Sleep Health, Inflammation, and Emotion Study

Late-life depression is a major public health burden due to its high prevalence and
associated morbidity, suicide risk, functional decline, and mortality. Unfortunately, current
antidepressant therapies have limited effectiveness; hence, biologically plausible models for
new treatments are being pursued. Systemic inflammation is hypothesized to play an important
role on the onset and perpetuation of depression, especially in older women. Aging processes
involve a heightened inflammatory state, and both inflammatory disorders and depression are
more prevalent in women than men. However, increased systemic inflammation does not
necessarily lead to depression in all women. Even when robust systemic inflammation is
experimentally induced (e.g. endotoxin administration), largely variable increases in
depressive symptoms are found. Defining the factors that account for this variability may
identify individuals at risk of developing depression when exposed to heightened inflammatory
states such as aging, obesity, and chronic disease, and informs future translational studies
of depression prevention. In particular, the role of sleep disturbance in explaining this
variability requires further attention because it is an independent risk factor for
depression and heightens systemic inflammation by increasing the production of
proinflammatory cytokines. The investigators have also discovered that women, but not men,
who report sleep disturbance including short sleep duration experience significantly more
depressive symptoms in response to an inflammatory challenge than women without sleep
disturbance. Thus, it is hypothesized that sleep loss is a vulnerability factor for
inflammation-induced depressive symptoms in women. However, to date, no experimental approach
has been used to evaluate the role of sleep loss on inflammation-induced depressive symptoms.
This proposal aims to examine this hypothesis by partial sleep deprivation (PSD) followed by
endotoxin challenge in older women. It also aims to explore genomic and socio- emotional
mechanisms underlying the association between sleep loss and depressive symptoms. In a
randomized controlled factorial design, 80 healthy female volunteers aged 60 to 80 will be
randomly assigned to one of 4 arms: 1) uninterrupted sleep followed by placebo; 2)
uninterrupted sleep followed by endotoxin; 3) PSD followed by placebo; or 4) PSD followed by
endotoxin. Subjects will be administered placebo or endotoxin in the morning after PSD or
uninterrupted sleep. Depressive symptoms will be repeatedly assessed over 6 hours after
placebo or endotoxin administration.