Strengths and Weaknesses of the Vascular Apathy Hypothesis:A Narrative Review

The vascular apathy hypothesis states that cerebral small vessel disease (CSVD) can cause apathy, even when no other symptoms of CSVD are present. In order to examine this hypothesis, the objectives of this narrative review are to evaluate the evidence for a pathophysiological mechanism linking CSVD to apathy and to examine whether CSVD can be a sole cause of apathy. The nature of the CSVD-apathy relationship was evaluated using the Bradford Hill criteria as a method for research on the distinction between association and causation. Pathological, neuroimaging, and behavioral studies show that CSVD can cause lesions in the reward network, which causes an apathy syndrome. Studies in healthy older individuals, stroke patients and cognitively impaired persons consistently show an association between CSVD markers and apathy, although studies in older persons suffering from depression are inconclusive. A biological gradient is confirmed, as well as a temporal relationship, although the evidence for the latter is still weak. The specificity of this causal relationship is low given there often are other contributing factors in CSVD patients with apathy, particularly depression and cognitive deterioration. Differentiating between vascular apathy and other apathy syndromes on the basis of clinical features is not yet possible, while in-depth knowledge about differences in the prognosis and efficacy of treatment options for apathy caused by CSVD and other apathy syndromes is lacking. Since we cannot differentiate between etiologically different apathy syndromes as yet, it is premature to use the term vascular apathy which would suggest a distinct clinical apathy syndrome

Cerebrovascular risk factors and subsequent depression in older general practice patients

Background: This general practice-based case-control study tested the association between cerebrovascular risk factors (CVRFs) and the development of later-life depression by focusing on the impact of exposure duration to CVRFs and the modifying influence of age at depression onset. Methods: Cases were 286 patients aged >/=50 years with a first diagnosis of depression at age >/=50 years. Nondepressed controls (N=832) were individually matched for age, gender and practice. CVRF diagnoses (hypertension, diabetes mellitus, cardiovascular conditions) prior to depression were determined. Analyses controlled for education, somatic and nondepressive psychiatric disease. Results: No CVRF variable examined was significantly associated with subsequent depression in the total sample. An unexpected impact of age at onset of depression was observed: the odds ratio associated with having any CVRF was smaller for patients with age at onset >/=70 years than for patients with onset between ages 50-59 years (p=.002) and 60-69 years (p=.067). Subsequent analyses excluding patients with onset at age >/=70 years revealed that CVRF variables, including long-term exposure to CVRFs, significantly increased the odds of subsequent depression with onset between ages 50 and 69 years. Limitations: Reliance on GPs' records of morbidity may have resulted in bias towards underestimation in patients with depression onset at age >/=70 years. Conclusions: Our findings suggest that CVRFs play a relevant role in the development of depression with onset between ages 50 and 69 years, but no evidence was found that they contribute to the occurrence of depression with onset at age >/=70 years. Replication is warranted to exclude the possibility of bias. (aut. ref.

Preventie van depressie en angst in verzorgingstehuizen

Achtergrond Bewoners van verzorgingshuizen vormen een risicogroep voor het ontwikkelen van een depressieve en/of angststoornis. Deze stoornissen komen veel voor en hebben een grote impact op het welzijn en functioneren van de betrokkene, maar worden vaak slecht herkend. Wij vroegen ons af of een stepped-care programma ter preventie van depressieve en angststoornissen in verzorgingshuizen haalbaar en effectief zou kunnen zijn. Methoden In een pragmatische gerandomiseerde gecontroleerde trial vergeleken we de effecten van het programma met gebruikelijke zorg in veertien verzorgingshuizen. In totaal deden 185 bewoners mee, die op de Centre for Epidemiologic Studies Depression Scale (CES-D) minstens 8 punten scoorden, niet leden aan een depressieve of angststoornis en ook niet aan een ernstige cognitieve stoornis. De deelnemers kregen een stepped-care preventieprogramma (n = 93) of gebruikelijke behandeling (n = 92). De deelnemers aan het preventieprogramma kregen eerst een afwachtend beleid en als ze niet opknapten achtereenvolgens een zelfhulpinterventie, een psychologische life-review en een verwijzing naar de huisarts. Onze primaire uitkomstmaat was de incidentie van een depressieve stoornis of angststoornis gedurende het jaar na inclusie. Resultaten De incidentie van depressie en angst samen nam niet af door de interventie: de gecombineerde incidence rate ratio (IRR) was 0,50 (95%-betrouwbaarheidsinterval (BI) 0,23 tot 1,12). Ten opzichte van de gebruikelijke zorg bracht het preventieprogramma wel het indicentierisico voor depressie omlaag (IRR 0,26; 95%-BI 0,12 tot 0,80) maar niet dat voor angst (IRR 1,32; 95%-BI 0,48 tot 3,62). Conclusie De resultaten suggereren dat het toegepaste steppedcare preventieprogramma bij ouderen in verzorgingshuizen wel helpt tegen depressie, maar niet tegen angst

Genetic liability for depression, social factors and their interaction effect in depressive symptoms and depression over time in older adults

Objectives The objectives of this study were to investigate the effect of genetic and social factors on depressive symptoms and depression over time and to test whether social factors moderate the relationship between depressive symptoms and its underlying genetics in later life. Methods The study included 2,279 participants with a mean follow-up of 15 years from the Longitudinal Aging Study Amsterdam with genotyping data. The personal genetic loading for depression was estimated for each participant by calculating a polygenic risk scores (PRS-D), based on 23,032 single nucleotide polymorphisms associated with major depression in a large genome-wide association study. Partner status, network size, received and given emotional support were assessed via questionnaires and depressive symptoms were assessed using the CES-D Scale. A CES-D Scale of 16 and higher was considered as clinically relevant depression. Results Higher PRS-D was associated with more depressive symptoms whereas having a partner and having a larger network size were independently associated with less depressive symptoms. After extra adjustment for education, cognitive function and functional limitations, giving more emotional support was also associated with less depressive symptoms. No evidence for gene-environment interaction between PRS-D and social factors was found. Similar results were found for clinically relevant depression. Conclusion Genetic and social factors are independently associated with depressive symptoms over time in older adults. Strategies that boost social functioning should be encouraged in the general population of older adults regardless of the genetic liability for depression

The Depression Initiative. Description of a collaborative care model for depression and of the factors influencing its implementation in the primary care setting in the Netherlands

BACKGROUND: In the Depression Initiative, a promising collaborative care model for depression that was developed in the US was adapted for implementation in the Netherlands. AIM: Description of a collaborative care model for major depressive disorder (MDD) and of the factors influencing its implementation in the primary care setting in the Netherlands. DATA SOURCES: Data collected during the preparation phase of the CC:DIP trial of the Depression Initiative, literature, policy documents, information sheets from professional associations. RESULTS: Factors facilitating the implementation of the collaborative care model are continuous supervision of the care managers by the consultant psychiatrist and the trainers, a supportive web-based tracking system and the new reimbursement system that allows for introduction of a mental health care-practice nurse (MHC-PN) in the general practices and coverage of the treatment costs. Impeding factors might be the relatively high percentage of solo-primary care practices, the small percentage of professionals that are located in the same building, unfamiliarity with the concept of collaboration as required for collaborative care, the reimbursement system that demands regular negotiations between each health care provider and the insurance companies and the reluctance general practitioners might feel to expand their responsibility for their depressed patients. CONCLUSION: Implementation of the collaborative care model in the Netherlands requires extensive training and supervision on micro level, facilitation of reimbursement on meso- and macro level and structural effort to change the treatment culture for chronic mental disorders in the primary care settin

Vitamin D Status and Depressive Symptoms in Older Adults:A Role for Physical Functioning?

Objectives: Depressive symptoms and low vitamin D status are common in older persons and may be associated, but findings are inconsistent. This study investigated whether 25-hydroxyvitamin D (25(OH)D) concentrations are associated with depressive symptoms in older adults, both cross-sectionally and longitudinally. We also examined whether physical functioning could explain this relationship, to gain a better understanding of the underlying mechanisms. Methods: Data from two independent prospective cohorts of the Longitudinal Aging Study Amsterdam were used: an older cohort (≥65 years, n = 1282, assessed from 1995–2002) and a younger-old cohort (55–65 years, n = 737, assessed from 2002–2009). Measurements: Depressive symptoms were measured at baseline and after 3 and 6 years with the Center of Epidemiological Studies Depression Scale. Cross-sectional and longitudinal linear regression techniques were used to examine the relationship between 25(OH)D and depressive symptoms. The mediating role of physical functioning was examined in the longitudinal models. Results: Cross-sectionally, associations were not significant after adjustment for confounders. Longitudinally, women in the older cohort with baseline 25(OH)D concentrations up to 75 nmol/L experienced 175 to 24% more depressive symptoms in the following 6 years, compared with women with 25(OH)D concentrations >75 nmol/L. Reduced physical performance partially mediated this relationship. In men and in the younger-old cohort, no significant associations were observed. Conclusions: Older women showed an inverse relationship between 25(OH)D and depressive symptoms over time, which may partially be explained by declining physical functioning. Replication of these findings by future studies is needed

Assessment of bidirectional relationships between physical activity and depression among adults a 2-sample Mendelian randomization study

IMPORTANCE Increasing evidence shows that physical activity is associated with reduced risk for depression, pointing to a potential modifiable target for prevention. However, the causality and direction of this association are not clear; physical activity may protect against depression, and/or depression may result in decreased physical activity. OBJECTIVE To examine bidirectional relationships between physical activity and depression using a genetically informed method for assessing potential causal inference. DESIGN, SETTING, AND PARTICIPANTS This 2-sample mendelian randomization (MR) used independent top genetic variants associated with 2 physical activity phenotypes-self-reported (n = 377 234) and objective accelerometer-based (n = 91 084)-and with major depressive disorder (MDD) (n = 143 265) as genetic instruments from the largest available, nonoverlapping genome-wide association studies (GWAS). GWAS were previously conducted in diverse observational cohorts, including the UK Biobank (for physical activity) and participating studies in the Psychiatric Genomics Consortium (for MDD) among adults of European ancestry. Mendelian randomization estimates from each genetic instrument were combined using inverse variance weighted meta-analysis, with alternate methods (eg, weighted median, MR Egger, MR-Pleiotropy Residual Sum and Outlier [PRESSO]) and multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers. Data were analyzed from May 10 through July 31, 2018. MAIN OUTCOMES AND MEASURES MDD and physical activity. RESULTS GWAS summary data were available for a combined sample size of 611 583 adult participants. Mendelian randomization evidence suggested a protective relationship between accelerometer-based activity and MDD (odds ratio [OR], 0.74 for MDD per 1-SD increase in mean acceleration; 95% CI, 0.59-0.92; P =.006). In contrast, there was no statistically significant relationship between MDD and accelerometer-based activity (β = −0.08 in mean acceleration per MDD vs control status; 95% CI, −0.47 to 0.32; P =.70). Furthermore, there was no significant relationship between self-reported activity and MDD (OR, 1.28 for MDD per 1-SD increase in metabolic-equivalent minutes of reported moderate-to-vigorous activity; 95% CI, 0.57-3.37; P =.48), or between MDD and self-reported activity (β = 0.02 per MDD in standardized metabolic-equivalent minutes of reported moderate-to-vigorous activity per MDD vs control status; 95% CI, −0.008 to 0.05; P =.15). CONCLUSIONS AND RELEVANCE Using genetic instruments identified from large-scale GWAS, robust evidence supports a protective relationship between objectively assessed-but not self-reported-physical activity and the risk for MDD. Findings point to the importance of objective measurement of physical activity in epidemiologic studies of mental health and support the hypothesis that enhancing physical activity may be an effective prevention strategy for depression