Redefining Therapeutic Outcomes of Depression Treatment

Responses to evidence-based interventions for depression are divergent: Some patients benefit more than others during treatment and some do not benefit at all or even deteriorate. Tailoring interventions to the individual may improve outcomes. However, such personalization of evidence-based treatment in depression requires investigation of individual outcomes and the individual trajectories towards these outcomes. This theoretical paper provides a critical reflection on individual outcomes of depression treatment. First, it is argued that outcomes should be broadened, from a focus on mainly depressive symptomatology to recovery in different domains. It is acknowledged that recovery from depression reflects a personal journey that differs from person to person. Second, outcome measures should be lengthened beyond the acute treatment phase, taking a lifetime perspective on depression. The challenge then is to discover which trajectories of what measures during what interventions result in personalized sustainable recovery and for whom. Routine outcome monitoring systems may be used to inform this quest towards assessment of personalized sustainable therapeutic outcomes. Adaptations to broaden and lengthen measurements in routine outcome monitoring systems are proposed to identify predictors of personalized sustainable recovery. Routine outcome monitoring systems may eventually be used to implement personalized treatments for depression that result in personalized sustainable recovery

Personalizing cognitive behavioral therapy for cancer-related fatigue using ecological momentary assessments followed by automated individual time series analyses:A case report series

Introduction: A common approach to personalizing psychological interventions is the allocation of treatment modules to individual patients based on cut-off scores on questionnaires, which are mostly based on group studies. However, this way, intraindividual variation and temporal dynamics are not taken into account. Automated individual time series analyses are a possible solution, since these can identify the factors influencing the targeted symptom in a specific individual, and associated modules can be allocated accordingly. The aim of this study was to illustrate how automated individual time series analyses can be applied to personalize cognitive behavioral therapy for cancer-related fatigue in cancer survivors and how this procedure differs from allocating modules based on questionnaires.Methods: This study was a case report series (n = 3). Patients completed ecological momentary assessments at the start of therapy, and after three treatment modules (approximately 14 weeks). Assessments were analyzed with AutoVAR, an R package that automates the process of finding optimal vector autoregressive models. The results informed the treatment plan.Results: Three cases were described. From the ecological momentary assessments and automated time series analyses three individual treatment plans were constructed, in which the most important predictor for cancer-related fatigue was treated first. For two patients, this led to the treatment ending after the follow-up ecological momentary assessments. One patient continued treatment until six months, the standard treatment time in regular treatment. All three treatment plans differed from the treatment plans informed by questionnaire scores.Discussion: This study is one of the first to apply time series analyses in systematically personalizing psychological treatment. An important strength of this approach is that it can be used for every modular cognitive behavioral intervention where each treatment module addresses specific maintaining factors. Whether or not personalized CBT is more efficacious than standard, non-personalized CBT remains to be determined in controlled studies comparing it to usual care.</p

Overnight affective dynamics and sleep characteristics as predictors of depression and its development

INTRODUCTION: Greater affective inertia during the day (higher carry-over effects of prior affect to the current moment) is associated with depression and its development. However, the role of overnight affective inertia (from evening to morning) in depression, and the role of sleep therein, has been scarcely studied. OBJECTIVES: We examined i) the difference in overnight inertia for positive (PA) and negative affect (NA) between individuals with past depression, current depression, and no depression; ii) how sleep duration and quality influence overnight affective inertia in these groups, and iii) whether overnight affective inertia predicts depression development. METHODS: We used data of 579 women from the East-Flanders Prospective Twin Survey. First, individuals with past (n=82), current (n=26), and no depression (n=471) at baseline were examined, and then individuals who did (n=58) and did not (n=319) develop depression at 12-months follow-up. Affect was assessed 10 times a day for 5 days. Sleep was assessed with sleep diaries. Affective inertia was operationalized as the influence of affect(t-1) on affect(t). Linear mixed-effect models were used to test the hypotheses. RESULTS: Overnight affective inertia was not associated with depression, neither was it differently associated with sleep characteristics in the depression groups. However, sleep characteristics were more negatively associated with morning NA in both depression groups compared to the non-depressed group. Overnight affective inertia did not predict the development of depression at follow-up. CONCLUSIONS: Depression and sleep characteristics might be more related to mean affect levels rather than to more complex emotion dynamics measures. Replication of these findings with longer time-series is needed

Single-Subject Research in Psychiatry:Facts and Fictions

Scientific evidence in the field of psychiatry is mainly derived from group-based ("nomothetic") studies that yield group-aggregated results, while often the need is to answer questions that apply to individuals. Particularly in the presence of great inter-individual differences and temporal complexities, information at the individual-person level may be valuable for personalized treatment decisions, individual predictions and diagnostics. The single-subject study design can be used to make inferences about individual persons. Yet, the single-subject study is not often used in the field of psychiatry. We believe that this is because of a lack of awareness of its value rather than a lack of usefulness or feasibility. In the present paper, we aimed to resolve some common misconceptions and beliefs about single-subject studies by discussing some commonly heard "facts and fictions." We also discuss some situations in which the single-subject study is more or less appropriate, and the potential of combining single-subject and group-based study designs into one study. While not intending to plea for single-subject studies at the expense of group-based studies, we hope to increase awareness of the value of single-subject research by informing the reader about several aspects of this design, resolving misunderstanding, and providing references for further reading

Transdiagnostic factors predicting the 2-year disability outcome in patients with anxiety and depressive disorders

Background: Both anxiety and depressive disorders are associated with significant long-term disability. Since experienced impairments vary between patients independent of diagnosis and disease severity, identifying transdiagnostic factors that predict the course of disability may provide new targets to reduce disability. This study examines transdiagnostic factors predicting the 2-year disability outcome in patients with anxiety and/or depressive disorders (ADD), focusing on potentially malleable factors.Methods: Six hundred fifteen participants with a current diagnosis of ADD from the Netherlands Study of Depression and Anxiety (NESDA) were included. Disability was assessed at baseline and after 2 years of follow-up, using the 32-item WHODAS II questionnaire. Transdiagnostic predictors of 2-year disability outcome were identified using linear regression analysis.Results: In univariable analyses, transdiagnostic factors associated with the 2-year disability outcome were locus of control (standardized β = -0.116, p = 0.011), extraversion (standardized β = -0.123 p = 0.004) and experiential avoidance (standardized β = 0.139, p = 0.001). In multivariable analysis, extraversion had a unique predictive value (standardized β = -0.143 p = 0.003). A combination of sociodemographic, clinical and transdiagnostic variables resulted in an explained variance (R2) of 0.090). The explained variance of a combination of transdiagnostic factors was 0.050.Conclusion: The studied transdiagnostic variables explain a small but unique part of variability in the 2-year disability outcome. Extraversion is the only malleable transdiagnostic factor predictive of the course of disability independent of other variables. Due to the small contribution to the variance in the disability outcome, the clinical relevance of targeting extraversion seems limited. However, its predictive value is comparable to that of accepted disease severity measures, supporting the importance of looking beyond using disease severity measures as predictors. Furthermore, studies including extraversion in combination with other transdiagnostic and environmental factors may elucidate the unexplained part of variability of the course of disability in patients with ADD.</p

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.</p

Level and timing of physical activity during normal daily life in depressed and non-depressed individuals

Engaging in physical activity is known to reduce depressive symptoms. However, little is known which behavioral factors are relevant, and how patterns of activity change during depressive episodes. We expected that compared to controls, in depressed individuals the level of activity would be lower, the amplitude of 24-h-actigraphy profiles more dampened and daytime activities would start later. We used 14-day continuous-actigraphy data from participants in the Netherlands Study of Depression and Anxiety (NESDA) who participated in an ambulatory assessment study. Participants with a depression diagnosis in the past 6 months (n = 58) or its subsample with acute depression (DSM diagnosis in the past 1 month, n = 43) were compared to controls without diagnoses (n = 63). Depression was diagnosed with a diagnostic interview. Actigraphy-derived variables were activity mean levels (MESOR), the difference between peak and mean level (amplitude) and the timing of the activity peak (acrophase), which were estimated with cosinor analysis. Compared to the control group, both depression groups (total: B = -0.003, p = 0.033; acute: B = -0.004, p = 0.005) had lower levels of physical activity. Amplitude was also dampened, but in the acute depression group only (total: B = -0.002, p = 0.065; acute: B = -0.003, p = 0.011). Similarly, the timing of activity was marginally significant towards a later timing of activity in the acute, but not total depression group (total: B = 0.206, p = 0.398; acute: B = 0.405, p = 0.084). In conclusion, our findings may be relevant for understanding how different aspects of activity (level and timing) contribute to depression. Further prospective research is needed to disentangle the direction of the association between depression and daily rest-activity rhythms

Reflections on psychological resilience:a comparison of three conceptually different operationalizations in predicting mental health

BACKGROUND: Psychological resilience refers to the ability to maintain mental health or recover quickly after stress. Despite the popularity of resilience research, there is no consensus understanding or operationalization of resilience. OBJECTIVE: We plan to compare three indicators of resilience that each involve a different operationalization of the construct: a) General resilience or one’s self-reported general ability to overcome adversities; b) Daily resilience as momentarily experienced ability to overcome adversities; and c) Recovery speed evident in the pattern of negative affect recovery after small adversities in daily life. These three indicators are constructed per person to investigate their cross-sectional associations, stability over time, and predictive validity regarding mental health. METHODS: Data will be derived from the prospective MIRORR study that comprises 96 individuals at different levels of psychosis risk and contains both single-time assessed questionnaires and 90-days intensive longitudinal data collection at baseline (T0) and three yearly follow-up waves (T1–T3). General resilience is assessed using the Brief Resilience Scale (BRS) at baseline. Daily resilience is measured by averaging daily resilience scores across 90 days. For recovery speed, vector-autoregressive models with consecutive impulse response simulations will be applied to diary data on negative affect and daily stressors to calculate pattern of affect recovery. These indicators will be correlated concurrently (at T0) to assess their overlap and prospectively (between T0 and T1) to estimate their stability. Their predictive potential will be assessed by regression analysis with mental health (SCL-90) as an outcome, resilience indicators as predictors, and stressful life events as a moderator. CONCLUSION: The comparison of different conceptualizations of psychological resilience can increase our understanding of its multifaceted nature and, in future, help improve diagnostic, prevention and intervention strategies aimed at increasing psychological resilience

Cortisol dynamics in depression:Application of a continuous-time process model

Background: The temporal dynamics of cortisol may be altered in depression. Optimally studying these dynamics in daily life requires specific analytical methods. We used a continuous-time multilevel process model to study set point (rhythm-corrected mean), variability around this set point, and regulation strength (speed with which cortisol levels regulate back to the set point after any perturbation). We examined the generalizability of the parameters across two data sets with different sampling and assay methods, and the hypothesis that regulation strength, but not set point or variability thereof, would be altered in depressed, compared to non-depressed individuals. Methods: The first data set is a general population sample of female twins (n = 523), of which 21 were depressed, with saliva samples collected 10 times a day for 5 days. The second data set consists of pair-matched clinically depressed and non-depressed individuals (n = 30), who collected saliva samples 3 times a day for 30 days. Set point, regulation strength and variability were examined using a Bayesian multilevel Ornstein-Uhlenbeck (OU) process model. They were first compared between samples, and thereafter assessed within samples in relation to depression. Results: Set point and variability of salivary cortisol were twice as high in the female twin sample, compared to the pair-matched sample. The ratio between set point and variability, as well as regulation strength, which are relative measures and therefore less affected by the specific assay method, were similar across samples. The average regulation strength was high; after an increase in cortisol, cortisol levels would decrease by 63 % after 10 min, and by 95 % after 30 min, but depressed individuals of the pair-matched sample displayed an even faster regulation strength. Conclusions: The relative parameters of the two data sets. The results suggest that regulation strength is increased in depressed individuals. We recommend the presented methodology for future studies and call for replications with more diverse depressed populations

Association of Use of Oral Contraceptives With Depressive Symptoms Among Adolescents and Young Women

Importance: Oral contraceptives have been associated with an increased risk of subsequent clinical depression in adolescents. However, the association of oral contraceptive use with concurrent depressive symptoms remains unclear. Objectives: To investigate the association between oral contraceptive use and depressive symptoms and to examine whether this association is affected by age and which specific symptoms are associated with oral contraceptive use. Design, Setting, and Participants: Data from the third to sixth wave of the prospective cohort study Tracking Adolescents' Individual Lives Survey (TRAILS), conducted from September 1, 2005, to December 31, 2016, among females aged 16 to 25 years who had filled out at least 1 and up to 4 assessments of oral contraceptive use, were used. Data analysis was performed from March 1, 2017, to May 31, 2019. Exposure: Oral contraceptive use at 16, 19, 22, and 25 years of age. Main Outcomes and Measures: Depressive symptoms were assessed by the DSM-IV-oriented affective problems scale of the Youth (aged 16 years) and Adult Self-Report (aged 19, 22, and 25 years). Results: Data from a total of 1010 girls (743-903 girls, depending on the wave) were analyzed (mean [SD] age at the first assessment of oral contraceptive use, 16.3 [0.7]; (mean [SD] age at the final assessment of oral contraceptive use, 25.6 [0.6] years). Oral contraceptive users particularly differed from nonusers at age 16 years, with nonusers having a higher mean (SD) socioeconomic status (0.17 [0.78] vs-0.15 [0.71]) and more often being virgins (424 of 533 [79.5%] vs 74 of 303 [24.4%]). Although all users combined (mean [SD] ages, 16.3 [0.7] to 25.6 [0.6] years) did not show higher depressive symptom scores compared with nonusers, adolescent users (mean [SD] age, 16.5 [0.7] years) reported higher depressive symptom scores compared with their nonusing counterparts (mean [SD] age, 16.1 [0.6] years) (mean [SD] score, 0.40 [0.30] vs 0.33 [0.30]), which persisted after adjustment for age, socioeconomic status and ethnicity (β coefficient for interaction with age,-0.021; 95% CI,-0.038 to-0.005; P =.0096). Adolescent contraceptive users particularly reported more crying (odds ratio, 1.89; 95% CI, 1.38-2.58; P <.001), hypersomnia (odds ratio, 1.68; 95% CI, 1.14-2.48; P =.006), and more eating problems (odds ratio, 1.54; 95% CI, 1.13-2.10; P =.009) than nonusers. Conclusions and Relevance: Although oral contraceptive use showed no association with depressive symptoms when all age groups were combined, 16-year-old girls reported higher depressive symptom scores when using oral contraceptives. Monitoring depressive symptoms in adolescents who are using oral contraceptives is important, as the use of oral contraceptives may affect their quality of life and put them at risk for nonadherence