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We examined the long-term association between objective neighbourhood sociodemographic characteristics (index of socioeconomic position (SEP), average income, percent low-income earners, average house price, percent immigrants and urban density) with depressive and anxiety symptoms, covering five 3-year waves of the Longitudinal Aging Study Amsterdam (n = 3,772). Multi-level regression models assessed each neighbourhood-level characteristic separately, adjusting for individual-level covariates. A higher percentage of immigrants and higher urban density, but not other neighbourhood characteristics, were significantly associated with depressive and anxiety symptoms over time in models adjusted for individual SEP. Results of time interaction models indicated that the associations were stable over the 15-year period., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Individual susceptibility to anxiety disorders after maladaptive responses to stress is not well understood. We now report that while exploring stress responses in mice after traumatic brain injury (TBI), a condition associated to stress susceptibility, we observed that the anxiogenic effects of either TBI or exposure to life-threatening experiences (predator) were blocked when both stressors were combined. Because TBI increases the entrance into the brain of serum insulin-like growth factor I (IGF-I), a known modulator of anxiety with a wide range of concentrations in the human population, we then determined whether circulating IGF-I is related to anxiety measures. In mice, anxiety-like responses to predator were inversely related to circulating IGF-I levels. Other indicators of mood regulation such as sensitivity to dexamethasone suppression and expression levels of blood and brain FK506 binding protein 5 (FKBP5), a co-chaperone of the glucocorticoid receptor that regulates its activity, were also associated to circulating IGF-I. Indeed, brain FKBP5 expression in mice was stimulated by IGF-I. In addition, we observed in a large human cohort (n = 2686) a significant relationship between plasma IGF-I and exposure to recent stressful life events, while FKBP5 expression in blood cells was significantly associated to plasma IGF-I levels. Collectively, these data indicate that circulating IGF-I appears to be involved in mood homeostasis across different species. Furthermore, the data in mice allow us to indicate that IGF-I may be acting at least in part by modulating FKBP5 expression.

Background: Physical inactivity has been identified as a risk factor for depression and, less often, as a long-term consequence of depression. Underexplored is whether similar bi-directional longitudinal relationships are observed for anxiety disorders, particularly in relation to three distinct indicators of activity levels - sports participation, general physical activity and sedentary behavior., Method: Participants were from the Netherlands Study of Depression and Anxiety (NESDA; N = 2932, 18-65 years old; 57% current anxiety or depressive disorder, 21% remitted disorder, 22% healthy controls). At baseline, 2, 4, and 6 years, participants completed a diagnostic interview and self-report questionnaires assessing psychopathology symptom severity, physical activity indicators, and sociodemographic and health covariates., Results: Consistently across assessment waves, people with anxiety and/or depressive disorders had lower sports participation and general physical activity compared to healthy controls. Greater anxiety or depressive symptoms were associated with lower activity according to all three indicators. Over time, a diagnosis or greater symptom severity at one assessment was associated with poorer sports participation and general physical activity 2 years later. In the opposite direction, only low sports participation was associated with greater symptom severity and increased odds of disorder onset 2 years later. Stronger effects were observed for chronicity, with lower activity according to all indicators increasing the odds of disorder chronicity after 2 years., Conclusions: Over time, there seems to a mutually reinforcing, bidirectional relationship between psychopathology and lower physical activity, particularly low sports participation. People with anxiety are as adversely affected as those with depression.

Background: High neuroticism is prospectively associated with psychopathology and physical health. However, within-subject changes in neuroticism due to life experiences (LEs) or state effects of current psychopathology are largely unexplored. In this 2-year follow-up study, four hypotheses were tested: (1) positive LEs (PLEs) decrease and negative LEs (NLEs) increase neuroticism; (2) LE-driven change in neuroticism is partly long-lasting; and (3) partly independent of LE-driven changes in anxiety/depression; and (4) childhood adversity (before age 16 years) moderates the influence of NLEs/PLEs on neuroticism scores in adult life., Method: Data came from the Netherlands Study of Depression and Anxiety [NESDA, n = 2981, mean age 41.99 years (s.d. = 13.08), 66.6% women]. At follow-up (T₂) we assessed PLEs/NLEs with the List of Threatening Experiences (LTE) over the prior 24 months and categorized them over recent and distant PLE/NLE measures (1-3 and 4-24 months prior to T₂ respectively) to distinguish distant NLE/PLE-driven change in trait neuroticism (using the Dutch version of the Neuroticism-Extroversion-Openness Five Factor Inventory, NEO-FFI) from state deviations due to changes in symptoms of depression (self-rated version of the 30-item Inventory of Depressive Symptomatology, IDS-SR30) and anxiety (Beck Anxiety Inventory, BAI)., Results: Distant NLEs were associated with higher and distant PLEs with lower neuroticism scores. The effects of distant LEs were weak but long-lasting, especially for distant PLEs. Distant NLE-driven change in neuroticism was associated with change in symptoms of anxiety/depression whereas the effect of distant PLEs on neuroticism was independent of any such changes. Childhood adversity weakened the impact of distant NLEs but enhanced the impact of distant PLEs on neuroticism., Conclusions: Distant PLEs are associated with small but long-lasting decreases in neuroticism regardless of changes in symptom levels of anxiety/depression. Long-lasting increases in neuroticism associated with distant NLEs are mediated by anxiety/depression.

Background: Different types of adverse events may have general or specific effects on depression and anxiety symptomatology. We examined the effects of adversities on the dimensions of the tripartite model: general distress, anhedonic depression and anxious arousal., Methods: Data were from 2615 individuals from the Netherlands Study for Depression and Anxiety (NESDA), with or without depressive or anxiety disorders. We analysed associations of childhood trauma, childhood life events (childhood trauma interview), and recent life events (List of Threatening Events Questionnaire, LTE-Q) with anhedonic depression, anxious arousal, and general distress (assessed by the adapted Mood and Anxiety Symptoms Questionnaire, MASQ-D30)., Results: We controlled for co-occurrence of adversities. Regarding childhood trauma, only emotional neglect was associated with all three symptom dimensions. Psychological and sexual abuse were associated with general distress and anxious arousal, whereas physical abuse was associated only with anxious arousal. Particularly strong associations were seen for emotional neglect with anhedonic depression and for sexual abuse with anxious arousal. Childhood life events showed no associations with symptom dimensions. The recent life events 'Serious problems with friend', 'Serious financial problems', and 'Becoming unemployed' were associated with all three dimensions. The recent life event 'death of parent/child/sibling' was associated with anxious arousal. Several associations remained significant when controlled for current diagnosis of depression or anxiety., Limitations: Our cross-sectional analyses do not allow for causal interpretation., Conclusions: Distinct childhood traumas had different effects on the symptom dimensions, whereas most recent adult life events were associated with all three symptom dimensions. Our observations help to understand the often reported associations of these adversities with depressive and anxiety symptomatology. In addition, symptom dimensions of the tripartite model were shown to capture effects of adverse events on top of those captured by diagnostic categories., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Aim: To describe the direct and indirect costs for people with anxiety and depressive disorders where guidelines are adhered to and patients' perceived needs are fully met., Method: Data were derived from the Netherlands Study of Depression and Anxiety. At baseline, adult patients were interviewed and they completed questionnaires to measure DSM-IV diagnoses, socio-demographic characteristics and perceived need for care. Actual care data were also derived from electronic medical records. Criteria for guideline adherence were based on general practice guidelines, issued by the Dutch College of General Practitioners. Direct and indirect costs were inferred from the Perceived Need for Care Questionnaire administered at baseline, and the Trimbos and iMTA questionnaire on Costs associated with Psychiatric illness administered at 1-year follow-up., Results: For 568 patients with a current anxiety or depressive disorder a complete dataset on health care use and absenteeism was available. Guideline adherence was significantly associated with increased care use and corresponding costs, while fully met perceived need was unrelated to costs. Socio-demographic characteristics, severity of symptoms and guideline adherence all affected the societal costs of patients with fully met perceived needs compared with patients with perceived unmet needs., Conclusion: It appears that guideline-concordant care for anxiety and depression costs more than non-concordant care, while care that has fulfilled all of a patient's needs seems not to be more expensive than care that has not met all perceived needs. However, randomized controlled trials should first confirm this conclusion., (© 2010 Blackwell Publishing Ltd.)

The first generation of genome-wide association studies (GWA studies) for psychiatric disorders has led to new insights regarding the genetic architecture of these disorders. We now start to realize that a larger number of genes, each with a small contribution, are likely to explain the heritability of psychiatric diseases. The contribution of a large number of genes to complex traits can be analyzed with genome-wide profiling. In a discovery sample, a genetic risk profile for depression was defined based on a GWA study of 1738 adult cases and 1802 controls. The genetic risk scores were tested in two population-based samples of elderly participants. The genetic risk profiles were evaluated for depression and anxiety in the Rotterdam Study cohort and the Erasmus Rucphen Family (ERF) study. The genetic risk scores were significantly associated with different measures of depression and explained up to ∼0.7% of the variance in depression in Rotterdam Study and up to ∼1% in ERF study. The genetic score for depression was also significantly associated with anxiety explaining up to 2.1% in Rotterdam study. These findings suggest the presence of many genetic loci of small effect that influence both depression and anxiety. Remarkably, the predictive value of these profiles was as large in the sample of elderly participants as in the middle-aged samples.

Background: There is no consensus on how to define subthreshold anxiety. Based on functional impairment, we aim to evaluate the use of a diagnostic instrument and an anxiety severity questionnaire to derive an empirical cut-off for defining clinically relevant, subthreshold anxiety., Methods: Our sample consisted of 1788 subjects without full-syndromal anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA). We used ANCOVA to compare the Composite International Diagnostic Interview (CIDI) and the Beck Anxiety Inventory (BAI) in their association with functional impairment, measured by the World Health Organization Disability Assessment Schedule (WHODAS II). The BAI was selected over the Fear Questionnaire (FQ) and the Penn State Worry Questionnaire (PSWQ) for its highest associations with anxiety disorders. ROC analysis determined the percentage of functionally impaired with subthreshold anxiety based on found cut-offs., Results: The CIDI was very modestly associated with functional impairment, possibly because of skip rules, wording or scoring, while the BAI was highly correlated to functional impairment. A score of 11 on the BAI defined clinically relevant subthreshold anxiety. This cut-off identified 36.0% of the most functionally impaired as having subthreshold anxiety., Limitations: No "natural" cut-off on the BAI for determining subthreshold anxiety could be determined. The cut-off point of 11, based on a large effect size relative to normal anxiety, thus remains somewhat arbitrary., Conclusions: The questionnaire BAI is more suitable than the interview CIDI to measure clinically relevant, subthreshold anxiety. The BAI score of 11 appeared to be the most appropriate cut-off for identifying clinically relevant subthreshold anxiety., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: The metabolic syndrome (MetSyn) predisposes to cardiovascular disease and diabetes mellitus. There might also be an association between the MetSyn and anxiety and depression, but its nature is unclear. We aimed to investigate whether diagnosis, symptom severity and antidepressant use are associated with the MetSyn., Method: We addressed the odds for the MetSyn and its components among 1217 depressed and/or anxious subjects and 629 controls, and their associations with symptom severity and antidepressant use., Results: Symptom severity was positively associated with prevalence of the MetSyn, [adjusted odds ratio (OR) 2.21 for very severe depression: 95% confidence interval (CI): 1.06-4.64, P = 0.04], which could be attributed to abdominal obesity and dyslipidemia. Tricyclic antidepressant (TCA) use also increased odds for the MetSyn (OR 2.30, 95% CI: 1.21-4.36, P = 0.01), independent of depression severity., Conclusion: The most severely depressed people and TCA users more often have the MetSyn, which is driven by abdominal adiposity and dyslipidemia.

The authors examined the relationship between anxiety, depression and physical disability, after controlling for demographic and health variables, in a sample of 374 adults aged 18-94. Results indicate that anxiety, depression and comorbid anxiety and depression are associated with higher levels of disability, after controlling for factors such as age, gender, income, self-rated health, number of medical conditions and number of physician visits in the past year. Furthermore, anxiety, depression and comorbid anxiety and depression have a differential effect on disability according to age, with older adults with any of these symptoms reporting higher levels of disability than younger adults. These findings suggest that physicians working with older adults should assess for and treat anxiety as well as depressive symptoms.

Objective: To investigate the association between the extent of pain and the severity of psychological distress in neck and upper limb pain, and to establish whether extent of pain is associated with consultation frequency in primary care., Methods: The study population was selected from responders to a general health survey conducted in a general practice in North Staffordshire, UK. Responders indicating pain in the neck or upper limb area were included. The survey included the Hospital Anxiety and Depression Scale (HADS). Consultation data were retrieved for a period of 12 months following the survey., Results: A total of 867 responders had experienced neck-upper limb pain in the month preceding the survey (33% of all responders). Responders with more generalized pain within the neck-upper limb area had significantly higher HADS scores compared to responders with pain in one area only, particularly for depression (median scores 5 vs 3 points). Annual consultation frequency was also higher among responders with generalized pain [adjusted OR for high consultation frequency (> or = 7 visits vs 0-2 visits) 1.6, 95% CI 1.1 to 2.4]. When the analysis was restricted to consultations specifically related to neck-upper limb pain, the association between extent of pain and consultation frequency was weak and not statistically significant., Conclusion: Our survey revealed a significant association between extent of pain in the neck-upper limb area and psychological distress, although scores for anxiety and depression were generally low, with only a small proportion of responders reporting moderate or severe symptoms. Responders with both generalized pain and depressive symptoms were more likely to consult their family doctor, but not specifically for musculoskeletal pain. These results confirm the hypothesis that general psychological well being rather than specific somatic symptoms predict consultation frequency.

Background: Childhood trauma (CT) is associated with severe sequelae, including stress‐related mental health disorders that can perpetuate long into adulthood. A key mechanism in this relationship seems to be emotion regulation. We aimed to investigate (1) whether childhood trauma is associated with anger in adulthood, and, if so, (2) to explore which types of childhood trauma predominate in the prediction of anger in a cohort that included participants with and without current affective disorders. Methods: In the Netherlands Study of Depression and Anxiety (NESDA), childhood trauma was assessed with a semi‐structured Childhood Trauma Interview (CTI) at baseline, and analyzed in relation to anger as measured at a 4‐year follow‐up with the Spielberger Trait Anger Subscale (STAS), the Anger Attacks Questionnaire, and cluster B personality traits (i.e., borderline, antisocial) of the Personality Disorder Questionnaire 4 (PDQ‐4), using analysis of covariance (ANCOVA) and multivariable logistic regression analyses. Post hoc analyses comprised cross‐sectional regression analyses, using the Childhood Trauma Questionnaire‐Short Form (CTQ‐SF) also obtained at a 4‐year follow‐up. Results: Participants (n = 2271) were on average 42.1 years (SD = 13.1), and 66.2% were female. Childhood trauma showed a dose–response association with all anger constructs. All types of childhood trauma were significantly associated with borderline personality traits, independently of depression and anxiety. Additionally, all types of childhood trauma except for sexual abuse were associated with higher levels of trait anger, and a higher prevalence of anger attacks and antisocial personality traits in adulthood. Cross‐sectionally, the effect sizes were larger compared with the analyses with the childhood trauma measured 4 years prior to the anger measures. Conclusions: Childhood trauma is linked with anger in adulthood, which could be of particular interest in the context of psychopathology. Focus on childhood traumatic experiences and adulthood anger may help to enhance the effectiveness of treatment for patients with depressive and anxiety disorders. Trauma‐focused interventions should be implemented when appropriate. [ABSTRACT FROM AUTHOR]

Background: Depression shows a large heterogeneity of symptoms between and within persons over time. However, most outcome studies have assessed depression as a single underlying latent construct, using the sum score on psychometric scales as an indicator for severity. This study assesses longitudinal symptom‐specific trajectories and within‐person variability of major depressive disorder over a 9‐year period. Methods: Data were derived from the Netherlands Study of Depression and Anxiety (NESDA). This study included 783 participants with a current major depressive disorder at baseline. The Inventory Depressive Symptomatology‐Self‐Report (IDS‐SR) was used to analyze 28 depressive symptoms at up to six time points during the 9‐year follow‐up. Results: The highest baseline severity scores were found for the items regarding energy and mood states. The core symptoms depressed mood and anhedonia had the most favorable course, whereas sleeping problems and (psycho‐)somatic symptoms were more persistent over 9‐year follow‐up. Within‐person variability was highest for symptoms related to energy and lowest for suicidal ideation. Conclusions: The severity, course, and within‐person variability differed markedly between depressive symptoms. Our findings strengthen the idea that employing a symptom‐focused approach in both clinical care and research is of value. [ABSTRACT FROM AUTHOR]

Backgrounds: Accelerated cellular ageing, which can be examined by telomere length (TL), may be an overarching mechanism underlying the association between personality and adverse health outcomes. This 6-year longitudinal study examined the relation between personality and leukocyte telomere length (LTL) across time among adults with a wide age-range. Methods: Data from the Netherlands Study of Depression and Anxiety were used and included patients with a depression and/or anxiety disorder and healthy controls. Overall, 2936 persons (18–65 years, 66% female) had data on LTL at baseline and 1883 persons had LTL at 6-year follow-up. The Big Five personality traits (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness) and Type D personality were assessed. Results: Neuroticism was negatively (B = −2.11, p = 0.03) and agreeableness was positively (B = 3.84, p = 0.03) related to LTL measured across two time points, which became just non-significant after adjusting for somatic health, lifestyle factors, and recent life stress (B = −1.99, p = 0.06; and B = 3.01, p = 0.10). Type D personality was negatively (B = −50.16, p < 0.01) related to LTL across two time points, which still remained statistically significant after full adjustment (B = −47.37, p = 0.01). Associations did not differ by age, gender, and current psychiatric status. Conclusions: The Big Five traits high neuroticism and low agreeableness, and Type D personality were associated with shorter LTL measured across a 6-year period. Associations with the Big Five traits became non-significant after controlling for somatic health, lifestyle factors, and recent life stress, yet similar trends were observed. Type D personality remained independently associated with shorter LTL after full adjustment. [ABSTRACT FROM AUTHOR]

Objective Adaptive social functioning is severely impeded in depressive and anxiety disorders, even after remission. However, a comprehensive overview is still lacking. Method Using data from the Netherlands Study of Depression and Anxiety ( NESDA), behavioural (network size, social activities, social support) and affective (loneliness, affiliation, perceived social disability) indicators of social functioning were analyzed in patients with anxiety ( N = 540), depressive ( N = 393), comorbid anxiety and depressive disorders ('comorbid', N = 748), remitted participants ( N = 621), and healthy control subjects ( N = 650). Results Analyses revealed an increasing trend of social dysfunction among patient groups, in patients with comorbid anxiety and depressive disorders, showing the most severe impairments, followed by depressed and anxious patients ( P's < 0.001 for all social functioning indicators). Affective indicators showed the largest effect sizes (Cohen's d range from 0.13 to 1.76). We also found impairments in social functioning among remitted patients. Furthermore, perceived social disability among patients was predictive of still having a depressive and/or anxiety diagnosis 2 years later ( P < 0.01). Conclusions Behavioural but especially affective indicators of social functioning are impaired in patients with anxiety or depressive disorders and most in patients with comorbid disorders. After remission of affective psychopathology, residual impairments tend to remain, while social dysfunction in patients seems predictive of future psychopathology. [ABSTRACT FROM AUTHOR]

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

Background: Clinical and aetiological heterogeneity have impeded our understanding of depression.Aims: To evaluate differences in psychiatric and somatic course between people with depression subtypes that differed clinically (severity) and aetiologically (melancholic v. atypical).Method: Data from baseline, 2-, 4- and 6-year follow-up of The Netherlands Study of Depression and Anxiety were used, and included 600 controls and 648 people with major depressive disorder (subtypes: severe melancholic n = 308; severe atypical n = 167; moderate n = 173, established using latent class analysis).Results: Those with the moderate subtype had a significantly better psychiatric clinical course than the severe melancholic and atypical subtype groups. Suicidal thoughts and anxiety persisted longer in those with the melancholic subtype. The atypical subtype group continued to have the highest body mass index and highest prevalence of metabolic syndrome during follow-up, although differences between groups became less pronounced over time.Conclusions: Course trajectories of depressive subtypes mostly ran parallel to each other, with baseline severity being the most important differentiator in course between groups. [ABSTRACT FROM AUTHOR]

Objective To examine the effect of implementing anxiety disorders guidelines on guideline adherence and patient outcomes in specialized mental health care. Method A treatment setting in which guidelines were implemented (intervention condition) was compared with one in which guidelines were only disseminated (control condition). Results Of 61.7% of 81 intervention-condition patients received treatment according to the guidelines vs. 40.6% of 69 control-condition patients ( P = 0.01). At 1-year follow-up, intervention-condition patients showed a greater decrease in anxiety symptoms ( d = 0.48, P < 0.05); higher percentages of response (52.6% vs. 33.8%; P = 0.025) and remission (33.3% vs.16.9%; P = 0.026); and a greater decrease in the rate of phobic avoidance ( d = 0.34, P < 0.05). At 2-year follow-up, control-condition patients had experienced a longer period of treatment, which had eroded most of these differences, except for phobic avoidance. Conclusion Systematic guideline implementation results in earlier gains and shorter treatment times. [ABSTRACT FROM AUTHOR]

It has been hypothesized that hypovitaminosis D is associated with depression but epidemiological evidence is limited. We investigated the association between depressive disorders and related clinical characteristics with blood concentrations of 25-hydroxyvitamin D [25(OH)D] in a large cohort. The sample consisted of participants (aged 18-65 years) from the Netherlands Study of Depression and Anxiety (NESDA) with a current (N=1102) or remitted (N=790) depressive disorder (major depressive disorder, dysthymia) defined according to DSM-IV criteria, and healthy controls (N=494). Serum levels of 25(OH)D measured and analyzed in multivariate analyses adjusting for sociodemographics, sunlight, urbanization, lifestyle and health. Of the sample, 33.6% had deficient or insufficient serum 25(OH)D (<50 nmol l−1). As compared with controls, lower 25(OH)D levels were found in participants with current depression (P=0.001, Cohen's d=0.21), particularly in those with the most severe symptoms (P=0.001, Cohen's d=0.44). In currently depressed persons, 25(OH)D was inversely associated with symptom severity (β=−0.19, s.e.=0.07, P=0.003) suggesting a dose-response gradient, and with risk (relative risk=0.90, 95% confidence interval=0.82-0.99, P=0.03) of having a depressive disorders at 2-year follow-up. This large cohort study indicates that low levels of 25(OH)D were associated to the presence and severity of depressive disorder suggesting that hypovitaminosis D may represent an underlying biological vulnerability for depression. Future studies should elucidate whether-the highly prevalent-hypovitaminosis D could be cost-effectively treated as part of preventive or treatment interventions for depression. [ABSTRACT FROM AUTHOR]

The rat genome sequencing and mapping consortium found evidence for an association between the catenin-δ2 gene ( CTNND2) and anxious behaviour. We replicated these results in humans by carrying out a genetic association test in patients with panic disorder, social phobia, generalized anxiety disorder and/or agoraphobia ( N = 1714) and controls ( N = 4125). We further explored the association between CTNND2 and other psychiatric disorders based on publicly available genome-wide association results. A gene-based test showed that single nucleotide polymorphisms ( SNPs) in CTNND2 have a significantly increased signal ( P < 1e−5) and decreased P-values. Single nucleotide polymorphism rs1012176 showed the strongest association with any anxiety disorder (odds ratio: 0.8128, SE = 0.063, P = 0.00099), but this effect was not significant after correction for multiple testing. In available genome-wide association results from the Psychiatric Genomics Consortium we found that SNPs in CTNND2 collectively showed an increased signal for schizophrenia ( P < 1e−5) and major depressive disorder ( P < 1e−5), but not for bipolar disorder. These signals remained significant after correction for potential confounders. The association between CTNND2 and anxiety was not strong enough to be picked up in the current generation of human genome-wide analyses, indicating the usefulness of and need for animal genetic studies to identify candidate genes for further study in human samples. [ABSTRACT FROM AUTHOR]

BackgroundCross-sectional studies show that neuroticism is strongly associated with affective disorders. We investigated whether neuroticism and affective disorders mutually reinforce each other over time, setting off a potential downward spiral.MethodA total of 2981 adults aged 18–65 years, consisting of healthy controls, persons with a prior history of affective disorders and persons with a current affective disorder were assessed at baseline (T1) and 2 (T2) and 4 years (T3) later. At each wave, affective disorders according to DSM-IV criteria were assessed with the Composite Interview Diagnostic Instrument (CIDI) version 2.1 and neuroticism with the Neuroticism–Extraversion–Openness Five Factor Inventory (NEO-FFI).ResultsUsing structural equation models the association of distress disorders (i.e. dysthymia, depressive disorder, generalized anxiety disorder) and fear disorders (i.e. social anxiety disorder, panic disorder, agoraphobia without panic) with neuroticism could be attributed to three components: (a) a strong correlation of the stable components of distress and fear disorders with the stable trait component of neuroticism; (b) a modest contemporaneous association of change in distress and fear disorders with change in neuroticism; (c) a small to modest delayed effect of change in distress and fear disorders on change in neuroticism. Moreover, neuroticism scores in participants newly affected at T2 but remitted at T3 did not differ from their pre-morbid scores at T1.ConclusionsOur results do not support a positive feedback cycle of changes in psychopathology and changes in neuroticism. In the context of a relative stability of neuroticism and affective disorders, only modest contemporaneous and small to modest delayed effects of psychopathology on neuroticism were observed. [ABSTRACT FROM PUBLISHER]

BackgroundA family history (FH) of alcohol dependence (AD) not only increases the risk for AD, but is also associated with an increased risk for mood and anxiety disorders. However, it is unknown how a FH of AD affects neural substrates in patients with mood and anxiety disorders. In this study we examined the effects of an alcoholic FH on cognitive and emotional functions in these patients using functional magnetic resonance imaging (fMRI).MethodIn a sample of non-alcoholic patients with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA) neuroimaging study, patients with a first-degree FH of AD (FH + ; n = 31) were compared with patients without a FH (FH–; n = 77) on performance and brain activation during visuospatial planning and emotional word encoding. Results were compared with those of healthy controls (HCs) without a FH of AD (n = 31).ResultsFH+ patients performed slower during planning with increasing task load, coupled with stronger blood oxygen level-dependent responses in dorsal prefrontal areas compared with FH− patients and HCs. FH was not associated with performance differences during word encoding, but right insula activation during positive word encoding was present in FH+ patients, comparable with HCs, but absent in FH− patients.ConclusionsThis study demonstrates subtle impairments during planning in FH+ compared with FH− patients and HCs, whereas activation during mood-incongruent stimuli in FH+ patients was similar to HCs but not FH− patients, suggesting that the presence of a FH of AD is a useful marker for the neurophysiological profile in mood/anxiety disorders and possible predictor for treatment success. [ABSTRACT FROM PUBLISHER]

Spinhoven P, Elzinga BM, Hovens JGFM, Roelofs K, van Oppen P, Zitman FG, Penninx BWJH. Positive and negative life events and personality traits in predicting course of depression and anxiety. Objective: To examine the prognostic value of personality dimensions and negative and positive life events for diagnostic and symptom course trajectories in depressive and anxiety disorder. Method: A total of 1209 subjects (18-65 years) with depressive and/or anxiety disorder were recruited in primary and specialized mental health care. Personality dimensions at baseline were assessed with the NEO-FFI and incidence and date of life events retrospectively with a structured interview at 2-year follow-up. DSM-IV-based diagnostic interviews as well as life chart assessments allowed course assessment at both the diagnostic and symptom trajectory level over 2 years. Results: Life events were significantly related to diagnostic and symptom course trajectories of depression and anxiety also after correcting for sociodemographic and clinical characteristics. Only negative life events prospectively predicted longer time to remission of depressive disorder. Prospective associations of neuroticism and extraversion with prognosis of anxiety and depression were greatly reduced after correcting for baseline severity and duration of index disorder. Personality traits did not moderate the effect of life events on 2-year course indicators. Conclusions: Negative life events have an independent effect on diagnostic and symptom course trajectories of depression and to a lesser extent anxiety unconfounded by sociodemographic, clinical, and personality characteristics. [ABSTRACT FROM AUTHOR]

Rhebergen D, Batelaan NM, de Graaf R, Nolen WA, Spijker J, Beekman ATF, Penninx BWJH. The 7-year course of depression and anxiety in the general population. Insight into the long-term course of depression and anxiety. Data were derived from Netherlands Mental Health Survey and Incidence Study/Netherlands Study of Depression and Anxiety, epidemiologic surveys in the adult population in the Netherlands. Three hundred and three respondents with depressive and/or anxiety Composite International Diagnostic Interview (CIDI) disorder were interviewed, examining the 7-year course of depression ( n = 141), anxiety ( n = 102) and the comorbid state ( n = 60) and possible prognostic factors. Outcomes were CIDI diagnostic status after 7 years and percentage of time during 7 years with depressive and/or anxiety symptoms, retrospectively assessed by the Life Chart Interview (LCI). After 7 years, 60.7% of the subjects were free from a 12-month CIDI depression or anxiety diagnosis. The odds were higher for subjects with anxiety and comorbidity compared to subjects with depression. Low physical functioning and high neuroticism predicted the presence of a diagnosis after 7 years. During 7-year follow-up, 37.3% of the subjects were free from depressive and anxiety symptoms according to the LCI, 51.8% had symptoms <50% of the time, and 10.9%≥50% of the time. (Comorbid) anxiety resulted in a poorer course. High neuroticism and childhood adversity predicted more follow-up time with symptoms. Course trajectories were more favorable than expected, although comorbidity resulted in poorer course. Neuroticism, physical functioning, and childhood adversity predicted an unfavorable course. [ABSTRACT FROM AUTHOR]

Hovens JGFM, Wiersma JE, Giltay EJ, van Oppen P, Spinhoven P, Penninx BWJH, Zitman FG. Childhood life events and childhood trauma in adult patients with depressive, anxiety and comorbid disorders vs. controls. Objective: To investigate the association between childhood life events, childhood trauma and the presence of anxiety, depressive or comorbid anxiety and depressive disorders in adulthood. Method: Data are from 1931 adult participants in the Netherlands Study of Depression and Anxiety (NESDA). Childhood life events included divorce of parents, early parental loss and ‘placed in care’, whereas childhood trauma was assessed as experienced emotional neglect, psychological, physical and sexual abuse prior to age 16. Results: Childhood life events were not associated with psychopathology, except for ‘placed in care’ in the comorbid group. All types of childhood trauma were increasingly prevalent in the following order: controls, anxiety, depression, and comorbid group ( P < 0.001). The higher the score was on the childhood trauma index, the stronger the association with psychopathology ( P < 0.001). Conclusion: Childhood trauma rather than childhood life events are related to anxiety and depressive disorders. The strong associations with the comorbid group suggest that childhood trauma contributes to the severity of psychopathology. Our study underscores the importance of heightened awareness of the possible presence of childhood trauma, especially in adult patients with comorbid anxiety and depressive disorders. [ABSTRACT FROM AUTHOR]

Introduction: Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that is estimated to be carried by one-third of the world population. While evidence has been found for a relationship between T. gondii infection and schizophrenia, its relationship with other psychiatric disorders like depressive and anxiety disorders shows inconsistent results. Objectives: The aim of the present study was to examine whether T. gondii seropositivity is associated with affective disorders, as well as with aggression reactivity and suicidal thoughts. Methods: In the Netherlands Study of Depression and Anxiety (NESDA), T. gondii antibodies were assessed in patients with current depressive (n=133), anxiety (n=188), comorbid depressive and anxiety (n=148), and remitted disorders (n=889), as well as in healthy controls (n=373) based on DSM-IV criteria. Seropositivity was analyzed in relation to disorder status, aggression reactivity and suicidal thoughts using multivariate analyses of covariance and regression analyses. Results: Participants were on average 51.2 years (SD = 13.2), and 64.4% were female. Seropositivity was found in 673 participants (38.9%). A strong positive association between T. gondii seropositivity and age was observed. No significant associations were found between T. gondii seropositivity and disorder status, aggression reactivity and suicidal thoughts. The adjusted odds ratio (OR) for any remitted disorder versus controls was 1.13 (95% CI: 0.87-1.49), and for any current disorder versus controlswas 0.94 (95%CI: 0.69-1.28). Conclusions: No evidence was found for a relationship between affective disorders and T. gondii infection. [ABSTRACT FROM AUTHOR]

Depression and anxiety are common and often comorbid mental health disorders that represent risk factors for aging-related conditions. Brain aging has shown to be more advanced in patients with Major Depressive Disorder (MDD). Here, we extend prior work by investigating multivariate brain aging in patients with MDD and/or anxiety disorders and examine which factors contribute to older appearing brains. Adults aged 18-57 years from theNetherlands Study of Depression and Anxiety underwent structural MRI. A pre-trained brain age prediction model based on >2,000 samples from the ENIGMA consortium was applied to obtain brain-predicted age differences (brain-PAD, predicted brain age minus chronological age) in 65 controls and 220 patients with currentMDDand/or anxiety. Brain-PAD estimates were associated with clinical, somatic, lifestyle, and biological factors. After correcting for antidepressant use, brain-PAD was significantly higher in MDD (+2.78 years, Cohen's d=0.25, 95% CI -0.10-0.60) and anxiety patients (+2.91 years, Cohen's d=0.27, 95% CI -0.08-0.61), compared to controls. There were no significant associations with lifestyle or biological stress systems. A multivariable model indicated unique contributions of higher severity of somatic depression symptoms (b=4.21 years per unit increase on average sum score) and antidepressant use (-2.53 years) to brain-PAD. Advanced brain aging in patients with MDD and anxiety was most strongly associated with somatic depressive symptomatology. We also present clinically relevant evidence for a potential neuroprotective antidepressant effect on the brain-PADmetric that requires follow-up in future research. [ABSTRACT FROM AUTHOR]

Background: Inconsistent findings regarding the pathophysiology of panic disorder (PD) could result from clinical heterogeneity. Identifying subtypes could enhance insights into the neurobiological substrates of PD.Methods: An emotional faces fMRI paradigm was used in a group of PD patients (n = 73) and healthy controls (n = 58). The overall PD group was further divided into three previously identified subtypes: a cognitive-autonomic (n = 22), an autonomic (n = 16) and an aspecific (n = 35) subtype. Differences in brain activity levels in response to emotional facial expressions between groups were examined for six regions of interests, namely the amygdala, ventromedial prefrontal cortex, anterior cingulate, fusiform gyrus, lingual gyrus and insula.Results: PD patients showed lower activity in the rostral anterior cingulate in response to angry faces than healthy controls, which was mainly driven by the autonomic subtype. No significant differences were found in other brain regions when comparing PD patients with controls or when comparing across PD subtypes.Limitations: Sample sizes in subgroups were relatively small CONCLUSIONS: The role of the rostral anterior cingulate cortex for emotional processes critical in panic disorder is highlighted by this study and provides, albeit preliminary, evidence for the use of a subtype approach to advance our neurobiological insights in PD considering its involvement in the appraisal of autonomic viscero-sensory symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Insomnia is common in many psychiatric disorders (1), especially so in affective disorders like major depressive disorder (MDD) (2) and anxiety disorder (2,3). Insomnia is moreover a cardinal risk factor for the development of MDD (4). Nevertheless, the neural correlates of insomnia complaints in psychiatric patients have hardly been investigated, hampering the development of rational treatment and prevention of these disabling symptoms. materials and methods: Fifty-nine patients with MDD as well as 61 patients with anxiety disorder filled out the Women’s Health Initiative Insomnia Rating Scale (WHIIRS) (5) and underwent structural magnetic resonance imaging of the brain. The WHIIRS is a brief, five-item scale evaluating insomnia symptoms, which yields a summary score that reflects complaints on sleep quality. Whole-brain voxel-based morphometry was used to investigate the association of the WHIIRS summary score with gray matter density. Results: In patients with MDD, the WHIIRS insomnia severity score showed a strong negative correlation with gray matter density in the pulvinar of the thalamus. Gray matter in this area showed no association at all with insomnia severity in patients with anxiety disorder. In contrast, anxiety disorder patients more severe insomnia showed lower frontopolar GM density, an association not found in MDD patients. Conclusion: This is the first study to directly compare structural brain correlates of insomnia severity between MDD and anxiety disorder. Unlike previous voxel-based morphometry findings that indicated particularly orbitofrontal involvement in sleep complaints in both well-sleeping (6) and poorly-sleeping (7) people without psychiatric disorder, we here found differential involvement of the pulvinar and frontopolar cortex. These triple dissociations have strong implications for our understanding of insomnia; depending on the psychiatric phenotype, remarkably different cerebral mechanisms can underlie seemingly similar subjective sleep complaints. References: 1. Benca RM, Obermeyer WH, Thisted RA, Gillin JC. Sleep and psychiatric disorders. A meta-analysis. Arch Gen Psychiatry 1992;49:651–668; discussion 669–670. 2. Tsuno N, Besset A, Ritchie K. Sleep and depression. J Clin Psychiatry 2005;66:1254–1269. 3. Soehner AM, Harvey AG. Prevalence and functional consequences of severe insomnia symptoms in mood and anxiety disorders: results from a nationally representative sample. Sleep 2012;35:1367–1375. 4. Baglioni C, Battagliese G, Feige B, et al. Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies. J Affect Disord 2011;135:10–19. 5. Levine DW, Kaplan RM, Kripke DF, Bowen DJ, Naughton MJ, Shumaker SA. Factor structure and measurement invariance of the Women’s Health Initiative Insomnia Rating Scale. Psychol Assess 2003;15:123–136. 6. Stoffers D, Moens S, Benjamins J, et al. Orbitofrontal gray matter relates to early morning awakening: a neural correlate of insomnia complaints? Front Neurol 2012;3:105. 7. Altena E, Vrenken H, Van Der Werf YD, van den Heuvel OA, Van Someren EJ. Reduced orbitofrontal and parietal gray matter in chronic insomnia: a voxel-based morphometric study. Biol Psychiatry 2010;67:182–185. Acknowledgements: Supported by the VICI Innovation Grant 453–07-001 of the Netherlands Organization of Scientific Research (NWO); The Hague, The Netherlands. [Copyright &y& Elsevier]

B Introduction: b Depression and anxiety are common and often comorbid mental health disorders that represent risk factors for ageing-related conditions with a premature onset [1]. A pre-trained ridge regression brain age prediction model based on >2,000 samples from the ENIGMA consortium [5] was applied to predict age in 65 controls and 220 patients with current MDD and/or anxiety disorder. [Extracted from the article]

Aims: To determine possible associations between guideline-concordant care and clinical outcome in general practice patients with anxiety and depression, and identification of patient characteristics associated with poor clinical outcome. Methods: Data from the Netherlands Study of Anxiety and Depression (NESDA) was used. NESDA is a longitudinal cohort study to measure the long-term course and consequences of anxiety and depressive disorders. Adult patients were interviewed to measure DSM-IV diagnoses during the baseline assessment, and completed questionnaires measuring symptom severity, sociodemographic variables and social support at baseline and 12 months later. The definition of guideline adherence was based on an algorithm on care that was received. Results: 721 patients with a current (6-month recency) anxiety or depressive disorder participated. While patients who received guideline-concordant care (N=281) suffered from more severe symptoms than patients who received non-guideline concordant care (N=440), both groups improved equally on their depressive or anxiety symptoms after 12 months. Patients who (still) had moderate or severe symptoms at follow-up, were more often unemployed, had smaller personal networks and more severe depressive symptoms at baseline than patients with low symptoms at follow-up. Conclusions: The added value of guideline-concordant care could not be demonstrated in this study. While patients with comorbidity of both anxiety and depressive disorders, those with smaller social networks and the unemployed were more likely to suffer from moderate or severe symptoms after 12 months, severity of depressive symptoms at baseline was most strongly associated. Findings have practical implications as well as implication for future research. [Copyright &y& Elsevier]