The associations of hair cortisol and DHEA with posttraumatic stress disorder symptoms in refugees.

BACKGROUND: Exposure to traumatic events, ongoing adversity, and posttraumatic stress disorder (PTSD) are associated with altered activity of the hypothalamic-pituitary-adrenal (HPA) axis, but findings are mixed. This may be explained in part by heterogeneity in PTSD symptom profiles. AIM: The aim of this study was to investigate the complex relationships between the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and dehydroepiandrosterone (DHEA) in refugees. METHODS: Adult (18+ years) Syrian refugees with increased levels of distress participating in a randomized controlled trial completed baseline measures to assess traumatic events (trauma checklist), post-displacement stressors (Post-Migration Living Difficulties checklist), symptoms of PTSD (PTSD Checklist for DSM-5; PCL-5), and provided a hair sample for additional stress hormone analyses. We used R-packages qgraph and bootnet to perform network analysis on the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and DHEA. The final network model was corrected for depression severity. RESULTS: 115 (53% male, M age = 36.9, SD = 12.7) of 206 participants provided a hair sample. A higher number of traumatic events was directly associated with three symptoms of the PTSD cluster arousal and reactivity, i.e., sleep disturbance, hypervigilance and physiological reactivity, and with three other PTSD symptoms, namely flashbacks, avoidance of reminders, and self-destructive behavior. A higher number of post-displacement stressors was associated with four symptoms of the PTSD cluster cognition and mood, i.e., trauma-related amnesia, negative beliefs, blaming of self/others, and detachment, as well as with intrusive thoughts, sleep disturbance, hypervigilance, and exaggerated startle response. The number of traumatic events and post-displacement stressors were not associated with cortisol or DHEA. Cortisol was positively associated with two symptoms of the PTSD cluster cognition and mood, i.e., negative beliefs and negative trauma-related emotions, and negatively associated with avoidance of reminders. DHEA was positively associated with restricted affect and with three symptoms of the PTSD symptom cluster arousal and reactivity, i.e., irritability/anger, sleep disturbance, and self-destructive behavior, and negatively associated with avoidance of thoughts. CONCLUSIONS: This study demonstrated that exposure to traumatic events and post-displacement stressors is not related to cortisol and DHEA, but that cortisol and DHEA are differentially related to individual symptoms of PTSD. While lower levels of both cortisol and DHEA were associated with increased avoidance, higher levels of cortisol were mostly associated with symptoms of the PTSD cluster cognition and mood and higher levels of DHEA were mostly associated with symptoms of the PTSD cluster arousal and reactivity. These findings contribute to explaining the variability of findings in the literature on HPA-axis activity in PTSD. ETHICS: The study was approved by the Research Ethics Review Committee at VU Medical Center, the Netherlands (Protocol ID: NL61361.029.17, 7 September 2017) and prospectively registered online (https://www.trialregister.nl/trial/6665).

Exploring the Association of Age with Depressive Symptomatology in Childhood and Adolescence: A Network Study.

OBJECTIVE: This study aimed to explore the association of age with individual depression and anxiety symptoms and their connectivity (i.e., number/strength of connections with other symptoms) in girls and boys. METHOD: Our study comprised cross-sectional data from 31,960 Dutch girls and 32,162 Dutch boys aged 8 to 18 and considered 11 depression symptoms and 14 anxiety symptoms measured by the Revised Child Anxiety and Depression Scale. Network estimations were used to examine whether age was associated with individual symptoms and, in a separate step, with the connectivity of depression symptoms with other depression symptoms and with the connectivity of depression symptoms with anxiety symptoms. RESULTS: Age was, in general, positively associated with depression symptoms in girls, but not in boys, and with the connectivity of depression symptoms with other depression symptoms in both sexes. These findings were the most profound for energy-related symptoms in girls. Age was, in general, negatively associated with anxiety symptoms and not or negatively associated with the connectivity of depression symptoms with anxiety symptoms in girls and boys, respectively. Substantial differences across symptoms were found. CONCLUSIONS: This study shows that it is important to focus on individual symptoms, for age is mainly associated with energy-related depression symptoms and their connectivity in girls. Future etiologic studies may examine the role of energy-related depression symptoms in the development of depressive symptomatology in girls as these symptoms seem potential targets for the prevention of depression in the female population.

Mental disorders as networks of problems: a review of recent insights.

PURPOSE: The network perspective on psychopathology understands mental disorders as complex networks of interacting symptoms. Despite its recent debut, with conceptual foundations in 2008 and empirical foundations in 2010, the framework has received considerable attention and recognition in the last years. METHODS: This paper provides a review of all empirical network studies published between 2010 and 2016 and discusses them according to three main themes: comorbidity, prediction, and clinical intervention. RESULTS: Pertaining to comorbidity, the network approach provides a powerful new framework to explain why certain disorders may co-occur more often than others. For prediction, studies have consistently found that symptom networks of people with mental disorders show different characteristics than that of healthy individuals, and preliminary evidence suggests that networks of healthy people show early warning signals before shifting into disordered states. For intervention, centrality-a metric that measures how connected and clinically relevant a symptom is in a network-is the most commonly studied topic, and numerous studies have suggested that targeting the most central symptoms may offer novel therapeutic strategies. CONCLUSIONS: We sketch future directions for the network approach pertaining to both clinical and methodological research, and conclude that network analysis has yielded important insights and may provide an important inroad towards personalized medicine by investigating the network structures of individual patients.

The four-year course of major depressive disorder: the role of staging and risk factor determination.

BACKGROUND: Much is still unclear about the mechanisms underlying the course of major depressive disorder (MDD). This study aimed to identify risk factors that predict a poor prognosis of MDD while taking into consideration its chronicity at baseline. METHODS: In patients with MDD (n = 767), we examined whether baseline clinical factors, sociodemographics, childhood trauma, personality and life events predicted the 4-year course (i.e., sustained recovery, temporary recovery and chronic course) of MDD. Baseline chronicity of MDD was taken into account by testing whether associations were different for patients with nonchronic versus chronic MDD at baseline. RESULTS: In patients with nonchronic MDD at baseline, 27.8% developed a chronic disorder during follow-up, whereas 53.0% of patients with chronic MDD at baseline had a persistent chronic disorder during follow-up. Severity of MDD, childhood trauma and greater age were important general risk factors for a poor prognosis, independent of MDD chronicity at baseline. In contrast, low extraversion was only important for the course of nonchronic MDD at baseline, while higher education and negative life events (in patients with high neuroticism) were only relevant for the course of chronic MDD at baseline. CONCLUSIONS: One out of 4 patients with nonchronic MDD progressed to a chronic disorder, while half of the patients with chronic MDD remained chronic during follow-up. Since several risk factors for a poor prognosis differed for patients with nonchronic and chronic MDD at baseline, treatment targets should be adjusted for current chronicity of MDD.

Applying polygenic risk scores to postpartum depression.

The etiology of major depressive disorder (MDD) is likely to be heterogeneous, but postpartum depression (PPD) is hypothesized to represent a more homogenous subset of MDD. We use genome-wide SNP data to explore this hypothesis. We assembled a total cohort of 1,420 self-report cases of PPD and 9,473 controls with genome-wide genotypes from Australia, The Netherlands, Sweden and the UK. We estimated the total variance attributable to genotyped variants. We used association results from the Psychiatric Genomics Consortia (PGC) of bipolar disorder (BPD) and MDD to create polygenic scores in PPD and related MDD data sets to estimate the genetic overlap between the disorders. We estimated that the percentage of variance on the liability scale explained by common genetic variants to be 0.22 with a standard error of 0.12, p = 0.02. The proportion of variance (R (2)) from a logistic regression of PPD case/control status in all four cohorts on a SNP profile score weighted by PGC-BPD association results was small (0.1 %) but significant (p = 0.004) indicating a genetic overlap between BPD and PPD. The results were highly significant in the Australian and Dutch cohorts (R (2) > 1.1 %, p < 0.008), where the majority of cases met criteria for MDD. The genetic overlap between BPD and MDD was not significant in larger Australian and Dutch MDD case/control cohorts after excluding PPD cases (R (2) = 0.06 %, p = 0.08), despite the larger MDD group affording more power. Our results suggest an empirical genetic evidence for a more important shared genetic etiology between BPD and PPD than between BPD and MDD.

The EPDS-Lifetime: assessment of lifetime prevalence and risk factors for perinatal depression in a large cohort of depressed women.

Perinatal depression (PND) is a common complication of pregnancy and postpartum associated with significant morbidity. We had three goals: (1) to explore the performance of a new lifetime version of the Edinburgh Postnatal Depression Scale (EPDS-Lifetime) to assess lifetime prevalence of PND; (2) to assess prevalence of lifetime PND in women with prior histories of major depressive episode (MDE); and (3) to evaluate risk factors for PND. Subjects were from the Netherlands Study of Depression and Anxiety (NESDA). The EPDS was modified by adding lifetime PND screening questions, assessing worst episode, and symptom timing of onset. Of 682 women with lifetime MDD and a live birth, 276 (40.4 %) had a positive EPDS score of ≥12 consistent with PND. Women with PND more often sought professional help (p < 0.001) and received treatment (p = 0.001). Independent risk indicators for PND included younger age, higher education, high neuroticism, childhood trauma, and sexual abuse. We found that two in five parous women with a history of MDD had lifetime PND and that the PND episodes were more severe than MDD occurring outside of the perinatal period. The EPDS-Lifetime shows promise as a tool for assessing lifetime histories of PND in clinical and research settings.

The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective.

The clinical response to selective serotonin reuptake inhibitors (SSRIs) in depression takes weeks to be fully developed and is still not entirely understood. This study aimed to determine the direct and indirect effects of SSRIs relative to a placebo control condition on clinical symptoms of depression. We included data of 8262 adult patients with major depression participating in 28 industry-sponsored US Food and Drug Administration (FDA) registered trials on the efficacy of SSRIs. Clinical symptoms of depression were assessed by the 17 separate items of the Hamilton Depression Rating Scale (HDRS) after 1, 2, 3, 4 and 6 weeks of treatment. Network estimation techniques showed that SSRIs had quick and strong direct effects on the two affective symptoms, i.e., depressed mood and psychic anxiety; direct effects on other symptoms were weak or absent. Substantial indirect effects were found for all four cognitive symptoms, which showed larger reductions in the SSRI condition but mainly in patients reporting larger reductions in depressed mood. Smaller indirect effects were found for two arousal/somatic symptoms via the direct effect on psychic anxiety. Both direct and indirect effects on sleep problems and most arousal/somatic symptoms were weak or absent. In conclusion, our study revealed that SSRIs primarily caused reductions in affective symptoms, which were related to reductions in mainly cognitive symptoms and some specific arousal/somatic symptoms. The results can contribute to disclosing the mechanisms of action of SSRIs, and has the potential to facilitate early detection of responders and non-responders in clinical practice.

Alcohol use disorders and the course of depressive and anxiety disorders.

BACKGROUND: Inconsistent findings have been reported on the role of comorbid alcohol use disorders as risk factors for a persistent course of depressive and anxiety disorders. AIMS: To determine whether the course of depressive and/or anxiety disorders is conditional on the type (abuse or dependence) or severity of comorbid alcohol use disorders. METHOD: In a large sample of participants with current depression and/or anxiety (n = 1369) we examined whether the presence and severity of DSM-IV alcohol abuse or alcohol dependence predicted the 2-year course of depressive and/or anxiety disorders. RESULTS: The persistence of depressive and/or anxiety disorders at the 2-year follow-up was significantly higher in those with remitted or current alcohol dependence (persistence 62% and 67% respectively), but not in those with remitted or current alcohol abuse (persistence 51% and 46% respectively), compared with no lifetime alcohol use disorder (persistence 53%). Severe (meeting six or seven diagnostic criteria) but not moderate (meeting three to five criteria) current dependence was a significant predictor as 95% of those in the former group still had a depressive and/or anxiety disorder at follow-up. This association remained significant after adjustment for severity of depression and anxiety, psychosocial factors and treatment factors. CONCLUSIONS: Alcohol dependence, especially severe current dependence, is a risk factor for an unfavourable course of depressive and/or anxiety disorders, whereas alcohol abuse is not.

Comparing network structures on three aspects: A permutation test.

Network approaches to psychometric constructs, in which constructs are modeled in terms of interactions between their constituent factors, have rapidly gained popularity in psychology. Applications of such network approaches to various psychological constructs have recently moved from a descriptive stance, in which the goal is to estimate the network structure that pertains to a construct, to a more comparative stance, in which the goal is to compare network structures across populations. However, the statistical tools to do so are lacking. In this article, we present the network comparison test (NCT), which uses resampling-based permutation testing to compare network structures from two independent, cross-sectional data sets on invariance of (a) network structure, (b) edge (connection) strength, and (c) global strength. Performance of NCT is evaluated in simulations that show NCT to perform well in various circumstances for all three tests: The Type I error rate is close to the nominal significance level, and power proves sufficiently high if sample size and difference between networks are substantial. We illustrate NCT by comparing depression symptom networks of males and females. Possible extensions of NCT are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

NET-RMDs study: networks of fatigue and pain in rheumatic and musculoskeletal diseases - protocol for an international cross-sectional study.

INTRODUCTION: Fatigue and pain are the main symptoms of rheumatic and musculoskeletal diseases (RMDs). Healthcare professionals have a primary role in helping patients to manage both these symptoms, which are part of a complex network of co-occurring factors including sleep problems, psychological distress, social support, body weight, diet, inactive lifestyle and disease activity. The patterns of relationships (networks) between these factors and these symptoms, fatigue and pain, are largely unknown. The current proposal aims to reveal them using network estimation techniques. We will also consider differences in networks for subgroups of people with (1) different RMDs and (2) different clusters (profiles) of biopsychosocial factors. METHODS AND ANALYSIS: Adults with at least one RMD will be recruited to this online cross-sectional observational project. To provide a complete overview, a large sample size from different countries will be included. A brief online survey, using 0-10 numeric rating scales will measure, for the past month, levels of fatigue and pain as well as scores on seven biopsychosocial factors. These factors were derived from literature and identified by interviews with patients, health professionals and rheumatologists. Using this input, the steering committee of the project decided the factors to be measured giving priority to those that can be modified in self-management support in community health centres worldwide. Network estimation techniques are used to detect the complex patterns of relationships between these biopsychosocial factors, fatigue and pain; and how these differ for subgroups of people with different RMDs and profiles. ETHICS AND DISSEMINATION: Ethical approval of national Institutional Review Boards was obtained. The online survey includes an information letter and informed consent form. The findings will be disseminated via conferences and publications in peer-reviewed scientific journals, while public media channels will be used to inform people with RMDs and other interested parties.

Maintaining Outcomes of Internet-Delivered Cognitive-Behavioral Therapy for Depression: A Network Analysis of Follow-Up Effects.

Background: Depression is a highly prevalent mental disorder, but only a fraction of those affected receive evidence-based treatments. Recently, Internet-based interventions were introduced as an efficacious and cost-effective approach. However, even though depression is a heterogenous construct, effects of treatments have mostly been determined using aggregated symptom scores. This carries the risk of concealing important effects and working mechanisms of those treatments. Methods: In this study, we analyze outcome and long-term follow-up data from the EVIDENT study, a large (N = 1,013) randomized-controlled trial comparing an Internet intervention for depression (Deprexis) with care as usual. We use Network Intervention Analysis to examine the symptom-specific effects of the intervention. Using data from intermediary and long-term assessments that have been conducted over 36 months, we intend to reveal how the treatment effects unfold sequentially and are maintained. Results: Item-level analysis showed that scale-level effects can be explained by small item-level effects on most depressive symptoms at all points of assessment. Higher scores on these items at baseline predicted overall symptom reduction throughout the whole assessment period. Network intervention analysis offered insights into potential working mechanisms: while deprexis directly affected certain symptoms of depression (e.g., worthlessness and fatigue) and certain aspects of the quality of life (e.g., overall impairment through emotional problems), other domains were affected indirectly (e.g., depressed mood and concentration as well as activity level). The configuration of direct and indirect effects replicates previous findings from another study examining the same intervention. Conclusions: Internet interventions for depression are not only effective in the short term, but also exert long-term effects. Their effects are likely to affect only a small subset of problems. Patients reporting these problems are likely to benefit more from the intervention. Future studies on online interventions should examine symptom-specific effects as they potentially reveal the potential of treatment tailoring. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT02178631.

Symptom-specific effectiveness of an internet-based intervention in the treatment of mild to moderate depressive symptomatology: The potential of network estimation techniques.

The internet-based intervention Deprexis® has proven to be effective in improving overall depression severity. The current pragmatic randomized controlled trial included 1013 participants with mild to moderate symptomatology and aimed to identify the symptom-specific effects of the internet-based intervention Deprexis (intervention group) in comparison to care as usual (control group). All participants -in both conditions- were permitted to use any type of treatment. Of the nine considered symptoms (assessed with the Patient Health Questionnaire), seven showed larger improvements in the intervention condition relative to care as usual (effect sizes ranging from 0.15 to 0.31). No significant differences were found for the two other symptoms. In a next step, a network was estimated including treatment condition as well as changes in all nine symptoms. The resulting network suggests that four of the seven identified symptom-specific effects were direct, whereas the three other symptom-specific effects were indirect and could be explained by effects on other symptoms. Lastly, exploratory analyses showed that the intervention was more effective in improving overall depression severity for participants with higher scores on those four symptoms that were directly affected by the intervention; consequently, the network estimation techniques showed potential in precision psychiatry.

The symptom-specific efficacy of antidepressant medication vs. cognitive behavioral therapy in the treatment of depression: results from an individual patient data meta-analysis.

A recent individual patient data meta-analysis showed that antidepressant medication is slightly more efficacious than cognitive behavioral therapy (CBT) in reducing overall depression severity in patients with a DSM-defined depressive disorder. We used an update of that dataset, based on seventeen randomized clinical trials, to examine the comparative efficacy of antidepressant medication vs. CBT in more detail by focusing on individual depressive symptoms as assessed with the 17-item Hamilton Rating Scale for Depression. Five symptoms (i.e., "depressed mood" , "feelings of guilt" , "suicidal thoughts" , "psychic anxiety" and "general somatic symptoms") showed larger improvements in the medication compared to the CBT condition (effect sizes ranging from .13 to .16), whereas no differences were found for the twelve other symptoms. In addition, network estimation techniques revealed that all effects, except that on "depressed mood" , were direct and could not be explained by any of the other direct or indirect treatment effects. Exploratory analyses showed that information about the symptom-specific efficacy could help in identifying those patients who, based on their pre-treatment symptomatology, are likely to benefit more from antidepressant medication than from CBT (effect size of .30) versus those for whom both treatments are likely to be equally efficacious. Overall, our symptom-oriented approach results in a more thorough evaluation of the efficacy of antidepressant medication over CBT and shows potential in "precision psychiatry" .

Zooming In and Zooming Out: A Network Perspective on the Comorbidity of Depression and Anxiety.

Several statistical techniques are available to shed light on the structure of psychopathology, and each is valuable in its own way. It is, however, important to realize that the results of these techniques are substantially influenced by the structure of the studied instrument. Network analyses are no exception and do not perform miracles. However, they are unique in embracing the diversity of psychopathology, as the approach is both specific, by zooming in on individual symptoms, and transdiagnostic, by zooming out on the broad spectrum of psychopathology. Therefore, I genuinely believe that it will move our field forward.

Offspring of depressed and anxious patients: Help-seeking after first onset of a mood and/or anxiety disorder.

BACKGROUND: Offspring of patients with depressive and/or anxiety disorders are at high risk of developing a similar disorder themselves. Early recognition and treatment may have substantial effects on prognosis. The main aim of this study was to examine the time to initial help-seeking and its determinants in offspring after the first onset of a mood and/or anxiety disorder. METHODS: Data are presented of 215 offspring with a mood and/or anxiety disorder participating in a cohort study with 10 year follow-up. We determined age of disorder onset and age of initial help-seeking. Offspring characteristics (gender, IQ, age of onset, disorder type, suicidal ideation) and family characteristics (socioeconomic status, family functioning) were investigated as potential predictors of the time to initial help-seeking. RESULTS: The estimated overall proportion of offspring of depressed/anxious patients who eventually seek help after onset of a mood and/or anxiety disorder was 91.9%. The time to initial help-seeking was more than two years in 39.6% of the offspring. Being female, having a mood disorder or comorbid mood and anxiety disorder (relative to anxiety) and a disorder onset in adolescence or adulthood (relative to childhood) predicted a shorter time to initial help-seeking. LIMITATIONS: Baseline information relied on retrospective reports. Age of onsets and age of initial help-seeking may therefore be subject to recall bias. CONCLUSION: Although most offspring eventually seek help after onset of a mood/anxiety disorder, delays in help-seeking were common, especially in specific subgroups of patients. This information may help to develop targeted strategies to reduce help-seeking delays.

Doomed for Disorder? High Incidence of Mood and Anxiety Disorders in Offspring of Depressed and Anxious Patients: A Prospective Cohort Study.

OBJECTIVE: Early recognition of individuals at risk for depressive and anxiety disorders is key in influencing onset and course of these disorders. Parental history is a potent risk factor for the development of these disorders in offspring. However, knowledge about the magnitude of this risk is limited as large-scale longitudinal studies with a follow-up into adulthood are scarce. Those offspring at highest risk may possibly be identified by easy-to-determine parental psychiatric characteristics, family context, and offspring characteristics. METHODS: From 2000-2002, we recruited 523 offspring (age 13-25 years) of 366 patients who had received specialized treatment for depressive and/or anxiety disorder. Offspring DSM-IV mood (major depressive disorder, dysthymia, and bipolar disorder) and anxiety disorders (generalized anxiety disorder, social phobia, panic disorder, and agoraphobia) were assessed at baseline and at 4-, 6-, 8-, and 10-year follow-up. RESULTS: Kaplan-Meier analysis showed that the cumulative incidence of mood and/or anxiety disorder was 38.0% at age 20 years and 64.7% at age 35 years. Parental early disorder onset (hazard ratio [HR] = 1.33; 95% CI, 1.00-1.77), having 2 affected parents (HR = 1.58; 95% CI, 1.10-2.27), and offspring female gender (HR = 2.34; 95% CI, 1.74-3.15) were independent predictors of offspring mood and/or anxiety disorder. Balanced family functioning (HR = 0.73; 95% CI, 0.56-0.96) was found to be protective against offspring risk. CONCLUSIONS: Offspring of depressed and anxious patients are at very high risk of a mood and/or anxiety disorder themselves. Parental early onset, having 2 affected parents, female gender, and family functioning are important additional markers that can be used in clinical practice to identify those offspring at greatest risk.

The impact of somatic symptoms on the course of major depressive disorder.

OBJECTIVE: Somatic symptoms have been suggested to negatively affect the course of major depressive disorder (MDD). Mechanisms behind this association, however, remain elusive. This study examines the impact of somatic symptoms on MDD prognosis and aims to determine whether this effect can be explained by psychiatric characteristics, somatic diseases, lifestyle factors, and disability. METHODS: In 463 MDD patients (mean age=44.9 years, 69.8% female) from the Netherlands Study of Depression and Anxiety (NESDA), we examined whether the type and number of somatic symptom clusters predicted the two-year persistence of MDD. Diagnoses of MDD were established with the Composite International Diagnostic Interview (CIDI) and somatic symptom clusters were assessed with the Four-Dimensional Symptom Questionnaire (4DSQ) somatization scale. Psychiatric characteristics, somatic diseases, lifestyle factors, and disability were taken into account as factors potentially underlying the association. RESULTS: The cardiopulmonary, gastrointestinal, and general cluster significantly predicted the two-year persistence of MDD, but only when two or more of these clusters were present (OR=2.32, 95% CI=1.51-3.57, p=<0.001). Although the association was partly explained by MDD severity, the presence of multiple somatic symptom clusters remained a significant predictor after considering all potentially underlying factors (OR=1.69, 95%CI=1.07-2.68, p=0.03). CONCLUSIONS: Somatic symptoms are predictors of a worse prognosis of MDD independent of psychiatric characteristics, somatic diseases, lifestyle factors, and disability. These results stress the importance of considering somatic symptoms in the diagnostic and treatment trajectory of patients with MDD. Future research should focus on identifying treatment modalities targeting depressive as well as somatic symptoms.