Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.

Understanding mechanisms of depression prevention: study protocol of a randomized cross-over trial to investigate mechanisms of mindfulness and positive fantasizing as intervention techniques for reducing perseverative cognition in remitted depressed individuals.

BACKGROUND: Major Depressive Disorder (MDD) is one of the most prevalent psychiatric disorders, and involves high relapse rates in which persistent negative thinking and rumination (i.e., perseverative cognition [PC]) play an important role. Positive fantasizing and mindfulness are common evidence-based psychological interventions that have been shown to effectively reduce PC and subsequent depressive relapse. How the interventions cause changes in PC over time, is unknown, but likely differ between the two. Whereas fantasizing may change the valence of thought content, mindfulness may operate through disengaging from automatic thought patterns. Comparing mechanisms of both interventions in a clinical sample and a non-clinical sample can give insight into the effectivity of interventions for different individuals. The current study aims to 1) test whether momentary psychological and psychophysiological indices of PC are differentially affected by positive fantasizing versus mindfulness-based interventions, 2) test whether the mechanisms of change by which fantasizing and mindfulness affect PC differ between remitted MDD versus never-depressed (ND) individuals, and 3) explore potential moderators of the main effects of the two interventions (i.e., what works for whom). METHODS: In this cross-over trial of fantasizing versus mindfulness interventions, we will include 50 remitted MDD and 50 ND individuals. Before the start of the measurements, participants complete several individual characteristics. Daily-life diary measures of thoughts and feelings (using an experience sampling method), behavioural measures of spontaneous thoughts (using the Sustained Attention to Response Task), actigraphy, physiological measures (impedance cardiography, electrocardiography, and electroencephalogram), and measures of depressive mood (self-report questionnaires) are performed during the week before (pre-) the interventions and the week during (peri-) the interventions. After a wash-out of at least one month, pre- and peri-intervention measures for the second intervention are repeated. DISCUSSION: This is the first study integrating self-reports, behavioural-, and physiological measures capturing dynamics at multiple time scales to examine the differential mechanisms of change in PC by psychological interventions in individuals remitted from multiple MDD episodes and ND individuals. Unravelling how therapeutic techniques affect PC in remitted individuals might generate insights that allows development of personalised targeted relapse prevention interventions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06145984, November 16, 2023.

Individual-specific change points in circadian rest-activity rhythm and sleep in individuals tapering their antidepressant medication: an actigraphy study.

Group-level studies showed associations between depressive symptoms and circadian rhythm elements, though whether these associations replicate at the within-person level remains unclear. We investigated whether changes in circadian rhythm elements (namely, rest-activity rhythm, physical activity, and sleep) occur close to depressive symptom transitions and whether there are differences in the amount and direction of circadian rhythm changes in individuals with and without transitions. We used 4 months of actigraphy data from 34 remitted individuals tapering antidepressants (20 with and 14 without depressive symptom transitions) to assess circadian rhythm variables. Within-person kernel change point analyses were used to detect change points (CPs) and their timing in circadian rhythm variables. In 69% of individuals experiencing transitions, CPs were detected near the time of the transition. No-transition participants had an average of 0.64 CPs per individual, which could not be attributed to other known events, compared to those with transitions, who averaged 1 CP per individual. The direction of change varied between individuals, although some variables showed clear patterns in one direction. Results supported the hypothesis that CPs in circadian rhythm occurred more frequently close to transitions in depression. However, a larger sample is needed to understand which circadian rhythm variables change for whom, and more single-subject research to untangle the meaning of the large individual differences.

Day-to-day affect fluctuations in adults with childhood trauma history: a two-week ecological momentary assessment study.

BACKGROUND: Childhood trauma (CT) may increase vulnerability to psychopathology through affective dysregulation (greater variability, autocorrelation, and instability of emotional symptoms). However, CT associations with dynamic affect fluctuations while considering differences in mean affect levels across CT status have been understudied. METHODS: 346 adults (age = 49.25 ± 12.55, 67.0% female) from the Netherlands Study of Depression and Anxiety participated in ecological momentary assessment. Positive and negative affect (PA, NA) were measured five times per day for two weeks by electronic diaries. Retrospectively-reported CT included emotional neglect and emotional/physical/sexual abuse. Linear regressions determined associations between CT and affect fluctuations, controlling for age, sex, education, and mean affect levels. RESULTS: Compared to those without CT, individuals with CT reported significantly lower mean PA levels (Cohen's d = -0.620) and higher mean NA levels (d = 0.556) throughout the two weeks. CT was linked to significantly greater PA variability (d = 0.336), NA variability (d = 0.353), and NA autocorrelation (d = 0.308), with strongest effects for individuals reporting higher CT scores. However, these effects were entirely explained by differences in mean affect levels between the CT groups. Findings suggested consistency of results in adults with and without lifetime depressive/anxiety disorders and across CT types, with sexual abuse showing the smallest effects. CONCLUSIONS: Individuals with CT show greater affective dysregulation during the two-week monitoring of emotional symptoms, likely due to their consistently lower PA and higher NA levels. It is essential to consider mean affect level when interpreting the impact of CT on affect dynamics.

Childhood abuse v. neglect and risk for major psychiatric disorders.

BACKGROUND: Childhood maltreatment (CM) is a strong risk factor for psychiatric disorders but serves in its current definitions as an umbrella for various fundamentally different childhood experiences. As first step toward a more refined analysis of the impact of CM, our objective is to revisit the relation of abuse and neglect, major subtypes of CM, with symptoms across disorders. METHODS: Three longitudinal studies of major depressive disorder (MDD, N = 1240), bipolar disorder (BD, N = 1339), and schizophrenia (SCZ, N = 577), each including controls (N = 881), were analyzed. Multivariate regression models were used to examine the relation between exposure to abuse, neglect, or their combination to the odds for MDD, BD, SCZ, and symptoms across disorders. Bidirectional Mendelian randomization (MR) was used to probe causality, using genetic instruments of abuse and neglect derived from UK Biobank data (N = 143 473). RESULTS: Abuse was the stronger risk factor for SCZ (OR 3.51, 95% CI 2.17-5.67) and neglect for BD (OR 2.69, 95% CI 2.09-3.46). Combined CM was related to increased risk exceeding additive effects of abuse and neglect for MDD (RERI = 1.4) and BD (RERI = 1.1). Across disorders, abuse was associated with hallucinations (OR 2.16, 95% CI 1.55-3.01) and suicide attempts (OR 2.16, 95% CI 1.55-3.01) whereas neglect was associated with agitation (OR 1.24, 95% CI 1.02-1.51) and reduced need for sleep (OR 1.64, 95% CI 1.08-2.48). MR analyses were consistent with a bidirectional causal effect of abuse with SCZ (IVWforward = 0.13, 95% CI 0.01-0.24). CONCLUSIONS: Childhood abuse and neglect are associated with different risks to psychiatric symptoms and disorders. Unraveling the origin of these differences may advance understanding of disease etiology and ultimately facilitate development of improved personalized treatment strategies.

Phenotypic but not genetically predicted heart rate variability associated with all-cause mortality.

Low heart rate variability (HRV) has been widely reported as a predictor for increased mortality. However, the molecular mechanisms are poorly understood. Therefore, this study aimed to identify novel genetic loci associated with HRV and assess the association of phenotypic HRV and genetically predicted HRV with mortality. In a GWAS of 46,075 European ancestry individuals from UK biobank, we identified 17 independent genome-wide significant genetic variants in 16 loci associated with HRV traits. Notably, eight of these loci (RNF220, GNB4, LINCR-002, KLHL3/HNRNPA0, CHRM2, KCNJ5, MED13L, and C160rf72) have not been reported previously. In a prospective phenotypic relationship between HRV and mortality during a median follow-up of seven years, individuals with lower HRV had higher risk of dying from any cause. Genetically predicted HRV, as determined by the genetic risk scores, was not associated with mortality. To the best of our knowledge, the findings provide novel biological insights into the mechanisms underlying HRV. These results also underline the role of the cardiac autonomic nervous system, as indexed by HRV, in predicting mortality.

Temporal associations between salivary cortisol and emotions in clinically depressed individuals and matched controls: A dynamic time warp analysis.

Depression can be understood as a complex dynamic system where depressive symptoms interact with one another. Cortisol is suggested to play a major role in the pathophysiology of depression, but knowledge on the temporal interplay between cortisol and depressive symptoms is scarce. We aimed to analyze the temporal connectivity between salivary cortisol and momentary affective states in depressed individuals and controls. Thirty pair-matched depressed and non-depressed participants completed questionnaires on momentary positive (PA) and negative (NA) affect and collected saliva three times a day for 30 days. The association between cortisol and affect was analyzed by dynamic time warp (DTW) analyses. These analyses involved lag-1 backward to lag-1 forward undirected analyses and lag-0 and lag-1 forward directed analyses. Large inter- and intra-individual variability in the networks were found. At the group level, with undirected analysis PA and NA were connected in the networks in depressed individuals and in controls. Directed analyses indicated that increases in cortisol preceded specific NA items in controls, but tended to follow upon specific affect items increase in depressed individuals. To conclude, at group level, changes in cortisol levels in individuals diagnosed with a depression may be a result of changes in affect, rather than a cause.

Increased affective reactivity among depressed individuals can be explained by floor effects: An experience sampling study.

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.

Predicting recurrence of depression using cardiac complexity in individuals tapering antidepressants.

It is currently unknown whether the complexity and variability of cardiac dynamics predicts future depression and whether within-subject change herein precedes the recurrence of depression. We tested this in an innovative repeated single-subject study in individuals who had a history of depression and were tapering their antidepressants. In 50 individuals, electrocardiogram (ECG) derived Interbeat-interval (IBI) time-series data were collected for 5 min every morning and evening, for 4 months. Usable data were obtained from 14 participants who experienced a transition (i.e., a clinically significant increase in depressive symptoms) and 14 who did not. The mean, standard deviation, Higuchi dimension and multiscale entropy, calculated from IBIs, were examined for time trends. These quantifiers were also averaged over a baseline period and compared between the groups. No consistent trends were observed in any quantifier before increases in depressive symptoms within individuals. The entropy baseline levels significantly differed between the two groups (morning: P value < 0.001, Cohen's d = -2.185; evening: P value < 0.001, Cohen's d = -1.797) and predicted the recurrence of depressive symptoms, in the current sample. Moreover, higher mean IBIs and Higuchi dimensions were observed in individuals who experienced transitions. While we found little evidence to support the existence of within- individual warning signals in IBI time-series data preceding an upcoming depressive transition, our results indicate that individuals who taper antidepressants and showed lower entropy of cardiac dynamics exhibited a higher chance of recurrence of depression. Hence, entropy could be a potential digital phenotype for assessing the risk of recurrence of depression in the short term while tapering antidepressants.

Integrating personalized experience sampling in psychotherapy: A case illustration of the Therap-i module.

Background: The experience sampling methodology (ESM) is increasingly being suggested as a clinical tool in mental health care, as it offers ecologically valid, microlevel information on psychopathological processes. Patients and clinicians have recommended that applications of ESM should be personalized and integrated into the existing clinical process, but there is still much uncertainty about how implementation may look like. Objective: To provide an example of personalized ESM assessment and feedback being integrated into psychotherapy for depression, specifically looking at the collaborative use of ESM in case conceptualization. Methods: George, a 27-year-old man diagnosed with depression, and his therapist participated in the Therap-i randomized controlled trial, which investigates the efficacy of a personalized ESM module added to psychotherapy. Together, they created a personalized ESM questionnaire, aiming to capture their hypotheses and questions regarding George's case conceptualization. George then filled out his ESM questionnaire five times per day, for 8 weeks. During this period, ESM data were discussed and interpreted by George, his therapist, and a researcher, in three feedback sessions. In these sessions, data were visualized in a flexible feedback interface that allowed for collaborative exploration of George's data. Both patient and therapist evaluated the module through questionnaires and George also participated in a semi-structured evaluation interview. Results: George's ESM questionnaire included personalized items on the topics of self-esteem and open versus withdrawn behavior. He completed 241 (89.3%) assessments. Discussions during the feedback sessions focused on two core themes: First, George's low energy level, which was further explored with regard to his sleep, medication, and activity patterns. Second, his low sense of self-esteem, which led to an in-depth exploration of his thinking patterns and social interactions. The ESM module was seen as useful and insightful by both George and therapist. Conclusions: This case shows how ESM and ESM-based feedback can stimulate the collaborative exploration of the patient's complaints, and how it can provide useful insights for treatment. We discuss how our personalized ESM module relates to current clinical principles and practices, and make suggestions for further implementation.

A clinical PREMISE for personalized models: Toward a formal integration of case formulations and statistical networks.

Over the past decade, the idiographic approach has received significant attention in clinical psychology, incentivizing the development of novel approaches to estimate statistical models, such as personalized networks. Although the notion of such networks aligns well with the way clinicians think and reason, there are currently several barriers to implementation that limit their clinical utility. To address these issues, we introduce the Prior Elicitation Module for Idiographic System Estimation (PREMISE), a novel approach that formally integrates case formulations with personalized network estimation via prior elicitation and Bayesian inference. PREMISE tackles current implementation barriers of personalized networks; incorporating clinical information into personalized network estimation systematically allows theoretical and data-driven integration, supporting clinician and patient collaboration when building a dynamic understanding of the patient's psychopathology. To illustrate its potential, we estimate clinically informed networks for a patient suffering from obsessive-compulsive disorder. We discuss open challenges in selecting statistical models for PREMISE, as well as specific future directions for clinical implementation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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.

Practitioner and researcher perspectives on the utility of ecological momentary assessment in mental health care: A survey study.

Background: Ecological momentary assessment (EMA) is a scientific self-monitoring method to capture individuals' daily life experiences. Early on, EMA has been suggested to have the potential to improve mental health care. However, it remains unclear if and how EMA should be implemented. This requires an in-depth investigation of how practitioners and researchers view the implementation of EMA. Objective: Explore the perspectives of mental health practitioners and EMA researchers on the utility of EMA for mental health care. Methods: Practitioners (n = 89; psychiatrists, psychologists, psychiatric nurses) and EMA researchers (n = 62) completed a survey about EMA in clinical practice. This survey addressed EMA goals for practitioner and patient, requirements regarding clinical use of EMA, and (dis)advantages of EMA compared to treatment-as-usual. t-Tests were used to determine agreement with each statement and whether practitioners' and researchers' views differed significantly. Linear regression was used to explore predictors of goals and preferences (e.g., EMA experience). Results: Practitioners and researchers considered EMA to be a useful clinical tool for diverse stages of care. They indicated EMA to be most useful for gaining insight into the context specificity of symptoms (55.0 %), whereas receiving alerts when symptoms increase was rated the least useful (11.3 %, alerts is in 95 % of bootstrap iterations between rank 8 and 10). Compared to treatment-as-usual, EMA was considered easier to use (M = 4.87, t = 5.30, p < .001) and interpret (M = 4.52, t = 3.61, p < .001), but also more burdensome for the patient (M = 4.48, t = 3.17, p < .001). Although participants preferred personalization of the EMA diary, they also suggested that EMA should cost practitioners and patients limited time. The preference for creating personalized EMA was related to the level of experience with EMA. Finally, they highlighted the need for practitioner training and patient full-time access to the EMA feedback. Conclusions: This survey study demonstrated that practitioners and researchers expect EMA to have added value for mental health care. Concrete recommendations for implementation of EMA are formulated. This may inform the development of specific clinical applications and user-friendly EMA software.

Designing daily-life research combining experience sampling method with parallel data.

BACKGROUND: Ambulatory monitoring is gaining popularity in mental and somatic health care to capture an individual's wellbeing or treatment course in daily-life. Experience sampling method collects subjective time-series data of patients' experiences, behavior, and context. At the same time, digital devices allow for less intrusive collection of more objective time-series data with higher sampling frequencies and for prolonged sampling periods. We refer to these data as parallel data. Combining these two data types holds the promise to revolutionize health care. However, existing ambulatory monitoring guidelines are too specific to each data type, and lack overall directions on how to effectively combine them. METHODS: Literature and expert opinions were integrated to formulate relevant guiding principles. RESULTS: Experience sampling and parallel data must be approached as one holistic time series right from the start, at the study design stage. The fluctuation pattern and volatility of the different variables of interest must be well understood to ensure that these data are compatible. Data have to be collected and operationalized in a manner that the minimal common denominator is able to answer the research question with regard to temporal and disease severity resolution. Furthermore, recommendations are provided for device selection, data management, and analysis. Open science practices are also highlighted throughout. Finally, we provide a practical checklist with the delineated considerations and an open-source example demonstrating how to apply it. CONCLUSIONS: The provided considerations aim to structure and support researchers as they undertake the new challenges presented by this exciting multidisciplinary research field.

A Web-Based Application for Personalized Ecological Momentary Assessment in Psychiatric Care: User-Centered Development of the PETRA Application.

BACKGROUND: Smartphone self-monitoring of mood, symptoms, and contextual factors through ecological momentary assessment (EMA) provides insights into the daily lives of people undergoing psychiatric treatment. Therefore, EMA has the potential to improve their care. To integrate EMA into treatment, a clinical tool that helps clients and clinicians create personalized EMA diaries and interpret the gathered data is needed. OBJECTIVE: This study aimed to develop a web-based application for personalized EMA in specialized psychiatric care in close collaboration with all stakeholders (ie, clients, clinicians, researchers, and software developers). METHODS: The participants were 52 clients with mood, anxiety, and psychotic disorders and 45 clinicians (psychiatrists, psychologists, and psychiatric nurses). We engaged them in interviews, focus groups, and usability sessions to determine the requirements for an EMA web application and repeatedly obtained feedback on iteratively improved high-fidelity EMA web application prototypes. We used human-centered design principles to determine important requirements for the web application and designed high-fidelity prototypes that were continuously re-evaluated and adapted. RESULTS: The iterative development process resulted in Personalized Treatment by Real-time Assessment (PETRA), which is a scientifically grounded web application for the integration of personalized EMA in Dutch clinical care. PETRA includes a decision aid to support clients and clinicians with constructing personalized EMA diaries, an EMA diary item repository, an SMS text message-based diary delivery system, and a feedback module for visualizing the gathered EMA data. PETRA is integrated into electronic health record systems to ensure ease of use and sustainable integration in clinical care and adheres to privacy regulations. CONCLUSIONS: PETRA was built to fulfill the needs of clients and clinicians for a user-friendly and personalized EMA tool embedded in routine psychiatric care. PETRA is unique in this codevelopment process, its extensive but user-friendly personalization options, its integration into electronic health record systems, its transdiagnostic focus, and its strong scientific foundation in the design of EMA diaries and feedback. The clinical effectiveness of integrating personalized diaries via PETRA into care requires further research. As such, PETRA paves the way for a systematic investigation of the utility of personalized EMA for routine mental health care.

Don't Miss the Moment: A Systematic Review of Ecological Momentary Assessment in Suicide Research.

Suicide and suicide-related behaviors are prevalent yet notoriously difficult to predict. Specifically, short-term predictors and correlates of suicide risk remain largely unknown. Ecological momentary assessment (EMA) may be used to assess how suicidal thoughts and behaviors (STBs) unfold in real-world contexts. We conducted a systematic literature review of EMA studies in suicide research to assess (1) how EMA has been utilized in the study of STBs (i.e., methodology, findings), and (2) the feasibility, validity and safety of EMA in the study of STBs. We identified 45 articles, detailing 23 studies. Studies mainly focused on examining how known longitudinal predictors of suicidal ideation perform within shorter (hourly, daily) time frames. Recent studies have explored the prospects of digital phenotyping of individuals with suicidal ideation. The results indicate that suicidal ideation fluctuates substantially over time (hours, days), and that individuals with higher mean ideation also have more fluctuations. Higher suicidal ideation instability may represent a phenotypic indicator for increased suicide risk. Few studies succeeded in establishing prospective predictors of suicidal ideation beyond prior ideation itself. Some studies show negative affect, hopelessness and burdensomeness to predict increased ideation within-day, and sleep characteristics to impact next-day ideation. The feasibility of EMA is encouraging: agreement to participate in EMA research was moderate to high (median = 77%), and compliance rates similar to those in other clinical samples (median response rate = 70%). More individuals reported suicidal ideation through EMA than traditional (retrospective) self-report measures. Regarding safety, no evidence was found of systematic reactivity of mood or suicidal ideation to repeated assessments of STBs. In conclusion, suicidal ideation can fluctuate substantially over short periods of time, and EMA is a suitable method for capturing these fluctuations. Some specific predictors of subsequent ideation have been identified, but these findings warrant further replication. While repeated EMA assessments do not appear to result in systematic reactivity in STBs, participant burden and safety remains a consideration when studying high-risk populations. Considerations for designing and reporting on EMA studies in suicide research are discussed.

The role of depressive symptoms and symptom dimensions in actigraphy-assessed sleep, circadian rhythm, and physical activity.

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: ß = -0.155, p < 0.001; RA: ß = -0.116, p = 0.002), somatic/vegetative (GMA: ß = -0.165, p < 0.001; RA: ß = -0.133, p < 0.001), sleep (GMA: ß = -0.169, p < 0.001; RA: ß = -0.190, p < 0.001). The association with sleep was more pronounced for two depression dimensions: longer SD was linked to somatic/vegetative (ß = 0.115, p = 0.015) dimension and lower SE was linked to sleep (ß = -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.

A Narrative Review of Network Studies in Depression: What Different Methodological Approaches Tell Us About Depression.

The network theory of psychopathology proposes that mental disorders arise from direct interactions between symptoms. This theory provides a promising framework to understand the development and maintenance of mental disorders such as depression. In this narrative review, we summarize the literature on network studies in the field of depression. Four methodological network approaches are distinguished: (i) studies focusing on symptoms at the macro-level vs. (ii) on momentary states at the micro-level, and (iii) studies based on cross-sectional vs. (iv) time-series (dynamic) data. Fifty-six studies were identified. We found that different methodological approaches to network theory yielded largely inconsistent findings on depression. Centrality is a notable exception: the majority of studies identified either positive affect or anhedonia as central nodes. To aid future research in this field, we outline a novel complementary network theory, the momentary affect dynamics (MAD) network theory, to understand the development of depression. Furthermore, we provide directions for future research and discuss if and how networks might be used in clinical practice. We conclude that more empirical network studies are needed to determine whether the network theory of psychopathology can indeed enhance our understanding of the underlying structure of depression and advance clinical treatment.

Psychological risk factors and the course of depression and anxiety disorders: A review of 15 years NESDA research.

BACKGROUND: The Netherlands Study of Depression and Anxiety (NESDA; Nbaseline=2981) is an ongoing longitudinal, multi-site, naturalistic, cohort study examining the etiology, course, and consequences of depression and anxiety. In this article we synthesize and evaluate fifteen years of NESDA research on prominent psychological risk factors for the onset, persistence, recurrence, and comorbidity of affective disorders. METHODS: A narrative review of 62 NESDA articles examining the specificity and predictive value of neuroticism, behavioral inhibition, repetitive negative thinking, experiential avoidance, cognitive reactivity, locus of control, (implicit) self-esteem, (implicit) disorder-specific self-associations, and attentional bias for the course of affective disorders. RESULTS: All self-reported risk factors showed cross-sectional relationships with singular and comorbid affective disorders, and prospective relationships with the development and chronicity of depression and anxiety disorders. High neuroticism, low self-esteem, and negative repetitive thinking showed most prominent transdiagnostic relationships, whereas cognitive reactivity showed most pronounced depression-specific associations. Implicit self-esteem showed predictive validity for the persistence and recurrence of anxiety and depression over and above self-reported risk factors. Automatic approach-avoidance behavior and attentional bias for negative, positive, or threat words showed no relationship with affective disorders. CONCLUSION: NESDA identified both (a) transdiagnostic factors (e.g., neuroticism, low implicit self-esteem, repetitive negative thinking) that may help explain the comorbidity between affective disorders and overlap in symptoms, and (b) indications for disorder-specific risk factors (e.g., cognitive responsivity) which support the relevance of distinct disorder categories and disorder-specific mechanisms. Thus, the results point to the relevance of both transdiagnostic and disorder-specific targets for therapeutic interventions.