Vascular Heart and Brain Disease and Incident Late-Life Depression

Depression is characterized by depressed mood, loss of interest, rumination, feelings of guilt and shame, suicidal ideation, disturbed sleep and loss of appetite (1). It is associated with limitations in physical and social functioning and places a severe burden on patients and relatives (2). Compared to depression in middle age, late-life depression has some specifi c characteristics. Depressive syndromes that escape the strict criteria of the Diagnostic and Statistical Manual of Psychiatric Disorders (DSM) for major depressive disorder and dysthymia are more common in the elderly (3-5). Many elderly have only some symptoms of depression. Such subthreshold depressive syndromes are considered clinically relevant, because they are related to increased disability and mortality, as are depressive disorders that meet DSM criteria (6-10). Moreover, depression is more common in the old age than in midlife. Th e prevalence ranges from 9 to 18 % in the general elderly population, to more than 30% in long-term care residents (3, 5, 11, 12). Depression in late life often has a chronic course (3, 5, 11, 13) Only 60% of patients recover in one year and 70-80% in two years (7, 9, 14-19). A number of risk factors for depression has been established, which predispose, precipitate, or perpetuate the disease. Female gender, adverse life events, and poverty are the most well known. Late-life depression has some additional specifi c risk factors. Depressive symptoms are very much related to cognitive decline, which occur as part of neurodegenerative brain diseases, such as Alzheimer’s disease, a

The effect of common genetic variation in 11β-hydroxysteroid dehydrogenase type 1 on hypothalamic-pituitary-adrenal axis activity and incident depression

Background: Accumulating evidence suggests that hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA axis) is involved in depression. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inert cortisone to active cortisol and is implicated in HPA axis regulation in animal studies. The aim of our study was to identify polymorphisms in 11β-HSD1 gene (HSD11B1) with consistent associations with increased HPA axis activity and relate those polymorphisms to depression. Methods: Twelve single-nucleotide polymorphisms (SNPs), including 11 tagging SNPs, were selected using the HapMap database and genotyped in 4228 participants of the population-based Rotterdam Study. The outcome measures were salivary cortisol levels after awakening, 30 min later, at 1700 h, at bedtime, and plasma levels of androstenedione (in women only). SNPs that were significantly associated with cortisol as well as androstenedione levels were also related to incident depression. Results: rs11119328 was associated with higher cortisol saliva samples collected at bedtime as well as higher androstenedione levels (P value after correction for multiple testing: 0.01 and 0.04, respectively). Carriers of this polymorphism had an increased risk of an incident depression (hazard ratio 1.28, 95% confidence interval 1.03-1.59). Two other SNPs, which were in high linkage disequilibrium with rs11119328, were related to higher cortisol levels but not with androstenedione levels. Conclusions: We identified one SNP, which was associated with increased salivary cortisol levels at nadir as well as higher androstenedione levels. Moreover, this SNP was also associated with a higher risk of an incident depression. This suggests that 11β-HSD1 is implicated in human HPA axis regulation and susceptibility to depression. Copyrigh

Sleep in depression and anxiety disorders: A population-based study of elderly persons

Objective: Sleep disturbance is common in psychiatric disorders. However, the relationships of core parameters in sleep research, such as total sleep time (TST), with depression and anxiety disorders are unclear and have rarely been investigated in large population-based studies. Method: This study was embedded in the Rotterdam Study, a community-based cohort study of elderly persons living in a district of Rotterdam, The Netherlands. Between January 2002 and December 2005, sleep parameters were assessed with the Pittsburgh Sleep Quality Index in 5,019 persons aged 58 to 100 years. DSM-IV-TR diagnoses of depressive and anxiety disorders were ascertained by psychiatric interview (the Schedules for Clinical Assessment in Neuropsychiatry for depressive disorders and a slightly adapted Munich version of the Composite International Diagnostic Interview for anxiety disorders). Associations between sleep parameters and psychiatric disorders were investigated with analyses of covariance and logistic regression models. Results: Both short-duration (< 6 hours per night) and long-duration (≥ 9 hours per night) sleepers were more likely to have a depressive disorder (P < .001) than were those sleeping 7 to < 8 hours per night; the association between TST and anxiety disorders was also U-shaped. These associations were stronger in people who did not use psychoactive medication but did not substantially change after exclusion of persons with probable sleep apnea or excessive alcohol use. Participants with a depressive disorder and a comorbid anxiety disorder reported a 1-hour shorter TST than persons with 1 disorder or no disorders (P < .001). On average, however, depressed persons spent more time in bed than did the nondepressed group. Conclusion: In a community-dwelling older population, not only insomnia or short sleep but also long sleep can be symptomatic of psychiatric disorders such as depression and anxiety disorders