Sleep Health, Inflammation, and Emotion Study
Condition: Depression
MeSH terms: Inflammation
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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.
    


Intervention name(s): Endotoxin; Partial sleep deprivation; Placebo; Uninterrupted sleep
Intervention type(s): Biological; Behavioral; Other; Other
Intervention description(s): Low dose endotoxin (0.8 ng/kg of body weight) as IV bolus; Partial night sleep deprivation by staying awake from 23:00 to 03:00; 0.9% saline as IV bolus; Uninterrupted sleep from 23:00 to 07:00
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science