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1.
Biol Psychiatry ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31635762

RESUMO

BACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. METHODS: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. RESULTS: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q < .05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. CONCLUSIONS: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity.

2.
Diabetes ; 68(12): 2247-2258, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31492661

RESUMO

Obesity-related insulin resistance (IR) may develop in multiple organs, representing various etiologies for cardiometabolic diseases. We identified abdominal subcutaneous adipose tissue (ScAT) transcriptome profiles in liver or muscle IR by means of RNA sequencing in overweight or obese participants of the Diet, Obesity, and Genes (DiOGenes) (NCT00390637, ClinicalTrials.gov) cohort (n = 368). Tissue-specific IR phenotypes were derived from a 5-point oral glucose tolerance test. Hepatic and muscle IR were characterized by distinct abdominal ScAT transcriptome profiles. Genes related to extracellular remodeling were upregulated in individuals with primarily hepatic IR, while genes related to inflammation were upregulated in individuals with primarily muscle IR. In line with this, in two independent cohorts, the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) (n = 325) and the Maastricht Study (n = 685), an increased systemic low-grade inflammation profile was specifically related to muscle IR but not to liver IR. We propose that increased ScAT inflammatory gene expression may translate into an increased systemic inflammatory profile, linking ScAT inflammation to the muscle IR phenotype. These distinct IR phenotypes may provide leads for more personalized prevention of cardiometabolic diseases.

3.
Sci Rep ; 9(1): 9439, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263163

RESUMO

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10-8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.

4.
Int J Obes (Lond) ; 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30242234

RESUMO

BACKGROUND/OBJECTIVES: Obesity-associated insulin resistance (IR) may develop in multiple organs, representing different aetiologies towards cardiometabolic diseases. This study aimed to identify distinct plasma lipid profiles in overweight/obese individuals who show muscle-IR and/or liver-IR. SUBJECTS/METHODS: Baseline data of the European multicenter DiOGenes project were used (n = 640; 401 women, nondiabetic BMI: 27-45 kg/m2). Muscle insulin sensitivity index (MISI) and hepatic insulin resistance index (HIRI) were derived from a 5-point oral glucose tolerance test. The 140 plasma lipids were quantified by liquid chromatography-mass spectrometry. Linear mixed models were used to evaluate associations between MISI, HIRI and plasma lipids. RESULTS: MISI was comparable between sexes while HIRI and triacylglycerol (TAG) levels were lower in women than in men. MISI was associated with higher lysophosphatidylcholine (LPC) levels (standardized (std)ß = 0.126; FDR-p = 0.032). Sex interactions were observed for associations between HIRI, TAG and diacylglycerol (DAG) lipid classes. In women, but not in men, HIRI was associated with higher levels of TAG (44 out of 55 species) and both DAG species (stdß: 0.139-0.313; FDR-p < 0.05), a lower odd-chain/even-chain TAG ratio (stdß = -0.182; FDR-p = 0.005) and a lower very-long-chain/long-chain TAG ratio (stdß = -0.156; FDR-p = 0.037). CONCLUSIONS: In overweight/obese individuals, muscle insulin sensitivity is associated with higher plasma LPC concentrations. Women have less hepatic IR and lower TAG than men. Nevertheless, hepatic IR is associated with higher plasma TAG and DAG concentrations and a lower abundance of odd-chain and very-long-chain TAG in women, but not in men. This suggests a more pronounced worsening of plasma lipid profile in women with the progression of hepatic IR.

5.
J Clin Endocrinol Metab ; 103(12): 4569-4579, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30113659

RESUMO

Objective: We studied whether blood metabolomic measures in people with type 2 diabetes (T2D) are associated with insufficient glycemic control and whether this association is influenced differentially by various diabetes drugs. We then tested whether the same metabolomic profiles were associated with the initiation of insulin therapy. Methods: A total of 162 metabolomic measures were analyzed using a nuclear magnetic resonance-based method in people with T2D from four cohort studies (n = 2641) and one replication cohort (n = 395). Linear and logistic regression analyses with adjustment for potential confounders, followed by meta-analyses, were performed to analyze associations with hemoglobin A1c levels, six glucose-lowering drug categories, and insulin initiation during a 7-year follow-up period (n = 698). Results: After Bonferroni correction, 26 measures were associated with insufficient glycemic control (HbA1c >53 mmol/mol). The strongest association was with glutamine (OR, 0.66; 95% CI, 0.61 to 0.73; P = 7.6 × 10-19). In addition, compared with treatment-naive patients, 31 metabolomic measures were associated with glucose-lowering drug use (representing various metabolite categories; P ≤ 3.1 × 10-4 for all). In drug-stratified analyses, associations with insufficient glycemic control were only mildly affected by different glucose-lowering drugs. Five of the 26 metabolomic measures (apolipoprotein A1 and medium high-density lipoprotein subclasses) were also associated with insulin initiation during follow-up in both discovery and replication. The strongest association was observed for medium high-density lipoprotein cholesteryl ester (OR, 0.54; 95% CI, 0.42 to 0.71; P = 4.5 × 10-6). Conclusion: Blood metabolomic measures were associated with present and future glycemic control and might thus provide relevant cues to identify those at increased risk of treatment failure.

6.
Sleep ; 40(1)2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28364456

RESUMO

Study objective: The temporal relationships among sleep, depressive symptoms, and pain are unclear. This longitudinal study examines whether insomnia and sleep duration predict the onset of chronic multisite musculoskeletal pain over 6 years and whether this association is mediated by depressive symptoms. Methods: 1860 subjects of the Netherlands Study of Depression and Anxiety, free from chronic multisite musculoskeletal pain at baseline, were followed up for the onset of chronic multisite musculoskeletal pain over 6 years (Chronic Pain Grade Questionnaire). We determined baseline insomnia (Women's Health Initiative Insomnia Rating Scale ≥9) and sleep duration (short: ≤6 hr, normal: 7-9 hr, long: ≥10 hr). Depressive symptoms were assessed at baseline and as a change score over time (Inventory of Depressive Symptomatology). Results: Insomnia (hazard ratio [HR] [95% confidence interval, 95%CI] = 1.60 [1.30-1.96], p < .001) and short sleep duration (HR [95%CI] = 1.52 [1.22-1.90], p < .001) were associated with chronic pain onset. Adding baseline depressive symptoms as a mediator attenuated the associations for insomnia and short sleep with chronic pain onset (∆B = 40% and 26%, respectively). Adding the change score of depressive symptoms further weakened the association for insomnia (∆B = 16%) but not for short sleep. All direct effects for sleep measures with chronic pain onset remained statistically significant (p < .05). Conclusions: This longitudinal study shows that insomnia and short sleep duration are risk factors for developing chronic pain. Depressive symptoms partially mediate the effect for insomnia and short sleep with developing chronic pain.


Assuntos
Dor Crônica/etiologia , Depressão/complicações , Dor Musculoesquelética/etiologia , Distúrbios do Início e da Manutenção do Sono/complicações , Sono , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Adulto Jovem
7.
J Pain ; 18(2): 155-165, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27825856

RESUMO

Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1) function of biological stress systems, 2) adverse life events, and 3) their combination predict the improvement of chronic multisite musculoskeletal pain. Subjects of the Netherlands Study of Depression and Anxiety (NESDA) with chronic multisite musculoskeletal pain at baseline (N = 665) were followed-up 2, 4, and 6 years later. The Chronic Pain Grade Questionnaire was used to determine improvement (not meeting the criteria) of chronic multisite musculoskeletal pain at follow-up. Baseline assessment of biological stress systems included function of hypothalamic-pituitary-adrenal axis (1-hour cortisol awakening response, evening level, and post dexamethasone level), the immune system (basal and lipopolysaccharide-stimulated inflammatory markers), the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, and respiratory sinus arrhythmia). The number of adverse life events were assessed at baseline and 2-year follow-up using the List of Threatening Events Questionnaire. We showed that hypothalamic-pituitary-adrenal axis, immune system, and autonomic nervous system functioning and adverse life events were not associated with the improvement of chronic multisite musculoskeletal pain, either as a main effect or in interaction. This longitudinal study could not confirm that biological stress system dysfunction and adverse life events affect the course of chronic multisite musculoskeletal pain. PERSPECTIVE: Biological stress systems and adverse life events are not associated with the improvement of chronic multisite musculoskeletal pain over 6 years of follow-up. Other determinants should thus be considered in future research to identify in which persons pain symptoms will improve.


Assuntos
Acontecimentos que Mudam a Vida , Dor Musculoesquelética/fisiopatologia , Dor Musculoesquelética/psicologia , Estresse Fisiológico/fisiologia , Adolescente , Adulto , Idoso , Proteína C-Reativa/metabolismo , Dor Crônica , Citocinas/metabolismo , Feminino , Humanos , Hidrocortisona/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
8.
Eur J Hum Genet ; 24(10): 1488-95, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27142678

RESUMO

Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta-analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P-values=5.77 × 10(-08), 6.59 × 10(-)(08) and 9.17 × 10(-)(08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 × 10(-)(02), 7.0 × 10(-)(03) and 2.5 × 10(-)(03); combined meta-analysis P-values=5.5 × 10(-07), 5.4 × 10(-07) and 1.0 × 10(-07)). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 × 10(-316)) and the central nervous system (P-value=7.5 × 10(-)(321)). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values<2.9 × 10(-11)) that are crucial in triggering the onset of sleep. To conclude, in this first large-scale GWAS of sleep latency we report a novel association of variants in RBFOX3 gene. Further, a functional prediction of RBFOX3 supports the involvement of RBFOX3 with sleep latency.


Assuntos
Antígenos Nucleares/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Sono/genética , Encéfalo/metabolismo , Humanos , Transmissão Sináptica/genética
9.
Ann Rheum Dis ; 75(5): 847-54, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25902791

RESUMO

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.


Assuntos
Dor Crônica/etiologia , Acontecimentos que Mudam a Vida , Dor Musculoesquelética/etiologia , Estresse Fisiológico/fisiologia , Adolescente , Adulto , Idoso , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/epidemiologia , Sistema Nervoso Autônomo/fisiopatologia , Dor Crônica/epidemiologia , Dor Crônica/fisiopatologia , Estudos de Coortes , Citocinas/sangue , Transtorno Depressivo/complicações , Transtorno Depressivo/epidemiologia , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Estilo de Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/epidemiologia , Dor Musculoesquelética/fisiopatologia , Países Baixos/epidemiologia , Medição da Dor/métodos , Sistema Hipófise-Suprarrenal/fisiopatologia , Fatores de Risco , Adulto Jovem
10.
Depress Anxiety ; 33(1): 75-83, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26367018

RESUMO

BACKGROUND: The chronotype, being a morning or an evening type, can influence an individual's psychological health. Studies have shown a link between depressed mood and being an evening type; however, most studies have used symptom scales and not diagnostic criteria, and confounding factors such as sleep patterns and somatic health factors have often not been considered. This study aims to examine the association between chronotype and depressive (major depressive disorder (MDD), dysthymia) and anxiety (generalized anxiety disorder, panic disorder, agoraphobia, and social phobia) disorders diagnosed using clinical interviews, while taking into account relevant sociodemographic, clinical, somatic health, and sleep parameters. METHODS: Data from a large cohort, the Netherlands Study of Depression and Anxiety were used (n = 1,944), which included 676 currently depressed and/or anxious patients, 831 remitted patients, and 437 healthy controls. Chronotype was assessed using the Munich Chronotype Questionnaire. RESULTS: Our results showed that current depressive and/or anxiety disorders were associated with a late chronotype (ß = .10, P = .004) even when adjusting for sociodemographic, somatic health, and sleep-related factors (ß = .09, P = .03). When examining each type of disorder separately, MDD only, but not dysthymia or specific anxiety disorders, was associated with the late chronotype. The late chronotype also reported significant diurnal mood variation (worse mood in the morning). CONCLUSIONS: Our findings show a clear association between MDD and late chronotype (being an evening type), after controlling for a range of pertinent factors. A late chronotype is therefore associated with a current status of MDD and deserves the relevant clinical attention when considering treatments.


Assuntos
Transtornos de Ansiedade/psicologia , Ritmo Circadiano , Transtorno Depressivo Maior/psicologia , Adulto , Idoso , Transtornos de Ansiedade/diagnóstico , Estudos de Coortes , Transtorno Depressivo Maior/diagnóstico , Feminino , Humanos , Entrevista Psicológica , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos , Inquéritos e Questionários , Adulto Jovem
11.
J Affect Disord ; 190: 156-161, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26519635

RESUMO

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.


Assuntos
Depressão/psicologia , Transtornos da Personalidade/psicologia , Personalidade , Apoio Social , Adulto , Ansiedade/psicologia , Transtornos de Ansiedade , Comorbidade , Depressão/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Neuroticismo , Transtornos da Personalidade/epidemiologia , Inventário de Personalidade , Índice de Gravidade de Doença
12.
J Psychosom Res ; 78(2): 123-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25454680

RESUMO

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 6years of follow-up was particularly increased in subjects with more symptoms, and in those using benzodiazepines.


Assuntos
Transtornos de Ansiedade/complicações , Benzodiazepinas/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/psicologia , Transtorno Depressivo/complicações , Adulto , Ansiedade/complicações , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/tratamento farmacológico , Benzodiazepinas/administração & dosagem , Depressão/complicações , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/tratamento farmacológico , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Razão de Chances , Inventário de Personalidade , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Autorrelato , Índice de Gravidade de Doença , Inquéritos e Questionários
13.
J Psychiatr Res ; 60: 95-102, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25307717

RESUMO

Systemic inflammation has emerged as a potential pathway linking depressive and anxiety disorders with disease risk. Short and long sleep duration, as well as insomnia, are common among psychiatric populations and have previously been related to increased inflammation. The aim of the present study was to investigate associations between sleep duration and insomnia with biomarkers of inflammation and to explore whether these associations varied by psychiatric diagnostic status. To this end, self-reported measures of sleep duration, insomnia symptoms, and markers of inflammation, including C-reactive protein (CRP), interleukin-(IL)-6, and tumor necrosis factor (TNF)-α, were obtained in 2553 adults (aged 18-65 years) diagnosed with current/recent or remitted depressive and/or anxiety disorders and healthy controls enrolled in the Netherlands Study of Depression and Anxiety (NESDA). Regression analyses revealed associations between sleep duration and levels of CRP and IL-6 with higher levels observed in long sleepers. These associations remained statistically significant after controlling for age, gender, education, body mass index, smoking, alcohol consumption, medical comorbidities, medication use, psychotropic medication use, and psychiatric diagnostic status. There were no clear associations between insomnia symptoms and levels of inflammation. Relationships between sleep duration and inflammation did not vary as a function of psychiatric diagnostic status. These findings suggest that elevated levels of systemic inflammation may represent a mechanism linking long sleep duration and disease risk among those with and without depressive and anxiety disorders.


Assuntos
Ansiedade/psicologia , Biomarcadores/sangue , Depressão/psicologia , Distúrbios do Início e da Manutenção do Sono/sangue , Sono/imunologia , Adolescente , Adulto , Idoso , Ansiedade/sangue , Proteína C-Reativa/imunologia , Depressão/sangue , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Análise de Regressão , Fatores Sexuais , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
14.
BMC Musculoskelet Disord ; 15: 227, 2014 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-25007969

RESUMO

BACKGROUND: Studies on hypothalamic-pituitary-adrenal axis (HPA-axis) function amongst patients with chronic pain show equivocal results and well-controlled cohort studies are rare in this field. The goal of our study was to examine whether HPA-axis dysfunction is associated with the presence and the severity of chronic multi-site musculoskeletal pain. METHODS: Data are from the Netherlands Study of Depression and Anxiety including 1125 subjects with and without lifetime depressive and anxiety disorders. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multi-site musculoskeletal pain. Subjects were categorized into a chronic multi-site musculoskeletal pain group (n = 471) and a control group (n = 654). Salivary cortisol samples were collected to assess HPA-axis function (awakening level, 1-h awakening response, evening level, diurnal slope and post-dexamethasone level). RESULTS: In comparison with the control group, subjects with chronic multi-site musculoskeletal pain showed significantly lower cortisol level at awakening, lower evening level and a blunted diurnal slope. Lower cortisol level at awakening and a blunted diurnal slope appeared to be restricted to those without depressive and/or anxiety disorders, who also showed a lower 1-h awakening response. CONCLUSIONS: Our results suggest hypocortisolemia in chronic multi-site musculoskeletal pain. However, if chronic pain is accompanied by a depressive or anxiety disorder, typically related to hypercortisolemia, the association between cortisol levels and chronic multi-site musculoskeletal pain appears to be partly masked. Future studies should take psychopathology into account when examining HPA-axis function in chronic pain.


Assuntos
Transtornos de Ansiedade/metabolismo , Dor Crônica/metabolismo , Transtorno Depressivo/metabolismo , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Dor Musculoesquelética/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Saliva/metabolismo , Idoso , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/fisiopatologia , Biomarcadores/metabolismo , Sensibilização do Sistema Nervoso Central , Dor Crônica/diagnóstico , Dor Crônica/epidemiologia , Dor Crônica/fisiopatologia , Ritmo Circadiano , Comorbidade , Estudos Transversais , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/fisiopatologia , Regulação para Baixo , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/diagnóstico , Dor Musculoesquelética/epidemiologia , Dor Musculoesquelética/fisiopatologia , Países Baixos/epidemiologia , Medição da Dor , Sistema Hipófise-Suprarrenal/fisiopatologia , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de Tempo
15.
Psychoneuroendocrinology ; 45: 202-10, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24845191

RESUMO

BACKGROUND: Several studies have suggested that induced tryptophan (TRP) degradation through the kynurenine (KYN) pathway by the enzyme indoleamine 2,3-dioxygenase (IDO) is implicated in the relation between depression and inflammation. We investigated the role of tryptophan degradation in the relationship between inflammatory markers and depressive symptoms in the Netherlands Study of Depression and Anxiety (NESDA) and hypothesized that tryptophan degradation would mediate (part of) this association. METHODS: 2812 Participants of NESDA were included in this study including 1042 persons with current major depressive disorder (MDD). Assessments of C-reactive protein (CRP), interleukin (IL)-6, tumor-necrosis factor (TNF)-α, KYN and TRP were obtained from fasting blood samples at the baseline assessment. Tryptophan degradation was estimated by calculating the ratio [KYN/TRP]. Depressive symptoms were measured with the Inventory of Depressive Symptomatology. RESULTS: Significant associations between inflammation and depressive symptoms were found for CRP and IL-6, for the total group and the subgroup of patients with current MDD. Adjustment for KYN/TRP did not attenuate these associations. There were no significant indirect effects for CRP on depressive symptoms mediated by KYN/TRP for the whole group (B=-0.032; 95% CI: -0.103 to 0.028) and for the subgroup of patients with current MDD (B=0.059; 95% CI: -0.037 to 0.165). Also IL-6 did not indirectly affect depressive symptoms through KYN/TRP in the total group (B=-0.023; 95% CI: -0.093 to 0.045) and in the MDD subgroup B=0.052; 95% CI: -0.019 to 0.144). Finally, no significant relation between depressive symptoms and KYN/TRP was found in the whole group (ß=-0.019, p=0.311) nor in the subgroup with MDD (ß=0.025, p=0.424). CONCLUSIONS: We did not find indications for tryptophan degradation, measured by KYN/TRP, to mediate the relationship between inflammation and depressive symptoms.


Assuntos
Depressão/imunologia , Depressão/metabolismo , Mediadores da Inflamação/metabolismo , Inflamação/imunologia , Cinurenina/metabolismo , Redes e Vias Metabólicas , Triptofano/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/metabolismo , Feminino , Humanos , Sistema Imunitário/metabolismo , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Países Baixos , Proteólise , Adulto Jovem
16.
Pain ; 155(8): 1605-12, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24813297

RESUMO

Dysregulation of the immune system may play a role in chronic pain, although study findings are inconsistent. This cross-sectional study examined whether basal inflammatory markers and the innate immune response are associated with the presence and severity of chronic multisite musculoskeletal pain. Data were used on 1632 subjects of the Netherlands Study of Depression and Anxiety. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multisite musculoskeletal pain. Subjects were categorized in a chronic multisite musculoskeletal pain group (n=754) and a control group (n=878). Blood levels of the basal inflammatory markers C-reactive protein, interleukin-6, and tumor necrosis factor-alpha were determined. To obtain a measure of the innate immune response, 13 inflammatory markers were assessed after lipopolysaccharide (LPS) stimulation in a subsample (n=707). Subjects with chronic multisite musculoskeletal pain showed elevated levels of basal inflammatory markers compared with controls, but statistical significance was lost after adjustment for lifestyle and disease variables. For some LPS-stimulated inflammatory markers, we did find elevated levels in subjects with chronic multisite musculoskeletal pain both before and after adjustment for covariates. Pain severity was not associated with inflammation within chronic pain subjects. An enhanced innate immune response in chronic multisite musculoskeletal pain may be examined as a potential biomarker for the onset or perpetuation of chronic pain.


Assuntos
Dor Crônica/imunologia , Imunidade Inata/fisiologia , Inflamação/imunologia , Dor Musculoesquelética/imunologia , Adulto , Fatores Etários , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Dor Crônica/sangue , Estudos Transversais , Feminino , Humanos , Inflamação/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/sangue , Fatores Sexuais , Inquéritos e Questionários , Fator de Necrose Tumoral alfa/sangue
17.
Brain Behav Immun ; 41: 109-15, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24838021

RESUMO

Growing evidence suggests immune and metabolic dysregulation among depressed persons, possibly restricted to specific subgroups. This study explores the association between depressive disorders and characteristics with immunometabolic functioning among older persons. Data are from the baseline assessment of the Netherlands Study of Depression in Older Persons, including 131 non-depressed and 358 depressed (6-month DSM-IV major depressive disorder) persons (60-93 years). Immune (C-reactive protein, interleukin [IL]-6) and metabolic (waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, fasting glucose) factors were measured. Depression characteristics included severity, age of onset, symptom profile (atypical/melancholic) and antidepressant use. Depressed persons showed lower IL-6 levels compared with non-depressed persons. Depressed persons, except those with atypical depression, had lower waist circumference, lower glucose levels and scored lower on an overall index including all immunometabolic factors. Low waist circumference was more pronounced among those with less severe depression and those with a later age of onset, whom also had lower blood pressure levels. Atypical depression was associated with higher triglyceride levels. Antidepressant use was not clearly associated with immunometabolic functioning. To conclude, contrary to our expectations, we found overall immunometabolic downregulation in older depressed persons, in particular among those with less severe symptoms and those with late-life onset. However, persons with atypical depression presented with metabolic upregulation compared with other depressed persons. Taking depression symptom profiles into account is important when examining biological dysregulation in late-life depression.


Assuntos
Transtorno Depressivo/imunologia , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/epidemiologia , Biomarcadores , Glicemia/análise , Pressão Sanguínea , Proteína C-Reativa/análise , Doença Crônica/epidemiologia , Comorbidade , Transtorno Depressivo/classificação , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/metabolismo , Feminino , Seguimentos , Humanos , Interleucina-6/sangue , Estilo de Vida , Lipídeos/sangue , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/imunologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/psicologia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Fumar/sangue , Fumar/epidemiologia
18.
J Affect Disord ; 161: 47-54, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24751307

RESUMO

BACKGROUND: It is not well-established whether excess mortality associated with depression is higher in men than in women. METHODS: We conducted a meta-analysis of prospective studies in which depression was measured at baseline, where mortality rates were reported at follow-up, and in which separate mortality rates for men and women were reported. We conducted systematic searches in bibliographical databases and calculated relative risks of excess mortality in men and women. RESULTS: Thirteen studies were included. Among the people with depression, excess mortality in men was higher than in women (RR=1.97; 1.63-2.37). Compared with non-depressed participants, excess mortality was increased in depressed women (RR=1.55; 95% CI: 1.32-1.82), but not as much as in men (RR=2.04; 95% CI: 1.76-2.37), and the difference between excess mortality in men was significantly higher than in women (p<0.05). CONCLUSIONS: Excess mortality related to depression is higher in men than in women. Although the exact mechanisms for this difference are not clear, it may point at differential or more intensified pathways leading from depression to increased mortality in depressed men compared to women.


Assuntos
Depressão/mortalidade , Transtorno Depressivo/mortalidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Fatores Sexuais
19.
Psychoneuroendocrinology ; 42: 1-10, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24636496

RESUMO

BACKGROUND: Evidence for a role of leptin in depression is limited and conflicting. Inconclusive findings may be explained by the complex effect of obesity on leptin signaling. In particular, both hyperleptinemia due to leptin resistance in obese persons as well as low leptin in lean persons can imply that low leptin biological signaling is associated with an increased risk of significant depressive symptoms. We tested whether the relationship between leptin and depressive symptoms is modulated by abdominal adiposity in two population-based studies. METHODS: Data were from 851 participants (65-94 years) of the InCHIANTI Study and 1064 (26-93 years) of the Baltimore Longitudinal Study of Aging (BLSA). Plasma concentrations of leptin, waist circumference and depressive symptoms via the Center for Epidemiological Studies-Depression scale (CES-D) were assessed. In longitudinal InCHIANTI analyses onset of depressed mood (CES-D≥20) was evaluated over a 9-year follow-up. RESULTS: In pooled cross-sectional analyses the interaction between leptin and waist circumference was significantly associated with CES-D scores ((log)leptin-by-waist interaction p=0.01). Also in longitudinal analyses, the (log)leptin-by-waist interaction term significantly (p=0.04) predicted depressed mood onset over time; depressed mood risk was especially increased for high levels of both leptin and waist circumference. CONCLUSIONS: The present findings suggest that low leptin signaling rather than low leptin concentration is a risk factor for depression. Future studies should develop proxy measures of leptin signaling by combining information on abdominal adiposity and leptin level to be used for clinical and research applications.


Assuntos
Gordura Abdominal/fisiopatologia , Adiposidade/fisiologia , Depressão/sangue , Leptina/sangue , Circunferência da Cintura/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Depressão/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
J Psychosom Res ; 76(4): 317-21, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24630183

RESUMO

OBJECTIVE: Both low and high hemoglobin levels lead to more physical diseases, and both are linked to mortality. Low hemoglobin, often classified as anemia, has also been linked to more depressive symptoms, but whether both hemoglobin extremes are associated with depressive disorder and potentially also with anxiety disorder has not been examined before. This study examines to which extent hemoglobin levels are associated with depression and anxiety disorders in a large cohort. METHODS: The study sample consisted of 2920 persons from the Netherlands Study of Depression and Anxiety. Hemoglobin levels were determined after venipuncture. Depressive and anxiety disorders were determined according to a DSM-IV-based psychiatric interview. Clinical psychiatric characteristics included the severity of depression and anxiety, the duration of symptoms, the age of onset and the antidepressant use. RESULTS: Higher hemoglobin levels were found in those with current depressive and/or anxiety disorders after sociodemographic adjustment and both higher, and lower hemoglobin levels were found in persons with higher depression and anxiety severity. However, after full adjustment for sociodemographics, disease indicators and lifestyle, associations were no longer significant. CONCLUSIONS: This cohort study showed that there is no independent association between depressive and/or anxiety disorders and hemoglobin levels or anemia status.


Assuntos
Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/diagnóstico , Transtorno Depressivo/sangue , Transtorno Depressivo/diagnóstico , Hemoglobinas/metabolismo , Adulto , Idade de Início , Antidepressivos/uso terapêutico , Ansiedade/sangue , Ansiedade/diagnóstico , Transtornos de Ansiedade/tratamento farmacológico , Estudos de Coortes , Depressão/sangue , Depressão/diagnóstico , Transtorno Depressivo/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Índice de Gravidade de Doença
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