Search

Background: Low-grade inflammation (LGI) and endothelial dysfunction (ED) might play a key role in the development of depression. We investigated the associations and mediation of LGI and ED with four-year incidence and course of depressive symptoms (remitted, recurrent or persistent)., Design, Setting, Participants, Measurements: In this prospective cohort study (mean age 59.6 ± 8.2 years, 48.9% women, 26.6% diabetes by design), Cox and multinomial regression analyses, adjusted for age, sex, educational level and diabetes status were used to investigate the associations of LGI and ED with onset and course of depressive symptoms as assessed by the PHQ-9 questionnaire., Results: During 10,847 person-years of follow-up, 264 participants developed incident depression. Higher levels of LGI (OR [95%CI] per SD 1.32[1.16-1.49], p < 0.001) and ED (1.26[1.11-1.43], p < 0.001) were associated with incident depressive symptoms. In mediation analysis, 60% of the total effect of ED with incident depressive symptoms could be attributed to LGI. 76 out of 2637 participants had a persistent course of depressive symptoms. Higher levels of LGI (1.75[1.40-2.19], p < 0.001) and ED (1.33[1.04-1.71], p = 0.021) were associated with a persistent course of depressive symptoms. Higher ED was more strongly associated with persistent depressive symptoms (1.33[1.04-1.71], p = 0.021), while LGI was associated with remission of depression symptoms., Conclusions: LGI and ED were both associated with incident depressive symptoms, where the latter association was substantially mediated by LGI. ED was further associated with a persistent course of depressive symptoms, while LGI was not. These results suggest a temporal, vascular contribution of both LGI and ED to the etiology and chronicity of depressive symptoms., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To identify caregiver profiles of persons with mild to moderate dementia and to investigate differences between identified caregiver profiles, using baseline data of the international prospective cohort study Actifcare., Methods: A latent class analysis was used to discover different caregiver profiles based on disease related characteristics of 453 persons with dementia and their 453 informal caregivers. These profiles were compared with regard to quality of life (CarerQoL score), depressive symptoms (HADS-D score) and perseverance time., Results: A 5-class model was identified, with the best Bayesian Information Criterion value, significant likelihood ratio test (p < 0.001), high entropy score (0.88) and substantive interpretability. The classes could be differentiated on two axes: (i) caregivers' age, relationship with persons with dementia, severity of dementia, and (ii) tendency towards stress and difficulty adapting to stress. Classes showed significant differences with all dependent variables, and were labelled 'older low strain', 'older intermediate strain', 'older high strain', 'younger low strain' and 'younger high strain'., Conclusion: Differences exist between types of caregivers that explain variability in quality of life, depressive symptoms and perseverance time. Our findings may give direction for tailored interventions for caregivers of persons with dementia, which may improve social health and reduce health care costs.

Background: Depression is a highly prevalent disease with a high morbidity and mortality risk. Its pathophysiology is not entirely clear. However, type 2 diabetes is an important risk factor for depression. One mechanism that may explain this association may include the formation of advanced glycation end products (AGEs). We therefore investigated the association of AGEs with depressive symptoms and depressive disorder. In addition, we examined whether the potential association was present for somatic and/or cognitive symptoms of depression., Methods: Cross-sectional data were used from the Maastricht Study (N = 862, mean age 59.8 ± 8.5 years, 55% men). AGE accumulation was measured with skin autofluorescence (SAF) by use of the AGE Reader. Plasma levels of protein-bound pentosidine were measured with high-performance liquid chromatography and fluorescence detection. Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) were measured with ultraperformance liquid chromatography and tandem mass spectrometry. Depressive symptoms and depressive disorder were assessed by the nine-item Patient Health Questionnaire and the Mini-International Neuropsychiatric Interview., Results: Higher SAF was associated with depressive symptoms (β = 0.42, 95% CI 0.12-0.73, P = .007) and depressive disorder (OR = 1.42, 95% CI 1.04-1.95, P = .028) after adjustment for age, sex, type 2 diabetes, smoking, BMI, and kidney function. Plasma pentosidine, CML, and CEL were not independently associated with depressive symptoms and depressive disorder., Conclusions: This study shows that AGE accumulation in the skin is independently associated with higher levels of depressive symptoms and depressive disorder. This association is present for both somatic and cognitive symptoms of depression. This might suggest that AGEs are involved in the development of depression., (© 2016 Wiley Periodicals, Inc.)

Objectives: To assess the psychometric properties and identify the best cutoff value of the Patient Health Questionnaire-9 (PHQ-9) for depression screening in individuals with type 2 diabetes mellitus (T2DM)., Design: Observational population-based cohort study., Setting: The Maastricht Study., Participants: Individuals with and without T2DM (mean age 58.6 ± 8.1, 44.6% male) according to an oral glucose tolerance test (N = 2,997)., Measurements: Depressive disorder and depressive symptoms were measured using the Mini-International Neuropsychiatric Interview (MINI) as the reference and the PHQ-9. Cronbach alpha, Cohen's kappa and receiver operating characteristic (ROC) analyses were used. Differences in factorial structure between participants with and without T2DM were tested using multigroup confirmatory factor analysis., Results: Based on the traditional PHQ-9 cutoff value, 133 (4.4%) participants had depressive symptoms (PHQ-9 score ≥10). Internal consistency of the PHQ-9 was good (Cronbach α = 0.87 with T2DM, 0.82 without T2DM), the kappa of agreement between the PHQ-9 and the MINI was moderate (0.40 with T2DM, 0.43 without T2DM). Area under the ROC curve for the PHQ-9 was 0.87 in participants with T2DM and 0.88 in those without. A PHQ-9 cutoff score of 5 provided the best sensitivity (92.3%), with acceptable specificity (70.4%), for T2DM, similar to sensitivity and specificity in individuals without T2DM. Factor analysis suggested a similar two-factor structure in both groups (affective and somatic symptoms)., Conclusion: Patient Health Questionnaire-9 performs well as a screening tool for depressive symptoms in individuals with and without T2DM based on the cutoff value of 5, indicating that the PHQ-9 can be used in two-stage screening in primary care to select individuals with T2DM for further psychological evaluation., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

Background: The pathogenesis of depression may involve low-grade inflammation and endothelial dysfunction. We aimed to evaluate the independent associations of inflammation and endothelial dysfunction with depressive symptoms and depressive disorder, and the role of lifestyle factors in this association., Methods: In The Maastricht Study, a population-based cohort study (n=852, 55% men, m=59.8±8.5years), depressive symptoms were assessed with the Patient Health Questionnaire-9 and (major and minor) depressive disorder with the Mini-International Neuropsychiatric Interview. Plasma biomarkers of inflammation (hsCRP, SAA, sICAM-1, IL-6, IL-8, TNF-α) and endothelial dysfunction (sVCAM-1, sICAM-1, sE-selectin, vWF) were measured with sandwich immunoassays and combined into two standardized sum scores., Results: Biomarkers of inflammation (hsCRP, TNF-α, SAA, sICAM-1) and endothelial dysfunction (sICAM-1, sE-Selectin) were univariately associated with depressive symptoms and depressive disorder. The sum scores of inflammation and endothelial dysfunction were associated with depressive disorder after adjustment for age, sex, type 2 diabetes, kidney function and prior cardiovascular disease (OR 1.54, p=0.001 and 1.40, p=0.006). Both sum scores remained significantly associated with depressive disorder after additional adjustment for lifestyle factors smoking, alcohol consumption and body mass index. The sum score of inflammation was also independently associated with depressive symptoms, while the sum score of endothelial dysfunction was not., Conclusions: Inflammation and endothelial dysfunction are both associated with depressive disorder, independent of lifestyle factors. Our results might suggest that inflammation and endothelial dysfunction are involved in depression., (Copyright © 2016. Published by Elsevier Inc.)

Objectives: The impact of the dementia might be more severe for caregivers of people with young onset dementia (YOD) compared with those who care for someone with late onset dementia (LOD), as a young age among caregivers has been identified as a predictor of increased burden. The present study compares well-being between LOD and YOD caregivers longitudinally because this knowledge is essential in order to develop adequate support programs., Design, Setting, and Participants: 220 YOD and 108 LOD patient-caregiver dyads were included from two prospective cohorts with a 2-year follow up. To assess well-being we used the Short Sense of Competence Questionnaire, the RAND-36, the Symptom Checklist 90, and the Montgomery Asberg Depression Rating Scale. The severity and the course of the different measures used to describe caregiver burden were analyzed with linear mixed models., Results: Caregivers in both groups experienced high levels of physical and psychological complaints, mild depressive symptoms, lower health-related quality of life (HRQoL), and decreased feelings of competence. The severity and the course of most measures were similar in both groups, although HRQoL on both the physical and the mental domain was lower for the YOD caregivers., Conclusions: The number of actual psychological and physical complaints does not differ between YOD and LOD caregivers. YOD caregivers have greater perceived difficulties in daily life because of these complaints, however., (Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Cognitive impairment and neuropsychiatric syndromes, like depression and apathy, are frequent residual consequences of stroke. These have a large impact on quality of life and long-term prognosis. Several factors are involved in the development of these residual syndromes, although their exact role and their interrelationships remain still rather unclear. The Cognition and Affect after Stroke: a Prospective Evaluation of Risks (CASPER) study has been primarily designed to examine whether stroke-specific (e.g. lesion location, volume, type, severity), cerebrovascular and neurodegenerative (e.g. white matter changes, atrophy, microbleeds, perivascular spaces), inflammatory, endothelial, and (epi)genetic markers are associated with cognitive impairment, post-stroke depression, and post-stroke apathy, and whether they predict their course over 12 months. The secondary aims are to investigate how the above-mentioned markers interact with each other, and to determine if patients with apathy and depression after stroke differ in pathogenesis, course, and outcome (e.g. functional outcome, neurocognitive performance, quality of life)., Methods/design: CASPER is a 1-year prospective clinical cohort follow-up study in 250 stroke patients recruited at the neurological in- and outpatient services at Maastricht University Medical Center (MUMC+, Maastricht, The Netherlands), and Zuyderland Medical Center (Sittard and Heerlen, The Netherlands). At baseline (3 months post-stroke), a neuropsychological assessment, neuropsychiatric interview, blood sample, and brain magnetic resonance imaging (MRI) scan are conducted. Assessment of neuropsychiatric and neurocognitive status are repeated 6 and 12 months later., Discussion: The CASPER study investigates stroke-specific, vascular, neurodegenerative, inflammatory, and genetic markers of the development of vascular cognitive impairment, depression, and apathy after stroke. This creates the possibility to study not only the contribution of these individual markers but also their joint contribution, which differentiates this study from earlier stroke cohorts who lacked long-term follow-up data, a large sample size, an extensive MRI protocol, and markers from the blood. The knowledge we derive from this study might help in identifying markers that are associated with, or can predict the onset, maintenance, and progression of vascular cognitive impairment, depression, and apathy after stroke, and could provide new insights into possibilities for treatment and rehabilitation that result in better functional outcome after stroke., Trial Registration: ClinicalTrials.gov NCT02585349.

Background: Strong longitudinal evidence exists that psychological distress is associated with a high morbidity and mortality risk in type 2 diabetes. Little is known about the biological and behavioral mechanisms that may explain this association. Moreover, the role of personality traits in these associations is still unclear. In this paper, we first describe the design of the psychological part of The Maastricht Study that aims to elucidate these mechanisms. Next, we present exploratory results on the prevalence of depression, anxiety and personality traits in type 2 diabetes. Finally, we briefly discuss the importance of these findings for clinical research and practice., Methods: We measured psychological distress and depression using the MINI diagnostic interview, the PHQ-9 and GAD-7 questionnaires in the first 864 participants of The Maastricht Study, a large, population-based cohort study. Personality traits were measured by the DS14 and Big Five personality questionnaires. Type 2 diabetes was assessed by an oral glucose tolerance test. Logistic regression analyses were used to estimate the associations of depression, anxiety and personality with type 2 diabetes, adjusted for age, sex and education level., Results: Individuals with type 2 diabetes had higher levels of depressive and anxiety symptoms, odds ratios (95 % CI) were 3.15 (1.49; 6.67), 1.73 (0.83-3.60), 1.50 (0.72-3.12), for PHQ-9 ≥ 10, current depressive disorder and GAD-7 ≥ 10, respectively. Type D personality, social inhibition and negative affectivity were more prevalent in type 2 diabetes, odds ratios were 1.95 (1.23-3.10), 1.35 (0.93-1.94) and 1.70 (1.14-2.51), respectively. Individuals with type 2 diabetes were less extraverted, less conscientious, less agreeable and less emotionally stable, and similar in openness to individuals without type 2 diabetes, although effect sizes were small., Conclusions: Individuals with type 2 diabetes experience more psychological distress and have different personality traits compared to individuals without type 2 diabetes. Future longitudinal analyses within The Maastricht Study will increase our understanding of biological and behavioral mechanisms that link psychological distress to morbidity and mortality in type 2 diabetes.

Background: Type D personality - the combination of negative affectivity (NA) and social inhibition (SI) - has been associated with depression but little is known about underlying mechanisms. We examined whether (1) Type D is a vulnerability factor for depression in general, (2) Type D is associated with inflammation or endothelial dysfunction, and (3) these biomarkers alter the possible association between Type D and depression., Methods: In the Maastricht Study, 712 subjects underwent assessment of NA, SI and Type D personality (DS14), depressive disorder (Mini-International Neuropsychiatric Interview) and depressive symptoms (Patient Health Questionnaire-9). Plasma biomarkers of inflammation (hsCRP, SAA, sICAM-1, IL-6, IL-8, TNF-α) and endothelial dysfunction (sVCAM-1, sICAM-1, E-selectin, vWF) were measured with sandwich immunoassays or ELISA and combined into standardized sumscores., Results: Regarding personality, 49% of the study population was low in NA and SI, 22% had SI only, 12% NA only and 17% had Type D. Depressive disorder and depressive symptoms were significantly more prevalent in Type D versus the other three personality subgroups. Multivariable regression analyses showed that Type D was associated with inflammation (β=0.228, p=0.014) and endothelial dysfunction (β=0.216, p=0.022). After adjustment for these biomarkers, Type D remained independently associated with increased vulnerability to depressive disorder (OR=13.20, p<0.001) and depressive symptoms (β=3.87, p<0.001)., Limitations: The cross-sectional design restrained us to draw any conclusions on causality. The relatively low prevalence of depressive disorder restrained us to adjust for more potential confounders., Conclusions: Type D personality may be a vulnerability factor for depression, irrespective of levels of inflammation or endothelial dysfunction. Future research should examine possible underlying mechanisms., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: To examine the relationships between executive functioning, coping, depressive symptoms, and quality of life in individuals with neuropsychiatric symptoms after acquired brain injury (ABI)., Design: Cross-sectional study., Methods: Individuals (n = 93) in the post-acute and chronic phase (>3 months) after ABI and their significant others (N = 58) were recruited from outpatient clinics of four mental health centres in the Netherlands. Outcome measures were the Trail Making Test, Stroop Colour Word Test, Frontal Systems Behavioural Scale, Utrecht Coping List, Patient Health Questionnaire, and Life Satisfaction Questionnaire. Data were analysed with multiple regression analyses., Results: Self-reported executive dysfunction was associated with greater use of passive coping styles (β = .37, p < .01), and passive coping, in turn, was associated with lower quality of life (β = -.57, p < .001) and more depressive symptoms (β = .65, p < .001). Problem-focused coping was associated with higher quality of life among individuals who reported better executive functioning (β = -.94, p < .05). Performances on executive functioning tests were not associated with coping, depressive symptoms, or quality of life., Conclusions: For clinicians, these data indicate that individuals who report greater difficulties with executive functioning after ABI are inclined to use maladaptive passive coping styles, which should be targeted in treatment. In comparison, individuals who report greater difficulties with executive functioning should not be prompted to use problem-focused coping styles. These individuals may benefit from other coping styles, such as the use of seeking social support or acceptance of problems., Practitioner Points: Coping influences the association between executive functioning and quality of life. Individuals who report difficulties with executive functioning after ABI may be inclined to use passive coping styles, which are maladaptive. Problem-focused coping strategies may be more useful for individuals who have strong executive abilities. This study was a cross-sectional study; thus, a cause-and-effect relationship could not be established between executive functioning, coping, and psychosocial functioning. As this research was part of standard clinical care, non-traditional tests for executive functioning were not administered., (© 2015 The British Psychological Society.)

Objective: To examine the association between depression and all-cause and cardiovascular mortality in people with diabetes by systematically reviewing the literature and carrying out a meta-analysis of relevant longitudinal studies., Research Design and Methods: PUBMED and PSYCINFO were searched for articles assessing mortality risk associated with depression in diabetes up until August 16, 2012. The pooled hazard ratios were calculated using random-effects models., Results: Sixteen studies met the inclusion criteria, which were pooled in an overall all-cause mortality estimate, and five in a cardiovascular mortality estimate. After adjustment for demographic variables and micro- and macrovascular complications, depression was associated with an increased risk of all-cause mortality (HR = 1.46, 95% CI = 1.29-1.66), and cardiovascular mortality (HR = 1.39, 95% CI = 1.11-1.73). Heterogeneity across studies was high for all-cause mortality and relatively low for cardiovascular mortality, with an I-squared of respectively 78.6% and 39.6%. Subgroup analyses showed that the association between depression and mortality not significantly change when excluding three articles presenting odds ratios, yet this decreased heterogeneity substantially (HR = 1.49, 95% CI = 1.39-1.61, I-squared = 15.1%). A comparison between type 1 and type 2 diabetes could not be undertaken, as only one study reported on type 1 diabetes specifically., Conclusions: Depression is associated with an almost 1.5-fold increased risk of mortality in people with diabetes. Research should focus on both cardiovascular and non-cardiovascular causes of death associated with depression, and determine the underlying behavioral and physiological mechanisms that may explain this association.

Background: Depression in later life is often accompanied by cognitive deficits that can mimic those of (beginning) dementia. These deficits are expected to vanish when the depression lifts, but this does not always happen., Aim: To provide an overview of recent research into cognitive deficits in older patients with depression., Method: The recent literature was reviewed selectively., Results: The cognitive deficits of older persons with depression often persist and are not related to the severity of the symptoms, remission status or the use of antidepressants. Imaging research in clinical and epidemiological populations strongly suggests that these cognitive deficits are due to neuropathological changes of microvascular origin. Some people with depression run an increased risk of developing dementia., Conclusion: The triad 'depression-cognitive impairment-vascular disease' may identify individuals at increased risk of dementia and is sometimes, accompanied by neurodegenerative and neuroinflammatory processes. The treatment of vascular disease in older adults with depression is therefore a promising starting-point for the selective prevention of dementia.

Objectives: To examine the temporal association between depressive symptoms and cognitive functioning and estimate the effect measure modification of the apolipoprotein E (APOE) epsilon4 allele on this relationship., Design: Prospective cohort study., Setting: General community., Participants: Population-based sample of 598 cognitively intact older adults aged 60 and older, with re-assessments after 3 (N=479) and 6 years (N=412)., Measurements: Depressive symptoms (Symptom Checklist) and neurocognitive functioning (memory, Visual Verbal Learning Test; attention, Stroop Color-Word Test; processing speed, Letter Digit Substitution Test; general cognition, Mini-Mental State Examination). Longitudinal associations were assessed using linear mixed models. The risk for cognitive impairment, no dementia (CIND) was examined using logistic regression., Results: Adjusting for age, sex, education, and baseline cognition, the rate of change in memory z-scores was 0.00, -0.11, -0.20, and -0.37 for those in the lowest (reference group), second, third, and highest depressive symptom quartiles at baseline, respectively (P<.001 for highest vs lowest quartile). The odds ratios for developing CIND with amnestic features were 1.00, 0.87, 0.69, and 2.98 for the four severity groups (P=.05 for highest vs lowest quartile). Associations were strongest for those with persistent depressive symptoms, defined as high depressive symptoms at baseline and at least one follow-up visit. Results were similar for processing speed and global cognitive function but were not as strong for attention. No APOE interaction was observed., Conclusion: Depression and APOE act independently to increase the risk for cognitive decline and may provide targets for prevention and early treatment.

Background: Although there are theoretical grounds for using hormone therapy to treat depressive symptoms in patients with hypothyroidism, the clinical evidence for this is unclear. objective To investigate the efficacy of treating depression with thyroid hormone in a population with subclinical hypothyroidism., Method: Literature search in various databases for double-blind randomised placebo-controlled studies that provided clinical evidence for the effect of thyroid hormone on depressive symptoms in a population with subclinical hypothyroidism. results Three randomized controlled trials (RCTS) were included. None of these was concerned primarily with patients suffering from depressive disorder, but focused mainly on subjects with subclinical hypothyroidism, with the score on the depressive scale as secondary outcome. In all the studies selected subclinical hypothyroidism was treated with levothyroxine which had no beneficial effect on depression., Conclusion: Since there is a lack of evidence of beneficial effects in a population with subclinical hypothyroidism and a lack of research into the effects in a depressive population, no definite answer can yet be given to the question posed in the title.

A 70-year-old female patient with Parkinson's disease was admitted to hospital with a medication-resistant depression. Electroconvulsion therapy was considered indicated, but it was decided to try treatment with bupropion chloride first. This resulted in a quick and complete remission of depressive symptoms, without any negative effects on motor symptoms. Bupropion has a unique mechanism of action: inhibition of the presynaptic reuptake of dopamine in addition to noradrenergic activity. Furthermore, it lacks the negative adverse effects on the extrapiramidal symptoms, that may be a problem if other antidepressants are used in the treatment. Bupropion is useful as an antidepressant in specific patient groups, notably patients with Parkinson's disease.

Purpose: To evaluate the validity of the Beck Depression Inventory (BDI) as a screening and diagnostic scale for depression in Parkinson's disease (PD)., Patients and Methods: Fifty-three nondemented patients with PD were diagnosed according to a standardized protocol consisting of the depression module of the Structured Clinical Interview for DSM axis I disorders (SCID) and the BDI. A "receiver operating characteristics" (ROC) curve was obtained and the sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively) were calculated for different cut-off points of the BDI., Results: Maximum discrimination was obtained with a cut-off score of 13/14. High sensitivity and NPV were obtained with cut-off scores of 8/9 or lower; a high specificity and PPV were obtained with cut-off scores of 16/17 or higher. The area under the ROC curve was 85.67%., Conclusion: A single cut-off score on the BDI to distinguish nondepressed from depressed patients with PD is not feasible. If one accepts the low specificity, then the BDI can be used as a valid screening instrument for depression in PD with a cut-off of 8/9. With a cut-off score of 16/17, it can be used as a diagnostic scale, at the cost of a low sensitivity. The use of diagnostic criteria for depression remains necessary.

Objective: To assess the prevalence of depression in subjects with preclinical Alzheimer's disease (AD) and to investigate the possibility of differentiating subjects with preclinical AD and depression from subjects with depression-related cognitive impairment., Design: A prospective, observational cohort study., Setting: An outpatient memory clinic of a university-affiliated hospital., Participants: Nondemented subjects with cognitive impairment older than 55 years (n = 111) without neurological or somatic causes for the cognitive impairment., Measurements: At baseline, data were collected on patient characteristics, the severity of depression, and cognitive functioning. The course of the cognitive impairment and the presence of dementia were assessed after 2 and 5 years., Results: Twenty-five subjects had preclinical dementia with Alzheimer's type dementia at follow-up. Sixty percent of these subjects (n = 15) were depressed at baseline. Subjects with depression and preclinical AD had at baseline a poorer performance on the cognitive tasks and were older than the subjects with depression-related cognitive impairment. Logistic regression with backward step selection selected age and memory performance as the best predictors for Alzheimer's type dementia in the depressed subjects. The specificity of these predictors for the diagnosis of future Alzheimer's type dementia in depressed subjects was 94%, sensitivity was 90%, positive predictive value was 90%, and negative predictive value was 94%., Conclusions: Depression is common in preclinical AD. Depressed subjects with preclinical AD can be accurately differentiated from subjects with depression-related cognitive impairment by age and the severity of the memory impairment. Research that aims to investigate preclinical AD should not exclude a priori subjects with depression inasmuch as preclinical AD is often accompanied by depression.