Smoking is a common risk factor for many diseases. We conducted genome-wide association meta-analyses for the number of cigarettes smoked per day (CPD) in smokers (n = 31,266) and smoking initiation ...(n = 46,481) using samples from the ENGAGE Consortium. In a second stage, we tested selected SNPs with in silico replication in the Tobacco and Genetics (TAG) and Glaxo Smith Kline (Ox-GSK) consortia cohorts (n = 45,691 smokers) and assessed some of those in a third sample of European ancestry (n = 9,040). Variants in three genomic regions associated with CPD (P < 5 × 10−8), including previously identified SNPs at 15q25 represented by rs1051730A (effect size = 0.80 CPD, P = 2.4 × 10−69), and SNPs at 19q13 and 8p11, represented by rs4105144C (effect size = 0.39 CPD, P = 2.2 × 10−12) and rs6474412-T (effect size = 0.29 CPD, P = 1.4 × 10−8), respectively. Among the genes at the two newly associated loci are genes encoding nicotine-metabolizing enzymes (CYP2A6 and CYP2B6) and nicotinic acetylcholine receptor subunits (CHRNB3 and CHRNA6), all of which have been highlighted in previous studies of smoking and nicotine dependence. Nominal associations with lung cancer were observed at both 8p11 (rs6474412T, odds ratio (OR) = 1.09, P = 0.04) and 19q13 (rs4105144C, OR = 1.12, P = 0.0006).
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Consistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = ...74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730A, β = 1.03, standard error (s.e.) = 0.053, P = 2.8 × 10−73). Two 10q25 SNPs (rs1329650G, β = 0.367, s.e. = 0.059, P = 5.7 × 10−10; and rs1028936A, β = 0.446, s.e. = 0.074, P = 1.3 × 10−9) and one 9q13 SNP in EGLN2 (rs3733829G, β = 0.333, s.e. = 0.058, P = 1.0 × 10−8) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265C, odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 × 10−8). One SNP located near DBH on chromosome 9 (rs3025343G, OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 × 10−8) was significantly associated with smoking cessation.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Objective Depression and anxiety are considered etiological factors in cardiovascular disease (CVD), though their relative contribution and differentiation by clinical characteristics have ...not been studied intensively. We examined 6-year associations between depressive and anxiety disorders, clinical characteristics and newly-developed CVD. Methods DSM-IV diagnoses were established in 2510 CVD-free participants of the Netherlands Study of Depression and Anxiety. Data on subtype, severity, and psychoactive medication were collected. The 6-year incidence of CVD was assessed using Cox regression analyses adjusted for sociodemographic, health and lifestyle factors. Results One-hundred-six subjects (4.2%) developed CVD. Having both current depressive and anxiety disorders (HR = 2.86, 95%CI 1.49–5.49) or current depression only (HR = 2.30; 95%CI 1.10–4.80) was significantly associated with increased CVD incidence, whereas current anxiety only (HR = 1.48; 95%CI 0.74–2.96) and remitted disorders (HR = 1.48; 95%CI 0.80–2.75) were not associated. Symptom severity was associated with increased CVD onset (e.g., Inventory of Depressive Symptomatology per SD increase: HR = 1.51; 95%CI 1.25–1.83). Benzodiazepine use was associated with additional CVD risk (HR = 1.95; 95%CI 1.16–3.31). Conclusions Current depressive (but not anxiety) disorder independently contributed to CVD in our sample of initially CVD-free participants. CVD incidence over 6 years of follow-up was particularly increased in subjects with more symptoms, and in those using benzodiazepines.
The course of depressive and anxiety disorders in a large, longitudinal cohort study was poorer when pain was present, which was partly mediated by baseline psychiatric characteristics.
The ...combination of pain and depression or anxiety is commonly seen in clinical practice. Little is known about the influence of pain on psychopathology over time, as previous studies have been mainly cross-sectional. The objectives of this study are to determine the impact of pain on the course of depressive and/or anxiety disorders, and investigate to what extent the association between pain and course of these mental disorders is mediated by psychiatric characteristics. Data from the Netherlands Study of Depression and Anxiety (NESDA), collected between 2004 and 2009, were used. A total of 1209 participants with a depressive and/or anxiety disorder at baseline were followed up for 2
years. Baseline pain was assessed by location, duration, use of pain medication, and severity (based on Chronic Pain Grade). Course of depressive and anxiety disorders was assessed by Composite International Diagnostic Interview (CIDI) and Life Chart Interview. A higher number of pain locations (OR
=
1.10;
P
=
.008), joint pain (OR
=
1.64;
P
<
.001), ⩾90
days of pain (OR
=
1.40;
P
=
.009), daily use of pain medication (OR
=
1.57;
P
=
.047), and a higher Chronic Pain Grade score (OR
=
1.27;
P
<
.001) were associated with worse course of depressive and anxiety disorders. These associations were largely mediated by baseline severity of the mental disorder. However, joint pain remained associated with a worse course independent of baseline psychiatric characteristics. This study shows that patients with pain are more prone to a chronic course of depressive and anxiety disorders. More attention to pain seems to be necessary when diagnosing and treating these disorders
. Future research should focus on treatment modalities for this co-occurrence, with joint pain in particular.
This study examines comorbidity of alcohol abuse and alcohol dependence as well as its risk indicators among anxious and/or depressed persons, also considering temporal sequencing of disorders.
...Baseline data from the Netherlands Study of Depression and Anxiety (NESDA) were used, including 2329 persons with lifetime DSM-IV anxiety (social phobia, generalized anxiety disorder, panic disorder, and agoraphobia) and/or depressive (major depressive disorder and dysthymia) disorders and 652 controls. Lifetime diagnoses of DSM-IV alcohol abuse and dependence were established, as well as information about socio-demographic, vulnerability, addiction-related and anxiety/depression-related characteristics. Temporal sequencing of disorders was established retrospectively, using age of onset.
Of persons with combined anxiety/depression 20.3% showed alcohol dependence versus 5.5% of controls. Prevalence of alcohol abuse was similar across groups (± 12%). Independent risk indicators for alcohol dependence among anxious and/or depressed persons were male gender, vulnerability factors (family history of alcohol dependence, family history of anxiety/depression, openness to experience, low conscientiousness, being single, and childhood trauma), addiction-related factors (smoking and illicit drug use) and early anxiety/depression onset. Persons with secondary alcohol dependence were more neurotic, more often single and lonelier, while persons with primary alcohol dependence were more often male and more extravert.
Alcohol dependence, but not abuse, is more prevalent in anxious and/or depressed persons. Persons with comorbid alcohol dependence constitute a distinct subgroup of anxious and/or depressed persons, characterized by addiction-related habits and vulnerability. However, considerable variation in characteristics exists depending on temporal sequencing of disorders. This knowledge may improve identification and treatment of those anxious and/or depressed patients who are additionally suffering from alcohol dependence.
Dysregulated biological stress systems and adverse life events, independently and in interaction, have been hypothesised to initiate chronic pain. We examine whether (1) function of biological stress ...systems, (2) adverse life events, and (3) their combination predict the onset of chronic multisite musculoskeletal pain.
Subjects (n=2039) of the Netherlands Study of Depression and Anxiety, free from chronic multisite musculoskeletal pain at baseline, were identified using the Chronic Pain Grade Questionnaire and followed up for the onset of chronic multisite musculoskeletal pain over 6 years. Baseline assessment of biological stress systems comprised function of the hypothalamic-pituitary-adrenal axis (1-h cortisol awakening response, evening levels, postdexamethasone levels), the immune system (basal and lipopolysaccharide-stimulated inflammation) and the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, respiratory sinus arrhythmia). The number of recent adverse life events was assessed at baseline using the List of Threatening Events Questionnaire.
Hypothalamic-pituitary-adrenal axis, immune system and autonomic nervous system functioning was not associated with onset of chronic multisite musculoskeletal pain, either by itself or in interaction with adverse life events. Adverse life events did predict onset of chronic multisite musculoskeletal pain (HR per event=1.14, 95% CI 1.04 to 1.24, p=0.005).
This longitudinal study could not confirm that dysregulated biological stress systems increase the risk of developing chronic multisite musculoskeletal pain. Adverse life events were a risk factor for the onset of chronic multisite musculoskeletal pain, suggesting that psychosocial factors play a role in triggering the development of this condition.
Disturbed sleep has a high impact on daily functioning and has been correlated with psychopathology. We investigated the extent to which insomnia and sleep duration were associated with both current ...and remitted depressive and anxiety disorders in a large-scale epidemiologic study, taking sociodemographics, health factors, and medication use into account.
Data of 2,619 individuals from the Netherlands Study of Depression and Anxiety (NESDA) were analyzed. Psychopathology was classified as no, current, or remitted DSM-IV-based diagnosis of major depressive or anxiety disorder. Outcome measures were insomnia (Women's Health Initiative Insomnia Rating Scale score >or= 9) and sleep duration (<or= 6 hours, 7-9 hours, >or= 10 hours). Baseline measurement was conducted between September 2004 and February 2007.
Both current and remitted depressive disorder and current anxiety disorder were associated with insomnia and short sleep duration with odds ratios (ORs) for insomnia ranging from 1.42 to 3.23 and for short sleep duration ranging from 1.41 to 2.53. Associations were stronger for current than for remitted diagnoses and stronger for depressive than for anxiety disorders. Also long sleep duration was associated with current depressive disorder and anxiety disorders (OR range, 1.53-2.66). Sociodemographic factors, health indicators, and psychotropic medication use did contribute to sleep outcomes but could not explain much of the psychopathology and sleep associations.
Depressive disorder-but also anxiety disorder-is strongly associated with sleep disturbances. Insomnia and short sleep duration persist after remittance of these disorders, suggesting that these are residual symptoms or possibly trait markers. Also, long sleep duration is associated with current depressive or anxiety disorders.
Abstract Background Depression is a prevalent psychiatric disorder with high personal and public health consequences, partly due to a high risk of recurrence. This longitudinal study examines ...personality traits, structural and subjective social support dimensions as predictors of first and recurrent episodes of depression in initially non-depressed subjects. Methods Data were obtained from the Netherlands Study of Depression and Anxiety (NESDA). 1085 respondents without a current depression or anxiety diagnosis were included. 437 respondents had a prior history of depression, 648 did not. Personality dimensions were measured with the NEO-FFI, network size, partner-status, negative and positive emotional support were measured with the Close Person Questionnaire. Logistic regression analyses ( unadjusted and adjusted for clinical variables and sociodemographic variables ) examined whether these psychosocial variables predict a new episode of depression at two year follow up and whether this differed among persons with or without a history of depression. Results In the unadjusted analyses high extraversion (OR:.93, 95% CI (.91–.96), P <.001), agreeableness (OR:.94, 95% CI (.90–.97), P <.001), conscientiousness (OR:.93, 95% CI (.90–.96), P <.001) and a larger network size (OR:.76, 95% CI (.64–.90), P =.001) significantly reduced the risk of a new episode of depression. Only neuroticism predicted a new episode of depression in both the unadjusted (OR:1.13, 95% CI (1.10–1.15), P <.001) and adjusted analyses (OR:1.06, 95% CI (1.03–1.10), P <.001). None of the predictors predicted first or recurrent episodes of depression differently. Limitations we used a relatively short follow up period and broad personality dimensions. Conclusions Neuroticism seems to predict both first and recurrent episodes of depression and may be suitable for screening for preventive interventions.
To examine the predictive role of insomnia and sleep duration on the 2-year course of depressive and anxiety disorders.
This study is a secondary data analysis based on data from the baseline ...(2004-2007) and 2-year assessment of the Netherlands Study of Depression and Anxiety. Participants were 1,069 individuals with DSM-IV-based depressive and/or anxiety disorders at baseline. Sleep measures included insomnia (Women's Health Initiative Insomnia Rating Scale score ≥ 9) and sleep duration (categorized as short ≤ 6 hours, normal 7-9 hours, or long ≥ 10 hours). Outcome measures were persistence of DSM-IV depressive and anxiety disorders (current diagnosis at 2-year follow-up), time to remission, and clinical course trajectory of symptoms (early sustained remission, late remission/recurrence, and chronic course). Logistic regression analyses were adjusted for sociodemographic characteristics and chronic medical disorders, psychotropic medications, and severity of depressive and anxiety symptoms.
The effect of insomnia on persistence of depressive and/or anxiety disorders (OR = 1.50; 95% CI, 1.16-1.94) was explained by severity of baseline depressive/anxiety symptoms (adjusted OR with severity = 1.04; 95% CI, 0.79-1.37). Long sleep duration was independently associated with persistence of depression/anxiety even after adjusting for severity of psychiatric symptoms (OR = 2.52; 95% CI, 1.27-4.99). For short sleep duration, the independent association with persistence of combined depression/anxiety showed a trend toward significance (OR = 1.32; 95% CI, 0.98-1.78), and a significant association for the persistence of depressive disorders (OR = 1.49; 95% CI, 1.11-2.00). Both short and long sleep duration were independently associated with a chronic course trajectory (short sleep: OR = 1.50; 95% CI, 1.04-2.16; long sleep: OR = 2.91, 95% CI, 1.22-6.93).
Both short and long sleep duration-but not insomnia-are important predictors of a chronic course, independent of symptom severity. It is to be determined whether treating these sleep conditions results in more favorable outcomes of depression and anxiety.
Scarce evidence suggests that inflammatory and metabolic dysregulation predicts poor response to antidepressants, which could result in worse depression outcome. This study prospectively examined ...whether inflammatory and metabolic dysregulation predicted the 2-year course of depressive disorders among antidepressant users. Data were from the Netherlands Study of Depression and Anxiety, including 315 persons (18-65 years) with a current depressive disorder (major depressive disorder, dysthymia) at baseline according to the DSM-IV criteria and using antidepressants. Inflammatory (C-reactive protein, interleukin-6 (IL-6), tumor-necrosis factor-α) and metabolic (waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, fasting glucose) factors were measured at baseline. Primary outcome for course of depression was indicated by whether or not a DSM-IV depressive disorder diagnosis was still/again present at 2-year follow-up, indicating chronicity of depression. Elevated IL-6, low HDL cholesterol, hypertriglyceridemia, and hyperglycemia were associated with chronicity of depression in antidepressant users. Persons showing ⩾ 4 inflammatory or metabolic dysregulations had a 1.90 increased odds of depression chronicity (95% CI = 1.12-3.23). Among persons who recently (ie, at most 3 months) started antidepressant medication (N = 103), having ⩾ 4 dysregulations was associated with a 6.85 increased odds of depression chronicity (95% CI = 1.95-24.06). In conclusion, inflammatory and metabolic dysregulations were found to predict a more chronic course of depressive disorders among patients using antidepressants. This could suggest that inflammatory and metabolic dysregulation worsens depression course owing to reduced antidepressant treatment response and that alternative intervention treatments may be needed for depressed persons with inflammatory and metabolic dysregulation.
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