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BACKGROUND: Alterations in heart rate (HR) may provide new information about physiological signatures of depression severity. This 2-year study in individuals with a history of recurrent major depressive disorder (MDD) explored the intra-individual variations in HR parameters and their relationship with depression severity. METHODS: Data from 510 participants (Number of observations of the HR parameters = 6666) were collected from three centres in the Netherlands, Spain, and the UK, as a part of the remote assessment of disease and relapse-MDD study. We analysed the relationship between depression severity, assessed every 2 weeks with the Patient Health Questionnaire-8, with HR parameters in the week before the assessment, such as HR features during all day, resting periods during the day and at night, and activity periods during the day evaluated with a wrist-worn Fitbit device. Linear mixed models were used with random intercepts for participants and countries. Covariates included in the models were age, sex, BMI, smoking and alcohol consumption, antidepressant use and co-morbidities with other medical health conditions. RESULTS: Decreases in HR variation during resting periods during the day were related with an increased severity of depression both in univariate and multivariate analyses. Mean HR during resting at night was higher in participants with more severe depressive symptoms. CONCLUSIONS: Our findings demonstrate that alterations in resting HR during all day and night are associated with depression severity. These findings may provide an early warning of worsening depression symptoms which could allow clinicians to take responsive treatment measures promptly.
Assuntos
Depressão , Transtorno Depressivo Maior , Humanos , Frequência Cardíaca/fisiologia , Transtorno Depressivo Maior/tratamento farmacológico , Antidepressivos/uso terapêutico , BiomarcadoresRESUMO
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.
Assuntos
Experiências Adversas da Infância , Humanos , Adulto , Feminino , Masculino , Estudos Transversais , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Ira , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Major depressive disorder (MDD) is a heterogeneous psychiatric disorder. Childhood trauma (CT, emotional/physical/sexual abuse or neglect before the age of 18) is one of the largest and most consistent risk factors for development and poor course of MDD. Overactivity of the HPA-axis and the stress hormone cortisol is thought to play a role in the vulnerability for MDD following exposure to CT. Rodent experiments showed that antagonism of the glucocorticoid receptor (GR) at adult age reversed the effects of early life stress. Similarly, we aim to target MDD in individuals with CT exposure using the GR antagonist mifepristone. METHODS: The RESET-medication study is a placebo-controlled double-blind randomized controlled trial (RCT) which aims to include 158 adults with MDD and CT. Participants will be randomized (1:1) to a 7-day treatment arm of mifepristone (1200 mg/day) or a control arm (placebo). Participants are allowed to receive usual care for MDD including antidepressants. Measurements include three face-to-face meetings at baseline (T0), day 8 (T1), week 6 (T2), and two online follow-up meetings at 12 weeks (T3) and 6 months (T4). A subgroup of participants (N = 80) are included in a fMRI sub-study (T0, T2). The main study outcome will be depressive symptom severity as measured with the Inventory of Depressive Symptomatology-Self Rated (IDS-SR) at T2. Secondary outcomes include, among others, depressive symptom severity at other time points, disability, anxiety, sleep and subjective stress. To address underlying mechanisms mifepristone plasma levels, cortisol, inflammation, epigenetic regulation and fMRI measurements are obtained. DISCUSSION: The RESET-medication study will provide clinical evidence whether GR antagonism is a disease-modifying treatment for MDD in individuals exposed to CT. If effective, this hypothesis-driven approach may extend to other psychiatric disorders where CT plays an important role. TRIAL REGISTRATION: The trial protocol has been registered 01-02-2022 on ClinicalTrials.gov with ID "NCT05217758".
Assuntos
Experiências Adversas da Infância , Transtorno Depressivo Maior , Mifepristona , Humanos , Experiências Adversas da Infância/psicologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/psicologia , Hidrocortisona , Mifepristona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Glucocorticoides/antagonistas & inibidores , Resultado do Tratamento , AdultoRESUMO
BACKGROUND: There is increasing interest in day-to-day affect fluctuations of patients with depressive and anxiety disorders. Few studies have compared repeated assessments of positive affect (PA) and negative affect (NA) across diagnostic groups, and fluctuation patterns were not uniformly defined. The aim of this study is to compare affect fluctuations in patients with a current episode of depressive or anxiety disorder, in remitted patients and in controls, using affect instability as a core concept but also describing other measures of variability and adjusting for possible confounders. METHODS: Ecological momentary assessment (EMA) data were obtained from 365 participants of the Netherlands Study of Depression and Anxiety with current (n = 95), remitted (n = 178) or no (n = 92) DSM-IV defined depression/anxiety disorder. For 2 weeks, five times per day, participants filled-out items on PA and NA. Affect instability was calculated as the root mean square of successive differences (RMSSD). Tests on group differences in RMSSD, within-person variance, and autocorrelation were performed, controlling for mean affect levels. RESULTS: Current depression/anxiety patients had the highest affect instability in both PA and NA, followed by remitters and then controls. Instability differences between groups remained significant when controlling for mean affect levels, but differences between current and remitted were no longer significant. CONCLUSIONS: Patients with a current disorder have higher instability of NA and PA than remitted patients and controls. Especially with regard to NA, this could be interpreted as patients with a current disorder being more sensitive to internal and external stressors and having suboptimal affect regulation.
Assuntos
Transtornos de Ansiedade/psicologia , Transtorno Depressivo/psicologia , Avaliação Momentânea Ecológica , Afeto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Studies investigating the link between depressive symptoms and inflammation have yielded inconsistent results, which may be due to two factors. First, studies differed regarding the specific inflammatory markers studied and covariates accounted for. Second, specific depressive symptoms may be differentially related to inflammation. We address both challenges using network psychometrics. METHODS: We estimated seven regularized Mixed Graphical Models in the Netherlands Study of Depression and Anxiety (NESDA) data (N = 2321) to explore shared variances among (1) depression severity, modeled via depression sum-score, nine DSM-5 symptoms, or 28 individual depressive symptoms; (2) inflammatory markers C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α); (3) before and after adjusting for sex, age, body mass index (BMI), exercise, smoking, alcohol, and chronic diseases. RESULTS: The depression sum-score was related to both IL-6 and CRP before, and only to IL-6 after covariate adjustment. When modeling the DSM-5 symptoms and CRP in a conceptual replication of Jokela et al., CRP was associated with 'sleep problems', 'energy level', and 'weight/appetite changes'; only the first two links survived covariate adjustment. In a conservative model with all 38 variables, symptoms and markers were unrelated. Following recent psychometric work, we re-estimated the full model without regularization: the depressive symptoms 'insomnia', 'hypersomnia', and 'aches and pain' showed unique positive relations to all inflammatory markers. CONCLUSIONS: We found evidence for differential relations between markers, depressive symptoms, and covariates. Associations between symptoms and markers were attenuated after covariate adjustment; BMI and sex consistently showed strong relations with inflammatory markers.
Assuntos
Depressão/fisiopatologia , Inflamação/psicologia , Psicopatologia/métodos , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/análise , Depressão/sangue , Depressão/epidemiologia , Feminino , Humanos , Inflamação/sangue , Inflamação/fisiopatologia , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Fumar/epidemiologia , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVE: Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acid (PUFA) alterations in patients with major depressive disorder (MDD) have been shown to persist after remission. Whether these alterations are risk factors for MDD recurrence remains unknown. Here, we examined whether fatty acids predict time until MDD recurrence in remitted MDD patients. METHODS: Data were used from remitted MDD patients of the Netherlands Study of Depression and Anxiety (n = 356) and the Depression Evaluation Longitudinal Therapy Assessment studies (n = 118). Associations of FAs with time until MDD recurrence up to 8-year follow-up were analyzed using Cox regression analyses. Study-specific estimates were pooled using mega- and meta-analysis techniques. RESULTS: 27.5% (NESDA) and 56.8% (DELTA) participants had an MDD recurrence. Pooled results showed that no FA was significantly associated with time until MDD recurrence (n-3 PUFAs: hazard ratio (HR) = 1.17, 95% confidence interval (CI) = 0.98-1.41, P = 0.082; n-6 PUFAs: HR = 1.08, 95% CI = 0.84-1.38, P = 0.55). CONCLUSION: In remitted MDD patients, circulating PUFAs were not associated with prospective risk of MDD recurrence. Consequently, circulating PUFAs are unlikely to reflect a vulnerability marker for recurrence, so correcting n-3 PUFA 'deficits' through supplementation does not seem a promising option to prevent MDD recurrence.
Assuntos
Transtorno Depressivo Maior/metabolismo , Ácidos Graxos/metabolismo , Adolescente , Adulto , Idoso , Transtorno Depressivo Maior/sangue , Ácidos Graxos/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/sangue , Ácidos Graxos Ômega-6/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Prospectivos , Recidiva , Análise de Regressão , Adulto JovemRESUMO
We aimed to detect Attention-deficit/hyperactivity (ADHD) risk-conferring genes in adults. In children, ADHD is characterized by age-inappropriate levels of inattention and/or hyperactivity-impulsivity and may persists into adulthood. Childhood and adulthood ADHD are heritable, and are thought to represent the clinical extreme of a continuous distribution of ADHD symptoms in the general population. We aimed to leverage the power of studies of quantitative ADHD symptoms in adults who were genotyped. Within the SAGA (Study of ADHD trait genetics in adults) consortium, we estimated the single nucleotide polymorphism (SNP)-based heritability of quantitative self-reported ADHD symptoms and carried out a genome-wide association meta-analysis in nine adult population-based and case-only cohorts of adults. A total of n = 14,689 individuals were included. In two of the SAGA cohorts we found a significant SNP-based heritability for self-rated ADHD symptom scores of respectively 15% (n = 3656) and 30% (n = 1841). The top hit of the genome-wide meta-analysis (SNP rs12661753; p-value = 3.02 × 10-7) was present in the long non-coding RNA gene STXBP5-AS1. This association was also observed in a meta-analysis of childhood ADHD symptom scores in eight population-based pediatric cohorts from the Early Genetics and Lifecourse Epidemiology (EAGLE) ADHD consortium (n = 14,776). Genome-wide meta-analysis of the SAGA and EAGLE data (n = 29,465) increased the strength of the association with the SNP rs12661753. In human HEK293 cells, expression of STXBP5-AS1 enhanced the expression of a reporter construct of STXBP5, a gene known to be involved in "SNAP" (Soluble NSF attachment protein) Receptor" (SNARE) complex formation. In mouse strains featuring different levels of impulsivity, transcript levels in the prefrontal cortex of the mouse ortholog Gm28905 strongly correlated negatively with motor impulsivity as measured in the five choice serial reaction time task (r2 = - 0.61; p = 0.004). Our results are consistent with an effect of the STXBP5-AS1 gene on ADHD symptom scores distribution and point to a possible biological mechanism, other than antisense RNA inhibition, involved in ADHD-related impulsivity levels.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Proteínas do Tecido Nervoso/genética , Proteínas R-SNARE/genética , RNA Longo não Codificante/genética , Adulto , Animais , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Estudos de Coortes , DNA Antissenso/genética , DNA Antissenso/metabolismo , Feminino , Predisposição Genética para Doença/genética , Genética Populacional/métodos , Estudo de Associação Genômica Ampla , Genótipo , Células HEK293 , Humanos , Masculino , Camundongos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , RNA Longo não Codificante/metabolismo , Fatores de RiscoRESUMO
Alterations in cellular aging, indexed by leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn), might partly account for the increased health risks in persons with depression. Although some studies indeed found cross-sectional associations of depression with LTL and mtDNAcn, the longitudinal associations remain unclear. This 10-year longitudinal study examined between- and within-person associations of depressive symptoms with LTL and mtDNAcn in a large community sample. Data are from years 15, 20 and 25 follow-up evaluations in 977 subjects from the Coronary Artery Risk Development in Young Adults study. Depressive symptoms (years 15, 20, 25) were assessed with the Center for Epidemiologic Studies Depression (CES-D) scale; LTL (years 15, 20, 25) and mtDNAcn (years 15, 25) were measured in whole blood by quantitative PCR. With mixed-model analyses, we explored between- and within-person associations between CES-D scores and cellular aging markers. Results showed that high levels of depressive symptomatology throughout the 10-year time span was associated with shorter average LTL over 10 years (B=-4.2; P=0.014) after covarying for age, sex, race and education. However, no within-person association was found between depressive symptoms and LTL at each year (B=-0.8; P=0.548). Further, we found no between-person (B=-0.2; P=0.744) or within-person (B=0.4; P=0.497) associations between depressive symptomatology and mtDNAcn. Our results provide evidence for a long-term, between-person relationship of depressive symptoms with LTL, rather than a dynamic and direct within-person relationship. In this study, we found no evidence for an association between depressive symptoms and mtDNAcn.
Assuntos
DNA Mitocondrial/genética , Depressão/genética , Telômero/genética , Adulto , Senescência Celular , Estudos Transversais , Variações do Número de Cópias de DNA/genética , Depressão/metabolismo , Transtorno Depressivo/metabolismo , Feminino , Estudos de Associação Genética/métodos , Humanos , Leucócitos/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mitocôndrias , Fatores de Risco , Encurtamento do TelômeroRESUMO
PURPOSE: To examine the moderating role of mastery in the association of local fast-food restaurants (FFR) with diet quality and systolic blood pressure (SBP). METHODS: We used cross-sectional data from 1543 adults participating in wave six of the Netherlands Study of Depression and Anxiety (NESDA). Data were collected between 2013 and 2016. Diet quality was defined by adherence with the dietary approaches to stop hypertension (DASH) diet. Individuals reported on their food consumption through a food frequency questionnaire and SBP was measured. Density of FFR in 1600 m, 800 m and 400 m circular buffers around the home postal code was calculated using Geographic Information Systems. We assessed the association between density of FFR, diet and SBP using linear regression analyses, testing for moderation by mastery. RESULTS: Mean age was 52 years and 32.2% of the sample were men. Exposure to FFR ranged from 0 to 35 FFR per km2. Density of FFR was not significantly associated with DASH adherence or SBP. Only one out of the six interaction terms was significant, suggesting that for individuals with lower levels of mastery, higher density of FFR in an 800-m buffer was negatively associated with DASH adherence, while for individuals with higher levels of mastery, this association was positive. CONCLUSIONS: Exposure to FFR was not associated with diet quality and SBP, and we observed little evidence for moderation by level of mastery. This research question should be further explored in a large sample of healthy adults.
Assuntos
Abordagens Dietéticas para Conter a Hipertensão/estatística & dados numéricos , Fast Foods/estatística & dados numéricos , Hipertensão/prevenção & controle , Cooperação do Paciente/estatística & dados numéricos , Pressão Sanguínea , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Restaurantes , Inquéritos e QuestionáriosRESUMO
Earlier cross-sectional research showed that a higher level of mindful eating is associated with less depression. This study investigated associations of attentive mindful eating with change in depressive symptoms, as well as mediation by psychological eating styles, in the Longitudinal Aging Study Amsterdam (nâ¯=â¯946). The mindful eating domains Focused Eating, Eating in response to Hunger and Satiety Cues, Eating with Awareness and Eating without Distraction were measured by the Mindful Eating Behavior Scale. Three-year change in depressive symptoms was measured with the Center for Epidemiologic Studies Depression Scale. Emotional, external and restrained eating were measured by the 20-item version of the Dutch Eating Behaviour Questionnaire. Higher baseline scores on Focused Eating, Eating with Awareness and Eating without Distraction were associated with a 3-year decrease in depressive symptoms. Eating in response to Hunger and Satiety Cues was not associated with a change in depressive symptoms. Multiple mediation models showed mediation by external eating for the domains Eating with Awareness, Eating without Distraction, and Eating in response to Hunger and Satiety Cues, but no mediation by emotional and restrained eating. No mediation by the eating styles was found for Focused Eating. In this study, higher scores on three mindful eating domains were associated with a decrease in depressive symptoms. Mediation analyses suggest that three domains are associated with depression through external eating.
Assuntos
Depressão/epidemiologia , Comportamento Alimentar/psicologia , Atenção Plena , Idoso , Conscientização , Sinais (Psicologia) , Feminino , Humanos , Fome , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos , SaciaçãoRESUMO
BACKGROUND: The naturalistic course of major depressive disorder (mdd) and risk indicators for recurrence and chronicity of mdd are best investigated using a psychiatric epidemiological population study without clear selection bias. However, such studies are scarce, thereby limiting clinical decision-making concerning the monitoring and maintenance of treatment.
AIM: To present findings from the Netherlands Mental Health Survey and Incidence Study-2 (nemesis-2) regarding the recurrence and chronicity of mdd and associated risk indicators in the general population.
METHOD: At baseline, two groups were selected to examine the recurrence and chronicity of mdd at follow-up. Diagnoses were assessed with the Composite International Diagnostic Interview (cidi) 3.0.
RESULTS: Among respondents with remitted mdd (n = 746), the cumulative recurrence rate was 4.3% at 5 years, 13.4% at 10 years, and 27.1% at 20 years. Time to recurrence was predicted by vulnerability characteristics (childhood abuse, negative life events, parental psychopathology), physical health, functioning, clinical characteristics of depression (previous episodes, severity, medication use), psychiatric comorbidity and mental health use. Among respondents with current mdd (n = 242), 12% developed a chronic depressive episode over 6 years. The chronic course was predicted by risk indicators similar to those for recurrence, except for vulnerability characteristics and physical health.
CONCLUSION: These risk indicators may help identify depressive patients requiring monitoring and who might benefit from preventive interventions or maintenance treatment.
RESUMO
BACKGROUND: Literature has shown that obesity, metabolic syndrome and inflammation are associated with depression, however, evidence suggests that these associations are specific to atypical depression. Which of the atypical symptoms are driving associations with obesity-related outcomes and inflammation is unknown. We evaluated associations between individual symptoms of depression (both atypical and non-atypical) and body mass index (BMI), metabolic syndrome components and inflammatory markers. METHODS: We included 808 persons with a current diagnosis of depression participating in the Netherlands Study of Depression and Anxiety (67% female, mean age 41.6 years). Depressive symptoms were derived from the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology. Univariable and multivariable regression analyses adjusting for sex, age, educational level, depression severity, current smoking, physical activity, anti-inflammatory medication use, and statin use were performed. RESULTS: Increased appetite was positively associated with BMI, number of metabolic syndrome components, waist circumference, C-reactive protein and tumor necrosis factor-α. Decreased appetite was negatively associated with BMI and waist circumference. Psychomotor retardation was positively associated with BMI, high-density lipoprotein cholesterol and triglycerides, and insomnia with number of metabolic syndrome components. CONCLUSION: Increased appetite - in the context of a depressive episode - was the only symptom that was associated with both metabolic as well as inflammatory markers, and could be a key feature of an immuno-metabolic form of depression. This immuno-metabolic depression should be considered in clinical trials evaluating effectiveness of compounds targeting metabolic and inflammatory pathways or lifestyle interventions.
Assuntos
Biomarcadores , Transtorno Depressivo/complicações , Inflamação/complicações , Síndrome Metabólica/complicações , Adulto , Índice de Massa Corporal , Proteína C-Reativa/análise , HDL-Colesterol/sangue , Transtorno Depressivo/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Estudos Longitudinais , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Países Baixos , Análise de Regressão , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue , Circunferência da CinturaRESUMO
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.
Assuntos
Leucócitos , Personalidade/genética , Telômero , Adulto , Transtornos de Ansiedade , Caráter , Comportamento Cooperativo , Transtorno Depressivo , Extroversão Psicológica , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos , Neuroticismo , Inventário de Personalidade , Estresse Psicológico/psicologia , Personalidade Tipo DRESUMO
The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
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Córtex Cerebral/patologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/patologia , Adolescente , Adulto , Encéfalo/patologia , Córtex Cerebral/diagnóstico por imagem , Feminino , Lobo Frontal/patologia , Substância Cinzenta/patologia , Giro do Cíngulo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Neuroimagem/métodos , Neuroimagem/psicologia , Córtex Pré-Frontal/patologia , Lobo Temporal/patologiaRESUMO
OBJECTIVE: The naturalistic course of major depressive disorder (MDD) and risk indicators for recurrence and chronicity are best studied using a population sample without clear selection bias. However, such studies are scarce. This limits clinical decision-making concerning monitoring and maintenance treatment. METHOD: Data were used from the Netherlands Mental Health Survey and Incidence Study-2, a psychiatric epidemiological cohort study among a representative adult population. Two groups at baseline were selected to study recurrence and chronicity of MDD at follow-up. Diagnoses were assessed with the Composite International Diagnostic Interview 3.0. RESULTS: Among remitted MDD cases (n = 746), the cumulative recurrence rate was 4.3% at 5 years, 13.4% at 10 years and 27.1% at 20 years. Time to recurrence was predicted by vulnerability characteristics (childhood abuse, negative life events, parental psychopathology), physical health, functioning, clinical characteristics of depression (previous episodes, severity, medication use), psychiatric comorbidity and mental health use. Among current MDD cases (n = 242), 12% developed a chronic depressive episode over 6 years. Chronic course was predicted by similar risk indicators as recurrence, except for vulnerability characteristics and physical health. CONCLUSION: These risk indicators may help to identify patients requiring monitoring and who could benefit from preventive interventions or maintenance treatment.
Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/estatística & dados numéricos , Filho de Pais com Deficiência/estatística & dados numéricos , Transtorno Depressivo Maior/epidemiologia , Progressão da Doença , Acontecimentos que Mudam a Vida , Adolescente , Adulto , Doença Crônica , Comorbidade , Transtorno Depressivo Maior/fisiopatologia , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Recidiva , Fatores de Risco , Adulto JovemRESUMO
Testosterone is involved in many processes like aggression and mood disorders. As it may easily diffuse from blood into saliva, salivary testosterone is thought to reflect plasma free testosterone level. If so, it would provide a welcome noninvasive and less stressful alternative to blood sampling. Past research did not reveal consensus regarding the strength of the association, but sample sizes were small. This study aimed to analyse the association in a large cohort. In total, 2,048 participants (age range 18-65 years; 696 males and 1,352 females) were included and saliva (using cotton Salivettes) and plasma were collected for testosterone measurements. Levels were determined by enzyme-linked immunosorbent assay and radioimmunoassay respectively. Free testosterone was calculated by the Vermeulen algorithm. Associations were determined using linear regression analyses. Plasma total and free testosterone showed a significant association with salivary testosterone in men (adjusted ß = .09, p = .01; and ß = .15, p < .001, respectively) and in women (adjusted ß = .08, p = .004; and crude ß = .09, p = .002 respectively). The modest associations indicate that there are many influencing factors of both technical and biological origin.
Assuntos
Saliva/química , Testosterona/análise , Adolescente , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Testosterona/sangue , Adulto JovemRESUMO
BACKGROUND: The goal of personalised medicine is to adapt the therapy precisely to an individual's specific needs. But how can we practise personalised medicine from a scientific perspective?
AIM: To discuss how we can progress from a science based on group findings to a science based on individual cases.
METHOD: We will outline various research designs that may be helpful for investigating an approach to personalised medicine.
RESULTS: One approach is to focus on more homogenous groups, e.g. using symptom dimensions or by dividing the groups on the basis of biomarkers, sociomarkers or psychomarkers. Another approach is to study variations within an individual, adjusting the intervention precisely to the individual, both in terms of content and timing.
CONCLUSION: Designs that allow for a scientific approach to personalised medicine should improve our understanding of what is happening to a specific individual and enable us to select the most suitable intervention for a specific individual.
Assuntos
Medicina de Precisão , Psiquiatria/tendências , Biomarcadores , Pesquisa Biomédica , HumanosRESUMO
BACKGROUND: Relatively little research has been conducted that can reliably be used by psychiatrists, psychologists and general practitioners to estimate the recovery time of their patients suffering from depression. The treatment guideline for depression submits that half of those with mdd will recover within three months.
AIM: To present the findings from nemesis-2 (the Netherlands Mental Health Survey and Incidence Study-2) on both the duration of depressive episodes in the general population and associated risk indicators.
METHOD: The respondents that had developed a depressive episode between the first two follow-up assessments were selected; 286 with a clinical depression according to dsm-iv criteria (mdd) and 107 with a subclinical depression (MinDD). The episode duration was assessed with the Life Chart Interview.
RESULTS: Half of the patients with mdd recovered within 6 months and 12% had not recovered after 3 years. The mean duration for mdd was 10.7 months. Better physical and mental health before depression onset predicted shorter duration. Longer duration was associated with comorbid dysthymia or anxiety disorder. In comparison, the median duration of MinDD was half the length of mdd (3 months), whereas the mean duration (8.7 months), the percentage that had not recovered after 3 years (10%) and risk indicators for episode duration hardly differed.
CONCLUSION: In the guideline for depression it is assumed that half of those with mdd will recover within three months. Our study, however, found the median duration of mdd to be twice as long. Consequently, only a short period without active treatment can be justified. This paper also concludes that MinDD cannot be regarded as a transient, self-limiting mood state.
RESUMO
BACKGROUND: Oxidative 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. METHOD: Data 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. RESULTS: F2-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). CONCLUSION: Contrary 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.