlafaxine XR and €1992 versus citalopram over a period of 26 weeks from a societal perspective. Escitalopram was also associated with a gains QALYs: 0.0062 versus venlafaxine XR and 0.0166 versus citalopram. Escitalopram was dominant over both venlafaxine XR and citalopram. Conclusion: Based on the findings from this cost-effectiveness analysis, the favorable clinical benefit of escitalopram resulted in a positive health economic benefit in the Netherlands. [Copyright &y& Elsevier]

Abstract: Background: Major depressive disorder (MDD) is a universally prevalent, genetic, and environment dependent mental condition that disables people of every culture, race, gender, and age. While the gender differences for MDD have been widely reported in literature, few genome-wide analyses of gender differences have been reported to date. Methods: We conducted a genome-wide association analysis of gender differences for MDD using the Netherlands NESDA and NTR population-based samples (1726 cases and 1630 controls). PLINK software was used to analyze the genome-wide association data of Perlegen 600K SNP Chips. Results: We identified 40 male-specific and 56 female-specific MDD associated SNPs with P-values less than 10−4. The best male-specific SNP was rs9352774 (P=2.26×10−6) within LGSN gene while the best female-specific SNP was rs2715148 (P=5.64×10−7) within PCLO gene. We also found 38 SNPs showing gene×gender interactions in influencing MDD (P<10−4). The best SNP was rs12692709 (P=5.75×10−6) near FIGN gene at 2q24.3 while the next best SNP was rs11039588 (P=1.16×10−5) within OR4B1 gene. Limitations: The findings from this study need be replicated in other populations. Conclusions: These results provide genetic basis for gender differences in MDD and will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in MDD. [Copyright &y& Elsevier]

Abstract: Background: No previous large scale studies have assessed gender differences in naturalistic samples of major depressive disorder (MDD) outpatients. We therefore determined gender differences in comorbidity, symptom patterns and subjective health status in these outpatients in a mental healthcare setting. Methods: Of 3798 consecutive adult patients (age range: 18–65), 1131 (65.1% women) fulfilled DSM-IV criteria of current MDD on the Mini-International Neuropsychiatric Interview (MINI-Plus). Patients were routinely assessed with Routine Outcome Monitoring (ROM), including the Montgomery–Äsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI-II), Brief Symptom Inventory (BSI) and Short Form-36 (SF-36). Results: No gender differences were found in disease severity using the clinician-rated MADRS. However, women showed a significant higher depression severity measured with the self-report BDI-II. Also, psychopathological symptoms self-reported with the BSI were higher, and reported health status on the SF-36 was lower in women. In men with MDD, social phobia, attention deficit hyperactivity disorder, and alcohol and drug misconduct were more common comorbid disorders, while in women with MDD posttraumatic stress disorder and bulimia nervosa were more common, as well as atypical features of depression. Limitations: The use of retrospective reports of lifetime psychopathology might have led to recall bias. 20% of subjects were excluded from ROM due to language problems or logistical reasons. Conclusions: Although women self-reported higher depression severity, more severe general psychopathological symptoms and lower health status, no differences in disease severity were found on interviewer ratings. These findings could have implications for clinical decision making and treatment. [ABSTRACT FROM AUTHOR]

Aims To investigate whether cannabis use predicted the first incidence of mood and anxiety disorders in adults during a 3-year follow-up period. Design and participants Data were derived from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a prospective study in the adult population of 18–64 years. The analysis was carried out on 3881 people who had no life-time mood disorders and on 3854 people who had no life-time anxiety disorders at baseline. Measurements Life-time cannabis use and DSM-III-R mood and anxiety disorders, assessed with the Composite International Diagnostic Interview (CIDI). Findings After adjustment for strong confounders, any use of cannabis at baseline predicted a modest increase in the risk of a first major depression (odds ratio 1.62; 95% confidence interval 1.06–2.48) and a stronger increase in the risk of a first bipolar disorder (odds ratio 4.98; 95% confidence interval 1.80–13.81). The risk of ‘any mood disorder’ was elevated for weekly and almost daily users but not for less frequent use patterns. However, dose–response relationships were less clear for major depression and bipolar disorder separately. None of the associations between cannabis use and anxiety disorders remained significant after adjustment for confounders. Conclusions The associations between cannabis use and the first incidence of depression and bipolar disorder, which remained significant after adjustment for strong confounders, warrant research into the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder is the leading cause of disability worldwide. Yet, there remain significant challenges in predicting new cases of major depression and devising strategies to prevent the disorder. An important first step in this process is identifying risk factors for the incidence of major depression. There is accumulating biological evidence linking insulin resistance, another highly prevalent condition, and depressive disorders. The objectives of this study were to examine whether three surrogate measures of insulin resistance (high triglyceride-HDL [high-density lipoprotein] ratio; prediabetes, as indicated by fasting plasma glucose level; and high central adiposity, as measured by waist circumference) at the time of study enrollment were associated with an increased rate of incident major depressive disorder over a 9-year follow-up period and to assess whether the new onset of these surrogate measures during the first 2 years after study enrollment was predictive of incident major depressive disorder during the subsequent follow-up period., Methods: The Netherlands Study of Depression and Anxiety (NESDA) is a multisite longitudinal study of the course and consequences of depressive and anxiety disorders in adults. The study population comprised 601 NESDA participants (18-65 years old) without a lifetime history of depression or anxiety disorders. The study's outcome was incident major depressive disorder, defined using DSM-IV criteria. Exposure measures included triglyceride-HDL ratio, fasting plasma glucose level, and waist circumference., Results: Fourteen percent of the sample developed major depressive disorder during follow-up. Cox proportional hazards models indicated that higher triglyceride-HDL ratio was positively associated with an increased risk for incident major depression (hazard ratio=1.89, 95% CI=1.15, 3.11), as were higher fasting plasma glucose levels (hazard ratio=1.37, 95% CI=1.05, 1.77) and higher waist circumference (hazard ratio=1.11 95% CI=1.01, 1.21). The development of prediabetes in the 2-year period after study enrollment was positively associated with incident major depressive disorder (hazard ratio=2.66, 95% CI=1.13, 6.27). The development of high triglyceride-HDL ratio and high central adiposity (cut-point ≥100 cm) in the same period was not associated with incident major depression., Conclusions: Three surrogate measures of insulin resistance positively predicted incident major depressive disorder in a 9-year follow-up period among adults with no history of depression or anxiety disorder. In addition, the development of prediabetes between enrollment and the 2-year study visit was positively associated with incident major depressive disorder. These findings may have utility for evaluating the risk for the development of major depression among patients with insulin resistance or metabolic pathology.

Background: Major depressive disorder (MDD) represents a leading cause of disability. This study examines the course of disability in patients with chronic, recurrent and remitting MDD compared to healthy controls and identifies predictors of disability in remitting MDD., Methods: We included 914 participants from the Netherlands Study of Depression and Anxiety (NESDA). DSM-IV MDD and WHO DAS II disability were assessed at baseline and at 2, 4 and 6 years. Six-year total and domain-specific disability were analysed and compared in participants with chronic (n = 57), recurrent (n = 120), remitting (n = 127) MDD and in healthy controls (n = 430). Predictors of residual disability were identified using linear regression analysis., Results: At baseline, most disability was found in chronic MDD, followed by recurrent MDD, remitting MDD and healthy controls. Across diagnostic groups, most disability was found in household activities, interpersonal functioning, participation in society and cognition. A chronic course was associated with chronic disability. Symptom remission was associated with a decrease in disability, but some disability remained. In remitting MDD, higher residual disability was predicted by older age, more severe avoidance symptoms, higher disability at baseline and late symptom remission. Severity of residual disability correlated with the severity of residual depressive symptoms., Conclusions: Symptomatic remission is a prerequisite for improvements in disability. However, disability persists despite symptom remission. Therefore, treatment of MDD should include an explicit focus on disability, especially on the more complex domains. To this end, treatments should promote behavioural activation and address subthreshold depressive symptoms in patients with remitted MDD.

Study Objectives: Major depressive disorder (MDD) is the leading cause of disability worldwide. Its high recurrence rate calls for prevention of first-onset MDD. Although meta-analysis suggested insomnia as the strongest modifiable risk factor, previous studies insufficiently addressed that insomnia might also occur as a residual symptom of unassessed prior depression, or as a comorbid complaint secondary to other depression risks., Methods: In total, 768 participants from the Netherlands Study of Depression and Anxiety who were free from current and lifetime MDD were followed-up for four repeated assessments, spanning 6 years in total. We performed separate Cox proportional hazard analyses to evaluate whether baseline insomnia severity, short-sleep duration, and individual insomnia complaints prospectively predicted first-onset MDD during follow-up. The novel method of network outcome analysis (NOA) allowed us to sort out whether there is any direct predictive value of individual insomnia complaints among several other complaints that are associated with insomnia., Results: Over 6-year follow-up, 141 (18.4%) were diagnosed with first-onset MDD. Insomnia severity but not sleep duration predicted first-onset MDD (HR = 1.11, 95% CI: 1.07-1.15), and this was driven solely by the insomnia complaint difficulty initiating sleep (DIS) (HR = 1.10, 95% CI: 1.04-1.16). NOA likewise identified DIS only to directly predict first-onset MDD, independent of four other associated depression complaints., Conclusions: We showed prospectively that DIS is a risk factor for first-onset MDD. Among the different other insomnia symptoms, the specific treatment of DIS might be the most sensible target to combat the global burden of depression through prevention., (© Sleep Research Society 2019. Published by Oxford University Press [on behalf of the Sleep Research Society].)

Background: Major Depressive Disorder (MDD) is a psychiatric disorder with a highly recurrent character, making prevention of relapse an important clinical goal. Preventive Cognitive Therapy (PCT) has been proven effective in preventing relapse, though not for every patient. A better understanding of relapse vulnerability and working mechanisms of preventive treatment may inform effective personalized intervention strategies. Neurocognitive models of MDD suggest that abnormalities in prefrontal control over limbic emotion-processing areas during emotional processing and regulation are important in understanding relapse vulnerability. Whether changes in these neurocognitive abnormalities are induced by PCT and thus play an important role in mediating the risk for recurrent depression, is currently unclear. In the Neurocognitive Working Mechanisms of the Prevention of Relapse In Depression (NEWPRIDE) study, we aim to 1) study neurocognitive factors underpinning the vulnerability for relapse, 2) understand the neurocognitive working mechanisms of PCT, 3) predict longitudinal treatment effects based on pre-treatment neurocognitive characteristics, and 4) validate the pupil dilation response as a marker for prefrontal activity, reflecting emotion regulation capacity and therapy success., Methods: In this randomized controlled trial, 75 remitted recurrent MDD (rrMDD) patients will be included. Detailed clinical and cognitive measurements, fMRI scanning and pupillometry will be performed at baseline and three-month follow-up. In the interval, 50 rrMDD patients will be randomized to eight sessions of PCT and 25 rrMDD patients to a waiting list. At baseline, 25 healthy control participants will be additionally included to objectify cross-sectional residual neurocognitive abnormalities in rrMDD. After 18 months, clinical assessments of relapse status are performed to investigate which therapy induced changes predict relapse in the 50 patients allocated to PCT., Discussion: The present trial is the first to study the neurocognitive vulnerability factors underlying relapse and mediating relapse prevention, their value for predicting PCT success and whether pupil dilation acts as a valuable marker in this regard. Ultimately, a deeper understanding of relapse prevention could contribute to the development of better targeted preventive interventions., Trial Registration: Trial registration: Netherlands Trial Register, August 18, 2015, trial number NL5219.

Results of a randomised controlled trial testing the EFFect Of Running Therapy on Depression. Background: This randomised controlled trial explored the anti-depressive and health effects of add-on exercise (running therapy or Nordic walking) in patients with Major Depressive Disorder (MDD). Methods: Patients were recruited at three specialised mental health care institutions. In the intervention group exercise was planned two times a week during 6 months, the control group received care as usual. Observer-blinded measurements included Hamilton-17 depression scores and several health and fitness parameters. Submaximal bicycle-tests were performed at inclusion, 3, 6 and 12 months. The effects of exercise were assessed by effect size, intention-to-treat and analysis per protocol using General Linear Models (GLM) with time x group interactions. Results: In total, 183 patients were assessed for eligibility and 135 were excluded (40% of the potential participants declined to participate mainly due to a lack of time and motivation). Together with a drop-out of 55% at 6 months, this reduced the power of the study severely. As a result, statistical analysis was performed only on the first 3 months of the study. Data were ultimately analysed from 46 patients, of which 24 were in the intervention group. Significantly more women were in the intervention group, and depression and fitness were higher in the control group. Participants showed 2–3 points less depression on average after 3 months. However, the GLM showed no effect on depression (Cohen's d < 0.2, F =.13, p =.73) in both the intention-to-treat and per protocol analyses. However, large effect sizes (Cohen's d > 0.8) were found for aerobic capacity (VO2max∙.kg− 1, F = 7.1, p =.02*), maximal external output (Wmax∙.kg− 1, F = 6.1, p =.03*), and Body Mass Index (F = 5, p =.04*), in favour of the intervention group. Conclusions: In this selective and relative small clinical population with MDD, an anti-depressive effect of the exercise intervention could not be measured and is also unlikely due to the very low effect size. An integrated lifestyle intervention will probably be more effective than a single add-on exercise intervention. However, significantly increased fitness levels may contribute to the alleviation of current cardio-metabolic risk factors or prevention of these in the future. Trial registration: Netherlands Trial Register (NTR): NTR1894 on July 2nd 2009. [ABSTRACT FROM AUTHOR]

Background: Selection of the optimal initial treatment in patients with major depressive disorder (MDD) in need of highly specialized care has the potential to benefit treatment outcomes and cost-effectiveness of treatment strategies. However, to date, there is a paucity of measures that could guide the selection of the initial treatment, in particular to indicate which patients with MDD are in need of highly specialized care. Recognizing this gap, this paper reports on the development and psychometric evaluation of the Decision Tool Unipolar Depression (DTUD), aimed to facilitate the early identification of patients with MDD in need of highly specialized care., Methods: The DTUD was developed using a mixed-methods approach, consisting of a systematic review and a concept mapping study. To evaluate the psychometric features of the DTUD, a cross-sectional multicenter study was conducted. A total of 243 patients with MDD were evaluated with the DTUD. Feasibility was operationalized as the time required to complete the DTUD and the content clarity of the DTUD. Inter-rater reliability was evaluated using Krippendorf's alpha. The Maudsley Staging Method (MSM) and the Dutch Measure for quantification of Treatment Resistance in Depression (DM-TRD) were administered to assess the convergent validity. A receiver operator characteristic curve was generated to evaluate the criterion validity and establish the optimal cut-off value., Results: The mean administration time was 4.49 min (SD = 2.71), and the content of the total DTUD was judged as clear in 94.7% of the evaluations. Inter-rater reliability values ranged from 0.69 to 0.91. Higher scores on the DTUD were associated with higher scores on the MSM (r s  = 0.47) and DM-TRD (r s  = 0.53). Based on the maximum Youden index (0.494), maximum discrimination was reached at a cut-off score of ≥5 (sensitivity 67%, specificity 83%)., Conclusion: The DTUD demonstrated to be a tool with solid psychometric properties and, therefore, is a promising measure for the early identification of patients with MDD in need of highly specialized care. Use of the DTUD has the potential to facilitate the selection and initiation of the optimal initial treatment in patients with MDD, which in turn may improve the clinical effectiveness and cost-effectiveness of treatment strategies.

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.

Although it has often been suggested that physical activity and depression are intertwined, only few studies have investigated whether specific aspects of physical activity predict the incidence of major depression in adolescents from the general population. Therefore the aim of this study was to investigate the effects of nature, frequency, duration and intensity of physical activity during early adolescence on the onset of a major depressive episode in early adulthood. In a population sample of adolescents (N = 1396), various aspects of physical activity were assessed at early adolescence (mean age 13.02, SD = 0.61). Major depressive episode onset was assessed using the Composite International Diagnostic Interview. A Cox regression model was performed to investigate whether physical activity characteristics and their interactions with gender predicted a major depressive episode onset up until mean age 18.5 (SD = 0.61). The individual characteristics of physical activity (nature, frequency, duration and intensity) or their interactions with gender did not predict a major depressive episode onset (p values >0.05). So far, there is no prospective evidence that physical activity protects against the development of adolescent depressive episodes in either boys or girls., (Copyright © 2013 Elsevier Ltd. All rights reserved.)