The impact of treatment resistance on outcome and course of electroconvulsive therapy in major depressive disorder.

INTRODUCTION: Major depressive disorder (MDD) is a common psychiatric disorder. Despite several treatment options, a subgroup of patients will not respond to the commonly used antidepressant treatments and thus express treatment resistance (TRD). TRD can be quantified with the Dutch Measure for Treatment Resistance in Depression (DM-TRD). Electroconvulsive therapy (ECT) is an effective treatment for MDD, also in TRD. Yet, the position of ECT as "treatment-of-last-resort" may decrease the likelihood of beneficial outcome. Our aim was to investigate the association between treatment resistance and outcome and course of ECT. METHODS: We performed a retrospective, multicenter cohort study with 440 patients of which data was retrieved from patient records as collected in the Dutch ECT Cohort database. Linear and logistic regression models were used to explore the association between level of treatment resistance and outcome of ECT. Median split was used to explore the differences between high and low level of TRD and course of treatment. RESULTS: A higher DM-TRD score was associated with significantly smaller reduction of depression symptoms (R2 = 0.160; ß = -2.968; p < 0.001) and lower chance of response (OR = 0.821 [95 CI: 0.760-0.888]; ß = -0.197; p < 0.001). Low level TRD patients underwent fewer ECT sessions (mean 13 ± 6 SD vs. 16 ± 7 SD; p < 0.001) and fewer switches from right unilateral tot bifrontotemporal electrode placement (29% vs. 40%; p = 0.032). CONCLUSION: Reserving ECT as "treatment-of-last-resort" in the treatment algorithm for MDD seems questionable, because in our study lower level of treatment resistance predicted more beneficial ECT-outcome. Moreover, providing ECT in less treatment resistant patients showed fewer needed ECT-sessions and less switches to BL electrode placement, which may decrease the risk for cognitive side-effects.

The course of apathy in late-life depression treated with electroconvulsive therapy; a prospective cohort study.

OBJECTIVES: Apathy, a lack of motivation, is frequently seen in older individuals, with and without depression, with substantial impact on quality of life. This prospective cohort study of patients with severe late-life depression treated with electroconvulsive therapy (ECT) aims to study the course of apathy and the predictive value of vascular burden and in particular white matter hyperintensities on apathy course. METHODS: Information on apathy (defined by a score of >13 on the Apathy Scale), depression severity, vascular burden, and other putative confounders was collected in at 2 psychiatric hospitals on patients with late-life depression (aged 55 to 87 years, N = 73). MRI data on white matter hyperintensities were available in 52 patients. Possible risk factors for apathy post-ECT were determined using regression analyses. RESULTS: After treatment with ECT, 52.0% (26/50) of the depression remitters still suffered from clinically relevant apathy symptoms. In the entire cohort, more patients remained apathetic (58.9%) than depressed (31.5%). Presence of apathy post-ECT was not associated with higher age, use of benzodiazepines, or severity of apathy and depression at baseline. Less response in depressive symptomatology after ECT predicted post-treatment apathy. The presence of vascular disease, diabetes mellitus and smoking, and white matter hyperintensities in the brain was not associated with post-treatment apathy. CONCLUSIONS: Apathy may perpetuate in individual patients, despite remission of depressive symptoms. In this cohort of patients with late-life depression, post-ECT apathy is not associated with white matter hyperintensities.

[ResPECT - a decade of Flemish-Dutch ECT research]. / ResPECT ­ een decennium Vlaams-Nederlands onderzoek naar elektroconvulsietherapie.

BACKGROUND: There is increasing clinical and scientific interest in electroconvulsive therapy (ECT). AIM: To provide an overview of the main research findings of the Flemish-Dutch research consortium ResPECT. METHOD: We report on our review of the relevant literature. RESULTS: Our studies confirm that ECT is one of the most efficient treatments for depression in later life and for depression with psychotic features. Older people with age-related brain pathology can respond well to ECT. It is still preferable to apply a standard pulse-width because this increases the efficacy of the treatment and minimises the cognitive impact. Even vulnerable older people can react favourably to ECT. CONCLUSION: Recent findings of the ResPECT consortium are providing new insights that are applicable in daily clinical practice. Research into mechanisms of action can also increase our understanding of the pathophysiology of severe depression.

[Hashimoto encephalitis and depression]. / Hashimoto-encefalitis en depressie.

Hashimoto encephalitis (he) is an auto-immune disease, with 40-50% of patients developing psychopathology. This could require targeted treatment. HE and prednison could both cloud the identification of a concurrent depressive disorder. We saw a 78-year-old woman with he and a severe depression, and treated her succesfully with ect.

Depression in systemic lupus erythematosus, dependent on or independent of severity of disease.

OBJECTIVES: To estimate the prevalence of depression in subjects with systemic lupus erythematosus (SLE) in relation to the general population and to unravel the relation between depression and SLE disease characteristics. METHODS: One hundred and two subjects with SLE (mean age 44.4 years) were studied using the Beck Depression Inventory (BDI) score to estimate the prevalence of depression. The BDI scores in subjects with SLE were compared with BDI scores from a pan-European population based study (Outcome in Depression International Network (ODIN) study, n = 7934), i.e. the general population. RESULTS: The mean BDI score was higher in SLE subjects (10.1 points) compared with the BDI scores derived from the general population (10.1 versus 5.6 points, respectively, p < 0.001). This corresponds to a prevalence of depression of 16.6% and 6.7%, respectively. There was no association between disease activity or organ damage and BDI scores in subjects with SLE (p > 0.1). Only 7% of SLE subjects with high BDI scores used antidepressants. CONCLUSION: The mean BDI score and prevalence of depression are significantly higher in SLE subjects compared with the general population. No association was found between SLE disease characteristics and BDI scores. The number of depressed SLE subjects treated with antidepressants is low, suggesting inadequate recognition and treatment of depression in SLE.

[The immune system and Alzheimer's disease]. / Het immuunsysteem en de ziekte van Alzheimer.

BACKGROUND: It has still not been established unequivocally whether vascular risk factors and inflammatory reactions, determined by heredity, are a cause or a result of Alzheimer's disease AIM: If the offspring of parents with AD have more risk factors and more frequent and severe inflammatory reactions than the offspring of parents without AD , this argues strongly in favor of a causal relationship between vascular risk factors, a pro-inflammatory cytokine response and AD. AIM: To determine whether the offspring of parents with ad have more risk factors and more frequent and severe inflammatory reactions than the offspring of parents without ad. method Vascular risk-factors, pro-inflammatory cytokines and the apoe genotype were determined in 206 offspring of parents with ad and in 200 offspring of parents without AD. RESULTS: Offspring of parents with ad carried more apoe epsilon4 than offspring of parents without ad (47% vs 21%). Middle-aged offspring of parents with a history of ad also had higher blood pressure and a greater atherosclerotic burden than the offspring of parents without AD. Also their response to the pro-inflammatory cytokine was significantly higher. CONCLUSION: Hypertension and an inherited pro-inflammatory cytokine profile in middle age are early risk factors that contribute to the development of ad in old age. Offspring with a parental history of AD should therefore be offered screening and treatment for hypertension and have their blood pressure checked so that the development of AD in old age can be prevented.

Inflammation in older subjects with early- and late-onset depression in the NESDO study: a cross-sectional and longitudinal case-only design.

OBJECTIVE: Different biological mechanisms may underlie depression beginning in early life (early-onset) and depression beginning later in life (late-onset). Although the relation between inflammation and depression has been studied extensively, the distinct role of inflammation in early and late-onset depression in older patients has not been addressed before. In the cross-sectional part of this study, we explored differences in levels of circulating inflammatory markers and cytokine levels in lipopolysaccharide (LPS) stimulated whole blood between older subjects with a late-life onset depression (≥60 years) and older subjects with an early-onset depression (<60 years). Secondly, in a 2-year follow-up study, we examined if circulating and stimulated inflammatory markers influenced the change in Inventory of Depressive Symptomatology (IDS) scores, and if this relation was different for early- and late-onset depression. METHODS: The study was part of the Netherlands Study of Depression in Older Persons (NESDO). We included 350 patients, all aged 60 and older, with a depressive episode in the previous 6 months: 119 with a late-onset depression and 231 with an early-onset depression. Blood samples were collected and CRP, IL-6, NGAL, GDF15, and, LPS plasma levels were determined and whole blood was LPS stimulated and cytokine levels IL-1ß, IL-6, TNFα, IFNγ, IL-10, and IL-1 receptor antagonist (IL-1ra) were determined. RESULTS: After adjustment for demographics, health indicators, and medication use, increased plasma CRP levels were more strongly associated with late-onset depression than early-onset depression (OR [95% CI]: 1.43 [1.05-1.94]). In the longitudinal analyses, higher circulating IL-6 levels were associated with a significantly slower decline in IDS scores in the crude and the adjusted models (p ≤ 0.027). This relation was not different between late- and early-onset depression. Other circulating and stimulated inflammatory markers were not associated with late- and/or early-onset depression. CONCLUSIONS: This study provides preliminary evidence that low-grade inflammation is more strongly associated with late-onset than early-onset depression in older adults, suggesting a distinct inflammatory etiology for late-onset depression. Cytokine production capacity did not distinguish between early- and late-onset depression.

[Thyroid function, activities of daily living and survival in extreme old age: the 'Leiden 85-plus Study']. / Schildklierfunctie, dagelijks functioneren en overleving van de oudste ouderen; de 'Leiden 85-plus Studie'.

OBJECTIVE: To determine the relationship between differences in thyroid function, changes in the activities of daily living and survival in the extremely-old segment of the general population in order to see whether screening for and treatment of subclinical thyroid-function disorders in the elderly will have a positive effect. DESIGN: Prospective observational population study among 85-year-olds. METHOD: As part of the 'Leiden 85-plus Study', all persons were followed who had their 85th birthday during the period from 1 September 1997 to 31 August 1999 (average length of time followed: 3.7 years; SD: 1.4). There were 558 participants. The thyroid function of these subjects was determined and the limitations in the activities of daily living, depressive symptoms, cognitive function and mortality were recorded annually. RESULTS: At the age of 85, there was no relation between the serum levels of thyroid-stimulating hormone (TSH) or free thyroxine (FT4) and limitations in the activities of daily living, the occurrence of depressive symptoms and cognitive deterioration. Neither was any relationship found during the period of follow-up. A higher TSH-level was associated with a lower mortality, even after correction for the differences in performance and health during the base measurement (mortality risk: 0.77 per SD-increase in TSH; 95% CI: 0.63-0.94). The mortality risk per SD-increase in FT4 was 1.16 (95% CI: 1.04-1.30). CONCLUSION: From the age of 85, there was no relationship between thyroid function and limitations in the activities of daily living, the occurrence of depressive symptoms or a deterioration in cognitive functions. Moreover, elderly persons with a less active thyroid gland lived longer. This raises the question whether the screening for and treatment of subclinical thyroid-function disorders in persons of extreme old age, as recommended, will have any positive effects.

Successful aging in the oldest old: Who can be characterized as successfully aged?

BACKGROUND: Successful aging is a worldwide aim, but it is less clear which indicators characterize elderly persons as successfully aged. We explored the meaning of successful aging from 2 perspectives. METHODS: Analysis of data from the first cross-sectional part of the longitudinal Leiden 85-plus Study, conducted in Leiden, the Netherlands. All inhabitants of Leiden aged 85 years were eligible. Data were obtained from 599 participants (response rate, 87%). Successful aging from a public health perspective was defined as a state of being. All participants were classified as successful or not successful based on optimal scores for physical, social, and psychocognitive functioning and on feelings of well-being, using validated quantitative instruments. Qualitative indepth interviews on the perspectives of elderly persons were held with a representative group of 27 participants. RESULTS: Although 45% (267/599) of the participants had optimal scores for well-being, only 13% (79/599) had optimal scores for overall functioning. In total, 10% (58/599) of the participants satisfied all the criteria and could be classified as successfully aged. The qualitative interviews showed that most elderly persons viewed success as a process of adaptation rather than a state of being. They recognized the various domains of successful aging, but valued well-being and social functioning more than physical and psychocognitive functioning. CONCLUSIONS: If successful aging is defined as an optimal state of overall functioning and well-being, only a happy few meet the criteria. However, elderly persons view successful aging as a process of adaptation. Using this perspective, many more persons could be considered to be successfully aged.

Inflammation and stroke: the Leiden 85-Plus Study .

BACKGROUND: Experimental evidence indicates that interleukin-10 (IL-10) deficiency is associated with the development of cardiovascular and cerebrovascular disease. We analyzed the relation between low IL-10 production levels, history of stroke, and incident fatal stroke. SUMMARY OF REPORT: All 85-year-old inhabitants of Leiden, Netherlands (n=599) were visited at their place of residence (response rate, 87%). Production levels of the anti-inflammatory cytokine IL-10 were assessed in a whole blood assay whereby lipopolysaccharide was used as a stimulus. Plasma concentrations of C-reactive protein (CRP) were also used as a marker of inflammation. A history of stroke was obtained at baseline (prevalence, 10%). The number of fatal strokes was prospectively obtained for a median follow-up of 2.6 years (incidence, 1.82 per 100 person-years at risk). Subjects with a history of stroke had significantly lower median IL-10 production levels at baseline than subjects without stroke (558 versus 764 pg/mL; P<0.05). They also had significantly higher median CRP concentrations (6 versus 3 mg/L; P<0.05). The odds ratio for a history of stroke increased to 2.30 (95% CI, 1.12 to 4.72) over strata representing decreasing production levels of IL-10. The relative risk for incident fatal stroke was 2.94 (95% CI, 1.01 to 8.53) when we compared subjects with low or intermediate baseline IL-10 production levels to those with high production levels of IL-10. CONCLUSIONS: Our data support the hypothesis that subjects with low IL-10 production levels have an increased risk of stroke.

Atherosclerosis and cognitive impairment are linked in the elderly. The Leiden 85-plus Study.

Post-mortem analyses suggest that atherosclerosis more often contributes to late-onset dementia than hitherto expected. We set out to further unravel the relation between atherosclerosis and cognitive impairment. We therefore tested the hypothesis that the number of cardiovascular pathologies is positively associated with cognitive impairment in elderly subjects, and that the smaller number of cardiovascular pathologies in women explains the better cognitive function of elderly women. Within the Leiden 85-plus Study, we assessed the atherosclerotic burden by counting the number of cardiovascular pathologies in the medical histories of a population-based sample of 599 subjects aged 85 years (response 87%). Significantly more men than women had a history of cardiovascular pathologies (67% compared to 59%, P<0.001). In addition, cognitive function was assessed. All subjects completed the Mini-Mental State Examination (MMSE). Cognitive speed and memory were determined with specific neuro-psychological tests in those with a MMSE-score above 18 points. There was a highly significant dose-response relationship between the number of cardiovascular pathologies and cognitive impairment for both men and women. The median MMSE-score was 26 points in subjects without cardiovascular disease and decreased to 25 points for subjects who had two or more cardiovascular pathologies (P for trend =0.003). Similar associations were found for cognitive speed but not for memory. Our data confirm that in old age atherosclerosis significantly contributes to cognitive impairment. Since treatments for atherosclerosis appear to be particularly effective in elderly people, we consider our finding of utmost clinical importance in possibly preventing cognitive impairment and late-onset dementia.

A high response is not essential to prevent selection bias: results from the Leiden 85-plus study.

We tested the hypothesis that an additional effort to increase the response rate would diminish selection bias in a community-based cohort study. In the Leiden 85-plus Study, all subjects of the town of Leiden who had reached their 85th birthday were informed of the study by mail and then asked to participate by telephone. In an additional recruitment stage, those subjects who did not participate directly were visited and personally asked to participate. When these subjects refused, some nonresponse questions were asked. In this way we collected data on the whole source population. Of 691 eligible elderly subjects, 511 subjects (74%) participated directly. Of those who did not participate directly, 88 subjects participated after the additional effort. The response rate increased from 74% to 87%. Compared to the 511 subjects who directly participated, the 88 subjects who entered the study after the additional effort had poorer health and lower survival. The subjects who refused were more healthy and had poorer mood. The direct sample did not differ from the source population with respect to socio-demographics, health, and mortality. In conclusion, we showed that given a moderately high direct response the additional effort was effective in increasing the response rate, but was also selective and was not necessary to prevent selection bias.

Disability in the oldest old: "can do" or "do do"?

OBJECTIVE: To investigate the discrepancies between outcomes for competence (can do) and actual performance (do do) in activities of daily living (ADLs). DESIGN: Baseline measurements of a population-based follow-up study. SETTING: Leiden 85-Plus Study, the Netherlands. PARTICIPANTS: Five hundred and ninety-nine persons, age 85. The response rate was 86%. MEASUREMENTS: Face-to-face interviews. Measurements of competence and actual performance were based on the Groningen Activity Restriction Scale. Help received was assessed for several domains. Prevalence rates for disability were assessed according to the concepts of both competence and actual performance. Analysis was performed separately for basic activities of daily living (BADLs) and instrumental activities of daily living (IADLs). RESULTS: Seventy-seven percent of the oldest old were competent to perform all the BADLs and performed them regularly. Fifteen percent were not competent to perform certain BADLs independently but performed them regularly with help from others. The prevalence of disability defined as inability in one or more BADLs was 22% for women and 10% for men. The prevalence of disability defined as inactivity in one or more BADLs was 16% for women and 17% for men. Only 5% of the oldest old were competent to perform all IADLs and performed them regularly. In spite of being competent, 70% did not perform certain IADLs regularly. The prevalence of disability defined as inability in one or more IADLs was 64% for women and 55% for men. The prevalence of disability defined as inactivity in one or more IADLs was 92% for women and 98% for men. CONCLUSION: The structural discrepancies between the outcomes of competence and actual performance have important consequences when estimating disability in old people. Promoting actual performance in IADLs may reduce disability.

[Causes and consequences of cognitive decline in the very elderly; the 'Leiden 85-plus Study']. / Oorzaken en gevolgen van cognitieve achteruitgang op hoge leeftijd; de 'Leiden 85-plus Studie'.

In view of the absolute and relative increase in the number of oldest old, it is important to identify the causes and consequences of disease in this group. One of the areas of focus in the 'Leiden 85-plus Study', a population-based prospective study amongst 85-year-olds in the Dutch town of Leiden, is therefore to study the causes and consequences of cognitive decline in the very elderly. Cognitive impairment is the main threat to independence in the oldest old; 85-year-old people with impaired cognitive function (prevalence: 35%) have a ten times greater risk of being limited in their activities of daily life. If this cognitive impairment could be prevented, a large proportion of the independence limitations in the general population could be prevented (population attributable risk: 70%). Limitations in cognitive functioning are strongly associated with the incidence of cardiovascular disease, as well as with a lower average HDL-cholesterol concentration and signs of inflammation. Vascular factors appear to be closely related to development of cognitive impairment in very elderly. Therefore, future therapeutic research will have to demonstrate to what extent influencing the cardiovascular risk factors can lead to the prevention of cognitive decline in the very elderly.

Insulin-like growth factor-1 and risk of late-onset Alzheimer's disease: findings from a family study.

Insulin-like growth factor-1 (IGF-1), part of an evolutionary conserved signaling pathway in both mammalian and non-mammalian species, is inferred in neurodegenerative disorders including Alzheimer's disease (AD). A murine model for AD shows that reduced IGF-1 signaling prevents AD-like characteristics. However, variation in serum levels of IGF-1 and risk of AD in humans has yet to be determined. We used a proven family design, comparing middle-aged offspring with and without a parental history of AD. The offspring under study carry an increased risk of AD but do not yet experience cognitive impairment. A total of 206 offspring from 92 families with a parental history of AD were compared with 200 offspring from 97 families without a parental history of AD. Apolipoprotein-E (APOE) genotypes and serum IGF-1 levels were compared in subjects with and without a parental history of AD using linear regression, adjusted for APOE genotype and other possible demographic and clinical confounders. Offspring with a parental history of AD were more likely to be an APOE ε4 allele carrier (46.5% vs. 21%, p = 0.001) than were offspring without such a parental history. Offspring with a parental history of AD had higher IGF-1 levels than subjects without such a history, in both unadjusted and adjusted analyses (18.3 mmol/L vs. 16.7 mmol/L, p = 0.001). In conclusion, higher serum IGF-1 levels in middle age are associated with risk of AD disease in older age, independent of APOE genotype.

The early involvement of the innate immunity in the pathogenesis of late-onset Alzheimer's disease: neuropathological, epidemiological and genetic evidence.

The idea that an inflammatory process is involved in Alzheimer's disease (AD) was proposed already hundred years ago but only the past twenty years inflammation-related proteins have been identified within plaques. A number of acute-phase proteins colocalize with the extracellular amyloid fibrils, the so called Aß-associated proteins. Activated microglia and astrocytes surrounding amyloid deposits express receptors of innate immunity and secrete pro-inflammatory cytokines. In this paper we review the evidence for involvement of innate immunity in the early stages of the pathological cascade of AD. Diffuse plaques, the initial neuropathological lesion in the cerebral neocortex, contain next to Aß also apolipoprotein E, clusterin, α1-antichymotrypsin and activated complement proteins. Interestingly, genetic studies have shown gene-loci to be associated with AD for all these proteins, except α1-antichymotrpsin. Fibrillar Aß can, through stimulation of toll-like receptors and CD-14 on glial cells, activate pathways for increased production of pro-inflammatory cytokines. This pathway, inducing production of proinflammatory cytokines, is under genetic control. The finding that the responsiveness of the innate immunity is higher in offspring with a parental history of late-onset AD indicates heritable traits for AD that are related to inflammatory processes. Prospective epidemiological studies which report that higher serum levels of certain acute-phase proteins are associated with cognitive decline or dementia provide additional evidence for the early involvement of inflammation in AD pathogenesis. The reviewed neuropathological, epidemiological and genetic findings show evidence for involvement of the innate-immunity in the early stages of pathological cascade as well as for the hypothesis that the innate immunity contributes to the etiology of late-onset AD.

Parental history of Alzheimer disease associated with lower plasma apolipoprotein E levels.

BACKGROUND: Variation in APOE genotype is a determinant of Alzheimer disease (AD), but the risk associated with variation in plasma apoE levels has yet to be determined. Here, we studied offspring with and without a parental history of AD to identify the effect of plasma apoE levels at middle age on the risk of late-onset AD. METHODS: Some 203 offspring from 92 families with a parental history of AD were compared with 197 offspring from 97 families without a parental history of AD. APOE genotypes and plasma apoE levels were assessed in all offspring. Difference in plasma apoE level between subjects with and without a parental history of AD was calculated using robust linear regression, both stratified and adjusted for APOE genotype. RESULTS: Offspring with a parental history of AD were more likely to be an APOE epsilon4 allele carrier (46% vs 21%, p < 0.001) than offspring without such a parental history. Mean plasma apoE levels strongly decreased from epsilon2 to epsilon3epsilon3 to epsilon4 carriers (p < 0.001). Offspring with a parental history of AD had lower plasma apoE levels than subjects without such a history, both in analyses adjusted for APOE genotype (difference: -0.21 mg/dL, p = 0.02) and when using standardized Z scores, when stratified for APOE genotype (difference: -0.22, p = 0.009). CONCLUSIONS: Our findings suggest that lower plasma apoE levels in middle age could be a risk factor for Alzheimer disease in old age, independent of APOE genotype.

Saccadic eye movements in hyperekplexia.

Hyperekplexia is an autosomal dominant disorder characterized by excessive startle responses followed by a temporary generalized stiffness. The startle response is generated in the medial bulbopontine reticular formation in the lower brainstem. The pulse generator of horizontal saccadic eye movements is localized in the pontine paramedian reticular formation. Measurements of horizontal visually evoked random saccades, antisaccades, and saccades toward remembered targets were performed in seven patients with familial hyperekplexia and seven health age-matched controls. The peak velocity of all three kinds of saccades was reduced (p < 0.0001) compared with that of controls. Latencies were marginally longer in the patient group (p = 0.0486). Saccadic gains did not differ between patients and controls. The ability to make antisaccades, saccades toward remembered targets, and the ability to suppress reflex saccades are similar in patients and controls. These data suggest that the origin of the excessive startle response is probably more due to a different modulation in the brainstem than to altered cortical influence.

The implication of selection bias in clinical studies of late life depression: an empirical approach.

OBJECTIVES: It is supposed that selection bias precludes the extrapolation of results of studies carried out in a clinical setting to the general population. There is little empirical evidence demonstrating the degree to which those depressed in the community are different from those treated in clinical settings. This study compared elderly patients with major depression admitted to a psychiatric hospital with those living in the community. METHODS: All elderly (55 years and older) patients admitted between 1990 and 1992 to a psychiatric hospital with DSM major depression as the primary diagnosis (n=104), were compared with all elderly patients with the same diagnosis (n=59) who were participating in a large community study (Longitudinal Aging Study, Amsterdam). Data were gathered from the clinical sample using chart-reviews while the community-based sample was interviewed. The two groups were compared with respect to differences in demographic variables, presenting symptoms, risk factors and treatment. RESULTS: The following characteristics were significantly more prevalent in the clinical sample: late onset of the depression, threat of suicide, conflicts with significant others and use of antidepressant medication. Chronic physical illness was the only characteristic that was more prevalent in the community sample. CONCLUSION: The results confirm that elderly patients treated in clinical psychiatry represent a group with more threatening and more disruptive depressive illness. Major depression in the community was more often associated with chronic physical illness, which may hamper the recognition and treatment of depression. As the two samples were similar in all other respects, selection bias, hampering comparison of results of studies carried out across treatment settings, appears to have a very limited effect.