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Background: Disease trajectories of patients with anxiety disorders are highly diverse and approximately 60% remain chronically ill. The ability to predict disease course in individual patients would enable personalized management of these patients. This study aimed to predict recovery from anxiety disorders within 2 years applying a machine learning approach. Methods: In total, 887 patients with anxiety disorders (panic disorder, generalized anxiety disorder, agoraphobia, or social phobia) were selected from a naturalistic cohort study. A wide array of baseline predictors (N = 569) from five domains (clinical, psychological, sociodemographic, biological, lifestyle) were used to predict recovery from anxiety disorders and recovery from all common mental disorders (CMDs: anxiety disorders, major depressive disorder, dysthymia, or alcohol dependency) at 2-year follow-up using random forest classifiers (RFCs). Results: At follow-up, 484 patients (54.6%) had recovered from anxiety disorders. RFCs achieved a cross-validated area-under-the-receiving-operator-characteristic-curve (AUC) of 0.67 when using the combination of all predictor domains (sensitivity: 62.0%, specificity 62.8%) for predicting recovery from anxiety disorders. Classification of recovery from CMDs yielded an AUC of 0.70 (sensitivity: 64.6%, specificity: 62.3%) when using all domains. In both cases, the clinical domain alone provided comparable performances. Feature analysis showed that prediction of recovery from anxiety disorders was primarily driven by anxiety features, whereas recovery from CMDs was primarily driven by depression features. Conclusions: The current study showed moderate performance in predicting recovery from anxiety disorders over a 2-year follow-up for individual patients and indicates that anxiety features are most indicative for anxiety improvement and depression features for improvement in general. [ABSTRACT FROM AUTHOR]

Objectives: To systematically describe the characteristics and techniques of prevention programmes for children of parents with mood/anxiety disorders. In addition, recruitment approaches and difficulties were identified and a meta‐analysis was conducted to examine the efficacy of these prevention programmes. Methods: Randomized controlled trials assessing the efficacy of a prevention programme for children (6–25 years) of parents with mood and/or anxiety disorders were included. A systematic literature search was conducted in PubMed, PsychINFO, and CENTRAL from the earliest record to March 2019. In addition, programme manuals of identified prevention programmes were requested for a content analysis. Results: Twenty‐two articles containing eight unique prevention programmes involving 1,325 subjects were identified. Programmes varied in the number and types of techniques, but all provided psychoeducation. Results suggested that recruitment via clinicians was more successful than recruitment via health maintenance organization databases. In a meta‐analysis, a significant risk difference was found in favour of prevention programmes on the risk of developing a depressive/anxiety disorder in offspring at short‐term (9–18 months follow‐up; RR = 0.37, 95% CI [0.21; 0.66]) and long‐term follow‐up (24 months or longer follow‐up; RR = 0.71, 95% CI [0.57; 0.87] and on symptom levels in offspring at post‐intervention (SMD = −0.19, 95% CI [−0.36; −0.02]) and at 12‐months follow‐up (SMD = −0.31, 95% CI [−0.57; −0.06]). Conclusions: The prevention programmes combined psychoeducational elements with skills training and/or cognitive‐behavioural therapy elements. The recruitment process and the content of these programmes are sometimes insufficiently described. Nevertheless, they appear to be effective, indicating a need to further examine how these programmes exactly work and for whom. Practitioner points: Preventive interventions for children of parents with mood/anxiety disorders appear to be effective in preventing these disorders in offspring.Available preventive intervention programmes focus mostly on psychoeducation, cognitive‐behavioural therapy, and family processes.More effort should be made into describing preventive interventions so that they can be easily implemented by practitioners.Studies should further examine why and for whom preventive interventions for children of parents with mood/anxiety disorders are effective. [ABSTRACT FROM AUTHOR]

Introduction: The Netherlands Study of Depression and Anxiety (NESDA, www.nesda.nl) is a longitudinal, multi-site, naturalistic, case-control cohort study set up to examine the etiology, course and consequences of depressive and anxiety disorders. This paper presents a cohort profile of NESDA.Methods and Results: The NESDA sample recruited initially 2329 persons with a remitted or current DSM-IV based depressive (major depressive disorder, dysthymia) and/or anxiety disorder (panic disorder, social phobia, agoraphobia, generalized anxiety disorder), 367 of their siblings and 652 healthy controls, yielding a total of 3348 participants. Half-day face-to-face assessments of participants started in 2004 and since then have been repeated six times over a period of 9 years. A 13-year follow-up assessment is ongoing, at what time we also recruit offspring of participants. Retention rates are generally high, ranging from 87.1% (after 2 years) to 69.4% (after 9 years). Psychiatric diagnostic interviews have been administered at all face-to-face assessments, as was monitoring of clinical characteristics, psychosocial functioning and somatic health. Assessed etiological factors include e.g. early and current environmental risk factors, psychological vulnerability and resilience factors as well as (neuro)biology through hypothesis-driven biomarker assessments, genome-wide and large-scale '-omics' assessments, and neuroimaging assessments.Limitations: The naturalistic design allows research into course and consequences of affective disorders but is limited in treatment response interpretation.Conclusions: NESDA provides a strong research infrastructure for research into depressive and/or anxiety disorders. Its data have been used for many scientific papers describing either NESDA-based analyses or joint collaborative consortia-projects, and are in principle available to researchers outside the NESDA consortium. [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: Childhood trauma (CT) has adverse consequences on mental health across the lifespan. The understanding of how CT increases vulnerability for psychiatric disorders is growing. However, lack of an integrative approach to psychological and biological mechanisms of CT hampers further advancement. This review integrates CT findings across explanatory levels from a longitudinal adult cohort - the Netherlands Study of Depression and Anxiety (NESDA).Methods: We reviewed all studies (k = 37) from the NESDA cohort (n = 2981) published from 2009 to 2020 containing CT findings related to psychopathology and potential psychological and biological mechanisms of CT.Results: CT was associated with a higher risk of anxiety and depressive disorders with the strongest associations in the comorbid group. CT predicted the onset of these disorders, recurrence, and poorer outcomes (more comorbidity and chronicity). CT was associated with maladaptive personality characteristics and cognitions (e.g., higher neuroticism and negative self-associations), mild stress systems dysregulations (heightened levels of cortisol and inflammation), advanced biological aging (increased epigenetic aging and telomere attrition), poorer lifestyle (higher smoking rate and body mass index), somatic health decline (e.g., increased metabolic syndrome dysregulations), and brain alterations (e.g., reduced mPFC volume and increased amygdala reactivity).Limitations: Literature review of one cohort using mixed analytical approaches.Conclusion: CT impacts the functioning of the brain, mind, and body, which together may contribute to a higher vulnerability for affective disorders. It is essential to employ an integrative approach combining different sources of data to understand the mechanisms of CT better. [ABSTRACT FROM AUTHOR]

Objective and Background: Insomnia is a neglected topic in psychiatric epidemiological studies. Despite the fact that insomnia is a common phenomenon and usually co-occurs with mental disorders, it remains to be addressed to what extent insomnia is associated with remitted and current common mental disorders and with impaired functioning in the population, after considering a wide variety of confounders.Patients and Methods: Data were used from three waves of the Netherlands Mental Health Survey and Incidence Study-2 (N = 4618), a nationally representative face-to-face survey of the general population. Insomnia was assessed at the third wave with the Women's Health Initiative Insomnia Rating Scale. Mental disorders were assessed at all waves with the Composite International Diagnostic Interview version 3.0. Confounders included sociodemographic characteristics, physical health, and psychotropic medication use. Role functioning was assessed with the Medical Outcomes Study Short Form Health Survey and work loss with the World Health Organization Disability Assessment Schedule.Results: Forty-two per cent of the population reported none to mild insomnia, 35% moderate insomnia, and 23% severe insomnia. Both current and remitted anxiety disorder and current mood disorder were significantly associated with severe insomnia with adjusted odds ratios ranging from 1.8 to 3.3. Current and remitted substance use disorders were associated with moderate insomnia (adjusted OR range: 1.3-1.8). Moderate and severe insomnia were significantly associated with impaired role functioning and work loss after adjustment for confounders.Conclusion: Insomnia is a prevalent problem across different categories of mental disorders, even in the remitted phase. As insomnia has a high impact on daily functioning, insomnia deserves wide clinical attention. [ABSTRACT FROM AUTHOR]

Objective: Several cross-sectional studies have related depressive and anxiety disorders to shorter leukocyte telomere length (LTL) as an indicator of cellular aging. However, these studies have left many unresolved questions about underlying causality and ordering of associations. The objective of the present large, longitudinal study was to examine the relationship between depressive and anxiety disorders and LTL over a 6-year time period.Method: Data are from the Netherlands Study of Depression and Anxiety, including 2,292 patients with remitted and current diagnoses of depressive or anxiety disorders and 644 healthy control subjects. LTL was assessed using quantitative PCR and measured at baseline and after 6 years; depressive and anxiety disorder diagnoses and characteristics (course, duration, and severity) were determined at baseline and after 2, 4, and 6 years.Results: Results showed that persons with remitted (B=-52.6) and current (B=-60.8) depressive or anxiety disorder had consistently shorter LTL compared with healthy control subjects across baseline and at the 6-year follow-up, remaining significant when controlling for lifestyle and somatic health variables. Changes in the course of depressive or anxiety disorder characteristics over 6 years, however, were not associated with different LTL attrition rates.Conclusions: This study confirmed robust associations of depressive and anxiety disorders with shorter telomeres, but interestingly, it did not demonstrate that depressive and anxiety disorders and LTL change together over time, suggesting the absence of a direct within-person relationship. Short LTL is suggested to be either a long-term consequence or an underlying vulnerability factor for depressive or anxiety disorders. [ABSTRACT FROM AUTHOR]

Background Although persons with subthreshold depression or anxiety are known to be at risk for full-syndromal disorders, little is known about their functioning over time. In this study, we investigate the functional impairment of persons with subthreshold depression or anxiety over time, compared to that of controls. Furthermore, we evaluate which illness, personal, and environmental risk factors influence its course. Methods Data come from the Netherlands Study of Depression and Anxiety (N = 1,266, aged 18-65). Linear mixed models were used to identify predictors of functional impairment at baseline, 1-, and 2-year follow-up. Risk factors were evaluated in their overall effect on functioning and on change in functioning over time, and whether they differed for respondents with and without subthreshold depression or anxiety. Results Functional impairment in subthreshold respondents improved over time, but remained much higher than in controls. Prior anxiety disorder, high neuroticism, low conscientiousness, more somatic conditions, and more childhood trauma all predicted greater functional impairment. Older age predicted lower functioning only in subthreshold respondents, while the effect of neuroticism was stronger in subthreshold respondents relative to controls. Conclusions Functional impairment in subthreshold respondents improved over time, but remained elevated compared to that of controls. Given continuously elevated levels of impairment, preventive interventions should be focused on persons with subthreshold symptoms; in particular those with prior anxiety disorder, high neuroticism, low conscientiousness, somatic conditions, or childhood trauma. [ABSTRACT FROM AUTHOR]

Objectives. Whereas animal models indicate that brain-derived neurotrophic factor (BDNF) plays a role in anxiety-related behaviour, little is known about BDNF in patients with an anxiety disorder. We tested the hypothesis that serum BDNF levels are low in patients with an anxiety disorder as compared to healthy controls. We further examined the associations of gender and some of the clinical characteristics of anxiety with BDNF levels. Methods. Serum BDNF levels were determined in 393 unmedicated, non-depressed patients with social anxiety disorder, panic disorder, agoraphobia, and generalised anxiety disorder (66.7% females) and in 382 healthy controls (62.0% females). Results. Overall, there were no differences in BDNF levels among patients and controls, regardless of type of anxiety disorder. Analyses stratified by gender revealed that female patients had lower levels of BDNF relative to female controls ( P < 0.05, d = 0.19), which was stronger in female patients with > 1 anxiety disorder ( P < 0.01, d = 0.32). BDNF levels were similar among male patients and controls and unrelated to the clinical characteristics of anxiety. Conclusion. Our results mirror preclinical findings indicating that gender plays a role in the association between BDNF and anxiety and suggest that BDNF might play a role in the pathophysiology of anxiety in women. [ABSTRACT FROM AUTHOR]

Abstract: Background: Neuroticism and extraversion are affected by depressive disorder state. Less is known about depressive state effects on conscientiousness, agreeableness and openness. Furthermore, state effects of anxiety disorders on personality have been far less studied than those of depressive disorder. Here, we aim to determine the extent of change in all five personality traits associated with the occurrence of or recovery from depressive and anxiety disorders. Methods: Using the Composite International Diagnostic Interview (CIDI) at baseline and two-year follow-up, respondents from the Netherlands Study of Depression and Anxiety (NESDA) were divided into four groups: unaffected at baseline and follow-up, occurrence, recovery, and affected at baseline and follow-up. Personality change (NEO-five factor inventory) was examined in the occurrence and recovery groups relative to the unaffected and affected groups, respectively. Analyses were repeated, differentiating between (specific) depressive and anxiety disorders. Results: We found small state effects of affective disorders on neuroticism, extraversion and conscientiousness. Corrected for each other, both depressive and anxiety disorders showed small state effects on neuroticism, but effects on extraversion and conscientiousness were mainly associated with depressive disorders. Conclusions: State effects were small. When assessing neuroticism, the presence of both depressive and anxiety disorders should be taken into account, as both may independently increase neuroticism scores. However, when assessing extraversion and conscientiousness, depressive disorders but not anxiety disorders are likely to be of influence. Agreeableness and openness are influenced by neither. [Copyright &y& Elsevier]

Objective. Mental health and cardiovascular disease have been associated, whereas the temporal course and underlying mechanisms are still incompletely understood. Our aims were to examine the presence of subclinical atherosclerosis in subjects with depressive or anxiety disorder, also taking into account disorder characteristics (subtype, severity, duration, age of onset, medication). Methods. The sample included 470 depression or anxiety cases and 179 controls, aged 20-66 years, participating in the Netherlands Study of Depression and Anxiety (NESDA). Diagnoses were assigned using the DSM-IV based Composite International Diagnostic Interview. Carotid intima-media thickness (CIMT) and plaque information were obtained using B-mode ultrasound imaging. Results. Overall, depressive and anxiety disorders were not associated with carotid atherosclerosis. However, age of depression onset was associated with CIMT (total: 0.01mm per 10 years, P == 0.01; bifurcation: 0.02mm per 10 years, P == 0.003) and plaque presence (OR == 1.35 per 10 years, 95%CI == 1.02-1.80, P == 0.04). When compared with controls, late-onset (≥ 40 years) depressed had an increased CIMT in the atherosclerosis progression-prone bifurcation segment (0.75 vs. 0.81 mm, P == 0.004). Conclusions. These findings suggest a distinct pathophysiology of late-onset as compared with early-onset depression, including a vascular component. [ABSTRACT FROM AUTHOR]

Abstract: Background: Whether course trajectories of depressive and anxiety disorders are different, remains an important question for clinical practice and informs future psychiatric nosology. This longitudinal study compares depressive and anxiety disorders in terms of diagnostic and symptom course trajectories, and examines clinical prognostic factors. Methods: Data are from 1209 depressive and/or anxiety patients residing in primary and specialized care settings, participating in the Netherlands Study of Depression and Anxiety. Diagnostic and Life Chart Interviews provided 2-year course information. Results: Course was more favorable for pure depression (n=267, median episode duration=6months, 24.5% chronic) than for pure anxiety (n=487, median duration=16months, 41.9% chronic). Worst course was observed in the comorbid depression–anxiety group (n=455, median duration >24months, 56.8% chronic). Independent predictors of poor diagnostic and symptom trajectory outcomes were severity and duration of index episode, comorbid depression–anxiety, earlier onset age and older age. With only these factors a reasonable discriminative ability (C-statistic 0.72–0.77) was reached in predicting 2-year prognosis. Limitation: Depression and anxiety cases concern prevalent – not incident – cases. This, however, reflects the actual patient population in primary and specialized care settings. Conclusions: Their differential course trajectory justifies separate consideration of pure depression, pure anxiety and comorbid anxiety–depression in clinical practice and psychiatric nosology. [Copyright &y& Elsevier]

Objective: There is evidence of more obesity among persons with depressive and depressive and anxiety disorders. However, the nature and the underlying mechanisms of the association are still unclear. This study examines the association between depressive and anxiety disorders and obesity, physical activity, and social activity, and examines whether social and physical activity are potential influencing factors in the association between depressive and anxiety disorders and obesity. Method: Cross-sectional data were used from the Netherlands Study of Depression and Anxiety. A total of 1,854 women and 955 men aged 18-65 years were recruited from the community, general practices, and specialized mental health care. Depressive and anxiety disorders were determined with the Composite International Diagnostic Interview. Body mass index (BMI<30 kg/m) was used to determine obesity. Physical and social activities were measured by self-report. Results: The odds of obesity adjusted for covariates was significantly higher among those with a current pure Major Depressive Disorder (MDD;odds ratio [OR] OR:1.43; 95% CI:1.07-1.92) compared to controls. Physical activity and social activities were lower among persons with depressive and anxiety disorders compared to controls. The association between MDD and obesity was influenced by social and physical activities. Conclusion: This study confirmed a link between depressive disorders and obesity that was influenced by lower social and physical activities among the depressed. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Background: Previous studies found that patients with depressive disorders frequently have lifetime manic symptoms or even an unrecognized bipolar disorder and that these patients have more severe illness. In this study we investigated whether the presence of significant manic symptoms among patients presenting with depressive and/or anxiety disorders is associated with more severe illness, more comorbidity, more suicidality and more atypical symptoms. Methods: In a large cohort (n =2012) of persons with lifetime depressive and/or anxiety disorders (as confirmed with the Composite International Diagnostic interview (CIDI)) we used the 15-item Mood Disorder Questionnaire (MDQ) to assess the presence of lifetime manic symptoms. Patients with clinically recognized bipolar disorders were excluded from the study. Results: Lifetime manic symptoms were present among 6.3% of the persons with depressive or anxiety disorders. Persons with lifetime manic symptoms more frequently had comorbid social phobia, generalized anxiety disorder and alcohol dependence, more frequently reported previous serious suicide attempts and their current depressive symptoms were more severe. Atypical depression symptoms were not more prevalent in persons with lifetime manic symptoms. Limitations: The presence of a lifetime manic or hypomanic episode was not assessed with the CIDI. Conclusions: Identifying lifetime manic symptoms with the MDQ in persons presenting with (unipolar) depressive or anxiety disorders, can not only help the recognition of actual bipolar disorder (as described in previous studies), but also the identification of a subgroup of patients with more severe symptomatology, more comorbid anxiety and alcohol dependence disorders, and more suicidality. [ABSTRACT FROM AUTHOR]

The Netherlands Study of Depression and Anxiety (NESDA) is a multi-site naturalistic cohort study to: (1) describe the long-term course and consequences of depressive and anxiety disorders, and (2) to integrate biological and psychosocial research paradigms within an epidemiological approach in order to examine (interaction between) predictors of the long-term course and consequences. Its design is an eight-year longitudinal cohort study among 2981 participants aged 18 through 65 years. The sample consists of 1701 persons with a current (six-month recency) diagnosis of depression and/or anxiety disorder, 907 persons with life-time diagnoses or at risk because of a family history or subthreshold depressive or anxiety symptoms, and 373 healthy controls. Recruitment took place in the general population, in general practices (through a three-stage screening procedure), and in mental health organizations in order to recruit persons reflecting various settings and developmental stages of psychopathology. During a four-hour baseline assessment including written questionnaires, interviews, a medical examination, a cognitive computer task and collection of blood and saliva samples, extensive information was gathered about key (mental) health outcomes and demographic, psychosocial, clinical, biological and genetic determinants. Detailed assessments will be repeated after one, two, four and eight years of follow-up. The findings of NESDA are expected to provide more detailed insight into (predictors of) the long-term course of depressive and anxiety disorders in adults. Besides its scientific relevance, this may contribute to more effective prevention and treatment of depressive and anxiety disorders. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Highlights • The highest level of hair cortisol was found in patients with current comorbid anxiety and depression. • Remitted depression and anxiety were not related to cortisol or cortisone levels assessed in hair. • Cortisone measured in hair and the ratio between cortisol and cortisone were not related to anxiety or depression diagnoses. Abstract Background Depressive and anxiety disorders have been linked to a dysregulated hypothalamus-pituitary-adrenal (HPA)-axis. Hair cortisol levels (HairF) reflect integrated long-term cortisol regulation and are therefore promising endocrine markers of chronic (psychological and physical) stress. Our aim was to assess hair cortisol levels in persons with a depressive and/or anxiety disorder and to compare their levels with that of persons in remission and healthy controls. Methods Data from 1166 participants of the Netherlands Study of Depression and Anxiety (NESDA) were used, including 266 participants with a recent (1-month) diagnosis of a depressive and/or anxiety disorder, 655 participants with a diagnosis in remission, and 245 healthy controls. HairF was measured in the proximal three cm of scalp hair, using LC–MS/MS. Results Compared to the healthy controls no differences on HairF or HairE levels were found for depressive and anxiety disorders alone. However the presence of a comorbid depressive and anxiety disorder was significantly associated with increased HairF levels (β = 0.07; p =.031), as was the severity of depressive symptoms (β = 0.06; p =.029), but no differences were found on HairE nor the HairF:HairE ratio. Conclusions Persons with current diagnosis of comorbid depression and anxiety show moderately higher levels of cortisol than patients with only depression or anxiety, or patients in remission and healthy controls, which may be indicative of a chronic state of hyperactivation of the HPA axis. [ABSTRACT FROM AUTHOR]

Antidepressant medication and running therapy are both effective treatments for patients with depressive and anxiety disorders. However, they may work through different pathophysiological mechanisms and could differ in their impact on physical health. This study examined effects of antidepressants versus running therapy on both mental and physical health. According to a partially randomized patient preference design, 141 patients with depression and/or anxiety disorder were randomized or offered preferred 16-week treatment: antidepressant medication (escitalopram or sertraline) or group-based running therapy ≥2 per week. Baseline (T0) and post-treatment assessment at week 16 (T16) included mental (diagnosis status and symptom severity) and physical health indicators (metabolic and immune indicators, heart rate (variability), weight, lung function, hand grip strength, fitness). Of the 141 participants (mean age 38.2 years; 58.2 % female), 45 participants received antidepressant medication and 96 underwent running therapy. Intention-to-treat analyses showed that remission rates at T16 were comparable (antidepressants: 44.8 %; running: 43.3 %; p =.881). However, the groups differed significantly on various changes in physical health: weight (d = 0.57; p =.001), waist circumference (d = 0.44; p =.011), systolic (d = 0.45; p =.011) and diastolic (d = 0.53; p =.002) blood pressure, heart rate (d = 0.36; p =.033) and heart rate variability (d = 0.48; p =.006). A minority of the participants was willing to be randomized; the running therapy was larger due to greater preference for this intervention. While the interventions had comparable effects on mental health, running therapy outperformed antidepressants on physical health, due to both larger improvements in the running therapy group as well as larger deterioration in the antidepressant group. Trialregister.nl Number of identification: NTR3460. • 141 patients with depression and/or anxiety disorder participated in this study. • Running therapy and antidepressant medication had similar effects on mental health (remission and response rates). • Running therapy outperformed antidepressant medication on physical health variables. • Running therapy is a valuable treatment strategy in mental health care. [ABSTRACT FROM AUTHOR]

It has been postulated that many peripheral and (neuro)biological systems are involved in psychiatric disorders such as depression. Some studies found associations of depression and antidepressant treatment with insulin-like growth factor 1 (IGF-I) – a pleiotropic hormone affecting neuronal growth, survival and plasticity – but evidence is mixed. We therefore studied whether depressive and anxiety disorders were associated with plasma IGF-I, and explored the role of antidepressant medication in this association in a large observational study. The sample consisted of 2714 participants enrolled in The Netherlands Study of Depression and Anxiety, classified as healthy controls (n = 602), antidepressant users (76 remitted and 571 with current depressive and/or anxiety disorder(s), n = 647), persons having remitted depressive and/or anxiety disorder(s) without antidepressant use (n = 502), and persons having current depressive and/or anxiety disorder(s) without antidepressant use (n = 963). Associations with IGF-I concentrations were studied and adjusted for socio-demographic, health, and lifestyle variables. Relative to healthy controls, antidepressant-free individuals with current disorders had significantly higher IGF-I levels (Cohen’s d = 0.08, p = 0.006), whereas antidepressant-free individuals with remitted disorders had a trend towards higher IGF-I levels (d = 0.06, p = 0.09). Associations were evident for depressive and for anxiety disorders. In contrast, antidepressant users had significantly lower IGF-I levels compared to healthy controls (d = −0.08, p = 0.028). Our findings suggests that antidepressant medication use modifies the association between depressive/anxiety disorders and plasma IGF-I. These results corroborate with findings of some previous small-scale case-control and intervention studies. The higher IGF-I levels related to depression and anxiety might point to a compensatory mechanism to counterbalance the impaired neurogenesis, although future studies are needed to support this hypothesis. [ABSTRACT FROM AUTHOR]

Background: Despite increasing evidence for the diagnostic instability between and within depressive and anxiety disorders, most studies report solely on the recurrence rates of the specific index disorders. Neglecting this evidence has an inherent risk of underestimating recurrence rates of depressive and anxiety disorders. This study investigates the impact of diagnostic instability of recurrence rates in depression and anxiety.Methods: Data were derived from the Netherlands Study of Depression and Anxiety (NESDA). The sample of 656 participants had a panic disorder with or without agoraphobia, agoraphobia, social phobia, generalized anxiety disorder, major depressive disorder or dysthymia, and a subsequent remission. Recurrence rates of index disorders (diagnostically stable recurrence) and newly arisen anxiety or depressive disorders (diagnostically unstable recurrence), were calculated over a 4-year follow-up period.Results: In anxiety disorders (n=281), the recurrence rate is more than doubled, from 23.8% with a stable recurrence, to 54.8%, when diagnostically unstable recurrences are included. In depressive disorders (N=173) the recurrence rate increases from 37.6% to 49.7%, and in comorbid anxiety and depressive disorders (N=202) the diagnostically unstable recurrences increase from 54.0% to 66.3%.Limitations: Attrition during follow up may have biased the results; remission was defined as absence of symptoms for 1 month; very short-term remission and recurrence patterns were not assessed.Conclusions: Diagnostically unstable recurrences have a significant impact on recurrence rates, with the greatest instability for anxiety disorders. When only diagnostically stable recurrences are assessed, recurrence rates are highly underrated and provide biased estimates of the true course of these disorders. [ABSTRACT FROM AUTHOR]

Background: Existing studies on disease course usually apply relatively short follow-up periods and narrow definitions of disease course resulting in too optimistic views on disease prognosis. This study explores the relevance of using a longer and broader (cross-disorder) perspective.Methods: Respondents with a 12-month disorder at baseline and available at 3-, 6- and 9-year follow-up were selected (major depressive disorder, MDD: n = 208; anxiety disorder: n = 220) from a general population study (N = 6646). DSM-IV disorders were assessed with the Composite International Diagnostic Interview. Disease course was described using a short and narrow perspective (i.e., 3-year follow-up, and considering presence of the index disorder only) and a long and broad perspective (9-year follow-up, and considering presence of any mood, anxiety or substance use disorder as outcome).Results: The recovery rates of both MDD and anxiety disorder reduced by half when the perspective switched from short and narrow (MDD: 74.0 %; anxiety disorder: 79.5 %) to long and broad (35.6 % and 40.0 % respectively). At 9-year follow-up, the rates of a persistent disorder (a disorder at each follow-up assessment) tripled when the perspective switched from narrow to broad (MDD: from 4.8 % to 13.9 %; anxiety disorder: from 4.5 % to 15.5 %).Limitations: The findings are not generalizable to the most severe depressed and anxious patients.Conclusions: Most people with MDD or anxiety disorder in the general population have a rather favourable prognosis when a narrow perspective is applied, but an unfavourable prognosis when a long-term and broad perspective is applied. Consequently, MDD and anxiety disorder should not merely be perceived as episodic disorders, and require longer-term disease monitoring and management. [ABSTRACT FROM AUTHOR]

• After adjustment for demographic, lifestyle, and health-related covariates, childhood trauma was associated with higher levels of 9 lipopolysaccharide stimulated cytokines, and 2 cumulative inflammation indices. • Associations were strongest for individuals with severe childhood trauma, reporting multiple types or higher frequencies of trauma. • Our results highlight a dysregulated innate immune system capacity in adults with childhood trauma, which could contribute to an increased vulnerability for psychopathology and somatic disorders across the lifespan. Childhood trauma (CT) is robustly associated with psychiatric disorders including major depressive and anxiety disorders across the life span. The innate immune system may play a role in the relation between CT and stress-related psychopathology. However, whether CT influences the innate production capacity of cytokine levels following ex vivo stimulation by lipopolysaccharide (LPS), is currently unknown. Using data from the Netherlands Study of Depression and Anxiety (NESDA, n=1237), we examined whether CT (emotional neglect, emotional, physical, and sexual abuse before the age of 16), assessed by the Childhood Trauma Interview, was associated with levels in supernatants of interferon (IFN)γ, interleukin-2 (IL-2), IL-4, IL-6, IL-8, IL-10, IL-18, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1β, matrix metalloproteinase-2 (MMP-2), TNFα and TNFβ after ex vivo stimulation with LPS. Cytokines were analysed individually and cumulatively (overall inflammation index and number of cytokines in high-risk quartile (HRQ)) using linear regression analyses. After adjustment for demographic, lifestyle, and health-related covariates, total CT severity was associated with the overall inflammation index (β = 0.085, P FDR = 0.011), the number of cytokines in HRQ (β = 0.063, P FDR = 0.036), and individual markers of IL-2 (β = 0.067, P FDR = 0.036), IL-6 (β = 0.091 P FDR = 0.011), IL-8 (β = 0.085 P FDR = 0.011), IL-10 (β = 0.094 P FDR = 0.011), MCP-1 (β = 0.081 P FDR = 0.011), MIP-1α (β = 0.061 P FDR = 0.047), MIP1-β (β = 0.077 P FDR = 0.016), MMP-2 (β = 0.070 P FDR = 0.027), and TNFβ (β = 0.078 P FDR = 0.016). Associations were strongest for individuals with severe CT, reporting multiple types or higher frequencies of trauma. Half of the findings persisted after adjustment for psychiatric status. The findings were consistent across different CT types. Childhood Trauma is associated with increased LPS-stimulated cytokine levels, with evidence for a dose-response relationship. Our results highlight a dysregulated innate immune system capacity in adults with CT, which could contribute to an increased vulnerability for psychopathology and somatic disorders across the lifespan. [ABSTRACT FROM AUTHOR]

Background: Structural brain alterations are observed in major depressive disorder (MDD). However, MDD is a highly heterogeneous disorder and specific clinical or biological characteristics of depression might relate to specific structural brain alterations. Clinical symptom subtypes of depression, as well as immuno-metabolic dysregulation associated with subtypes of depression, have been associated with brain alterations. Therefore, we examined if specific clinical and biological characteristics of depression show different brain alterations compared to overall depression.Method: Individuals with and without depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA) (328 participants from three timepoints leading to 541 observations) and the Mood Treatment with Antidepressants or Running (MOTAR) study (123 baseline participants) were included. Symptom profiles (atypical energy-related profile, melancholic profile and depression severity) and biological indices (inflammatory, metabolic syndrome, and immuno-metabolic indices) were created. The associations of the clinical and biological profiles with depression-related structural brain measures (anterior cingulate cortex [ACC], orbitofrontal cortex, insula, and nucleus accumbens) were examined dimensionally in both studies and meta-analysed.Results: Depression severity was negatively associated with rostral ACC thickness (B = -0.55, pFDR = 0.03), and melancholic symptoms were negatively associated with caudal ACC thickness (B = -0.42, pFDR = 0.03). The atypical energy-related symptom profile and immuno-metabolic indices did not show a consistent association with structural brain measures across studies.Conclusion: Overall depression- and melancholic symptom severity showed a dose-response relationship with reduced ACC thickness. No associations between immuno-metabolic dysregulation and structural brain alterations were found, suggesting that although both are associated with depression, distinct mechanisms may be involved. [ABSTRACT FROM AUTHOR]

Background: Childhood trauma (CT) is a risk factor for depressive and anxiety disorders. However, whether CT is more strongly linked to specific clinical features of these disorders remains inconclusive. The current study comprehensively examined cross-sectional and longitudinal associations between CT and depressive/anxiety symptomatology in a large adult sample with current and remitted depressive and/or anxiety disorders.Methods: Baseline (n = 1803), 2-year (n = 1735), 4-year (n = 1585), and 6-year follow-up (n = 1475) data from the Netherlands Study of Depression and Anxiety were used. CT (emotional neglect, emotional/physical/sexual abuse) was assessed at baseline, while depressive/anxiety symptomatology with relevant dimensions (e.g., mood/cognitive, melancholic, general distress, and somatic depression) was assessed at each wave using self-reported questionnaires. Linear regressions and linear mixed models determined cross-sectional and longitudinal associations.Results: Individuals with CT, especially, severe CT, compared to those without CT, had significantly higher scores in overall depressive symptomatology (Cohen's d = 0.674), mood/cognitive depression (d = 0.691), melancholic depression (d = 0.587), general distress (d = 0.561), and somatic depression severity (d = 0.549). Differences were lower, but still highly significant for anxiety (d = 0.418), worry (d = 0.362), and fear/phobic symptomatology (d = 0.359). Effects were consistent across CT types and maintained over six years.Limitations: Retrospectively-reported CT.Conclusions: CT is a risk factor for depressive and anxiety symptomatology across all dimensions and enduring over multiple years. Screening for CT is essential to identify individuals at risk for more severe and chronic manifestations of affective disorders. [ABSTRACT FROM AUTHOR]

Background The receiver operating characteristics (ROC) of anhedonic depression and anxious arousal to detect the distress- (major depression, dysthymia, generalized anxiety disorder) and fear-disorder clusters (i.e. panic disorder, agoraphobia, social phobia) have not been reported in a large sample. Methods A sample of 2981 persons underwent structured psychiatric interview; n =652 were without lifetime depression and anxiety disorder history. Participants also completed a neuroticism scale (Revised NEO Five Factor Inventory [NEO-FFI]), and the 30-item short adaptation of the Mood and Anxiety Symptoms Questionnaire (MASQ-D30) measuring anhedonic depression, anxious arousal and general distress. Maximal sensitivity and specificity was determined by the Youden Index and the area-under-the-curve (AUC) in ROC analysis. Results A total of 2624 completed all measures (age M =42.4 years±13.1, 1760 females [67.1%]), including 1060 (40.4%) persons who met criteria for a distress-disorder, and 973 (37.1%) who met criteria for a fear-disorder. The general distress dimension provided the highest ROC values in the detection of the distress-disorders (AUC=.814, sensitivity=71.95%, specificity=76.34%, positive predictive value=67.33, negative predictive value=80.07). None of the measures provided suitable operating characteristics in the detection of the fear-disorders with specificity values <75%. Limitations Over sampling of depression and anxiety disorders may lead to inflated positive- and negative predictive values. Conclusions The MASQ-D30 general distress dimension showed clinically suitable operating characteristics in the detection of distress-disorders. Neither neuroticism nor the MASQ-D30 dimensions provided suitable operating characteristics in the detection of the fear-disorders. [ABSTRACT FROM AUTHOR]

Background Smoking, especially nicotine dependence is associated with more severe symptoms of depression and anxiety disorders. However, the mechanisms underlying this association are unclear. We investigated the effect of brain-derived neurotrophic factor (BDNF) Val 66 Met polymorphism on the severity of depressive and anxiety symptoms in never-smokers, former smokers, non-dependent, and nicotine-dependent smokers with a current diagnosis of depression and/or anxiety. Methods Patients with depressive or anxiety disorders and with available BDNF Val 66 Met polymorphism data ( N = 1271) were selected from Netherlands Study of Depression and Anxiety (NESDA). Dependent variables were severity of symptoms. Independent variables were smoking status and BDNF genotype. Age, sex, education, recent negative life events, alcohol use, body mass index, and physical activity were treated as covariates. Results After controlling for covariates, nicotine-dependent smokers had more severe depressive symptoms than non-dependent smokers, former and never-smokers. The latter three groups did not differ in severity of depression. In Val 66 Val carriers, nicotine-dependent smokers had more severe symptoms of depression and anxiety than the other three groups, which were comparable in symptom severity. In Met 66 carriers, there were no group differences on severity of depression and anxiety. Nicotine dependence was the strongest predictor of severity of symptoms only in Val 66 Val carriers. Conclusions In patients with a current diagnosis of depression or anxiety, the relationship between nicotine dependence and symptom severity may be moderated by BDNF Val 66 Met. These results suggest that inherent genetic differences may be crucial for the worse behavioral outcome of nicotine, and that Val 66 Val carriers may benefit most in mental health from smoking cessation. [ABSTRACT FROM AUTHOR]

Abstract: All guidelines on major depressive disorder (MDD) and anxiety disorders recommend pharmacotherapy and/or psychological treatment for moderate to severe disease. The aim of this cross-sectional study was to investigate treatment inadequacy, both pharmacological and psychological, in a large naturalistic cohort of subjects with MDD and anxiety disorders from the Netherlands Study of Depression and Anxiety. All subjects with a current 6-month diagnosis were included (n=1662). Demographic data, clinical features and actual medication use were assessed in face-to-face interviews. In moderate to severe MDD, 43% of the subjects were not treated sufficiently with antidepressants or psychological treatment. In primary health care patients, this undertreatment was 70%. In moderate to severe anxiety disorders, 44% of the subjects were not treated sufficiently with antidepressants, benzodiazepines or psychological treatment. Among antidepressant users with moderate to severe MDD, 21% of the pharmacotherapy was inadequate with respect to drug choice, dose and every day use. Undertreatment and pharmacotherapeutic inadequacy are common in moderate to severe MDD and anxiety disorders. Both are more pronounced in primary care than in specialized care. This may be partly due to differences in disease recognition and help seeking behaviour. [Copyright &y& Elsevier]

• Better understanding of biological correlates of suicidal behavior in depressive and/or anxiety patients is needed. • Higher levels of individual immune-inflammatory markers were associated with suicide attempt outcomes. • Cumulative inflammatory dysregulations increase the likelihood of a suicide attempt. • Separate and cumulative stress system dysregulations were not associated with suicide ideation. • Immune system dysregulation may be involved in the pathophysiology of suicidal behavior. People with depressive and/or anxiety disorders are at increased risk of suicidal ideation and suicide attempts, but biological correlates signaling such risk remain unclear. Independent and cumulative dysregulations in physiological stress systems, in particular the hypothalamic–pituitaryadrenal axis (HPA-axis), immune-inflammatory system, and autonomous nervous system (ANS), may contribute to this risk. However, findings have either been heterogeneous or absent thus far. Associations between individual markers and cumulative indices of the HPA-axis (cortisol awakening response and evening cortisol), immune-inflammatory system (C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor-α), and the ANS (heart rate, respiratory sinus arrhythmia, and pre-ejection period) and the outcomes no suicide ideation with suicide attempt (SI-SA+), suicide ideation without suicide attempt (SI+SA-) and suicide ideation with suicide attempt (SI+SA+) were investigated in 1749 persons with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA). High levels of CRP and IL-6 were associated with SI-SA+ and SI+SA+ respectively when compared to non-suicidal patients after adjusting for confounders and multiple testing. Also, cumulative immune-inflammatory dysregulations were positively associated with SI+SA+, suggesting a dose–response effect. No significant associations were found between HPA-axis or ANS indicators and suicide-outcomes and between immune-inflammatory system markers or cumulative stress system dysregulations and SI+SA-. Although stress system markers could not differentiate between SI+SA- and non-suicidal patients, findings indicate that dysregulations of individual and cumulative immune-inflammatory markers are associated with suicide attempts in depressive and/or anxiety patients. Thus, immune-inflammatory system dysregulation may be involved in the pathophysiology of suicidal behavior, supporting further examination of the effects of anti-inflammatory interventions on suicidality. [ABSTRACT FROM AUTHOR]

Abstract: Dysfunctional self-beliefs are assumed to play an important role in maintaining depression and anxiety. Current dual-process models emphasize the relevance of differentiating between implicit and explicit self-beliefs. Therefore, this study tested the prognostic value of automatic and explicit self-associations for the naturalistic course of depressive and anxiety disorders over two years follow-up. Both self-depressed and self-anxious associations were measured in unipolar depressed patients (n = 313), anxious patients (n = 566), and patients with comorbid depressive and anxiety disorders (n = 577) as part of the Netherlands Study of Depression and Anxiety. Outcomes showed that in single predictor models specifically automatic self-anxious associations were related to a reduced chance of remission from anxiety, whereas automatic self-depressed associations were related to a reduced chance of remission from depression. Explicit self-anxious associations and fearful avoidance behaviour showed independent predictive validity for remission from anxiety, whereas explicit self-depressed associations and having both major depressive disorder and dysthymia showed independent predictive validity for remission from depression. These findings are not only consistent with the view that both implicit and explicit dysfunctional self-associations are related to the course of anxiety and unipolar depressive disorders, but also suggest that both types of self-beliefs are proper targets for therapeutic interventions. [Copyright &y& Elsevier]

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

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

Background: Investigating siblings of probands with affective disorders enables the identification of psychopathology-related risk features. Leveraging data from an older adult sample, as compared to most previous sibling studies, enabled us to study more definitive clinical profiling across the lifespan. We examined prevalence of depressive/anxiety disorders in siblings, proband-sibling resemblance in psychopathology-related features, and whether unaffected siblings showed higher levels of these features than healthy controls.Methods: The sample (N=929; Mage=50.6) consisted of 256 probands with lifetime depressive and/or anxiety disorders, their 380 siblings, and 293 healthy controls without affected relatives. Fifteen psychopathology-related features were investigated across four domains: mental health symptoms, social vulnerabilities, cognitive vulnerabilities, and personality.Results: Lifetime disorders were present in 50.3% of siblings. Prevalence was 2-3 times higher than Dutch population frequencies. We found small to medium probandsibling resemblance across psychopathology-related features (ρ=0.10-0.32). Unaffected siblings reported poorer interpersonal functioning and more negative life events, childhood trauma, and rumination than healthy controls.Limitations: Due to the cross-sectional study design, the directionality of effects cannot be determined. No inferences can be made about potential differences in familial resemblance in psychopathology-related features between high- and low-risk families.Conclusions: Siblings of probands with affective disorders are at higher risk for depressive/anxiety disorders. Even when unaffected, still show higher psychosocial vulnerability than healthy controls. Nevertheless, the only modest proband-sibling resemblance across psychopathology-related features suggests that individual mechanisms differentiate clinical trajectories across the lifespan. Identification of these mechanisms is crucial to improve resilience in subjects with familial risk. [ABSTRACT FROM AUTHOR]

Background: Given the strong relationship between depression and anxiety, there is an urge to investigate their shared and specific long-term course determinants. The current study aimed to identify and compare the main determinants of the 9-year trajectories of combined and pure depression and anxiety symptom severity.Methods: Respondents with a 6-month depression and/or anxiety diagnosis (n=1,701) provided baseline data on 152 sociodemographic, clinical and biological variables. Depression and anxiety symptom severity assessed at baseline, 2-, 4-, 6- and 9-year follow-up, were used to identify data-driven course-trajectory subgroups for general psychological distress, pure depression, and pure anxiety severity scores. For each outcome (class-probability), a Superlearner (SL) algorithm identified an optimally weighted (minimum mean squared error) combination of machine-learning prediction algorithms. For each outcome, the top determinants in the SL were identified by determining variable-importance and correlations between each SL-predicted and observed outcome (ρpred) were calculated.Results: Low to high prediction correlations (ρpred: 0.41-0.91, median=0.73) were found. In the SL, important determinants of psychological distress were age, young age of onset, respiratory rate, participation disability, somatic disease, low income, minor depressive disorder and mastery score. For course of pure depression and anxiety symptom severity, similar determinants were found. Specific determinants of pure depression included several types of healthcare-use, and of pure-anxiety course included somatic arousal and psychological distress.Limitations: Limited sample size for machine learning.Conclusions: The determinants of depression- and anxiety-severity course are mostly shared. Domain-specific exceptions are healthcare use for depression and somatic arousal and distress for anxiety-severity course. [ABSTRACT FROM AUTHOR]

Background: Comorbidity of depressive and anxiety disorders is common and remains incompletely comprehended. This paper summarizes findings from the Netherlands Study of Depression and Anxiety (NESDA) regarding prevalence, temporal sequence, course and longitudinal patterns; sociodemographic, vulnerability and neurobiological indicators; and functional, somatic and mental health indicators of comorbidity.Methods: Narrative synthesis of earlier NESDA based papers on comorbidity (n=76).Results: Comorbidity was the rule in over three-quarter of subjects with depressive and/or anxiety disorders, most often preceded by an anxiety disorder. Higher severity and chronicity characterized a poorer comorbidity course. Over time, transitions between depressive and anxiety disorders were common. Consistent comorbidity risk indicators in subjects with depressive and anxiety disorders were childhood trauma, neuroticism and early age of onset. Psychological vulnerabilities, such as trait avoidance tendencies, were more pronounced in comorbid than in single disorders. In general, there were few differences in biological markers and neuroimaging findings between persons with comorbid versus single disorders. Most functional, somatic, and other mental health indicators, ranging from disability to cardiovascular and psychiatric multimorbidity, were highest in comorbid disorders.Limitations: The observational design of NESDA limits causal inference. Attrition was higher in comorbid relative to single disorders.Conclusions: As compared to single disorders, persons with comorbid depressive and anxiety disorders were characterized by more psychosocial risk determinants, more somatic and other psychiatric morbidities, more functional impairments, and poorer outcome. These results justify specific attention for comorbidity of depressive and anxiety disorders, particularly in treatment settings. [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: Depressive and anxiety disorders are often associated with suicide ideation (SI) and attempt (SA). However, analyses of prevalence, course, and more specific risk mechanisms are needed to improve knowledge and detection of high risk individuals with depressive and anxiety disorders. Previous studies often lacked statistical power, assessment of detailed determinants and follow-up measurements.Methods: The Netherlands Study of Depression and Anxiety (NESDA), a large cohort study, overcomes some earlier limitations. Scale for Suicide Ideation and Compositive Interview Diagnostic Instrument data were analyzed to report on prevalence of SI and SA. Additionally, important sociodemographic, clinical, psychological, environmental, and neurobiological determinants and course of SI and SA identified in depressive and/or anxiety disorder respondents in 16 NESDA articles were summarized.Results: Within respondents with 12-month diagnosis (n=1,783), SI and 12-month SA prevalence ranged from 17.1-20.1% and 0.8-3.0% respectively across 5 waves during 9-year follow-up and SI was highly recurrent. Both SI and SA were especially associated with comorbid depression and anxiety, higher clinical severity, sleep dysfunctions, higher aggression and hopelessness, and childhood trauma. In the (neuro)biological domain, SI was linked with immune dysregulation and SA with abnormal brain activity during emotion processing and genetic risk.Limitations: Most articles were cross-sectional in nature, preventing causal inferences and no conclusions could be drawn about the overall magnitude of results.Conclusion: SI and SA are multifactorial phenomena and especially prevalent amongst comorbid depressive and anxiety respondents. Considering many overlapping SI and SA determinants, more neurobiological determinants and use of innovative methodological techniques are desirable. [ABSTRACT FROM AUTHOR]

Background: Patients with various psychiatric disorders may suffer from feelings of anger, sometimes leading to maladaptive (e.g., aggressive) behaviors. We examined to what extent depressive and anxiety disorders, relevant clinical correlates, and sociodemographics determined the level of trait anger and the prevalence of recent anger attacks.Methods: In the Netherlands Study of Depression and Anxiety (NESDA), the Spielberger Trait Anger Subscale and the Anger Attacks Questionnaire were analyzed in patients with depressive (n = 204), anxiety (n = 288), comorbid (n = 222), and remitted disorders (n = 1,107), as well as in healthy controls (n = 470) based on DSM-IV criteria.Results: On average, participants were 46.2 years old (SD = 13.1) and 66.3% were female. Trait anger and anger attacks were most prevalent in the comorbid group (M = 18.5, SD = 5.9, and prevalence 22.1%), followed by anxiety disorder, depressive disorder, remitted disorder, and controls (M = 12.7; SD = 2.9, and prevalence 1.3%). Major depressive disorder, social phobia, panic disorder, and generalized anxiety disorder were most strongly associated to trait anger and anger attacks.Limitations: Due to a cross-sectional design, it was not possible to provide evidence for temporal or causal relationships between anger and depressive and anxiety disorders.Conclusions: Trait anger and anger attacks are linked to depressive and anxiety disorders, although the strength of the relationship differed among both anger constructs. [ABSTRACT FROM AUTHOR]

Affective (i.e. depressive and anxiety) disorders often co-occur with immunometabolic diseases and related biological pathways. Although many large population-based and meta-analytic studies have confirmed this link in community and clinical samples, studies in at-risk samples of siblings of persons with affective disorders are lacking. Furthermore, this somatic-mental co-occurrence may be partially explained by familial clustering of the conditions. First, we examined whether the association between a wide range of immunometabolic diseases and related biomarker based risk-profiles with psychological symptoms replicates in at-risk siblings of probands with affective disorders. Second, leveraging on a sibling-pair design, we disentangled and quantified the effect of probands' immunometabolic health on siblings' psychological symptoms and on the association between immunometabolic health and these symptoms in siblings. The sample included 636 participants (M age = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and at least one of their sibling(s) (N = 380 proband-sibling pairs). Immunometabolic health included cardiometabolic and inflammatory diseases, body mass index (BMI), and composite metabolic (based on the five metabolic syndrome components) and inflammatory (based on interleukin-6 and C-reactive protein) biomarker indices. Overall affective symptoms and specific atypical, energy-related depressive symptoms were derived from self-report questionnaires. Mixed-effects analyses were used to model familial clustering. In siblings, inflammatory disease (γ = 0.25, p = 0.013), higher BMI (γ = 0.10, p = 0.033) and metabolic index (γ = 0.28, p < 0.001) were associated with higher affective symptoms, with stronger associations for atypical, energy-related depressive symptoms (additionally associated with cardiometabolic disease; γ = 0.56, p = 0.048). Immunometabolic health in probands was not independently associated with psychological symptoms in siblings nor did it moderate the association between immunometabolic health and psychological symptoms estimated in siblings. Our findings demonstrate that the link between later life immunometabolic health and psychological symptoms is consistently present also in adult siblings at high risk for affective disorders. Familial clustering did not appear to have a substantial impact on this association. Instead, individual lifestyle, rather than familial factors, may have a relatively higher impact in the clustering of later life immunometabolic conditions with psychological symptoms in at-risk adult individuals. Furthermore, results highlighted the importance of focusing on specific depression profiles when investigating the overlap with immunometabolic health. • Unclear whether the link of somatic with mental health replicates in at-risk siblings. • A sibling-pair design allows to adequately study the effect of familial clustering. • In at-risk siblings, poor somatic health is associated with more affective symptoms. • Associations are stronger for specific atypical/energy-related depressive symptoms. • No independent or moderating effects of co-sibling poor somatic health. [ABSTRACT FROM AUTHOR]

Abstract Objective This study examines the association of depressive and anxiety disorders and their clinical characteristics (disorder type, severity, chronicity and clinical subtypes) with diet quality. Method Data from 1634 adults (controls = 336, current disorder = 414, remitted = 886) were sourced from the 9-year follow-up of the Netherlands Study of Depression and Anxiety. Depressive and anxiety disorders were established with Composite International Diagnostic Interviews. Severity was measured with the Inventory of Depressive Symptomatology (IDS), Fear Questionnaire and the Beck Anxiety Inventory. Chronicity was measured with life-chart interviews expressed as percentage time with a disorder(s). Diet quality was evaluated using the Mediterranean Diet Score (MDS) and the Alternative Healthy Eating Index (AHEI). Results Diet quality was significantly worse among subjects with a current disorder than among healthy controls. Subdividing subjects showed that those with concurrent depressive and anxiety disorders had the lowest diet quality score (MDS: β = −0.41 per SD, 95% Confidence interval (95%CI) = -0.60, −0.21; AHEI β = −0.22 per SD 95% CI = −0.42,-0.03). More chronic depression or anxiety disorders and increased severity in all participants showed a dose-response association with poorer diet quality. There was no distinct pattern between IDS items related to depression subtypes and diet quality. Conclusion Diet quality is poorer in persons with depressive and anxiety disorders; in particular in those with comorbidity. The more severe and chronic the symptoms, the poorer the diet quality. Prospective studies are needed to confirm the direction of the relationship of depressive and anxiety disorders with diet quality and to examine whether improving diet quality could improve mental health. [ABSTRACT FROM AUTHOR]

High scores on markers of psychological vulnerability have been associated with a worse course of affective disorders. However, little is known about the specificity of those associations in predicting the course of different depressive and anxiety disorders. We examined the impact of psychological vulnerability on the short- and long-term course of depressive and anxiety disorders. Participants from the Netherlands Study of Depression and Anxiety with a current diagnosis of depression or anxiety (n = 1256) were reassessed after 2 and 6 years. Diagnostic status and chronic duration (>85% of the time) of symptoms were the outcomes. Predictors were neuroticism, extraversion, locus of control, cognitive reactivity (rumination and hopelessness reactivity), worry and anxiety sensitivity. High neuroticism, low extraversion and external locus of control predicted chronicity of various affective disorders. Rumination, however, predicted chronicity of depressive but not anxiety disorders. Worry specifically predicted chronicity of GAD and anxiety sensitivity predicted chronicity of panic disorder and social anxiety disorder. These patterns were present both at short-term and at long-term, without losing predictive accuracy. Psychological vulnerabilities that are theoretically specific to certain disorders indeed selectively predict the course of these disorders. General markers of vulnerability predicted the course of multiple affective disorders. This pattern of results supports the notion of specific as well as transdiagnostic predictors of the course of affective disorders and is consistent with hierarchical models of psychopathology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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]

Anxiety is linked to increased avoidance and inhibition, whereas depression is linked to decreased approach and diminished behavioral activation. Although these notions are widely recognized, systematic investigation of approach-avoidance tendencies is lacking across these diagnostic groups. Participants (mean age = 45.6; 65.8% female) were subdivided in healthy controls (405), remitted patients (877) and currently anxious (217), depressed (154) or comorbid (154) patients. Automatic approach-avoidance tendencies in reaction to facial expression were assessed using the Approach-Avoidance-Task (AAT). Self-reported trait approach and avoidance tendencies were assessed using the BIS/BAS scale. Severity of psychopathology was assessed to examine dose-response relationships. We did not find any consistent associations of automatic approach-avoidance tendencies with psychiatric variables. In contrast, medium to large differences in BIS scores showed increased trait avoidance tendencies in all patient groups relative to healthy controls. Overall, it seems that increased trait avoidance, rather than decreased approach, is a characteristic of affective disorders. This holds for both depressed and anxious patients and more strongly so in severe and chronic patients. It underlines the importance to address trait avoidance tendencies in the treatment of affective disorders. [ABSTRACT FROM AUTHOR]

Objective: To examine longitudinal associations of multiple physical symptoms with recurrence of depressive and anxiety disorders.Methods: Follow-up data of 584 participants with remitted depressive or anxiety disorders were used from the Netherlands Study of Depressive and Anxiety disorders. Multiple physical symptoms were measured at baseline (T1) and two-year follow-up (T2) by the Four-Dimensional Symptom Questionnaire (4DSQ) somatization subscale. Recurrence of depressive and anxiety disorders was assessed at two-year (T2) and four-year (T4) follow-up with the Composite International Diagnostic Interview. Logistic Generalized Estimating Equations were used to examine associations of multiple physical symptoms with recurrence of depressive and anxiety disorders. Depressive (IDS-SR) and anxiety symptoms (BAI), and other relevant covariates were taken into account.Results: Multiple physical symptoms were significantly associated with recurrence of depression (OR=1.04, 95%CI=1.00-1.08), anxiety (OR=1.07, 95%CI=1.03-1.12), and depressive or anxiety disorders (OR=1.06, 95%CI=1.02-1.10), on average over time. Odds ratios did not change substantially when the IDS-SR mood-cognition and BAI subjective scale were included as covariates.Conclusion: The presence of multiple physical symptoms was positively related to recurrence of depressive and anxiety disorders, independent of depressive and anxiety symptoms. Knowledge of risk factors for recurrence of depressive and anxiety disorders, such as the presence of multiple physical symptoms, could provide possibilities for better targeting interventions to prevent recurrence. [ABSTRACT FROM AUTHOR]

Physical activity, alcohol use and smoking might affect cardiovascular disease through modifying autonomic nervous system (ANS) activity. We investigated: 1) whether there are consistent relationships between lifestyle factors and cardiac ANS activity over time, and 2) whether 2-year changes in lifestyle factors relate to 2-year changes in cardiac activity. Baseline (n=2618) and 2-year follow-up (n=2010) data of the Netherlands Study of Depression and Anxiety was combined. Baseline data was collected in the Netherlands from 2004-2007. Lifestyle factors were habitual physical activity, frequency of sport activities, alcohol use, and smoking. Indicators of cardiac activity were heart rate (HR), respiratory sinus arrhythmia (RSA) and pre-ejection period (PEP) (100min of registration). The results showed that high physical activity (-1.8beats/min compared to low activity), high frequency of sport activities ('couple of times/week': -2.5beats/min compared to 'almost never') and mild/moderate alcohol use (-1.2beats/min compared to non-drinking) were related to low HR. Heavy smoking was related to high HR (>30cigarettes/day: +5.1beats/min compared to non-smoking). High frequency of sport activities was associated with high RSA ('couple of times/week':+1.7ms compared to 'almost never') and moderate smoking with longer PEP (11-20cigarettes/day: +2.8ms compared to non-smoking). Associations were consistent across waves. Furthermore, 2-year change in frequency of sport activities and number of smoked cigarettes/day was accompanied by 2-year change in HR (β=-0.076 and β=0.101, respectively) and RSA (β=0.046 and β=-0.040, respectively). Our findings support consistent effects of lifestyle on HR and parasympathetic activity in the expected direction. Cardiac autonomic dysregulation may be partly mediating the relationship between lifestyle and subsequent cardiovascular health. [ABSTRACT FROM AUTHOR]