Insomnia is a consistent risk factor for mood and anxiety disorders. However, the neural mechanisms underlying this risk relationship are poorly understood. In this exploratory study, we will collect preliminary data to test a novel hypothesis addressing these mechanisms: That insomnia is associated with dysregulation of positive and negative affect systems, similar to that seen in depression. More specifically, we hypothesize that insomnia is associated with increased activation of subcortical structures subserving negative affect, reduced activation of subcortical structures subserving reward and positive affect, and altered prefrontal control of both positive and negative affect. In order to better defne the dysregulation associated with insomnia, we will use both well-validated and more exploratory tasks affective tasks designed to evaluate affective processing at multiple levels, from affective processing, to voluntary regulation of affect, to personally-relevant sustained affect. Recognizing that sleep disturbances such as insomnia form a continuum with normal sleep, we will use the PROMIS Sleep Disturbance (PSD) scale, a dimensional measure with established population norms, as the independent variable. We will conduct clinical assessments, including dimensional and categorical measures of sleep and mood, in participants sampled from the full range of the PSD (n=60, 20 per PSD tertile). We will conduct functional magnetic resonance imaging (fMRI) studies to examine the neural mechanisms underlying positive and negative affect, which constitute the dependent variables. We will address the following Specific Aims:
Specific Aim 1. To examine neural mechanisms subserving positive affect as a function of insomnia severity. We hypothesize that greater insomnia severity will be associated with reduced activation of ventral striatum and increased activation of medial prefrontal cortex during anticipation and receipt of monetary reward;in response to a voluntary affect regulation task (increase positive affect);and in response to a personally-relevant sustained positive affect (savoring) task.
Specific Aim 2. To examine neural mechanisms subserving negative affective as a function of insomnia severity. We hypothesize that greater insomnia severity will be associated with increased activation of amygdala and reduced activation of dorsolateral and ventromedial prefrontal cortex in response to angry facial expressions during an acute threat task;in response a voluntary emotion regulation task (decrease negative affect);and during a personally-relevant sustained negative affect (rumination) task. We will also address exploratory aims focused on activation of other brain regions, connectivity between key brain structures, and responses among categorical participant groups. Innovative features of our study include the use of a continuous insomnia measure as the independent variable, and the use of novel activation tasks relevant to the phenomenology of insomnia and depression. This study addresses a plausible mechanism linking insomnia to affective disorders, and will support a subsequent R01 focusing on neural mechanisms of affect in insomnia and their modulation by behavioral treatment.

Public Health Relevance

Sleep disturbances such as insomnia increase the risk of developing conditions characterized by high negative emotion and low positive emotion, such as depression. However, we do not know how insomnia increases this risk. The aim of this research is to examine one likely hypothesis: That insomnia is associated with abnormal function of emotion circuits in the brain, even before a person manifests depression.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH102412-01A1
Application #
8765960
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Muehrer, Peter R
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213